ChemWiki - User contributions [en]

Talk:Mod:AM8709mod1

2011-12-01T21:35:18Z

Bnguyen: Created page with "As your submission is so late, the marking is very complicated so I actually include the mark of each round and your overall mark to explain why you get the mark at the end. We d..."

As your submission is so late, the marking is very complicated so I actually include the mark of each round and your overall mark to explain why you get the mark at the end. We don't normally release it here, but I hope this help you focus on the next two modules.

'''First marking round at the deadline 17.00 25/11/2011'''
====Q1====
*"However, Once endo isomers"
*"That is, in thermodynamically controlled conditions exo products are more likely to be formed as a major product, not exo products."
*I'm under the impression that you mix the endo-exo geometry of the products with endo-exo transition states.
*"Because the molecular wavefunctions of the species at the transition states have to be taken into account". No, because MM cannot form and break bonds!
*Your energies quote are beyond the accuracy limit of the technique.
*Wrong understanding of torsion energy.

Mark: 3/15
Total mark: 3/100

'''Second marking round at 17.00 26/11/2011, 15% penalty'''
====Q1====
*Same Jmol structure for 3 and 4.
*Still too many digits after the dot for energies. Correct energies though.
*Correct analysis of bend energy contribution "(Guozhu Liu 2005 Ind Eng Chem Res)" you should have learnt how to quote a reference in the write up page. What's the page number of the paper in question? and the volume?
*"Unlike the dimerisation, the hydrogenation of the endo dimer is a thermodynamically controlled reaction." Hydrogenation is almost never under thermodynamic control.

Mark: 5/15

====Q2====
*"(Bringmann G, Mortimer AJP 2005 Angew Chemie Int)" same problem as in question 1.
*"two chair conformations A and B" I think they're one chair, one twisted-boat.
*All your Jmols in Table 3 belong to question 1. Both MM2 and MMFF94 data are wrong, most like also taken from question 1.

Mark: 2/15
Total mark: 7/100. Applying 15% penalty gives 6/100. Adding the previous mark gives 9/100.

'''Third marking round at 17.00 27/11/2011, 30% penalty'''
====Q2====
*Jmols are now updated. But 9B and 10B are mixed up.
*The optimised energies seem correct, but still too many digits.
*" Therefore, we can conclude that the atropisomer with the carbonyl pointing below the ring 9 is thermodynamically more stable than 10. " Wrong, 10A is more stable than 9A.
*" The conformers 9A and 10A have larger dihedral angles compared to the the conformers 9B and 10B." where is the proof?
*" the dihedral angle for 10A is 167° while for 9A is 56°" A picture is required here. Your steric hindrance argument is not correct. The stabilisation comes from the near antiperiplanar arrangement of the alpha C-H and the C=O group, and is explained by MOs, which may not have been factored in MM2. The answer for the energy difference is elsewhere.
*"Hyperstable alkenes": you only provided bits of information from literature, but don't seem to understand the real reason here. Calculation of the energy of the hydrogenated product is required.

Mark: 6/15
Total mark: 6/100. Applying 30% penalty gives 4/100. Adding previous mark gives 13/100.

'''Fourth and final marking round, 45% penalty. We don't usually go beyond 72h, as the penalty by then is too high.'''
====Q3====
*MOs are ok, but I can only see the chlorine in some structures.
*Correct prediction of reactivity.
*IR frequencies correct.
*However, you completely failed to spot that the two double bonds are different in bond strength, bond length and vibrational frequencies. The reason for this was included in one of the references in the question.

Mark: 8/15. No Dspace link for SCAN calculation so that part receive zero mark, which leaves 4/15.
====Q4====
*You didn't explain your choice of the R group.
*your A and B' Jmols are wrong. The OAc groups are nowhere near the oxonium.
*PM6 energies are all wrong. How can it be the better method with those numbers?
*No calculation for C, C', D and D'.

Mark: 2/15
====Mini project====
*No Dspace link, no mark.
*No defined question. What structure are you calculating your C13 NMR for? Why?

Total mark: 6/15. Applying 45% penalty gives 3/15. Adding to previous mark gives 16/100.

Talk:Mod:RUNAOns1

2011-12-01T21:28:34Z

Bnguyen: Created page with "Overall, you did show good insights in some places, but the submission was rushed. I'm aware that you lost 1 day due to an interview, but you'll need to improve your time managem..."

Overall, you did show good insights in some places, but the submission was rushed. I'm aware that you lost 1 day due to an interview, but you'll need to improve your time management in the following modules.
====Q1====
*Computational chemists prefer to see kcal/mol.
*For torsion energy, you should have looked at the dihedral angles.
*Correct energies for 1, 2, 3 and 4.
*"Molecular mechanics tells chemists the most thermodynamic product." should be " Molecular mechanics tells chemists the most thermodynamically stable product."
*"It's transition state is more stabilised" should be " Its transition state is more stabilised".
*" Again, this information does not confirm the experimental major product." Good insight!
*If you go back to the diene 2 and look at the bond angles, you'll know the selectivity of the hydrogenation.
====Q2====
*" carbony group"
*" These are atropisomers, the rotation around a single bond is large enough" there's a barrier in there somewhare.
*"electrophiic additions"
*"This reactivity is expected when considering the rehybridisation required (sp2 to sp2) in such a reaction and the diasterous consequence this would have on angle strain."
*I think you need to put in a lot more analysis and explanation for the hyperstable alkenes here.
====Q3====
*Good analysis of the MOs and the selectivity.
*You should have used DFT to optimise the structures of 7 an 7'. Without that, your frequencies are significantly off.
*" the arguement put forward"
*" structure 8"
*You did look at the bond lengths, although the difference was small.
*No link to Dspace! This was later included.
====Q4====
*Jmol of anomer b missing.
====Mini project====
*Defined question.
*" it has the smalles deviation from literature"
*Again, no Dspace link. I had to ask you to login to SCAN to check the data a week after submission. The penanlty was 5%.
*You didn't correct the NMR of carbons next to a heavy atom as instructed in the wiki page.
*How did you determine which structure fits better? Based on the total difference? It's actually the wrong approach. You should have focus on the carbons whose chemicals shifts are likely to be different for the two structures.
*"a varity of equipement"

Talk:Mod:ss7009

2011-12-01T21:24:13Z

Bnguyen: Created page with "====Q1==== *There's no " mimicking" here, Cp acts as both diene and dienophile. *Your Jmol for 1 and 2 are for 3 and 4. *Correct energies for 1 and 2 and analysis of torsion ener..."

====Q1====
*There's no " mimicking" here, Cp acts as both diene and dienophile.
*Your Jmol for 1 and 2 are for 3 and 4.
*Correct energies for 1 and 2 and analysis of torsion energy.
*Correct energies for 3 and 4 and analysis of bend energy.
*Good appreciation of the 'wrong approach' for part 2
====Q2====
*" This type of isomerism is especially common in the Taxol precursor " only one compound, so it can't be common.
*Reasonable arguments and analysis of the data, although your structure for 9 isn't yet the lowest energy. But it's close enough.
*"Hyperstable alkenes": you understand the concept, but could have calculated the alkane to compare for the olefin strain.
====Q3====
*" Therefore, reaction with dichlorocarbene would render the endo double bond more susceptible to electrophilic attack."
*Your LUMO doesn't match your analysis, i.e. anti-bonding orbital of the double bond. Upon examining your Chem3D file, it turns out to be a bad picture. But you should have chosen a better view angle.
*Your vibrational frequencies are significantly off, presumably due to inadequate optimisation.
*No bond length analysis.
====Q4====
*"The neighbouring group affect is shown in Figure 15" should be " The neighbouring group effect is shown in Figure 15"
*" In addition, the acetyl groups possess oxygens and hydrogens, leading to strong hydrogens bonds." which hydrogen bond?
*" –OME (R=CH3)"
*Correct preference of PM6 over MM2.
*Correct structures for both MM2 and PM6.
*You spotted the energies for A and C are the same using PM6, but surely you must have checked the structure to see if they are identical?
*"A and B are more reactive than A’ and B’", wrong, A and B are more stable than A' and B'.
====Mini project====
*No defined question!
*your comparison between experimental data and calculated data is very difficult to follow, especially when only one set of experimental data was compared. Are the assignment included in the literature? Did you have to assign the individual carbon chemical shifts yourself?
*Correct spotting of the C4 which will have the most difference in chemical shift between the two structures. Again, this important point should have been made much more obvious. I had to hunt for it.
*Most argument on the selectivity is invalid here. One will to consider the transition states from the Crigee intermediates, which is beyond the scope of the techniques available to you.

Talk:Mod:jm3109

2011-12-01T21:21:36Z

Bnguyen: Created page with "Overall, your analysis is rather lacking, and causes most of the lost marks. ====Q1==== *"The dimer returns to a polymer upon heating." I don't think so. *Mixed up Jmols of 1 and..."

Overall, your analysis is rather lacking, and causes most of the lost marks.
====Q1====
*"The dimer returns to a polymer upon heating." I don't think so.
*Mixed up Jmols of 1 and 2.
*Correct energies for all compounds.
*You didn't give any analysis on the torsion energies of 1 and 2, other than mentioning the 1,4-strain.
*So which one, 3 or 4, is the major product of hydrogenation of 2?
====Q2====
*I would have liked to see the Jmol of the optimised structures for 9 and 10 here.
*"due to s(C-H) orbital overlapping with p*(C=O) orbital when the carbonyl group is "down" providing stability" you need to show this on the molecule.
*"Hyperstable alkenes": too brief! and "positioning of the double bond which gives a more cage like structure and decreasing the reactivity" isn't the reason for the stability. You need to analyse the hydrogenated product.
====Q3====
*How was the structure optimised?
*Your frequencies for hydrogenated 12 are correct.
*No bond length analysis!
====Q4====
*Correct choice of Me group
*You didn't specify which method you think is the better choice for the job.
*A/C and B/D are actually identical species, if you look at the structures.
*Your A' structure is wrong in both MM2 and PM6. The OAc group is nowhere near the oxonium.
*How does all these link to the diastereoselectivity?
====Mini project====
*You should cross-compare the experimental and calculated spectra to test the real ability of the technique to differentiate these isomers.
*Correct identification of C7-8 and C1-2 in the two structures as the key carbons.
*Were the IR frequencies corrected?

Talk:Mod:SJN2511

2011-12-01T21:19:20Z

Bnguyen: Created page with "====Q1==== *Correct energies for all compounds. *" 1.12 kcal.mol-1" *The second half could use some visual aid. I know what you're talking about, but a new reader would have stru..."

====Q1====
*Correct energies for all compounds.
*" 1.12 kcal.mol-1"
*The second half could use some visual aid. I know what you're talking about, but a new reader would have struggled to follow.
====Q2====
*"the "up" conformer (9) is less energetically favourable on account of inducing a higher-energy twist-boat conformation on the adjacent cyclohexane ring" the structure you showed actually is chair for the cyclohexane ring, as you pointed out later.
*"Which may be due to strain on the carbonyl sp2 carbon: even assuming ideal C-Ccarbonyl-C bond angle of 120° (it's usually a bit less), compound (9) exhibits 126°, compared to 120° for compound (10). " It's hard to ignore the opposite trend for the C=C double bond here.
*Comparing 10 and hydrogenated 10: you must balance the equation!
*Good explanation of the hyperstability of the alkene.
====Q3====
*Your MOs don't have the correct symmetry. There is an error in the software during optimisation process, which you're expected to spotted and rectify or discuss with us.
*"the LUMO is located around the anti-alkene bond, meaning that this bond will more readily undergo nucleophilic attack instead of acting as an nucleophile. The LUMO+1 and LUMO+2 calculations serve to show that even the chlorine-carbon bond would undergo nucleophilic attack before the endo-alkene bond would" you need to read the reference included in the question.
*Vibrational frequencies for 12 are slightly off. Again, this has to do with the optimisation process.
*Bond length discussion missing. The discussion on the interaction between the anti double bond and the C-Cl anti-bonding orbital is too brief.
====Q4====
*"diastereoisomery"
*"the oxocarbenium and dioxolonium conjugated systems"
*Correct choice of the Me group.
*B' Jmols are wrong diastereomers. So are D and D'.
*Much more analysis can be done here For example the difference between MM2 and PM6 results. The energies of intermediates and the diastereoselectivity of the reaction.
====Mini project====
*Distinguishing between 5 and 6 is so trivial, it doesn't require computational chemistry. The diastereoselectivity of the reduction (to give either 5 or 6) is worth studying and you were meant to do that.
*Optical rotation: what you have for 6a is the epimer of 6, not enantiomer. Hence the same sign of rotation for both compounds.
*I'm not following your HOMO/LUMO argument here. In any case, modelling radical reactions, particularly the transition states, is extremely tricky and require much higher level of theory. Brave attempt though.

Talk:Mod:mtr09mod1

2011-12-01T21:16:34Z

Bnguyen: Created page with "Overall, I like you way of presenting the data, especially the Jmols, which prevents cluttered tables and give the data some clarity. ====Q1==== *Correct energies, correct analys..."

Overall, I like you way of presenting the data, especially the Jmols, which prevents cluttered tables and give the data some clarity.
====Q1====
*Correct energies, correct analysis of endo-exo-thermodynamics-kinetics.
*Correct analysis of torsion energy.
*You used product 3 and 4, but list product C and D in the table.
*Very detailed analysis of the energy components of 3 and 4. But a bit more on the selectivity of the reaction itself would be great.
====Q2====
*You've shown some understanding about the difference between MM2 and MMFF94, which isn't always appreciated by undergraduates.
*"For Molecule 9, this antiperiplanar relation is lost, and replaced by a highly unfavourable synperiplanar arrangement. The unfavourable nature of these interactions causes Molecule 9 to undergo isomerisation to form Molecule 10" Why is the antiperiplanar arrangement is better than the synperiplanar? You'll need to explain this, perhaps with a diagram.
*"very large rings effectively have allyic alkene bonds" should be "very large rings effectively have allylic alkene bonds"?
*"The value of total energy is lower for the hydrogenated product than for the its alkene precursor", should be "higher". The correct analysis when comparing 10 and hydrogenated-10 should yield bend and 1,4 WDW energies as the main contributor.
*You must balance your equation when comparing the energies of different system!
====Q3====
*The reason that the MOs aren't strictly symmetrical is because the optimisation went wrong and slightly remove the symmetry. Re-optimisation via a different method helps!
*"the electrophillic chlorocarbene species" should be "the electrophillic dichlorocarbene species"
*You didn't specify whether you saw the interaction described by Rzepa in your MOs calculation. You also need to be more explicit in explaining the different in reactivity between the two double bond. What is controlling the reactivity with electrophiles? And how the listed factors influence that.
*"Upon optimisation, it was noted that the saturated ring became slightly more bent". It actually went into staggered conformation, which is preferred for alkanes.
*Dspace link could be more obvious rather than being reference. No penalty here, but it would certainly help the marking process.
*You completely ignored the bond lengths while analysing bond strength.
*Your frequencies for 13 are off. Did you optimise the structure using DFT prior to frequencies calculation? Still the argument was correct.
====Q4====
*"The disparity between methods is evident for larger systems, such as the ones we are currently analysing". Actually the real reason why MM2 is completely inadequate here is because it can't deal with either the oxonium (non-classical cation) and the interaction between that and the lone pair rbitals on OAc.
*Correct choice of Me group, but you didn't discuss why we can't go with just OH.
*Your MM2 Jmols are fine, but your numbering is different from that in the question (A and A'). Since the oxonium ring has a very different shape from cyclohexane, axial and equatorial don't have any meaning anymore.
*PM6 Jmols: A is wrong (the CH2OMe is now swinged in to stabilise the oxonium while OAc is pointing away), B' is most certainly wrong as all these groups get lumped up, this is where the software fails and you have to be the brain.
*Well spotted A = C, B = D. Your calculation is probably correct, but the much easier one is K = exp(-dG/RT). The conclusion is still the same! Remember the difference for C/C' and D/D' calculated by MM2? It's very very different from the PM6 results.
====Mini project====
*Your question isn't well defined. You elaborated later on, but maybe a short summary at the beginning would help. It's a lot of work you've done and readers may find it difficult to follow.
*Minimisation using just AM1 might be a problem, as NMR calculations are highly sensitive to conformational changes.
*I think you're trying to handle too much data at once, which somewhat affect the effectiveness of the analysis and data presentation.
*Correct focus on the relevant carbons.
*15N NMR: what are the literature values? Quite hard to find, actually. SO we can't check if the prediction is good! If you forget the 4-membered ring, the one N is next to a carbonyl and a C-O2C, the other is next to a carbonyl and a C-CO2 (very much like in proteins, for which 15H NMR data is plentiful).
*IR spectra is very tricky in this case, as predictions aren't accurate enough, and the region in question normally has other peaks in them.

Talk:Mod:NishMeisterG

2011-12-01T21:10:43Z

Bnguyen: Created page with "====Q1==== *“one is more kinetically stable” wrong term! *Correct energies for 1, 2, 3 and 4. But your energies cannot be accurate to the 4th digit after the dot. *Correct an..."

====Q1====
*“one is more kinetically stable” wrong term!
*Correct energies for 1, 2, 3 and 4. But your energies cannot be accurate to the 4th digit after the dot.
*Correct analysis of torsion and bend energy.
*Hydrogenation is actually under kinetic control (irreversible!), so looking at the product as we did is the wrong approach. But that’s what we have to start with.
====Q2====
*Correct energies all around.
*Can’t seem to get the energies reported from the Jmol structures included for chair 9 and 10. Ask for chem3D files.
*Correct analysis and reasonable explanation of hyperstable alkenes.
====Q3====
*Reasonable MOs, but not perfect as they’re not close to symmetrical.
*Good account for the reactivity using HOMO, and the s-p* interaction.
*Wrong vibrational frequencies for monohydrogenated 12, and the analysis afterward
*No analysis on bond lengths.
====Q4====
*What’s the reason for the Me group?
*Jmol of PM6 structure missing. Energies seem correct.
*“the conformations of A and B are lower in energy, and are more reactive than A' and B'.” If A and B are lower in energy then they’re less reactive. Think of the population distribution!
*Overall, you could have analyse much more the results, especially comparing the structure of A and C, B and D from PM6 calculation.
====Mini project====
*Not well defined question at all!
*“However the energies are still very similar indicating that the reaction would yield both products.”, again you need to discuss the thermodynamics vs kinetics argument here. *Is the reaction reversible?
*“The minimised energies for 11a and 12a, using Gaussian were -443147 kcal/mol and -443903 kcal/mol respectively.” Non-sensible numbers! We can only take the difference in energy here.
*Correct focus on the C in the 4-member ring. But where is the experimental data?
*Overall, you tried to do too much, and your data presentation did not help your case. Some discussion with us during the process would have helped.

Talk:Mod:PAP0801

2011-12-01T21:07:52Z

Bnguyen: Created page with "====Q1==== *Which method did you use for your calculation? This is really important. *“the kinetically more stable product” isn’t correct. *“The derivative does not have ..."

====Q1====
*Which method did you use for your calculation? This is really important.
*“the kinetically more stable product” isn’t correct.
*“The derivative does not have a specific stereochemistry because bond rotation is no longer restricted by the presence of C=C double bonds” ???
*You studied the wrong structures for 3
*The analysis of bend energy is correct.
====Q2====
*“Both MM2 force-field and MMFF92 field” should be “Both MM2 force-field and MMFF94 field”
*“hyperstable alkenes” question was not dealt with properly. Your explanation was simply too brief.
====Q3====
*Your Jmol structures don’t look like they’ve been optimised.
*The MOs don’t look symmetrical, due to a software generated error in optimising your structures. But you should have spotted this.
*Correct analysis of HOMO and prediction of reactivity.
*Your IR frequencies are correct. But you should have comment on the different frequencies for the two double bonds in 12. The bond lengths also deserve mentioning.
====Q4====
*“The MM2 force field and MOPAC/PM6 force fields“, PM6 is a quantum mechanics technique and doesn’t have a force field.
*In your A’ and B’ Jmols, the OAc group is nowhere near the oxonium. It is actually possible to bring it in, and you should have asked us to show you.
*PM6 structures are presumably quite different, and worth showing.
*Wrong conclusion on MM2 vs PM6. PM6 actually take the full effect of neighbouring group into account and optimise A straight to C, which is the more stable intermediate.
*How do all these link to the observed selectivity? K = epx(-E/RT)?
====Mini project====
*MM2 is rather inadequate for optimisation in this case. Even a small change in conformation can have large consequences in 13C shifts.
*“The MOPAC results show very little difference in the energy of the isomers so it is not a good method to use for the minimisation of energy in this example”, what’s the justification for this?
*There is actually a huge difference in 13C NMR of A and B, both in experimental data and calculated data if you focus on the carbons which matter: C1 and C2. Analysis of 13C NMR calculation, especially in cases where one try to differentiate between structures, must focus on the carbons whose environment changes, not all the carbons as that would dilute the difference.
*In terms of methodology, you should have compared the two calculated spectra with each experimental spectrum to see if their assignment was correct. Not to compare A and calculated A, B and calculated B.
*1H, J coupling constant and IR are all inappropriate in this case, so there’s no point in doing them.

Talk:Mod:CN2209

2011-12-01T21:04:10Z

Bnguyen: Created page with "====Q1==== *Which 1,4-repulsive interaction are you talking about? If it's the torsion component of the MM2 energy, it has little to do with Figure 3. Torsion is all about dihedr..."

====Q1====
*Which 1,4-repulsive interaction are you talking about? If it's the torsion component of the MM2 energy, it has little to do with Figure 3. Torsion is all about dihedral angles.
*Good explanation of the thermodynamics vs kinetics consideration.
*" two more stereospecific dihydro derivatives": wrong term.
*Good analysis on the bend components of 3 and 4.
====Q2====
*Correct optimised structures of 9 and 10.
*Don't speculate about things you don't know in any scientific communication: MM2 vs MMFF94.
*Calculated energy of H2 in MM2 is 0 kcal/mol.
*Overall, I think you understand the concept of hyperstable alkenes, and how they come about.
*Energy of 9-chair off by 1 kcal/mol. Assumed typo but must subtract 2%.
====Q3====
*How was the structure optimised? It's actually very important.
*Correct prediction of reactivity with Cl2C:
*Reasonable account for the vibrational frequencies. As often, you also neglected the bond lengths of the bonds in question.
====Q4====
*A isn't the lowest energy which could be found. You made the mistake of taking the lowest energy conformation in MM2 and perform PM6 on it.
*You failed to spot A = C and B = D in PM6 but not in MM2. This is a perfect case for comparing MM2 and PM6 as computational methods in organic chemistry.
*A translation from the difference in energy for C/C' and D/D' to equilibrium constants would give some numbers to explain the diastereoselectivity here. It's very important to be able to translate energy in kcal/mol to observed selectivity.
====Mini project====
*You failed to cite the references for the ruthenium-catalysed reactions you mentioned.
*Overall, your comparison is flawed and your question not well defined. You should have compared experimental data with both calculated spectra, and see if it fits the correct prediction better. Focus should have been on the carbons which one can predict to have significantly different chemical shifts between two structures, rather than average over the whole structure.
*5% taken for late Dspace links

Talk:Mod:lp0190 module1

2011-12-01T20:52:24Z

Bnguyen: Created page with "====Q1==== *Correct energies for 1, 2, 3 an 4. *You seem to have some understanding of the thermodynamic and kinetic products. But the explanation could have been clearer. *When ..."

====Q1====
*Correct energies for 1, 2, 3 an 4.
*You seem to have some understanding of the thermodynamic and kinetic products. But the explanation could have been clearer.
*When comparing 3 and 4, a picture showing the bond angles in question would be great help. There're four bond angles in total involving the double bonds.
====Q2====
*"an example of altropisomerism" should be "an example of atropisomerism"
*Are the included Jmols from MM2 or MMFF4?
*"lower in energy by 5.16 Kcal/mol" according to which method?
*"Hyperstable alkenes": again, you seem to understand the concept, but struggled to explain it. The use of pictures certainly helped your cause. If you had included the energies of the two compounds in question, it would be even better.
====Q3====
*You need to give the information on how the structure was optimised before the MO calculation.
*Correct analysis of the HOMO and the interaction between the anti-double bond and the C-Cl anti-bonding orbital.
*The original reference of previous computational study on this system (in the question) should have been cited.
*You did not analyse the bond lengths which is also a very informative factor when discussing bond strength.
====Q4====
*Your optimised structures are not yet the lowest energies for A, A', B, and B'.
*A' and B' PM6 structures: no interaction between the OAc and the oxonium. You're expected to give an explanation here.
*In fact, for PM6 A = C, B = D.
*" The computational results can therefore be used to rationalise the diastereospecificity in glycosidation". What's the experimental diastereoselectivity for this reaction? Does the difference in energies between C and C', D and D' agree with that number?
====Mini Project====
*No well defined question. Calculated data is bound to be different from experimental data. You can only compare different structures, or different methods of calculation and find which one fits better. You should have discussed this with us.
*There seems to be a huge different for the IR O-H stretch. You mentioned that these are systematically higher than experimental data by 8%, but need to give a reference for that statement.
*" optical rotation is much more sensible to conformations" should be " optical rotation is much more sensitive to conformations"
*The optical rotation results is interesting as the sign of rotation is everything here. The absolute rotational power is very often wrong. We don't tend to use them as the diagnostic tool.

Talk:Mod1:zy909

2011-12-01T20:47:57Z

Bnguyen: Created page with "====Q1==== *Well researched and written introduction. *"ring A (blue - see structure)" I could find this, even including the Jmol structures. *It's not MM2 fault for not being ab..."

====Q1====
*Well researched and written introduction.
*"ring A (blue - see structure)" I could find this, even including the Jmol structures.
*It's not MM2 fault for not being able to predict the major product as implied in your text. We're only examining the products here. The question highlights that one need to consider all factors in a reaction before making prediction of the major product.
*Good arguments on the torsion and bend energy.
*you could have reported the bond angles for 3 and 4 to illustrate your point.
====Q2====
*"isomerises to the down position" should be "isomerises to the 'down' position"
*Reasonably optimised structures. But you didn't specify which method was used for the Jmol? Were the two results independently optimised by MM2 and MMFF94? Or did you use the optimised structure of one method and just calculate the energy using the other?
*Overall, I think you made very good analysis of the data from your "hyperstable alkenes" calculation. However, the work might have benefited from a more detailed explanation of "hyperstable alkenes". You're making the assumption that the readers know the subject.
*One important thing when comparing energies of different compounds (not isomer) is that you must balance the equation. In this case, the energy of H2 (0 kcal/mol) should have been mentioned in the comparison betwee3n 10 and 11.
====Q3====
*syn/anti terminology is preferred here for consistency with the question.
*The facial selectivity was well spotted and easy to explain. Maybe you should have explained it.
*You're the first one this year who put down why the calculated MOs were not symmetrical as they should be, and how to solve it.
*Your MOs were clearly visualised in Gaussview and not Chem3D. How were they calculated (PM6 or DFT)?
*Correct analysis of HOMO and mixing between two MOs.
*How did you calculate your vibrational frequencies? It seems to me that structure 15 wasn't properly optimised.
*You forgot to measure the bond lengths to back all the arguments on bond strength up.
====Q4====
*The picture A/A' could have benefited from an clarification on the method used.
*The orientation of the 6-OMe group is quite interesting. In MM2, certain arrangement can bring the energy extremely low. I'm not sure I understand your argument that"this hampered the interaction between the 2-OAc and the oxonium". More clarification is needed here.
*The fact that you included the Jmol of all methods is much appreciated.
*A' (MM2) is off.
*Did you notice that for PM6, A = C, B = D? They are the same structure. Again, the almost identical energies are the clue.
*Your energies are generally alright, but the link to the experimental diastereoselectivity is missing. Energies of intermediates in different pathways are quite important when it comes to explaining the diastereoselectivity of the reaction.
====Mini project====
*5% for your own mini project
*Well defined question!
*The difference between experimental and calculated data shouldn't have been taken as absolute value. See the example from Rzepa and Braddock in my talk for data presentation.
*The comparison between calculated and experimental data you did is very tricky when difference were taken as absolute values.
*Generally the average difference is quite uninformative. We tend to focus on the C's we expect to have significant change in chemical shifts. The reason for the change in the carbonyl carbon chemical shifts is quite interesting here.
*Nevertheless, a quick look at your raw data led me to suspect (6S, 11R) to fit the chemical shifts of C6 and C11 better. Obviously, the project would have benefited much more from a discussion with us.

Talk:Mod:SergioGeorgini

2011-11-19T17:20:13Z

Bnguyen: Created page with "Please make sure you put in references before submission, particularly for Figure 4. ====Q1==== *Torsion energy explanation: dihedral angles. *Your analysis on the source of the ..."

Please make sure you put in references before submission, particularly for Figure 4.
====Q1====
*Torsion energy explanation: dihedral angles.
*Your analysis on the source of the difference in bend energies is correct, but Figure 6 and 7 are hard to see until I click on the picture. Tip: remove empty space.
====Q2====
*You seem to be fixed on 10 being more stable at the beginning even before showing the calculation results.
*"lowest totsl energy"
*Table 4: you need to clarify where the breakdown of energies come from. Are there any significant difference using MMFF94?
*You seem to understand the point I raised above with your comparison. However, the more corrected comparison between different techniques is the absolute difference in energy between 10 and 9. This is an observable quantity, which is directly related to the equilibrium constant between 9 and 10. Do MM2 and MMFF94 agree with each other?
*You were spot-on with hyperstable alkenes and the comparison in energy with hydrogenated product is appropriate. However, if you want to compare the energies of two different systems, you must BALANCE THE EQUATION.
====Q3====
*You might want to clearly explain how the structures were optimised and how the MOs were calculated. Instructions are included in the question, but we would still want to be absolutely certain which techniques students used. Sometime you guys even do a better job than we prescribed.
*Figure 14 -15: the main gripe is that there is too much empty space and the molecules I can see are consequently small. Clicking on the picture helps, but if you can please trim the pictures.
*Your MOs could be made smoother and nicer using Chem3D options. Talk to us if you don't know how.
*You talked about PM6 at the beginning, and then PM3 at the end. Please double check!
*Correct spotting of the ?*-? interaction, but you'll need to provide a better explanation for the selectivity. What is the carbene looking for to react? What's the mechanism?
====Q4====
*A' picture missing.
*A' MM2 and PM6 jmol missing. I do like it that you included the jmols from both methods.
*Please double check D and D'.
*You correctly spotted that energies of A and C are the same using PM6. Are the structures the same? and if MM2 gives different results, which method is wrong?
*From the energies for intermediate C/C' and D/D' can you calculate their equilibrium constants and predict the diastereoselectivity of the reactions?
====Overall====
I think you did a good job for week 1. Obviously more careful analysis and tuning to data presentation is required, but most of the data is solid. If you still aren't sure about something, do come and talk with us.

Talk:Mod:SAMROWE001

2011-11-19T17:16:47Z

Bnguyen: /* Q3 */

====Q1====
*Correct calculation for the dimers, but we're looking for some analysis as well. Where do you think the difference in energy come from? Which part of the molecules is responsible for it? The two hydrogens you mentioned is part of it, but there's more. You'll need to go back to the meaning of each component of the overall energy.
*Again, which part of the monohydrogenated compounds is responsible for the difference in bend energy?
====Q2====
*I appreciate that you discussed the twisted-boat conformers and explained how you arrived at the final optimised structures.
A bit more analysis on the MMFF94 data and components would be great here. Does it give the same structure as MM2?
*I think you 'get' the concept of hyperstable alkenes, but will need to explain it more clearly. Why didn't you show more calculation results of the hydrogenated compound? Can you compare that with the alkene (BIG CLUE: balance the equation!).
====Q3====
*Your picture size is good, but from this point of view I can't see the other half of the molecule. This is important when looking at MOs, so please adjust the pictures.
*A bit more elaboration on the σ*-π interaction (specifying each orbitals are involved and the consequences which you will observe later with your vibrational frequencies calculation) would be great.

====Q4====
*Which complex interactions are we talking about? and why can't MM2 handle them?
*From the energies for intermediate C/C' and D/D' can you calculate their equilibrium constants and predict the diastereoselectivity of the reactions?
*Your MM2 structures (which I can't find) aren't the lowest in energy, although your PM6 energies are close (not quite yet). However, it's the analysis and explanation that matter here.
*It would be very important to have a figure showing which structures are A/A' B/B' C/C' and D/D'. I already think you're using a different system from the one in the question.
*" it is able to detect that ring B' shows many unfavourable orbital interactions and therefore distorts the entire geometry to produce a structure which is very similar to that of ring B. " I don't think there is unfavourable interaction here. B is just so more stable. Did you start off with structure B from MM2? Again, since I'm not seeing the jmol, it's all guess work.
*The whole purpose of this question is to let students find out the origin of the diastereoselectivity observed for this kind of reaction. From the energies for intermediate C/C' and D/D' can you calculate their equilibrium constants and predict the diastereoselectivity of the reactions?

====Overall====
I think you made a good start, but the analysis side is still lacking for really good mark. Nevertheless, I hope the feeback help and would welcome any further discussion.

Talk:Mod:SAMROWE001

2011-11-19T17:16:04Z

Bnguyen: Created page with "====Q1==== *Correct calculation for the dimers, but we're looking for some analysis as well. Where do you think the difference in energy come from? Which part of the molecules is..."

====Q1====
*Correct calculation for the dimers, but we're looking for some analysis as well. Where do you think the difference in energy come from? Which part of the molecules is responsible for it? The two hydrogens you mentioned is part of it, but there's more. You'll need to go back to the meaning of each component of the overall energy.
*Again, which part of the monohydrogenated compounds is responsible for the difference in bend energy?
====Q2====
*I appreciate that you discussed the twisted-boat conformers and explained how you arrived at the final optimised structures.
A bit more analysis on the MMFF94 data and components would be great here. Does it give the same structure as MM2?
*I think you 'get' the concept of hyperstable alkenes, but will need to explain it more clearly. Why didn't you show more calculation results of the hydrogenated compound? Can you compare that with the alkene (BIG CLUE: balance the equation!).
====Q3====
*Your picture size is good, but from this point of view I can't see the other half of the molecule. This is important when looking at MOs, so please adjust the pictures.
*A bit more elaboration on the ?*-? interaction (specifying each orbitals are involved and the consequences which you will observe later with your vibrational frequencies calculation) would be great.
====Q4====
*Which complex interactions are we talking about? and why can't MM2 handle them?
*From the energies for intermediate C/C' and D/D' can you calculate their equilibrium constants and predict the diastereoselectivity of the reactions?
*Your MM2 structures (which I can't find) aren't the lowest in energy, although your PM6 energies are close (not quite yet). However, it's the analysis and explanation that matter here.
*It would be very important to have a figure showing which structures are A/A' B/B' C/C' and D/D'. I already think you're using a different system from the one in the question.
*" it is able to detect that ring B' shows many unfavourable orbital interactions and therefore distorts the entire geometry to produce a structure which is very similar to that of ring B. " I don't think there is unfavourable interaction here. B is just so more stable. Did you start off with structure B from MM2? Again, since I'm not seeing the jmol, it's all guess work.
*The whole purpose of this question is to let students find out the origin of the diastereoselectivity observed for this kind of reaction. From the energies for intermediate C/C' and D/D' can you calculate their equilibrium constants and predict the diastereoselectivity of the reactions?

====Overall====
I think you made a good start, but the analysis side is still lacking for really good mark. Nevertheless, I hope the feeback help and would welcome any further discussion.

Mod:organic

2011-11-18T13:49:55Z

Bnguyen: /* : Structure based Mini project using DFT-based Molecular orbital methods */

See also: [[Mod:timetable|Timetable]],[[Mod:lectures|Intro lecture]],[[mod:laptop|Laptop use]], [[mod:programs|Programs]], [[mod:organic|Module 1]], [[Mod:inorganic|Module 2]], [[Mod:phys3|Module 3]],[[Mod:writeup|Writing up]], [[Mod:dont_panic|Don't panic]].

----
This module comes in two parts, examples of the use of the basic tools, followed by a mini-project.
= The basic techniques of molecular mechanics and semi-empirical molecular orbital methods for structural and spectroscopic evaluations =

==Objectives of this module of the course:==
It is now possible using a computer to accurately model many aspects of organic structure and reactivity, and such modelling can often be used not only to rationalise the outcomes of reactions, but to predict useful modifications or even new types of reaction. The selection of (short) modelling experiments contained in this module of the course attempts to illustrate some of the diversity of such molecular modelling. The module ends with a more open-ended exploration or ''mini-research'' exercise typical of that very often experienced in synthetic chemistry labs; namely is the structure of my final product correct?
#To use molecular mechanics (< 10 hours) to predict the geometry and regioselectivity of:
##the hydrogenation of cyclopentadiene dimer
##the stereochemistry of nucleophilic addition to two different pyridinium rings([[organic:NAD|NAD+ analogues]])
##the conformation/atropisomerism of a large ring ketone intermediate in one synthesis of the anti-cancer drug Taxol
#To use semi-empirical and DFT molecular orbital theory (< 10 hours) to investigate:
##the origins of the regioselectivity of the electrophilic carbenylation of a chloro-substituted bicyclic diene,
##the use of DFT molecular orbital theory to investigate Neighbouring group participation ([[organic:NGP|NGP]]) on the C-Cl and/or C=C stretching frequency of the above bicyclic diene
##concluding with a Mini-project investigating spectroscopic simulation in an organic molecule.
#To gain familiarity with the use of a institutional digital repository (< 5 minutes)
#To perform searches of the literature for each topic in order to cite in your final report any relevant references to each experiment as appropriate (< 1 hour)
#To present the results in the form of a Wiki page, with credit given for any annotation of these course notes, either to pages created here, or Wikipedia entries.
=== Background information ===
A general coverage of many of the topics in this module can be found in the [http://www.ch.ic.ac.uk/local/organic/mod 3rd year course on molecular modelling]. Podcasts (including slides and additional links to other related materials) can be found at this site.

A [http://www.mendeley.com/groups/4657/molecular-modelling-course/ Mendeley shared course page] has been set up as a pilot project. You will have to register with Mendeley to participate.

==Modelling using Molecular Mechanics==

A general introduction to the [[mod:molecular_mechanics|Molecular Mechanics]] (MM) method should be consulted before attempting any calculations. The present techniques illustrate several more complex applications of this method to typical chemical problems and the type of information that such modelling is capable of providing. This involves optimising molecular geometry to an energy minimum and analysing the final energy in terms of bond length and angle strain, steric effects and van der Waals contributions.

Before discussing specific applications of such a model, it is worth noting some of the limitations of the molecular mechanics approach. It is essentially a parametric method, using data from experimentally well characterised and known molecules. It is therefore used as an interpolative rather than an extrapolative technique, which cannot stray too far from "known chemistry". Thus it is not easily possible to model "kinetic control" of a reaction using the standard approach, since that requires knowledge of the transition state structure and energy. For the same reason, new molecules with unusual bonding are rarely amenable to modelling, and recourse has to be sought in the full quantum mechanical treatment of the system. Similarly, for molecular properties such as stereoelectronic effects, aromaticity, hyperconjugation and frontier orbital interactions which require a knowledge of the electron distribution within the molecule, recourse has to be made to quantum mechanical methods such as molecular orbital theory. Finally, molecular mechanics parameters are available only for certain types of bonds, and frequently are not available for many functional groups. Metal ions are also a category less easily handled at present by this type of model.

You will be using the Allinger MM2 molecular mechanics models<ref>Conformational analysis. 130. MM2. A hydrocarbon
force field utilizing V1 and V2 torsional terms {{DOI|10.1021/ja00467a001}}</ref> as implemented in the ChemBio3D program (which also supports MMFF94, useful for modelling biological systems, such as DNA, proteins, carbohydrates). MM3, MM4, Amber 11, force fields have also been developed, but are not implemented in ChemBio3D. You could alternatively use programs other than ChemBio3D, such as '''Ghemical''' (which you may remember from 2nd year), or the newer '''Avogadro'''.

'''Information Produced by the Programs''': ChemBio3D using MM2 produces an energy (in kcal mol-1) together with optimised values for bond lengths, angles etc. This energy is a rather odd quantity. It is NOT related to any thermodynamic quantity such as ΔH, and energies obtained using two different force fields CANNOT be compared. You CAN however compare two energies calculated using the same force field for two different ISOMERS. You can also calculate energy differences for simple reactions such as the hydrogenation of alkenes, particularly if this is compared across a series of related reactions. The energy itself can be dissected into contributions from the stretching ('''str'''), bending ('''bnd'''), torsion ('''tor'''), van der Waals ('''vdw''') and hydrogen bonding ('''H-Bond''') energy terms. Each term indicates the deviation from "normality" of the particular function. For example, a very positive stretch term would indicate the predicted bonds are far from the "natural" lengths, due to some geometrical feature of the molecule. Comparing these terms across say two isomers provides a natural explanation for why one isomer may be more stable than the other. Documentation for the programs being used is found here:
# Molecular Mechanics, Semi-empirical MO, Ab initio/DFT MO: [[mod:chem3d|ChemDraw/ChemBio3D]].
# Ab initio/DFT MO: [[mod:gaussview|Gaussian/Gaussview]]

===The Hydrogenation of Cyclopentadiene Dimer===

[[Image:t51.gif|right]]Cyclopentadiene dimerises to produce specifically the endo dimer '''2''' rather than the exo dimer '''1'''. Hydrogenation of this dimer proceeds to give initially one of the dihydro derivatives '''3''' or '''4'''. Only after prolonged hydrogenation is the tetrahydro derivative formed. The modelling technique here involves calculation of the geometries and energies of all four species '''1-4'''. 

The relative stabilities of the pairs of compounds '''1'''/'''2''' and '''3'''/'''4''' should indicate which of each pair is the less strained and/or hindered in a thermodynamic sense. The observed reactivity towards cyclodimerisation and hydrogenation can of course be due to either thermodynamic (''ie'' product stability) or kinetic (''ie'' transition state stability) factors. In pericyclic reactions in particular, regio and/or stereoselectivity is controlled by the electronic properties of the molecules (stereoelectronic control), and hence can only be understood in terms of ''eg'' the molecular wavefunction (''cf'' 2nd year lectures on pericyclic reactions). On the basis of the results obtained from the molecular mechanics technique you should be able to suggest whether the cyclodimerisation of cyclopentadiene and the hydrogenation of the dimer is kinetically or thermodynamically controlled.

You might wish to revisit this particular experiment in [[Mod:physical|Module 3]] of this laboratory course.

====Procedure====

Using Chem3D, define the two products '''1''' and '''2''' and optimise their geometries using the MM2 force field option. In the light of the above discussion, relate your results to the observed mode of dimerisation. The two products of hydrogenation '''3''' and '''4''' can be similarly compared so that a thermodynamic prediction of the relative ease of hydrogenation of each of the double bonds in '''2''' can be obtained. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and hydrogen bonding (H-Bond) energy terms in terms of the relative stability of '''3''' and '''4'''.

Estimated time for completion: < 30 min.

===Stereochemistry and Reactivity of an Intermediate in the Synthesis of Taxol.===

[[Image:Taxol_molecules.gif|right]]A key intermediate '''9''' or '''10''' in the total synthesis of Taxol (an important drug in the treatment of ovarian cancers) proposed by Paquette is initially synthesised with the carbonyl group pointing either up or down. On standing, the compound apparently isomerises to the alternative carbonyl isomer. This is an example of [[organic:atropisomerism|atropisomerism]]. Clearly the stereochemistry of carbonyl addition depends on which isomer is the most stable. It is also noted that during subsequent functionalisation of the alkene, this reacted abnormally slowly!

====Procedure====

Using molecular mechanics MM2 force-field to determine the most stable isomer '''9''' or '''10''', and to rationalise why the alkene reacts slowly (hint: find literature on hyperstable alkenes!). Pay particular attention to the conformation of the resulting optimised structure, to see if any aspect of this structure could be improved by further minimisations (preceeded if necessary by a manual edit of the structure to move atoms into more correct orientations). Does the MMFF94 field produce similar results?

Estimated time for completion: < 2 hour in total.

==== Key literature ====

# S. W. Elmore and L. Paquette, ''Tetrahedron Letters'', '''1991''', 319; {{DOI|10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0}}
# See J. G. Vinter and H. M. R. Hoffman, ''J. Am. Chem. Soc.'', '''1974''', ''96'', 5466 ({{DOI|10.1021/ja00824a025}} {{DOI|10.1021/ja00824a025}}) and '''95''', 3051 for another nice example of atropisomerism.
# Another well known example is within Vancomycin: ''J. Am. Chem. Soc.'', '''1999''', ''121'', 3226. DOI: [http://dx.doi.org/10.1021/ja990189i 10.1021/ja990189i]
# An interesting variation is of "atropenantioselective cycloetherification" (G. ÊIslas-Gonzalez, M. ÊBois-Choussy and J. ÊZhu, ''Org. Biomol. Chem.'', '''2003''', 30-32. DOI: [http://dx.doi.org/10.1039/b208905 10.1039/b208905].
# First paper formally recognizing the new class of "hyperstable" olefins (Wilhelm F. Maier, Paul Von Rague Schleyer, ''J. Am. Chem. Soc.'', '''1981''', ''103'', 1891. DOI: [http://dx.doi.org/10.1021/ja00398a003 10.1021/ja00398a003]

==Modelling Using Semi-empirical Molecular Orbital Theory.==

In part 1, the strengths and weaknesses of a purely mechanical molecular model were illustrated. In particular, the ''endo'' stereoselectivity in Diels Alder cycloadditions was attributed to "secondary orbital" interactions, which the Molecular Mechanics approach cannot handle. In this section, such electronic aspects of reactivity will be illustrated, showing how explicit consideration of the electrons in molecules must be taken into account, and how the electrons influence bonds and derived spectroscopic properties.

===Regioselective Addition of Dichlorocarbene===

#[[Image:t55.gif|right]]'''Part 1:''' Orbital control of reactivity is illustrated in the reaction of compound '''12''' with electrophilic reagents such as dichlorocarbene or peracid. In modelling such a reaction, we require a program where the geometry of '''12''' can be predicted, and the energy of the orbitals calculated and their form displayed graphically. This experiment serves to illustrate the transition from a purely classical mechanical treatment of a molecule to a quantum mechanical treatment which includes the wave-description of the electrons. Use the ChemBio3D program and select the following methods to calculate the energy and geometry of this molecule:
## MM2 (this runs in just a few seconds and cleans the geometry up prior to applying an electronic method).
## MOPAC/PM6 or MOPAC/RM1 MO methods provide an approximate representation of the valence-electron molecular wavefunction, and in particular of the HOMO (Highest Occupied Molecular Orbital), presumed to be the most reactive towards electrophilic attack (this runs in 30 seconds or less). Does this method discriminate between the two alkene bonds? Reaction with dichlorocarbene is similar to electrophilic addition, and the HOMO indicates which of the two alkenes is the most nucleophilic.
#'''Part 2:''' The purpose here is to calculate the influence of the Cl-C bond on the vibrational frequencies of this molecule. You will compare two molecules; compound '''12''' which contains a double bond anti to the Cl-C bond and a hydrogenated version where this anti (or exo) double bond (but not the other) is replaced by a C-C single bond. The most reliable procedure for obtaining vibrations is the '''density functional''' approach (but you could use the far faster MOPAC/RM1 method and check this assertion!).
#*Using the geometry of '''12''' optimized by the previous methods, subject it and its dihydro derivative to B3LYP/6-31G(d,p) Gaussian geometry optimization and frequency calculation (see [[Mod:chem3d| instructions here]] using the keywords OPT and FREQ). Each calculation will take 1-2 hours, and is far better done using the SCAN than the laptop.
#*Load up the output LOG or FCHK (you get this from the SCAN) file (into ChemBio3D or Gaussview) and inspect any Cl-C stretching frequencies (see [[Mod:chem3d| instructions]]). Look in particular for any with a large IR intensity, and identify the two C=C stretches for the diene and the single C=C stretch for the monohydrogenated derivative. Comment on their values and any differences between the diene and the monoene. If you do spot changes, comment on whether they make sense in terms of your analysis in part one above.
#'''Part 3 (optional):''' If your curiosity has been aroused by the previous step, try modifying the substituents on the ''anti/exo'' alkene (i.e. change the =C-H group to =C-OH, =C-CN, =C-BH2, =C-SiH3) etc. Does this have any (electronic) effect on the Cl-C and C=C frequencies and is it in the expected direction? Is any effect also reproduced using MM2?
====Procedures====

#Using the Chem3D program, draw the molecule, and to perform e.g. first the MM2 step and then the MOPAC/PM6 step as above, select '''Calculations/MOPAC Interface/Minimise energy''' option from the top menus, and from the '''Job & Theory''' pane, select '''Method=PM6'''. From the Properties page, tick '''Molecular Surfaces'''. From the '''General''' pane, change the default location of the '''Results in''' folder to e.g. your documents folder (if you do not do this, the program will report that e.g. \\icfs7.cc.ic.ac.uk\yourloginname\Mopac Interface\ cannot be written to). Click '''Run''' and watch the messages at the bottom. This should take ~10 seconds (if the geometry has been pre-optimized using MM2). When this is complete, select , '''Surfaces/Molecular orbitals'''. The HOMO appears by default.
#Select '''Surfaces/Select molecular orbital''' to view the HOMO-1, the LUMO, LUMO+1 and LUMO+2. You might also want to adjust '''Surfaces/Isocontour''' to produce a more pleasing appearance for each orbital. Save each orbital as a .jpg file for insertion into your Wiki report.
#'''HINT''': Inspect the shape of your orbitals very carefully, to see if they make sense, before committing them to your report. In particular focus on whether the molecular orbital reflects the molecular symmetry of the molecule. If not, do any solutions suggest themselves? Comment on the outcome in your report.

Estimated time for completion: < 2 hour.
#Using the PM6 or RM1 optimized geometry, select the Gaussian interface and save an input file to run B3LYP/6-31G(d,p). Do the same for the monoalkene with the remaining double bond on the same side as the Cl. Save both molecules as Gaussian inputs (.gjf) files, and edit both files (using e.g. Wordpad) so that the very top line of the file shows as follows;

<pre># b3lyp/6-31G(d,p) opt freq</pre>

Any lines above this one should be deleted. Submit both jobs to the SCAN under the queue '''Chem Lab 1'''. The calculation should take <1 hour (if your starting geometry was the PM6 optimised one) to complete (provided the backlog of jobs is not high!). Do not try this on the laptop, since it will take many more hours, and the laptop may overheat! (Hint: the di-alkene can be defined as having Cs symmetry in Gaussview, and if you do this before submitting the job, the calculation will take half the time! What about the monohydrogenated system? Does that have Cs symmetry? ). When complete, download the '''Formatted checkpoint file''' for each molecule from the Web page, which should appear on your desktop. Double click this file if it does not open automatically in Gaussview 5.09, select 'open with' and navigate to Disk C/g09w/gview, and in '''Results/vibrations''' track down the Cl-C and C=C stretching vibrations in each system.

Estimated work time for completion: < 1 hour preparation time; ~4 hours elapsed time.

==== Key literature ====
#B. Halton, R. Boese and H. S. Rzepa., ''J. Chem. Soc., Perkin Trans 2'', 1992, 447. {{DOI|10.1039/P29920000447}}

=== Monosaccharide chemistry: glycosidation ===

{| cellpadding="0" cellspacing="0"

|<jmol><jmolApplet><title>Glucose02-nge</title><color>white</color>
<size>200</size><script>measure 5 8 22;zoom 150; cpk -20;</script>
<uploadedFileContents>GLUCSE02-nge.mol</uploadedFileContents>
</jmolApplet></jmol> || [[Image:anomer1.jpg|right|250px|glycosidation]]Glycosidation involves replacing the group X by reaction with a nucleophile Nu. The two sugars shown to the right give different anomers (with almost complete diastereospecificity) depending on the orientation of the OAc group on the adjacent carbon.
This effect is due to neighbouring-group-participation from the adjacent acetyl group. For the β-anomer, the intermediate oxonium cation must be attacked from the bottom face, to then allow the incoming nucleophile to replace it from the top face. Likewise, the α-anomer is formed by the acetyl oxygen attacking from the top face of the oxonium cation, allowing the nucleophile to come in from the bottom face.
|-
| <jmol><jmolApplet><title>Glucose02-nge-epi</title><color>white</color>
<size>200</size><script>measure 5 8 22;zoom 150; cpk -20;</script>
<uploadedFileContents>GLUCSE02-nge-epi.mol</uploadedFileContents>
</jmolApplet></jmol> ||[[Image:anomer2.jpg|right|430px|Neighbouring group participation]]
|}
Your task is to model these facial preferences, i.e. the diastereospecificity, using both MM2 and MOPAC/PM6 methods.
====Procedure====
#Sketch the oxonium cation rings A and B. Which group do you think is an appropriate R group to represent the chemistry while keeping the computational demand minimal? Which methods between MM2 and MOPAC/PM6 do you think is better suited for the task? Why?
#For each structure, use both methods to try to find two conformers differing in whether the acyl group is pointing '''above''' or '''below''' the plane of the oxonium cation (A and A', B and B'). Which ones of the pairs have the lower energy? Hint: use the MM2 geometry as the starting point for obtaining a PM6 geometry.
#You could try the same again but now using the intermediates C and D. You should carry out the calculation using both methods and determine the stabilisation energy by neighbouring-group-participation. Compare the results of the two methods (energy, bond lengths, bond angles, etc.). Is it still possible to get two isomers (C and C', D and D') for each?
#Can you rationalise the diastereospecificity in glycosidation using the computational results?

Estimated time for completion < 3 hours.

====Key Literature====
#D. M. Whitfield, T. Nukada, ''Carbohydr. Res.'', 2007, 342, 1291. {{DOI|10.1016/j.carres.2007.03.030}}

=: Structure based Mini project using DFT-based Molecular orbital methods =
Many (most?) reactions carried out by synthetic chemists can (and do) give mixtures of products. Often, these products are isomers (for example stereoisomers, or regioisomers which can arise from reaction at more than one site in a molecule, or from different orientations of the reacting groups). Having isolated (and ideally having separated) these isomeric products, it is important to know which isomer(s) have been formed. Often, an understanding of the mechanism of the reaction that was carried out will allow us to predict fairly confidently which isomer will predominate. You have met many key mechanistic ideas in Years 1 and 2 that enable you to do this (particularly by considering steric and electronic effects). However, it is still necessary to conclusively confirm that the expected product has been obtained, and if more than one isomer is produced, to be able to say for sure which-is-which. Sometimes, the reaction products will be solids which can be crystallised and their structures determined by X-ray crystallography, which gives detailed structural information. However, many organic compounds are oils or liquids and structure determination relies on spectroscopic methods. Mass spectrometry is a useful starting point, and high resolution mass spectrometry (HRMS) allows the molecular formula to be determined. UV and IR spectroscopy provide information on the functional groups present in the molecule. These techniques do not often allow us to distinguish between isomeric organic compounds, though. For this purpose, NMR is a primary tool because it provides information on molecular environment (chemical shifts) and connectivity (analysis of couplings between nuclei). In analysing chemical shifts, the chemist traditionally compared the observed chemical shifts to those of similar known compounds in the literature, looking for similarities to provide evidence for a structural assignment. Modern computational chemistry can provide an alternative: the 13C (also 15N,19F, 31P) spin-spin decoupled spectrum of a molecule can be predicted, often with acceptable accuracy. Computational chemistry also allows prediction of other useful spectroscopic properties, such as IR spectra and (for chiral compounds) optical rotations. For determining stereochemistry, extremely useful information can be obtained from 3-bond 1H J values, since these depend on the dihedral angle between the two protons according to the [http://en.wikipedia.org/wiki/Karplus_equation Karplus equation]. Again, molecular modelling can be used to predict dihedral angles and [http://www.stenutz.eu/conf/jhh.html hence the expected J-values].

In this experiment, you will choose a reaction from the primary literature which either is reported to give two or more isomeric reaction products, or which (based on your mechanistic understanding of the chemistry employed) has the potential to do so, even if only one isomer was reported. Ultimately, you will investigate whether 13C prediction using the GIAO approach helps in assigning the structures of the isomeric products. You might even find a paper where the original authors were uncertain as to the product structures, and be able to solve their problem! If any of the other computational techniques are useful for your example, please use them as well. The general approach to the task is as follows:
# Choose a reaction to study. You will gain extra credit (+ 5%) for finding a suitable reaction from the literature yourself. In choosing reactions, bear in mind the comment below (in the section describing how to do the 13C prediction) about the need to choose molecules that are not highly conformationally flexible. A good starting point is to look at recent issues of journals containing synthetic chemistry (e.g.[http://pubs.acs.org/journals/joceah/index.html ''Journal of Organic Chemistry''], [http://pubs.acs.org/journals/orlef7/index.html ''Organic Letters''], [http://www.rsc.org/Publishing/Journals/OB/index.asp ''Organic and Biomolecular Chemistry''], ''Tetrahedron''). Ideally, you need to choose papers which include experimental 13C NMR data for the isomeric products: this may be in the Experimental section for full papers, or in the Supporting Information which is usually available online. If you can’t (or don’t wish to) find your own reaction, some suggested examples are given below, which you may use for restricted credit. Associated with each of these are some questions to think about – even if you’ve chosen your own example, reading these may give you some idea of the kinds of question you might ask yourself when analysing your problem.
# Think about the following points and discuss them in your answer:
##How would you differentiate spectroscopically between the isomeric products? What methods would you use, and what would be the '''key''' spectroscopic differences you would look for in the spectra of the isomers in order to tell which sample is which? This is rarely discussed explicitly in synthetic papers, but the researchers doing the work will have done this as part of the research process, and thinking about how this is done is a very useful exercise for those intending on a research career!)
##Calculate the predicted 13C spectra for the isomers using the GIAO method. Include a listing of the data and assignments in your report.
##Compare your predicted data to the experimental 13C data in the paper. Do they match? Do they support the structural assignment in the paper? If not – why might this be? '''Note''': it is quite possible that your calculated data will '''not''' match those in the literature. Don’t worry! Apart from the conformational flexibility problem, there are other limitations in the computational approach. In this regard, your work is truly a research exercise – the use of this technique is at the cutting edge, and your calculations will help to determine when the method works and when it does not!
##This aspect of the course mirrors an approach commonly taken by computational and synthetic chemists. A review of the area is found here ({{DOI|10.1021/cr200106v}}) and shows in detail the way in which such problems are tackled.
# If you can, discuss the mechanism of the reaction and why the reaction shows (or doesn’t show) selectivity for one particular product isomer. Can any of the other computational techniques you’ve met in the course be used help to explain the selectivity?

== Objectives and Suggested Structural Explorations ==

You will be given full credit for attempting '''ONE''' of the below (and 5% bonus for one of your own devising not listed below). This part of the module should take < 10 hours spread out over two days to complete.
==== Stereoselective dissolving metal reductions ====
[[image:reduct1.jpg|right]]You met the use of dissolving metals (e.g. Li/NH3) for reduction of carbonyl compounds and aromatic rings (Birch reduction) in Year 2 (Functional Group Interconversions course). In a recent natural product total synthesis ({{DOI|10.1016/j.tet.2006.12.019}}), these conditions were used for stereoselective reduction of a cyclic ketone to an alcohol: ketone '''5''' was reduced with complete stereoselectivity to give alcohol '''6''' (Scheme 1 in the paper). How would you tell the reaction had worked, and which stereoisomer had formed? Do the predicted 13C (and 3JH-H) data match the reported? Why was this stereoisomer obtained? The optical rotation of '''6''' is reported. Does it match calculation? (you may have to play with the orientation of both the OH and propenyl groups to get a good match).

=== Regio- and stereoselective conversion of alkenes to epoxides ===
[[image:epoxide.jpg|right|thumb]]As you know from Years 1 and 2 (especially Year 2 Functional Group Interconversions course), epoxides are highly versatile synthetic intermediates because they undergo ring opening with a wide range of nucleophiles. In a recent paper ({{DOI|10.1016/j.tetasy.2005.02.012}}), it was shown (Scheme 6 in the paper) that a 1,3-diene (compound '''13''') can be regioselectively epoxidized to give either stereoisomer '''14''' or '''15''' depending on the reaction conditions used. How would you tell that the “correct” alkene had been epoxidised? Unfortunately the authors don’t include 13C data for their products in the paper, but they are available in the literature (do a search on Beilstein). Do the products’ 13C data match your calculations? Why do the two sets of epoxidation conditions give different stereoisomers?

=== Assigning regioisomers in "Click Chemistry" ===
[[Image:Click.gif|left]]The 1,3-dipolar cycloaddition between an azide and an alkyne to give a 1,2,3-triazole has been known for a long time. However, in 2002, two groups reported independently that the use of a Cu(I)-catalyst greatly speeds up the reaction. So facile is the catalysed chemistry that it is now often called the “click reaction”, being a classic example of the philosophy of “[http://en.wikipedia.org/wiki/Click_chemistry click chemistry]” introduced by Nobel Laureate K. Barry Sharpless, which aims to exploit reactions which “are tailored to generate substances quickly and reliably by joining small units together”. The ease and high selectivity of the click reaction has led to its widespread use in important fields such as materials science and biology – for example, the specific introduction of tags and labels into proteins.
When substituted alkynes and azides are used, there are two possible regioisomeric products, '''A''' and '''B'''. Under Cu(I) catalysis, the 1,4-isomer '''A''' predominates; interestingly, however, Ru(II)-catalysed reactions give mostly the 1,5-isomer '''B''' instead. How can we tell these apart spectroscopically? Look at the original paper (''J. Am. Chem. Soc.'' '''2005''', ''127'', 15998; {{DOI|10.1021/ja054114s}}). For the example in Table 1, entry 1, calculate the 13C spectra for the depicted product isomer and for the alternative regioisomer. Which best matches the data reported in the paper? For comparison, can you find data for the other isomer anywhere in the literature?

=== Investigating the regioselectivity of the Baeyer-Villiger reaction ===
[[image:bv2a.jpg|left|thumb]][[image:bva1.jpg|right]]The [http://en.wikipedia.org/wiki/Baeyer-Villiger_oxidation Baeyer-Villiger reaction] converts ketones into esters, effectively inserting an oxygen atom between the carbonyl group and the alpha-carbon. It is usually carried out using mCPBA. For unsymmetrical ketones, there are two possible regioisomeric products; usually it is possible to predict which isomer will predominate in line with the migratory aptitude of the ketone substituents. Investigate '''ONE''' of two recent literature examples where the reasons for the regiochemical outcome are not so obvious:
*The Baeyer-Villiger reaction was used ({{DOI|10.1021/jo030377y}}) in a recent synthesis of analogues of beta-lactam antibiotics. In Scheme 5, reaction of '''10d''' gives '''11d''' and '''12d'''. Are the regiochemical assignments correct, and why is the regioselectivity low in this case?
*During a total synthesis of the natural product (-)-kainic acid ({{DOI|10.1016/S0040-4020(02)00379-4}}), a neuropharmacological tool, a highly regioselective Baeyer-Villiger reaction was a key step (conversion of compound '''14''' into '''15'''). Do the predicted 13C data fit with the reported ones? Why is this reaction so regioselective?

=== The total synthesis of (-)Cubebol ===

[[Image:cubebol.gif|right]] Cubebol is a natural sesquiterpene alcohol with a cooling and refreshing taste. It was patented as a cooling agent (i.e. to make you feel you are eating ice-cream without actually having to freeze the ingredients!). The total synthesis has recently been reported: {{DOI|10.1021/jo9022974}} in which much spectroscopic information about the molecule is available. Your project will involve testing that this information and the assignments are correct for the absolute configuration shown.

=== General Reference===
K. Mori, ''The Chemical Record'', '''2005''', ii5'', 1-16. {{DOI|10.1002/tcr.20030}}

== Relevant computational techniques for Mini-project ==

===Predicting the 13C NMR Spectrum of a compound===

The 13C (also 15N,1NF, 31P) spin-spin decoupled spectrum of a molecule can be predicted using two quite different methods.
# The first is a rule-based approach is derived from a fragment library, and is applicable mostly for organic molecules. The advantage is that the prediction is extremely rapid, and fairly general. The downside is that the accuracy is only around 3-5 ppm, and does not take into account local conformations, differential solvation of different groups, etc. It is not applicable for many organometallic and inorganic systems.
# The second is the so-called GIAO approach using quantum mechanical density functional theory. The background to this, and a famous recent example can be found in the article by Rychnovsky1 on a revision of the structure of '''Hexacyclinol''' ( {{DOI|10.1021/ol0611346}}). He reports that the mean error for the 23 carbon shifts in the predicted structure was around ± 1.8 ppm, with a maximum error of around 5.8 ppm. An improved procedure which reduces the mean and maximum errors by one half will be used here2 ({{DOI|10.1021/np0705918}}), although a number of caveats for successful prediction should be noted. The most serious is that the method is '''highly''' sensitive to the conformation of the molecule. If various different conformations are possible (and for some molecules, 100s of reasonable conformations can sometimes be imagined), they should all be scanned by this method. Since this is clearly not feasible in a reasonable time, you should not choose a problem that has conformational ambiguity.

====Procedure====

=====Creating an initial Molecule input file =====
You will need to sketch your molecule in ChemDrawPro+ChemBio3D/Gaussview and perform an initial refinement of its 3D geometry using MM2. If it contains only simple elements (CHNO, Si, P, S, halogens) then the chances are that a molecular mechanics refinement will be possible. At this stage, whilst the calculations still take only a few seconds, you might wish to investigate several conformational possibilities to see which might be the lowest (but don't try more than say 5). Some conformations can be preset (a worthwhile one is to always try to get 6-membered rings into a chair, and e.g. esters R-CO-O-R' oriented such that the R-C bond is antiperiplanar to the O-R' bond). If the mechanics procedure fails because of lack of parameters, try eg the MOPAC/AM1 approach instead. If both of these fail, try the Gaussian procedure, using the HF (Hartree-Fock) method and an STO-3G basis set. This initial geometry will then have to be '''refined/optimized''' using the following method.
# In ChemBio3D, go to Calculations/Gaussian/Create Input File.
# Select Job Type/Minimise; Method DFT=mpw1pw91
#*'''A note on DFT methods:'''. A wide variety of DFT methods have been proposed {{DOI|10.1021/jp710179r}}. This particular one has been extensively tested for the calculation of NMR properties and found to be somewhat superior to the more common B3LYP procedure.
# The Basis set to be set to 6-31G(d,p)
#*'''A note on basis sets:''' A wide variety of basis sets have been [https://bse.pnl.gov/bse/portal described] (including a set optimized specifically for NMR shift calculations, {{DOI|10.1021/ct800013z}}, type '''pcS''' into the search box [https://bse.pnl.gov/bse/portal here]) and often a decision on which basis set is most appropriate for which property being computed has to be made. In the case of NMR as a property, it is not necessarily true that the larger basis set is the better one! You will revisit basis sets in modules 2 and 3 of this course.
# Save the resulting file to your H: drive, making sure it is saved as a '''Gaussian Input file''', with the suffix '''.gjf'''.
# Find the file in Windows Explorer, and with a right-mouse-click, open it with the WordPad program.
# Delete all lines at the top, leaving only the following line, which should be edited to show something like the following
<pre># mpw1pw91/6-31g(d,p) opt(maxcycle=25)

Geometry optimization for literature compound

0 1
atom1-symbol 0 x-cooordinate of atom1 y-cooordinate of atom1 z-cooordinate of atom1
atom2-symbol 0 x-cooordinate of atom2 y-cooordinate of atom2 z-cooordinate of atom2
... ... ...</pre>This shows the keyword line at the top, a blank line, a title card, another blank line, a charge/spin card (we will assume that your unknown is neutral, i.e. charge=0 and a singlet spin state, i.e. spin=1) and the first line of atom coordinates. If you need to calculate a charged species, change the '''0''' to e.g. '''-1''' (for an anionic species). Whilst you are at it, check to see if your coordinates have any atom type designated '''Lp'''. If any such lines are present, delete the entire line. Lp is a Lone-pair, and is sometimes added by the Molecular Mechanics part of the program. However, if Gaussian sees it, it gets very confused, and will not run at all!. The keyword value maxcycle=25 is because sometimes the geometry optimization meanders very close to convergence, and this limits this meander. Re-save this file, making sure you save it as '''TEXT''' and ''NOT'' RTF and that it retains the suffix '''.gjf'''.

==== Submitting this file to the SCAN for geometry optimization ====
#[[Image:scan2.jpg|thumb|left]] [[Image:scan1.jpg|thumb|right]] Go to [https://scanweb.cc.imperial.ac.uk/uportal2/ the SCAN Webpage], log in, and first create a project (it could simply be called Mini-project). Then, '''New Job/Chemistry Lab 1''', then select Gaussian/Your project, and finally the name of the Gaussian input file you have just saved, along with a descriptive title.
#You can view your job list, when a display of the type shown below should appear: Jobs in the '''Chemistry Lab 1''' pool also run during the day, but with a r concurrency of 8. When there are many jobs you may have to wait overnight for yours to finish. The status of the pools can be inspected by selecting Pools from the menu on the left: If your suspected molecule is large (more than about 30 non-hydrogen atoms) it may require more than about 9 hours of '''wall''' time. If the job returns no output overnight, it may well have run out of time (it has about 9 hours in which to complete the calculation). The '''Chemistry Lab 1''' will run the job to completion, but you may have to wait a while for it to start running in the first place.
# [[Image:scan3.jpg|thumb|right]]When the job shows as Finished, select the Gaussian Checkpoint file as the required output and download it (probably to the desktop, or wherever the browser tells you). Double-click the file to open Gaussview (it may happen automatically) and check that the optimised geometry is still reasonable. Invoke '''File/Save as''' and replace the original Gaussian input file you created with Chem3D. It now has a fully optimised geometry at the mpw1pw91/6-31(d,p) level, rather than the initial sketch of before.

==== Troubleshooting ====
# If the system responds that the formatted checkpoint file '''does not exist''' its quite probable that the calculation failed. Try instead to download the Log file, which may have error messages that help you diagnose what has gone wrong. Two common reasons for the failure are
## There was an error in the input .gjf file. A common error is the positioning or omission of blank lines. Check with the above to ensure they are correctly positioned. Another error is that the keywords are mis-typed. Gaussian will fail for either reason, but it should put out an error message in the log file.
##The best way to eradicate syntax errors before submission to SCAN is to run Gaussian on your laptop for a few seconds at least, this being better than waiting up to 24 hours to find that a trivial error stopped the calculation. You can run a Gaussian input either from ChemBio3D, or Gaussview.
## The calculation may have run for 9 hours and then run out of time. This means that the molecule may be rather large (> 30 non hydrogen atoms), or very conformationally mobile. You could try resubmitting with maxcycles set to something lower.

==== Submitting this file to the SCAN for NMR Chemical Shift calculation ====
# Having created a new .gjf file containing the optimized geometry, repeat the Wordpad editing procedure as described above, but this time ensure the top line of your .gjf file contains the following (if the literature reports a different solvent, replace chloroform with that solvent): (a list of defined solvents is available at the bottom of [http://www.gaussian.com/g_tech/g_ur/k_scrf.htm this page])
<pre># mpw1pw91/6-31(d,p) NMR scrf(cpcm,solvent=chloroform)

NMR calculation for literature compound

0 1
atom1_symbol 0 optimized-x-cooordinate of atom1 optimized-cooordinate of atom2 optimized-cooordinate of atom3</pre>
Resubmit this new input file for calculation as described above. This will take much less time to calculate than before. Whilst it is possible to catenate the two jobs you have run (the optimization and the NMR calculation), this requires a great deal more editing of the .gjf file, and hence scope for errors.

==== Analyzing the NMR Chemical Shift calculation ====
#[[Image:scan4.jpg|right|thumb]] When this second calculation is finished, download this time the Gaussian Log file (instead of the checkpoint file). Open this in Gaussview and from that program, select '''Results/NMR''' (if the NMR keyword is greyed out, it means the calculations was not in fact successful).
# From the Spectral display that appears, select the '''C''' nucleus, and the appropriate Reference Value. Click on any peak to find out what its chemical shift is, and compare with the spectrumreported in the literature.
# You should note that carbons attached to "heavy" elements (particularly eg halogens) have shifts which need correction for so-called Spin-orbit coupling errors. Typically, C-Cl needs correcting by -3 ppm, C-Br by -12 ppm, and C-I by about -28 ppm. First row transition metals are around -3ppm. Other elements to be determined!2. Another systematic error present is that the carbonyl of esters, amides etc tends to be out by about 5ppm. Use the following simple correction for such carbons only: δcorr = 0.96δcalc + 12.2.
# You can probably use your calculation to actually assign the 13C shifts to the carbons of your molecule. If you spot one or more carbons out by more than about 5ppm, its quite likely that you have the wrong conformation of your molecule in that region (i.e. the method can actually be used for conformational analysis), or of course that the original assigment in the literature is wrong. This actually happens quite often!
# The method should work for other nuclei (except hydrogen, which requires much greater accuracies to be really useful). First row transition metals (organometallics) appear to be reasonably handled.
# Complete this section by returning to [https://scanweb.cc.imperial.ac.uk/uportal2/ the SCAN portal] and click on the '''publish''' link next to the job that carries the NMR prediction. This will deposit your calculation into a so-called '''Digital repository'''. Quote the entry in your Wiki pages as <nowiki>{{DOI|10042/to-xyz}}</nowiki> where xyz is the entry generated by the previous operation.

====References====

# S. D. Rychnovsky, ''Org. Lett.,'' '''2006''', ''13'', 2895-2898. {{DOI|10.1021/ol0611346}}
# C. Braddock and H. S. Rzepa, ''J. Nat. Prod.,'' '''2008''', ''71'', 728-730. {{DOI|10.1021/np0705918}}
# A recent development is an enhanced technique for accurately computing 1H chemical shifts: {{DOI|10.1021/jo900482q}}
# Goodman has produced some interesting tools for aiding NMR analysis.
## {{DOI|10.1021/jo900408d}}
##[http://www-jmg.ch.cam.ac.uk/tools/nmr/ Applet]
## {{DOI|10.1021/ja105035r}}
## [http://www.spectroscopynow.com/coi/cda/detail.cda?id=24215&type=Feature&chId=5&page=1 Blog commentary]

===Predicting the 3J H-H couplings of your compound===

The above technique is reliable for 13C shifts, but less so for 1H shifts. However, three-bond couplings can be predicted reasonably well using a very rapid and simple method based on the Karplus equations. To do this, you will need to have a 3D model of your unknown, which should emerge out of your 13C prediction in the preceeding section. The start point should be to use Chem3D to save an MDL Molfile of your final coordinates. This can then be read into [http://www.ch.ic.ac.uk/local/organic/janocchio/index.html Janocchio,] to provide the coupling constants.

It is also possible to compute J couplings using quantum mechanical methods (Gaussian keyword '''NMR(spinspin)''') but these calculations are '''highly''' time consuming if accurate results are to be obtained.

====Reference ====

D. A. Evans, M. J. Bodkin, S. R. Baker, G. J. Sharman, ''J. Magn. Reson,'', '''2007'''. * {{DOI|10.1002/mrc.2016}}

=== Predicting the IR Spectrum of a compound ===

Calculating the vibrational normal modes of a molecule is simpler than NMR since it can be done in a single job, but it may also be more time consuming. Only try this for smaller molecules (<25 non hydrogen atoms, including the first row transition metal series).
==== Procedure ====
Create an initial .gjf file, and modify it thus;
<pre># b3lyp/6-31G(d,p) opt freq

Geometry optimization and vibrational frequencies for literature compound

0 1
atom1-symbol 0 x-cooordinate of atom1 2-cooordinate of atom2 -cooordinate of atom3
atom2-symbol 0 x-cooordinate of atom1 2-cooordinate of atom2 -cooordinate of atom3
... ... ...</pre>
In the resulting output, <pre>Sum of electronic and thermal Free Energies= -3170.440313</pre>
gives you in effect ΔG = ΔH - T.ΔS. You can use this term to compare the '''difference''' in free energies between two molecules, remembering that it is expressed in Hartrees; 1 Hartree = 627.5 kcal/mol.
==== Analyzing the Vibrational Spectrum ====

Download the.fchk file from the SCAN page, and by double-clicking, open it in Gaussview. From '''Results/Vibrations''', select the '''Save normal modes''' from the '''Run FreqChk''' pop-up box and inspect the normal modes and their predicted intensities, using the animation feature to help describe them. Errors in the predicted wavenumbers are systematically too high for stretches (which means they can be corrected using empirical factors) by around 8%; bending and lower frequency modes are normally about right. Pay particular attention to the predicted intensities, which may help you to assign the vibrations. If you get any apparently negative modes, you will have in fact obtained a transition state (or higher order) stationary point.

==== Reference ====

R. Janoschek, ''Pure and Applied Chemistry'', '''2001''', ''73'', 1521-1553. {{DOI|10.1351/pac200173091521}}

=== Predicting the Optical Rotation (OR) and the Electronic Circular Dichroism (CD/UV-Visible) Spectrum of a compound ===
Measuring optical rotations is one of the oldest spectroscopic techniques, dating back well into the 19th century, and a mainstay of organic chemistry until IR/NMR etc came along mid 20th century. Although the theory of how molecules interact with polarized light has been known for a long time, it is only in the last 5 years or so that computers have become sufficiently fast to solve the problem to the required accuracy, which in fact comes in two parts. The simpler is to see if the absolute sign of the optical rotation predicted for a given absolute configuration of a molecule corresponds to that measured. Because the sign can easily change as a result of apparently minor changes to the structure of the molecule (or even in extreme cases, its conformation), there is little ''intuition'' that can be applied, or indeed simple rules. A full quantum mechanical calculation is pretty much the only reliable method for predicting the absolute sign of the OR. The second aspect is predicting the magnitude of the rotation. This again can vary from close to zero, to many thousands! It is generally accepted that only compounds with ORs of magnitude >|100| (or at a pinch >50) can be successfully used to predict absolute configurations with near total confidence. So you should only attempt to predict the OR of an asymmetric molecule if it fulfills these criteria. Another chiro-optical property is the CD spectrum. This is essentially the UV spectrum of the molecule, with the difference that it is recorded with '''chiral''' light. The two enantiomers of a disymmetric molecule interact differently with this light (think of it as opto-electronic diastereomers), and particularly the sign of the intensity of each electron transition can be either positive or negative. The resulting CD spectra are exact mirror images of each other for each enantiomer of the molecule, which means that distinguishing between them is trivial. The crucial difference between CD and OR is that the former is very much less sensitive to conformation, and hence the answer so much more definitive. There are other types of '''chiro-optical''' spectroscopies (Vibrational circular dichroism, Raman Optical Activity) which can be even more definitive, but these are still rarely used.

Proceed as follows:
==== Procedure for Optical Rotation====
Take the output of the previous frequency or NMR calculation (i.e. the optimized geometry), and run a job of the following type:

<pre>
# cam-b3lyp/ 6-311G(d,p) polar(optrot) scrf(IEFPCM,solvent=chloroform) CPHF=RdFreq
This is a blank line; put no text in it
Optical rotation for literature compound
This is a blank line; put no text in it
0 1
firstatom-symbol 0 x-cooordinate of atom1 2-cooordinate of atom1 -cooordinate of atom1
...
lastatom-symbol 0 x-cooordinate of lastatom 2-cooordinate of lastatom -cooordinate of lastatom
This is a blank line; put no text in it
589nm
This is a blank line; put no text in it
</pre>
The Cambridge variation on the B3LYP density functional method is used, which improves the prediction of chiro-optical properties compared to the normal B3LYP version. The keyword '''aug-cc-pvdz''' invokes an augmented (i.e. with additional diffuse basis functions), correlation-consistent double-ζ valence polarization basis set suitable for optical rotation calculations and polar(optrot) calculates the [alpha]D optical rotation components of an asymmetric mol. The i wavelength of the incident light (589nm is the sodium D line) is read in using the keyword CPHF=RdFreq and the line appended as 589nm after a blank line following the coordinates. A final blank line follows the frequency line. Specify the appropriate solvent in the SCRF keyword. If this recipe fails to converge (it can do occasionally), try instead a faster and simpler basis set to replace the aug-cc-pvdz one: '''6-31G(d,p)'''.

In the resulting output, e.g. [ALPHA] ( 5890.0 A) = -324.5 deg gives the estimated optical rotation for the exact enantiomer that you built (try submitting the other enantiomer and see if you get the opposite rotation). The value given by [Alpha]D is misleading, it being the non-frequency dependent approximation to this parameter (and regarded as less accurate than the frequency dependent value at 589nm which follows). The method will reliably predict whether the optical rotation corresponds to the enantiomer you have built if [Alpha]D > 100°, but becomes increasingly unreliable for lower values. The OR is also highly sensitive to conformation; even a 60° rotation of an OH group can alter its value by a factor of two! Turned on its head, predicting OR could be regarded as a highly sensitive method for conformational analysis! You should be aware that this calculation an be quite time consuming, and molecules with > 20 non hydrogen atoms should not be attempted.

==== Procedure for the CD (Circular Dichroism) Spectrum ====

Use the following keywords, which invokes the so-called time-dependent DFT method, where the first 20 electronic singlet excitations are included (you can reduce this to a much smaller value, eg 3 or 5, or a much higher one if you want to simulate the high energy/UV region of the spectrum).

<pre># cam-b3lyp/6-311G(d,p) td(NStates=20) scrf(IEFPCM,solvent=chloroform)

Circular dichroism for literature compound

0 1
atom1-symbol 0 x-cooordinate of atom1 2-cooordinate of atom2 -cooordinate of atom3
atom2-symbol 0 x-cooordinate of atom1 2-cooordinate of atom2 -cooordinate of atom3
... ... ...</pre>

The spectrum can be viewed using the ''Results/UV-Vis'' option in Gaussview 3 or 5. The regular UV spectrum is shown first, followed by the CD version.

==== References ====

# P. J. Stephens et al, ''Chirality'', '''2008''', ''20'', 454-470. {{DOI|10.1002/chir.20466}} {{DOI|10.1063/1.1477925}} {{DOI|10.1063/1.1436466}}
# B. Mennucci, M. Claps, A. Evidente, and C. Rosini, ''J. Org. Chem.,'' '''2007''', ''72'', 6680-6691. {{DOI|10.1021/jo070806i}}
# For an example of a calculation, see that for pentahelicene ([alpha]D 2061°) {{DOI|10042/to-888}} If you really want to entertain yourself, try something larger such as decahelicene!
# For a recent application to another type of highly chiral molecule, see {{DOI|10.1021/ol901172g}}

===Using the SCAN for Density functional MO calculations===

You can use the '''SCAN''' to run a Gaussian calculation. Using ChemBio3D, pre-optimise the structure using a fast method such as Molecular mechanics before submitting the DFT calculation. If you do not do this, the latter will take much longer! Create a Gaussian input file (a '''.gjf''' file) as [[mod:chem3d|described]] in the instructions, and then
# Go to [https://scanweb.cc.imperial.ac.uk/uportal2/ https://scanweb.cc.imperial.ac.uk/uportal2/] and log in.
# Select '''Projects''' and '''create a project name''' suitable for your needs.
# Select '''New Job''', then:
##'''Chemistry lab 1''' (a queue of width 8 which runs during the day)

# Then enter your project, and upload the .gjf or .com file. Put in a descriptive title to help remind you of the purpose of the calculation, and click on submit. The Job will show as either pending (for all overnight jobs) or running (for the first 8 jobs on Chemistry Lab 1). When complete, it can be collected from the same web page. In particular, if you select the '''Formatted checkpoint file''' from output list, and download it, Gaussview will open it and display the result of your calculation. You can also open this file with ChemBio3D.
# The SCAN is powerful enough that if you wished, all the molecules in this section could be submitted using the Gaussian program. You can submit multiple jobs, one after another using this technique. You could also increase the level of theory. In this case, change the basis set from 6-31G(d) to e.g. cc-pVTZ, or you could e.g. include a vibrational analysis ('''freq''' keyword) which in fact will result in an entropy correction to the energy, to give in effect a ΔG for your energy (this energy is labelled <tt>Sum of electronic and thermal Free Energies=</tt>)

==== Troubleshooting the SCAN outputs ====

The following lists some of the things that might go wrong, and what to do about them. If you identify a reproducible cause of failure yourself, please feel free to add to the list below!
* A job is finished but it returns no formatted checkpoint file. It is likely that there was an error in the input .gjf file. A common error is the positioning or omission of blank lines in this file or that one of the keywords is mis-typed. Another error is that a keyword may be repeated (thus Gaussian does not much like repetition of the '''opt''' keyword). Download the log file (if it exists) and open it with eg '''Wordpad'''. Check that blanks lines are all correctly present and positioned and for keyword errors or duplication. The output may give a clue of sorts, but the presence or absence of blank lines often confuse it. The below is an example of how an unrecognized keyword is flagged.
<pre>
# b3lyp/6-31G(d) nopt
---------------------
QPERR --- A SYNTAX ERROR WAS DETECTED IN THE INPUT LINE.
# b3lyp/6-31G(d) nopt
^</pre>
*If you cannot get a log file from the finished job, it is likely it ran out of time (each job has a limit of 48 hours). Put simply, your molecule (or the property you are trying to calculate) is a tad too big/demanding!
*It is important if a job fails, to provide as much evidence as you can to demonstrators. Thus at a minimum, you should have to hand the input file (.gjf), and ascertain if running it produces any output. Do also remember that computers are relatively reproducible. If a job fails, resubmitting it will most likely produce a second failure. Rather than simply resubmitting a job, you '''must''' resolve the undoubted error the input contains. Remember that errors can be caused by what is called '''white space''' (which of course since it consists of nothing much, is easily disregarded), and that often even experienced demonstrators might fail to spot that extra bit of white space that is causing the error. If nothing obvious strikes you about an input, it might be easier to throw it away and start again rather than wait eg 24 hours to find it has (reproducibly) failed again!
*It is also a good idea to '''run Gaussian on your laptop for a few seconds at least, this being better than waiting up to 24 hours to find that a trivial error stopped the calculation.''' You can run a Gaussian input either from ChemBio3D, or Gaussview (by now you will appreciate that Gaussian itself is really not very good at handling and describing errors).

= Help =

#In addition to demonstrators and staff, you may wish to keep an eye out on the [[Mod:latebreak|late breaking news]] page for general updates, and the discussion areas for [[Talk:Mod:organic|Module 1]], [[Talk:Mod:inorganic|module 2]] and [[Talk:Mod:physical|module 3]] where people document their experiences, suggest bug fixes etc.

= General References =

<references/>

= Module 1 Marking =

The marks for this module are split 60% for the four components of part '''1.2''' and '''1.3''' (15% each) and 40% for the miniproject part '''2'''. You will be assessed not simply on whether you got the ''right'' answer, but on your analysis of the problem, how you might have designed control calculations, or e.g. worked out ways of making the modelling more efficient. The project is at least as much about how you go about organising your '''workflows''' in the time you have decided to spend on it, as it is about getting the right answer. Marks for each individual component will also be awarded for how you cite and quote the literature (in particular for citing any relevant references that we do '''not''' give you in the notes). Remember, being critical is more important than merely reproducing quotes from an article. After all, the original people who reported the chemistry may have not understood what happened themselves, and it is perfectly possible that you may actually be able to critically improve that understanding!

Your grade will be recorded in Blackboard and comments on your experiment will appear in the discussion section of your Wiki report. If you want to discuss your experiment and its grade, please contact Prof Alan Armstrong directly or Dr Bao Nguyen directly.

----
See also: [[Mod:timetable|Timetable]],[[Mod:lectures|Intro lecture]],[[mod:laptop|Laptop use]], [[mod:programs|Programs]], [[mod:organic|Module 1]], [[Mod:inorganic|Module 2]], [[Mod:phys3|Module 3]],[[Mod:writeup|Writing up]]

Mod:lectures

2011-11-14T16:21:10Z

Bnguyen: /* Lectures */

See also: [[Mod:timetable|Timetable]], [[mod:laptop|Laptop use]], [[Mod:lectures|Intro lecture]], [[mod:programs|Programs]], [[mod:organic|Module 1]], [[Mod:inorganic|Module 2]], [[Mod:physical|Module 3]], [[Mod:writeup|Writing up]]

= Computational Chemistry Course: Introductory lectures =

== Preliminaries ==
#Access the course via '''http://www.ch.imperial.ac.uk/''' and follow the links down to the '''Computational Chemistry Course'''.
#[[Mod:timetable|Timetable]]
#{{Pdf|Lab_intro_admin_2011.pdf|Administrative details}}

== Lectures ==
Because some of the aspects of molecular modelling have not hitherto appeared in 1st/2nd year lectures, and in the past have only been scheduled in the spring term of 3rd year, we will be introducing them at the start of the modelling lab. This will help you understand the background to the experiments, and to produce a better informed write up. The lectures will be delivered in ~20 minute segments during the afternoon of the first day of the course, in the tutorial room, interspersed with questions and clarifications. The topics are listed below:
* [[mod:context|Why computational chemistry?]]
* [[mod:mechanics|Introduction to molecular mechanics and force fields]], or [[mod:Module_1_intro|Module 1 Introduction]] (Module 1)
* {{Pdf|Basis_sets_and_Methods.pdf|Introduction to the use of basis sets and methods}} (Module 2)
* [[mod:geom_opt|Introduction to the technique of geometry optimisation and frequency analysis]] (Module 3)

== Other Materials ==

#Link for [http://scistore.cambridgesoft.com/sitelicense.cfm?sid=948 ChemBio3D] if you wish to use your own computer (Module 1 particularly).
# If you come across any Web-based materials to which links can be usefully placed on this page, please do not hesitate to edit this page and add them yourself.
# Some background material for the [http://www.ch.ic.ac.uk/local/organic/mod/ module 1] might be helpful

See also: [[Mod:timetable|Timetable]], [[mod:laptop|Laptop use]], [[Mod:lectures|Intro lecture]], [[mod:programs|Programs]], [[mod:organic|Module 1]], [[Mod:inorganic|Module 2]], [[Mod:physical|Module 3]], [[Mod:writeup|Writing up]]

Rep:Mod:context

2011-11-14T16:19:00Z

Bnguyen: /* Why do computational chemistry? */

See also: [[mod:context|Modelling in context]], [[mod:mechanics|Molecular mechanics and force fields]], [[mod:basis_sets|Basis sets and Methods]], [[mod:geom_opt|Geometry optimisation and frequency analysis]], [[mod:laptop|Laptop use]], [[mod:programs|Programs]], [[mod:organic|Module 1]], [[Mod:inorganic|Module 2]], [[Mod:physical|Module 3]],[[Mod:writeup|Writing up]]

=Why do computational chemistry?=
Computational chemistry was once considered entirely the domain of specialists, and something that many synthetic chemists shied away from. With the arrival of modern, user-friendly software packages, greater computing power that allows ever-more-realistic systems to be tackled, and an increasing appreciation of the extremely useful information and insights that can be obtained, computational calculations are now important tools accessible to laboratory experimentalists and widely used by them. The purpose of this course is to introduce you to the main computational methods and approaches available through some common software packages (especially ChemBio3D, Gaussian). We hope to show you how they can be used to help and support your lab experiments, enrich your understanding of theory, and aid in the design of new molecules with a range of important properties.

Some examples of the uses of computational chemistry:
*''Energy minimisation and molecule visualisation'' – leading to insights into possible reactivity and stereocontrol
*''Comparison of energies'' of (stereo)isomers to help understand and predict reaction outcomes
*''Spectroscopic prediction'' – Many spectroscopic properties (NMR, IR, UV-Vis, optical rotation, electronic and vibrational circular dichroism) can now be calculated reliably with good levels of accuracy. This can greatly assist in assigning structures and configurations.
** Example: {{DOI|10.1021/np0705918}} with [http://pubs.acs.org/doi/media/10.1021/np0705918/index.html direct link]
*''Molecular orbital calculations'' – which allow calculation of energy levels and visualisation of key orbitals to improve our understanding of bonding and reactivity
** Example: {{DOI|10.1021/jp902176a}} with [http://pubs.acs.org/doi/media/10.1021/jp902176a/index.html direct link]
*''Transition state modelling'' – the TS and the energy barrier to it are the key to reactivity and selectivity in kinetically controlled reactions (the majority of synthetic processes!), but TSs are very difficult to characterise experimentally. Their structures and energies can be predicted by MO calculations, which are therefore outstandingly useful for charting reaction mechanisms and predicting and rationalising structure/reactivity effects.
** Example 1: {{DOI|10.1021/jo900840v}} ''Constrained β-Proline Analogues in Organocatalytic Aldol Reactions: The Influence of Acid Geometry''
** Example 2: {{DOI|10.1021/ja905615a}} ''Heavier Group 2 Metals and Intermolecular Hydroamination: A Computational and Synthetic Assessment''
** Example 3: {{DOI|10.1021/jo048213k}} ''An Experimental and Computational Investigation of the Diels−Alder Cycloadditions of Halogen-Substituted 2(H)-Pyran-2-ones''
** Example 4: {{DOI|10.1021/jo1002906}} ''Delineating Origins of Stereocontrol in Asymmetric Pd-Catalyzed α-Hydroxylation of 1,3-Ketoesters''

The course is divided into three modules, each of which starts with prescribed experiments to take you through the computational methods and approaches. Two of them end with a mini-project which is more open-ended and gives you considerable scope to choose the problem and the appropriate computational tools yourself! We hope that this will not only give you a flavour of computational chemistry research tools, but will also inspire you to spot opportunities to use the techniques to enhance your understanding of lecture material, your future lab courses, your research project work and beyond.

= Pdf of slides {{Pdf|BN_Why_computational_chemistry.pdf|here}} =

Mod:Why computational chemistry

2011-11-14T16:17:56Z

Bnguyen: Created page with "See also: Modelling in context, Molecular mechanics and force fields, Basis sets and Methods, [[mod:geom_opt|Geometry optimi..."

Rep:Mod:Module 1 intro

2011-11-14T16:16:47Z

Bnguyen: Created page with "See also: Modelling in context, Molecular mechanics and force fields, Basis sets and Methods, [[mod:geom_opt|Geometry optimi..."

File:BN Why computational chemistry.pdf

2011-11-14T16:15:53Z

Bnguyen: uploaded a new version of "File:BN Why computational chemistry.pdf"

File:BN Module 1 Introductory talk.pdf

2011-11-14T16:15:52Z

Bnguyen: uploaded a new version of "File:BN Module 1 Introductory talk.pdf"

File:BN Why computational chemistry.pdf

2011-11-14T16:15:18Z

Bnguyen:

File:BN Module 1 Introductory talk.pdf

2011-11-14T16:15:17Z

Bnguyen:

Mod:dont panic

2011-11-14T14:57:40Z

Bnguyen: /* Molecular Mechanics */

[[Image:A_beginners_guide.jpg|center|800px]]
[[Image:dont_panic.jpg|center|200px]]

So you've done your calculations as instructed, and got your optimised structures with a whole lot of properties to boot. What else is expected of you? What does analysis exactly mean, anyway? Don't panic! Here you'll find most of what you need to know to survive Module 1 and beyond.

==Analysis==

"How much analysis is expected from us?", I hear you ask. The answer is: AS MUCH AS 60% OF YOUR MARK! Getting the lowest in energy conformers is quite a challenge which will test your chemical knowledge and patience to the limit, but it wouldn't do you much good if you can't extract chemical information from the exercise. There are several types of information which can be discussed from the calculated structures of compounds or transition states in organic chemistry. The most common ones are listed below:

*Energies
*Bond angles and dihedral angles
*Molecular orbitals
*Bond strength, bond lengths and vibrational frequencies

====Energies====

Energies show how stable your structure is and when it comes to energy, the lower the better. Watch out when you compare energies of different structures, unless the number and types of atoms involved are the same, the comparison isn't valid. Under equilibrium, species of different energies will follow the same relationship as that between Gibbs free energy and equilibrium constant.

Comparing absolute energies between different computational methods is impossible, as they are calculated as the sum of different factors. However, the difference in energy between isomeric transition states calculated by different methods has often been compared with experimentally measured selectivity to judge the accuracy of computational methods.

====Bond angles and dihedral angels====

These values are very useful in intepreting the breakdown components of energy from Molecular Mechanics calculation. They're still useful in quantum mechanics, although there won't be any tangible result you can directly relate them to. A strained structure is a strained structure regardless of how you calculate it.

====Bond strength, bond lengths and vibrational frequencies====

A bond is defined and displayed differently by Molecular Mechanics and quantum mechanics techniques. Be mindful as what you see in the visualisation doesn't necessarily be what your calculation results mean. The strength of a bond, and to some extent its multiplicity, is best judged by examining the bond length and its vibrational frequencies.

====Molecular orbitals====

MOs are only accessible via quantum mechanics. In organic chemistry, we're mostly concerned with the frontier orbitals. Examining their position, shape and symmetry often gives clues about the nature of the MOs (bonding vs antibonding, σ-π interaction, etc.), and more importantly the reactivity and selectivity of the molecule in reactions.

==Data presentation==

So you aren't as good at writing wikis as the geeks who live in a garage, who shower once a month and are on a permanent supplement course of caffeine. Neither are we!

There is no doctor-ordered style for your report and marks won't be given for visual effects or creative designs of your wiki pages. Instead, we want clear, concise communication from you so that we can fully appreciate your work. One golden rule must be remembered: IF WE CAN'T SEE IT (CLEARLY), WE CAN'T MARK IT. The same goes for your analysis. If your visual aid helps the readers understand your points, by all means include it.

Another issue, which is most relevant with the mini projects, is the context of your work. Tell us why and how. More importantly, tell us EXACTLY WHAT QUESTION ARE YOU TRYING TO ANSWER WITH YOUR CALCULATION, other than for getting marks, of course.

Occasionally, we'll contact you during the marking for your original files if we find some of your results interesting, or if we feel there wasn't enough information in your wiki page. Remember to keep your files, and name them in a way that the future you won't struggle to comprehend.

==Methods of calculation==

====Molecular Mechanics====

An excellent description of molecular mechanics has already been included at [[Mod:mechanics|this page]]. Here we'll simply summarise that it's basically balls and sophisticated springs. It's fast, cheap to compute but has to rely on carefully developed force field information (the anharmonic oscillator parameters). Thus, molecular mechanics can only handle structures it has been taught to handle and those unfortunately don't include organometallic compounds.

Of particular note, bonds are treated as springs and have to be specified in the starting structure. As a results, molecular mechanics performs poorly when it comes to electronic interactions, or bond forming-breaking processes. In these cases, molecular mechanics is often employed to clean up the structure, before a more appropriate method is applied.

====Semi-empirical methods====

To cut computational cost in quantum mechanics, approximations were made to simplify the Schrödinger equation. Semi-empricial molecular orbitals methods were born. They're still fast, albeit at the cost of accuracy, compared to ''ab initio'' methods. Semi-quantitative description of electronic distribution, molecular structure, MOs and energies can be quickly derived using these methods. They're also capable of calculations for organometallic compounds.

Being quantum mechanic techniques, they can model electronic effect, orbital interactions or hydrogen bondings, bond formation/breaking, and transition states (all the things Molecular Mechanics can't do!).

====''Ab initio'' calculations====

These fully-fledged quantum mechanic techniques are the current last words, if not the only words, in computational chemistry. They can also handle every chemical structure you can come up with, given an infinite amount of time. The price is that you'll need a supercomputer with 'brain the size of a planet', and the geeks, who write wikis for breakfast, to run it. Users are protected by a web-based or a console-based submission system. Submitted jobs will join queue and occasionally get trapped in an endless loop when you will have to contact the aforementioned IT experts to intervene.

One can optimise structure (can be quite time consumming, depending on how many electrons you have in your structure), calculate energy (enthalpy, entropy) in gas and liquid phases. Recent advances allow fairly accurate prediction of NMR chemical shifts, CD spetrum and optical rotation, as well as IR vibrational frequencies. Bewarned: optical rotation and IR vibrational frequencies calculations are time consumming and shouldn't be carried out unless there's good justification (the submission deadline on Friday is infinitesimally close compared to infinity!).

==Starting structure==

Just as in life, your starting point affects your destination in molecular modelling. A poor starting structure will give you a poorly optimised end-product. Your software doesn't come with an AI (yet!) and so your chemical intuition will have to suffice. Crystal structures, if found, are good places to start as they are at least real minima in solid phase. Most of your calculations, however, will be in gas phase or in solvents.

==Thermodynamics vs kinetics==

Reactions under equilibrium are under thermodynamic control and the more stable product will be formed predominantly, hence the term 'thermodynamic product'. When the reaction is irreversible (very slow reverse reaction), the distribution of products, i.e. the selectivity, is dictated by the relative energies of the corresponding transition states, which also means the relative rates of different pathways (Arrhenius equation), and not that of the products. The major product in this case is called 'kinetic product'.

The arbitrary end-point to a reaction also gives rise to a grey area in which the reaction mixture is approaching but has not yet reached equilibrium the “control” is effectively a mixture. One can use this knowledge to manipulate the outcome of the reaction. All reactions are initially under kinetic control, when no product means no reverse reaction.

'Thermodynamic product' and 'kinetic product' refers to the energy of different species (products and transition states), and therefore, are not mutually exclusive. It is NOT possible to define the kinetic product with knowledge of the thermodynamic product and vice versa. In many reactions, both of these are the same.

==Other things==

If you have questions about anything not covered on this page, talk to us. In fact, talk to us in any case. Mini project, especially, shouldn't even be attempted before some interaction with us. Computational chemistry can get extremely complicated very quickly and a chat with us would prevent you from realising you've bitten up more than you can chew the night before submission. This of course in theory can't happen because you've been following our advice to start your mini project as early as Monday of the second week.

Mod:dont panic

2011-11-04T14:34:13Z

Bnguyen: /* Thermodynamics vs kinetics */

[[Image:A_beginners_guide.jpg|center|800px]]
[[Image:dont_panic.jpg|center|200px]]

So you've done your calculations as instructed, and got your optimised structures with a whole lot of properties to boot. What else is expected of you? What does analysis exactly mean, anyway? Don't panic! Here you'll find most of what you need to know to survive Module 1 and beyond.

==Analysis==

"How much analysis is expected from us?", I hear you ask. The answer is: AS MUCH AS 60% OF YOUR MARK! Getting the lowest in energy conformers is quite a challenge which will test your chemical knowledge and patience to the limit, but it wouldn't do you much good if you can't extract chemical information from the exercise. There are several types of information which can be discussed from the calculated structures of compounds or transition states in organic chemistry. The most common ones are listed below:

*Energies
*Bond angles and dihedral angles
*Molecular orbitals
*Bond strength, bond lengths and vibrational frequencies

====Energies====

Energies show how stable your structure is and when it comes to energy, the lower the better. Watch out when you compare energies of different structures, unless the number and types of atoms involved are the same, the comparison isn't valid. Under equilibrium, species of different energies will follow the same relationship as that between Gibbs free energy and equilibrium constant.

Comparing absolute energies between different computational methods is impossible, as they are calculated as the sum of different factors. However, the difference in energy between isomeric transition states calculated by different methods has often been compared with experimentally measured selectivity to judge the accuracy of computational methods.

====Bond angles and dihedral angels====

These values are very useful in intepreting the breakdown components of energy from Molecular Mechanics calculation. They're still useful in quantum mechanics, although there won't be any tangible result you can directly relate them to. A strained structure is a strained structure regardless of how you calculate it.

====Bond strength, bond lengths and vibrational frequencies====

A bond is defined and displayed differently by Molecular Mechanics and quantum mechanics techniques. Be mindful as what you see in the visualisation doesn't necessarily be what your calculation results mean. The strength of a bond, and to some extent its multiplicity, is best judged by examining the bond length and its vibrational frequencies.

====Molecular orbitals====

MOs are only accessible via quantum mechanics. In organic chemistry, we're mostly concerned with the frontier orbitals. Examining their position, shape and symmetry often gives clues about the nature of the MOs (bonding vs antibonding, σ-π interaction, etc.), and more importantly the reactivity and selectivity of the molecule in reactions.

==Data presentation==

So you aren't as good at writing wikis as the geeks who live in a garage, who shower once a month and are on a permanent supplement course of caffeine. Neither are we!

There is no doctor-ordered style for your report and marks won't be given for visual effects or creative designs of your wiki pages. Instead, we want clear, concise communication from you so that we can fully appreciate your work. One golden rule must be remembered: IF WE CAN'T SEE IT (CLEARLY), WE CAN'T MARK IT. The same goes for your analysis. If your visual aid helps the readers understand your points, by all means include it.

Another issue, which is most relevant with the mini projects, is the context of your work. Tell us why and how. More importantly, tell us EXACTLY WHAT QUESTION ARE YOU TRYING TO ANSWER WITH YOUR CALCULATION, other than for getting marks, of course.

Occasionally, we'll contact you during the marking for your original files if we find some of your results interesting, or if we feel there wasn't enough information in your wiki page. Remember to keep your files, and name them in a way that the future you won't struggle to comprehend.

==Methods of calculation==

====Molecular Mechanics====

An excellent description of molecular mechanics has already been included at [[Mod:molecular_mechanics|this page]]. Here we'll simply summarise that it's basically balls and sophisticated springs. It's fast, cheap to compute but has to rely on carefully developed force field information (the anharmonic oscillator parameters). Thus, molecular mechanics can only handle structures it has been taught to handle and those unfortunately don't include organometallic compounds.

Of particular note, bonds are treated as springs and have to be specified in the starting structure. As a results, molecular mechanics performs poorly when it comes to electronic interactions, or bond forming-breaking processes. In these cases, molecular mechanics is often employed to clean up the structure, before a more appropriate method is applied.

====Semi-empirical methods====

To cut computational cost in quantum mechanics, approximations were made to simplify the Schrödinger equation. Semi-empricial molecular orbitals methods were born. They're still fast, albeit at the cost of accuracy, compared to ''ab initio'' methods. Semi-quantitative description of electronic distribution, molecular structure, MOs and energies can be quickly derived using these methods. They're also capable of calculations for organometallic compounds.

Being quantum mechanic techniques, they can model electronic effect, orbital interactions or hydrogen bondings, bond formation/breaking, and transition states (all the things Molecular Mechanics can't do!).

====''Ab initio'' calculations====

These fully-fledged quantum mechanic techniques are the current last words, if not the only words, in computational chemistry. They can also handle every chemical structure you can come up with, given an infinite amount of time. The price is that you'll need a supercomputer with 'brain the size of a planet', and the geeks, who write wikis for breakfast, to run it. Users are protected by a web-based or a console-based submission system. Submitted jobs will join queue and occasionally get trapped in an endless loop when you will have to contact the aforementioned IT experts to intervene.

One can optimise structure (can be quite time consumming, depending on how many electrons you have in your structure), calculate energy (enthalpy, entropy) in gas and liquid phases. Recent advances allow fairly accurate prediction of NMR chemical shifts, CD spetrum and optical rotation, as well as IR vibrational frequencies. Bewarned: optical rotation and IR vibrational frequencies calculations are time consumming and shouldn't be carried out unless there's good justification (the submission deadline on Friday is infinitesimally close compared to infinity!).

==Starting structure==

Just as in life, your starting point affects your destination in molecular modelling. A poor starting structure will give you a poorly optimised end-product. Your software doesn't come with an AI (yet!) and so your chemical intuition will have to suffice. Crystal structures, if found, are good places to start as they are at least real minima in solid phase. Most of your calculations, however, will be in gas phase or in solvents.

==Thermodynamics vs kinetics==

Reactions under equilibrium are under thermodynamic control and the more stable product will be formed predominantly, hence the term 'thermodynamic product'. When the reaction is irreversible (very slow reverse reaction), the distribution of products, i.e. the selectivity, is dictated by the relative energies of the corresponding transition states, which also means the relative rates of different pathways (Arrhenius equation), and not that of the products. The major product in this case is called 'kinetic product'.

The arbitrary end-point to a reaction also gives rise to a grey area in which the reaction mixture is approaching but has not yet reached equilibrium the “control” is effectively a mixture. One can use this knowledge to manipulate the outcome of the reaction. All reactions are initially under kinetic control, when no product means no reverse reaction.

'Thermodynamic product' and 'kinetic product' refers to the energy of different species (products and transition states), and therefore, are not mutually exclusive. It is NOT possible to define the kinetic product with knowledge of the thermodynamic product and vice versa. In many reactions, both of these are the same.

==Other things==

If you have questions about anything not covered on this page, talk to us. In fact, talk to us in any case. Mini project, especially, shouldn't even be attempted before some interaction with us. Computational chemistry can get extremely complicated very quickly and a chat with us would prevent you from realising you've bitten up more than you can chew the night before submission. This of course in theory can't happen because you've been following our advice to start your mini project as early as Monday of the second week.

Mod:organic

2011-11-01T09:44:55Z

Bnguyen:

See also: [[Mod:timetable|Timetable]],[[Mod:lectures|Intro lecture]],[[mod:laptop|Laptop use]], [[mod:programs|Programs]], [[mod:organic|Module 1]], [[Mod:inorganic|Module 2]], [[Mod:phys3|Module 3]],[[Mod:writeup|Writing up]], [[Mod:dont_panic|Don't panic]].

----
This module comes in two parts, examples of the use of the basic tools, followed by a mini-project.
= The basic techniques of molecular mechanics and semi-empirical molecular orbital methods for structural and spectroscopic evaluations =

==Objectives of this module of the course:==
It is now possible using a computer to accurately model many aspects of organic structure and reactivity, and such modelling can often be used not only to rationalise the outcomes of reactions, but to predict useful modifications or even new types of reaction. The selection of (short) modelling experiments contained in this module of the course attempts to illustrate some of the diversity of such molecular modelling. The module ends with a more open-ended exploration or ''mini-research'' exercise typical of that very often experienced in synthetic chemistry labs; namely is the structure of my final product correct?
#To use molecular mechanics (< 10 hours) to predict the geometry and regioselectivity of:
##the hydrogenation of cyclopentadiene dimer
##the stereochemistry of nucleophilic addition to two different pyridinium rings([[organic:NAD|NAD+ analogues]])
##the conformation/atropisomerism of a large ring ketone intermediate in one synthesis of the anti-cancer drug Taxol
#To use semi-empirical and DFT molecular orbital theory (< 10 hours) to investigate:
##the origins of the regioselectivity of the electrophilic carbenylation of a chloro-substituted bicyclic diene,
##the use of DFT molecular orbital theory to investigate Neighbouring group participation ([[organic:NGP|NGP]]) on the C-Cl and/or C=C stretching frequency of the above bicyclic diene
##concluding with a Mini-project investigating spectroscopic simulation in an organic molecule.
#To gain familiarity with the use of a institutional digital repository (< 5 minutes)
#To perform searches of the literature for each topic in order to cite in your final report any relevant references to each experiment as appropriate (< 1 hour)
#To present the results in the form of a Wiki page, with credit given for any annotation of these course notes, either to pages created here, or Wikipedia entries.
=== Background information ===
A general coverage of many of the topics in this module can be found in the [http://www.ch.ic.ac.uk/local/organic/mod 3rd year course on molecular modelling]. Podcasts (including slides and additional links to other related materials) can be found at this site.

A [http://www.mendeley.com/groups/4657/molecular-modelling-course/ Mendeley shared course page] has been set up as a pilot project. You will have to register with Mendeley to participate.

==Modelling using Molecular Mechanics==

A general introduction to the [[mod:molecular_mechanics|Molecular Mechanics]] (MM) method should be consulted before attempting any calculations. The present techniques illustrate several more complex applications of this method to typical chemical problems and the type of information that such modelling is capable of providing. This involves optimising molecular geometry to an energy minimum and analysing the final energy in terms of bond length and angle strain, steric effects and van der Waals contributions.

Before discussing specific applications of such a model, it is worth noting some of the limitations of the molecular mechanics approach. It is essentially a parametric method, using data from experimentally well characterised and known molecules. It is therefore used as an interpolative rather than an extrapolative technique, which cannot stray too far from "known chemistry". Thus it is not easily possible to model "kinetic control" of a reaction using the standard approach, since that requires knowledge of the transition state structure and energy. For the same reason, new molecules with unusual bonding are rarely amenable to modelling, and recourse has to be sought in the full quantum mechanical treatment of the system. Similarly, for molecular properties such as stereoelectronic effects, aromaticity, hyperconjugation and frontier orbital interactions which require a knowledge of the electron distribution within the molecule, recourse has to be made to quantum mechanical methods such as molecular orbital theory. Finally, molecular mechanics parameters are available only for certain types of bonds, and frequently are not available for many functional groups. Metal ions are also a category less easily handled at present by this type of model.

You will be using the Allinger MM2 molecular mechanics models<ref>Conformational analysis. 130. MM2. A hydrocarbon
force field utilizing V1 and V2 torsional terms {{DOI|10.1021/ja00467a001}}</ref> as implemented in the ChemBio3D program (which also supports MMFF94, useful for modelling biological systems, such as DNA, proteins, carbohydrates). MM3, MM4, Amber 11, force fields have also been developed, but are not implemented in ChemBio3D. You could alternatively use programs other than ChemBio3D, such as '''Ghemical''' (which you may remember from 2nd year), or the newer '''Avogadro'''.

'''Information Produced by the Programs''': ChemBio3D using MM2 produces an energy (in kcal mol-1) together with optimised values for bond lengths, angles etc. This energy is a rather odd quantity. It is NOT related to any thermodynamic quantity such as ΔH, and energies obtained using two different force fields CANNOT be compared. You CAN however compare two energies calculated using the same force field for two different ISOMERS. You can also calculate energy differences for simple reactions such as the hydrogenation of alkenes, particularly if this is compared across a series of related reactions. The energy itself can be dissected into contributions from the stretching ('''str'''), bending ('''bnd'''), torsion ('''tor'''), van der Waals ('''vdw''') and hydrogen bonding ('''H-Bond''') energy terms. Each term indicates the deviation from "normality" of the particular function. For example, a very positive stretch term would indicate the predicted bonds are far from the "natural" lengths, due to some geometrical feature of the molecule. Comparing these terms across say two isomers provides a natural explanation for why one isomer may be more stable than the other. Documentation for the programs being used is found here:
# Molecular Mechanics, Semi-empirical MO, Ab initio/DFT MO: [[mod:chem3d|ChemDraw/ChemBio3D]].
# Ab initio/DFT MO: [[mod:gaussview|Gaussian/Gaussview]]

===The Hydrogenation of Cyclopentadiene Dimer===

[[Image:t51.gif|right]]Cyclopentadiene dimerises to produce specifically the endo dimer '''2''' rather than the exo dimer '''1'''. Hydrogenation of this dimer proceeds to give initially one of the dihydro derivatives '''3''' or '''4'''. Only after prolonged hydrogenation is the tetrahydro derivative formed. The modelling technique here involves calculation of the geometries and energies of all four species '''1-4'''. 

The relative stabilities of the pairs of compounds '''1'''/'''2''' and '''3'''/'''4''' should indicate which of each pair is the less strained and/or hindered in a thermodynamic sense. The observed reactivity towards cyclodimerisation and hydrogenation can of course be due to either thermodynamic (''ie'' product stability) or kinetic (''ie'' transition state stability) factors. In pericyclic reactions in particular, regio and/or stereoselectivity is controlled by the electronic properties of the molecules (stereoelectronic control), and hence can only be understood in terms of ''eg'' the molecular wavefunction (''cf'' 2nd year lectures on pericyclic reactions). On the basis of the results obtained from the molecular mechanics technique you should be able to suggest whether the cyclodimerisation of cyclopentadiene and the hydrogenation of the dimer is kinetically or thermodynamically controlled.

You might wish to revisit this particular experiment in [[Mod:physical|Module 3]] of this laboratory course.

====Procedure====

Using Chem3D, define the two products '''1''' and '''2''' and optimise their geometries using the MM2 force field option. In the light of the above discussion, relate your results to the observed mode of dimerisation. The two products of hydrogenation '''3''' and '''4''' can be similarly compared so that a thermodynamic prediction of the relative ease of hydrogenation of each of the double bonds in '''2''' can be obtained. Analyse the relative contributions from the stretching (str), bending (bnd),torsion (tor), van der Waals (vdw) and hydrogen bonding (H-Bond) energy terms in terms of the relative stability of '''3''' and '''4'''.

Estimated time for completion: < 30 min.

===Stereochemistry and Reactivity of an Intermediate in the Synthesis of Taxol.===

[[Image:Taxol_molecules.gif|right]]A key intermediate '''9''' or '''10''' in the total synthesis of Taxol (an important drug in the treatment of ovarian cancers) proposed by Paquette is initially synthesised with the carbonyl group pointing either up or down. On standing, the compound apparently isomerises to the alternative carbonyl isomer. This is an example of [[organic:atropisomerism|atropisomerism]]. Clearly the stereochemistry of carbonyl addition depends on which isomer is the most stable. It is also noted that during subsequent functionalisation of the alkene, this reacted abnormally slowly!

====Procedure====

Using molecular mechanics MM2 force-field to determine the most stable isomer '''9''' or '''10''', and to rationalise why the alkene reacts slowly (hint: find literature on hyperstable alkenes!). Pay particular attention to the conformation of the resulting optimised structure, to see if any aspect of this structure could be improved by further minimisations (preceeded if necessary by a manual edit of the structure to move atoms into more correct orientations). Does the MMFF94 field produce similar results?

Estimated time for completion: < 2 hour in total.

==== Key literature ====

# S. W. Elmore and L. Paquette, ''Tetrahedron Letters'', '''1991''', 319; {{DOI|10.1016/S0040-4039(00)92617-0 10.1016/S0040-4039(00)92617-0}}
# See J. G. Vinter and H. M. R. Hoffman, ''J. Am. Chem. Soc.'', '''1974''', ''96'', 5466 ({{DOI|10.1021/ja00824a025}} {{DOI|10.1021/ja00824a025}}) and '''95''', 3051 for another nice example of atropisomerism.
# Another well known example is within Vancomycin: ''J. Am. Chem. Soc.'', '''1999''', ''121'', 3226. DOI: [http://dx.doi.org/10.1021/ja990189i 10.1021/ja990189i]
# An interesting variation is of "atropenantioselective cycloetherification" (G. ÊIslas-Gonzalez, M. ÊBois-Choussy and J. ÊZhu, ''Org. Biomol. Chem.'', '''2003''', 30-32. DOI: [http://dx.doi.org/10.1039/b208905 10.1039/b208905].
# First paper formally recognizing the new class of "hyperstable" olefins (Wilhelm F. Maier, Paul Von Rague Schleyer, ''J. Am. Chem. Soc.'', '''1981''', ''103'', 1891. DOI: [http://dx.doi.org/10.1021/ja00398a003 10.1021/ja00398a003]

==Modelling Using Semi-empirical Molecular Orbital Theory.==

In part 1, the strengths and weaknesses of a purely mechanical molecular model were illustrated. In particular, the ''endo'' stereoselectivity in Diels Alder cycloadditions was attributed to "secondary orbital" interactions, which the Molecular Mechanics approach cannot handle. In this section, such electronic aspects of reactivity will be illustrated, showing how explicit consideration of the electrons in molecules must be taken into account, and how the electrons influence bonds and derived spectroscopic properties.

===Regioselective Addition of Dichlorocarbene===

#[[Image:t55.gif|right]]'''Part 1:''' Orbital control of reactivity is illustrated in the reaction of compound '''12''' with electrophilic reagents such as dichlorocarbene or peracid. In modelling such a reaction, we require a program where the geometry of '''12''' can be predicted, and the energy of the orbitals calculated and their form displayed graphically. This experiment serves to illustrate the transition from a purely classical mechanical treatment of a molecule to a quantum mechanical treatment which includes the wave-description of the electrons. Use the ChemBio3D program and select the following methods to calculate the energy and geometry of this molecule:
## MM2 (this runs in just a few seconds and cleans the geometry up prior to applying an electronic method).
## MOPAC/PM6 or MOPAC/RM1 MO methods provide an approximate representation of the valence-electron molecular wavefunction, and in particular of the HOMO (Highest Occupied Molecular Orbital), presumed to be the most reactive towards electrophilic attack (this runs in 30 seconds or less). Does this method discriminate between the two alkene bonds? Reaction with dichlorocarbene is similar to electrophilic addition, and the HOMO indicates which of the two alkenes is the most nucleophilic.
#'''Part 2:''' The purpose here is to calculate the influence of the Cl-C bond on the vibrational frequencies of this molecule. You will compare two molecules; compound '''12''' which contains a double bond anti to the Cl-C bond and a hydrogenated version where this anti (or exo) double bond (but not the other) is replaced by a C-C single bond. The most reliable procedure for obtaining vibrations is the '''density functional''' approach (but you could use the far faster MOPAC/RM1 method and check this assertion!).
#*Using the geometry of '''12''' optimized by the previous methods, subject it and its dihydro derivative to B3LYP/6-31G(d,p) Gaussian geometry optimization and frequency calculation (see [[Mod:chem3d| instructions here]] using the keywords OPT and FREQ). Each calculation will take 1-2 hours, and is far better done using the SCAN than the laptop.
#*Load up the output LOG or FCHK (you get this from the SCAN) file (into ChemBio3D or Gaussview) and inspect any Cl-C stretching frequencies (see [[Mod:chem3d| instructions]]). Look in particular for any with a large IR intensity, and identify the two C=C stretches for the diene and the single C=C stretch for the monohydrogenated derivative. Comment on their values and any differences between the diene and the monoene. If you do spot changes, comment on whether they make sense in terms of your analysis in part one above.
#'''Part 3 (optional):''' If your curiosity has been aroused by the previous step, try modifying the substituents on the ''anti/exo'' alkene (i.e. change the =C-H group to =C-OH, =C-CN, =C-BH2, =C-SiH3) etc. Does this have any (electronic) effect on the Cl-C and C=C frequencies and is it in the expected direction? Is any effect also reproduced using MM2?
====Procedures====

#Using the Chem3D program, draw the molecule, and to perform e.g. first the MM2 step and then the MOPAC/PM6 step as above, select '''Calculations/MOPAC Interface/Minimise energy''' option from the top menus, and from the '''Job & Theory''' pane, select '''Method=PM6'''. From the Properties page, tick '''Molecular Surfaces'''. From the '''General''' pane, change the default location of the '''Results in''' folder to e.g. your documents folder (if you do not do this, the program will report that e.g. \\icfs7.cc.ic.ac.uk\yourloginname\Mopac Interface\ cannot be written to). Click '''Run''' and watch the messages at the bottom. This should take ~10 seconds (if the geometry has been pre-optimized using MM2). When this is complete, select , '''Surfaces/Molecular orbitals'''. The HOMO appears by default.
#Select '''Surfaces/Select molecular orbital''' to view the HOMO-1, the LUMO, LUMO+1 and LUMO+2. You might also want to adjust '''Surfaces/Isocontour''' to produce a more pleasing appearance for each orbital. Save each orbital as a .jpg file for insertion into your Wiki report.
#'''HINT''': Inspect the shape of your orbitals very carefully, to see if they make sense, before committing them to your report. In particular focus on whether the molecular orbital reflects the molecular symmetry of the molecule. If not, do any solutions suggest themselves? Comment on the outcome in your report.

Estimated time for completion: < 2 hour.
#Using the PM6 or RM1 optimized geometry, select the Gaussian interface and save an input file to run B3LYP/6-31G(d,p). Do the same for the monoalkene with the remaining double bond on the same side as the Cl. Save both molecules as Gaussian inputs (.gjf) files, and edit both files (using e.g. Wordpad) so that the very top line of the file shows as follows;

<pre># b3lyp/6-31G(d,p) opt freq</pre>

Any lines above this one should be deleted. Submit both jobs to the SCAN under the queue '''Chem Lab 1'''. The calculation should take <1 hour (if your starting geometry was the PM6 optimised one) to complete (provided the backlog of jobs is not high!). Do not try this on the laptop, since it will take many more hours, and the laptop may overheat! (Hint: the di-alkene can be defined as having Cs symmetry in Gaussview, and if you do this before submitting the job, the calculation will take half the time! What about the monohydrogenated system? Does that have Cs symmetry? ). When complete, download the '''Formatted checkpoint file''' for each molecule from the Web page, which should appear on your desktop. Double click this file if it does not open automatically in Gaussview 5.09, select 'open with' and navigate to Disk C/g09w/gview, and in '''Results/vibrations''' track down the Cl-C and C=C stretching vibrations in each system.

Estimated work time for completion: < 1 hour preparation time; ~4 hours elapsed time.

==== Key literature ====
#B. Halton, R. Boese and H. S. Rzepa., ''J. Chem. Soc., Perkin Trans 2'', 1992, 447. {{DOI|10.1039/P29920000447}}

=== Monosaccharide chemistry: glycosidation ===

{| cellpadding="0" cellspacing="0"

|<jmol><jmolApplet><title>Glucose02-nge</title><color>white</color>
<size>200</size><script>measure 5 8 22;zoom 150; cpk -20;</script>
<uploadedFileContents>GLUCSE02-nge.mol</uploadedFileContents>
</jmolApplet></jmol> || [[Image:anomer1.jpg|right|250px|glycosidation]]Glycosidation involves replacing the group X by reaction with a nucleophile Nu. The two sugars shown to the right give different anomers (with almost complete diastereospecificity) depending on the orientation of the OAc group on the adjacent carbon.
This effect is due to neighbouring-group-participation from the adjacent acetyl group. For the β-anomer, the intermediate oxonium cation must be attacked from the bottom face, to then allow the incoming nucleophile to replace it from the top face. Likewise, the α-anomer is formed by the acetyl oxygen attacking from the top face of the oxonium cation, allowing the nucleophile to come in from the bottom face.
|-
| <jmol><jmolApplet><title>Glucose02-nge-epi</title><color>white</color>
<size>200</size><script>measure 5 8 22;zoom 150; cpk -20;</script>
<uploadedFileContents>GLUCSE02-nge-epi.mol</uploadedFileContents>
</jmolApplet></jmol> ||[[Image:anomer2.jpg|right|430px|Neighbouring group participation]]
|}
Your task is to model these facial preferences, i.e. the diastereospecificity, using both MM2 and MOPAC/PM6 methods.
====Procedure====
#Sketch the oxonium cation rings A and B. Which group do you think is an appropriate R group to represent the chemistry while keeping the computational demand minimal? Which methods between MM2 and MOPAC/PM6 do you think is better suited for the task? Why?
#For each structure, use both methods to try to find two conformers differing in whether the acyl group is pointing '''above''' or '''below''' the plane of the oxonium cation (A and A', B and B'). Which ones of the pairs have the lower energy? Hint: use the MM2 geometry as the starting point for obtaining a PM6 geometry.
#You could try the same again but now using the intermediates C and D. You should carry out the calculation using both methods and determine the stabilisation energy by neighbouring-group-participation. Compare the results of the two methods (energy, bond lengths, bond angles, etc.). Is it still possible to get two isomers (C and C', D and D') for each?
#Can you rationalise the diastereospecificity in glycosidation using the computational results?

Estimated time for completion < 3 hours.

====Key Literature====
#D. M. Whitfield, T. Nukada, ''Carbohydr. Res.'', 2007, 342, 1291. {{DOI|10.1016/j.carres.2007.03.030}}

=: Structure based Mini project using DFT-based Molecular orbital methods =
Many (most?) reactions carried out by synthetic chemists can (and do) give mixtures of products. Often, these products are isomers (for example stereoisomers, or regioisomers which can arise from reaction at more than one site in a molecule, or from different orientations of the reacting groups). Having isolated (and ideally having separated) these isomeric products, it is important to know which isomer(s) have been formed. Often, an understanding of the mechanism of the reaction that was carried out will allow us to predict fairly confidently which isomer will predominate. You have met many key mechanistic ideas in Years 1 and 2 that enable you to do this (particularly by considering steric and electronic effects). However, it is still necessary to conclusively confirm that the expected product has been obtained, and if more than one isomer is produced, to be able to say for sure which-is-which. Sometimes, the reaction products will be solids which can be crystallised and their structures determined by X-ray crystallography, which gives detailed structural information. However, many organic compounds are oils or liquids and structure determination relies on spectroscopic methods. Mass spectrometry is a useful starting point, and high resolution mass spectrometry (HRMS) allows the molecular formula to be determined. UV and IR spectroscopy provide information on the functional groups present in the molecule. These techniques do not often allow us to distinguish between isomeric organic compounds, though. For this purpose, NMR is a primary tool because it provides information on molecular environment (chemical shifts) and connectivity (analysis of couplings between nuclei). In analysing chemical shifts, the chemist traditionally compared the observed chemical shifts to those of similar known compounds in the literature, looking for similarities to provide evidence for a structural assignment. Modern computational chemistry can provide an alternative: the 13C (also 15N,19F, 31P) spin-spin decoupled spectrum of a molecule can be predicted, often with acceptable accuracy. Computational chemistry also allows prediction of other useful spectroscopic properties, such as IR spectra and (for chiral compounds) optical rotations. For determining stereochemistry, extremely useful information can be obtained from 3-bond 1H J values, since these depend on the dihedral angle between the two protons according to the [http://en.wikipedia.org/wiki/Karplus_equation Karplus equation]. Again, molecular modelling can be used to predict dihedral angles and [http://www.stenutz.eu/conf/jhh.html hence the expected J-values].

In this experiment, you will choose a reaction from the primary literature which either is reported to give two or more isomeric reaction products, or which (based on your mechanistic understanding of the chemistry employed) has the potential to do so, even if only one isomer was reported. Ultimately, you will investigate whether 13C prediction using the GIAO approach helps in assigning the structures of the isomeric products. You might even find a paper where the original authors were uncertain as to the product structures, and be able to solve their problem! If any of the other computational techniques are useful for your example, please use them as well. The general approach to the task is as follows:
# Choose a reaction to study. You will gain extra credit (+ 5%) for finding a suitable reaction from the literature yourself. In choosing reactions, bear in mind the comment below (in the section describing how to do the 13C prediction) about the need to choose molecules that are not highly conformationally flexible. A good starting point is to look at recent issues of journals containing synthetic chemistry (e.g.[http://pubs.acs.org/journals/joceah/index.html ''Journal of Organic Chemistry''], [http://pubs.acs.org/journals/orlef7/index.html ''Organic Letters''], [http://www.rsc.org/Publishing/Journals/OB/index.asp ''Organic and Biomolecular Chemistry''], ''Tetrahedron''). Ideally, you need to choose papers which include experimental 13C NMR data for the isomeric products: this may be in the Experimental section for full papers, or in the Supporting Information which is usually available online. If you can’t (or don’t wish to) find your own reaction, some suggested examples are given below, which you may use for restricted credit. Associated with each of these are some questions to think about – even if you’ve chosen your own example, reading these may give you some idea of the kinds of question you might ask yourself when analysing your problem.
# Think about the following points and discuss them in your answer:
##How would you differentiate spectroscopically between the isomeric products? What methods would you use, and what would be the '''key''' spectroscopic differences you would look for in the spectra of the isomers in order to tell which sample is which? This is rarely discussed explicitly in synthetic papers, but the researchers doing the work will have done this as part of the research process, and thinking about how this is done is a very useful exercise for those intending on a research career!)
##Calculate the predicted 13C spectra for the isomers using the GIAO method. Include a listing of the data and assignments in your report.
##Compare your predicted data to the experimental 13C data in the paper. Do they match? Do they support the structural assignment in the paper? If not – why might this be? '''Note''': it is quite possible that your calculated data will '''not''' match those in the literature. Don’t worry! Apart from the conformational flexibility problem, there are other limitations in the computational approach. In this regard, your work is truly a research exercise – the use of this technique is at the cutting edge, and your calculations will help to determine when the method works and when it does not!
# If you can, discuss the mechanism of the reaction and why the reaction shows (or doesn’t show) selectivity for one particular product isomer. Can any of the other computational techniques you’ve met in the course be used help to explain the selectivity?

== Objectives and Suggested Structural Explorations ==

You will be given full credit for attempting '''ONE''' of the below (and 5% bonus for one of your own devising not listed below). This part of the module should take < 10 hours spread out over two days to complete.
==== Stereoselective dissolving metal reductions ====
[[image:reduct1.jpg|right]]You met the use of dissolving metals (e.g. Li/NH3) for reduction of carbonyl compounds and aromatic rings (Birch reduction) in Year 2 (Functional Group Interconversions course). In a recent natural product total synthesis ({{DOI|10.1016/j.tet.2006.12.019}}), these conditions were used for stereoselective reduction of a cyclic ketone to an alcohol: ketone '''5''' was reduced with complete stereoselectivity to give alcohol '''6''' (Scheme 1 in the paper). How would you tell the reaction had worked, and which stereoisomer had formed? Do the predicted 13C (and 3JH-H) data match the reported? Why was this stereoisomer obtained? The optical rotation of '''6''' is reported. Does it match calculation? (you may have to play with the orientation of both the OH and propenyl groups to get a good match).

=== Regio- and stereoselective conversion of alkenes to epoxides ===
[[image:epoxide.jpg|right|thumb]]As you know from Years 1 and 2 (especially Year 2 Functional Group Interconversions course), epoxides are highly versatile synthetic intermediates because they undergo ring opening with a wide range of nucleophiles. In a recent paper ({{DOI|10.1016/j.tetasy.2005.02.012}}), it was shown (Scheme 6 in the paper) that a 1,3-diene (compound '''13''') can be regioselectively epoxidized to give either stereoisomer '''14''' or '''15''' depending on the reaction conditions used. How would you tell that the “correct” alkene had been epoxidised? Unfortunately the authors don’t include 13C data for their products in the paper, but they are available in the literature (do a search on Beilstein). Do the products’ 13C data match your calculations? Why do the two sets of epoxidation conditions give different stereoisomers?

=== Assigning regioisomers in "Click Chemistry" ===
[[Image:Click.gif|left]]The 1,3-dipolar cycloaddition between an azide and an alkyne to give a 1,2,3-triazole has been known for a long time. However, in 2002, two groups reported independently that the use of a Cu(I)-catalyst greatly speeds up the reaction. So facile is the catalysed chemistry that it is now often called the “click reaction”, being a classic example of the philosophy of “[http://en.wikipedia.org/wiki/Click_chemistry click chemistry]” introduced by Nobel Laureate K. Barry Sharpless, which aims to exploit reactions which “are tailored to generate substances quickly and reliably by joining small units together”. The ease and high selectivity of the click reaction has led to its widespread use in important fields such as materials science and biology – for example, the specific introduction of tags and labels into proteins.
When substituted alkynes and azides are used, there are two possible regioisomeric products, '''A''' and '''B'''. Under Cu(I) catalysis, the 1,4-isomer '''A''' predominates; interestingly, however, Ru(II)-catalysed reactions give mostly the 1,5-isomer '''B''' instead. How can we tell these apart spectroscopically? Look at the original paper (''J. Am. Chem. Soc.'' '''2005''', ''127'', 15998; {{DOI|10.1021/ja054114s}}). For the example in Table 1, entry 1, calculate the 13C spectra for the depicted product isomer and for the alternative regioisomer. Which best matches the data reported in the paper? For comparison, can you find data for the other isomer anywhere in the literature?

=== Investigating the regioselectivity of the Baeyer-Villiger reaction ===
[[image:bv2a.jpg|left|thumb]][[image:bva1.jpg|right]]The [http://en.wikipedia.org/wiki/Baeyer-Villiger_oxidation Baeyer-Villiger reaction] converts ketones into esters, effectively inserting an oxygen atom between the carbonyl group and the alpha-carbon. It is usually carried out using mCPBA. For unsymmetrical ketones, there are two possible regioisomeric products; usually it is possible to predict which isomer will predominate in line with the migratory aptitude of the ketone substituents. Investigate '''ONE''' of two recent literature examples where the reasons for the regiochemical outcome are not so obvious:
*The Baeyer-Villiger reaction was used ({{DOI|10.1021/jo030377y}}) in a recent synthesis of analogues of beta-lactam antibiotics. In Scheme 5, reaction of '''10d''' gives '''11d''' and '''12d'''. Are the regiochemical assignments correct, and why is the regioselectivity low in this case?
*During a total synthesis of the natural product (-)-kainic acid ({{DOI|10.1016/S0040-4020(02)00379-4}}), a neuropharmacological tool, a highly regioselective Baeyer-Villiger reaction was a key step (conversion of compound '''14''' into '''15'''). Do the predicted 13C data fit with the reported ones? Why is this reaction so regioselective?

=== The total synthesis of (-)Cubebol ===

[[Image:cubebol.gif|right]] Cubebol is a natural sesquiterpene alcohol with a cooling and refreshing taste. It was patented as a cooling agent (i.e. to make you feel you are eating ice-cream without actually having to freeze the ingredients!). The total synthesis has recently been reported: {{DOI|10.1021/jo9022974}} in which much spectroscopic information about the molecule is available. Your project will involve testing that this information and the assignments are correct for the absolute configuration shown.

=== General Reference===
K. Mori, ''The Chemical Record'', '''2005''', ii5'', 1-16. {{DOI|10.1002/tcr.20030}}

== Relevant computational techniques for Mini-project ==

===Predicting the 13C NMR Spectrum of a compound===

The 13C (also 15N,1NF, 31P) spin-spin decoupled spectrum of a molecule can be predicted using two quite different methods.
# The first is a rule-based approach is derived from a fragment library, and is applicable mostly for organic molecules. The advantage is that the prediction is extremely rapid, and fairly general. The downside is that the accuracy is only around 3-5 ppm, and does not take into account local conformations, differential solvation of different groups, etc. It is not applicable for many organometallic and inorganic systems.
# The second is the so-called GIAO approach using quantum mechanical density functional theory. The background to this, and a famous recent example can be found in the article by Rychnovsky1 on a revision of the structure of '''Hexacyclinol''' ( {{DOI|10.1021/ol0611346}}). He reports that the mean error for the 23 carbon shifts in the predicted structure was around ± 1.8 ppm, with a maximum error of around 5.8 ppm. An improved procedure which reduces the mean and maximum errors by one half will be used here2 ({{DOI|10.1021/np0705918}}), although a number of caveats for successful prediction should be noted. The most serious is that the method is '''highly''' sensitive to the conformation of the molecule. If various different conformations are possible (and for some molecules, 100s of reasonable conformations can sometimes be imagined), they should all be scanned by this method. Since this is clearly not feasible in a reasonable time, you should not choose a problem that has conformational ambiguity.

====Procedure====

=====Creating an initial Molecule input file =====
You will need to sketch your molecule in ChemDrawPro+ChemBio3D/Gaussview and perform an initial refinement of its 3D geometry using MM2. If it contains only simple elements (CHNO, Si, P, S, halogens) then the chances are that a molecular mechanics refinement will be possible. At this stage, whilst the calculations still take only a few seconds, you might wish to investigate several conformational possibilities to see which might be the lowest (but don't try more than say 5). Some conformations can be preset (a worthwhile one is to always try to get 6-membered rings into a chair, and e.g. esters R-CO-O-R' oriented such that the R-C bond is antiperiplanar to the O-R' bond). If the mechanics procedure fails because of lack of parameters, try eg the MOPAC/AM1 approach instead. If both of these fail, try the Gaussian procedure, using the HF (Hartree-Fock) method and an STO-3G basis set. This initial geometry will then have to be '''refined/optimized''' using the following method.
# In ChemBio3D, go to Calculations/Gaussian/Create Input File.
# Select Job Type/Minimise; Method DFT=mpw1pw91
#*'''A note on DFT methods:'''. A wide variety of DFT methods have been proposed {{DOI|10.1021/jp710179r}}. This particular one has been extensively tested for the calculation of NMR properties and found to be somewhat superior to the more common B3LYP procedure.
# The Basis set to be set to 6-31G(d,p)
#*'''A note on basis sets:''' A wide variety of basis sets have been [https://bse.pnl.gov/bse/portal described] (including a set optimized specifically for NMR shift calculations, {{DOI|10.1021/ct800013z}}, type '''pcS''' into the search box [https://bse.pnl.gov/bse/portal here]) and often a decision on which basis set is most appropriate for which property being computed has to be made. In the case of NMR as a property, it is not necessarily true that the larger basis set is the better one! You will revisit basis sets in modules 2 and 3 of this course.
# Save the resulting file to your H: drive, making sure it is saved as a '''Gaussian Input file''', with the suffix '''.gjf'''.
# Find the file in Windows Explorer, and with a right-mouse-click, open it with the WordPad program.
# Delete all lines at the top, leaving only the following line, which should be edited to show something like the following
<pre># mpw1pw91/6-31g(d,p) opt(maxcycle=25)

Geometry optimization for literature compound

0 1
atom1-symbol 0 x-cooordinate of atom1 y-cooordinate of atom1 z-cooordinate of atom1
atom2-symbol 0 x-cooordinate of atom2 y-cooordinate of atom2 z-cooordinate of atom2
... ... ...</pre>This shows the keyword line at the top, a blank line, a title card, another blank line, a charge/spin card (we will assume that your unknown is neutral, i.e. charge=0 and a singlet spin state, i.e. spin=1) and the first line of atom coordinates. If you need to calculate a charged species, change the '''0''' to e.g. '''-1''' (for an anionic species). Whilst you are at it, check to see if your coordinates have any atom type designated '''Lp'''. If any such lines are present, delete the entire line. Lp is a Lone-pair, and is sometimes added by the Molecular Mechanics part of the program. However, if Gaussian sees it, it gets very confused, and will not run at all!. The keyword value maxcycle=25 is because sometimes the geometry optimization meanders very close to convergence, and this limits this meander. Re-save this file, making sure you save it as '''TEXT''' and ''NOT'' RTF and that it retains the suffix '''.gjf'''.

==== Submitting this file to the SCAN for geometry optimization ====
#[[Image:scan2.jpg|thumb|left]] [[Image:scan1.jpg|thumb|right]] Go to [https://scanweb.cc.imperial.ac.uk/uportal2/ the SCAN Webpage], log in, and first create a project (it could simply be called Mini-project). Then, '''New Job/Chemistry Lab 1''', then select Gaussian/Your project, and finally the name of the Gaussian input file you have just saved, along with a descriptive title.
#You can view your job list, when a display of the type shown below should appear: Jobs in the '''Chemistry Lab 1''' pool also run during the day, but with a r concurrency of 8. When there are many jobs you may have to wait overnight for yours to finish. The status of the pools can be inspected by selecting Pools from the menu on the left: If your suspected molecule is large (more than about 30 non-hydrogen atoms) it may require more than about 9 hours of '''wall''' time. If the job returns no output overnight, it may well have run out of time (it has about 9 hours in which to complete the calculation). The '''Chemistry Lab 1''' will run the job to completion, but you may have to wait a while for it to start running in the first place.
# [[Image:scan3.jpg|thumb|right]]When the job shows as Finished, select the Gaussian Checkpoint file as the required output and download it (probably to the desktop, or wherever the browser tells you). Double-click the file to open Gaussview (it may happen automatically) and check that the optimised geometry is still reasonable. Invoke '''File/Save as''' and replace the original Gaussian input file you created with Chem3D. It now has a fully optimised geometry at the mpw1pw91/6-31(d,p) level, rather than the initial sketch of before.

==== Troubleshooting ====
# If the system responds that the formatted checkpoint file '''does not exist''' its quite probable that the calculation failed. Try instead to download the Log file, which may have error messages that help you diagnose what has gone wrong. Two common reasons for the failure are
## There was an error in the input .gjf file. A common error is the positioning or omission of blank lines. Check with the above to ensure they are correctly positioned. Another error is that the keywords are mis-typed. Gaussian will fail for either reason, but it should put out an error message in the log file.
##The best way to eradicate syntax errors before submission to SCAN is to run Gaussian on your laptop for a few seconds at least, this being better than waiting up to 24 hours to find that a trivial error stopped the calculation. You can run a Gaussian input either from ChemBio3D, or Gaussview.
## The calculation may have run for 9 hours and then run out of time. This means that the molecule may be rather large (> 30 non hydrogen atoms), or very conformationally mobile. You could try resubmitting with maxcycles set to something lower.

==== Submitting this file to the SCAN for NMR Chemical Shift calculation ====
# Having created a new .gjf file containing the optimized geometry, repeat the Wordpad editing procedure as described above, but this time ensure the top line of your .gjf file contains the following (if the literature reports a different solvent, replace chloroform with that solvent): (a list of defined solvents is available at the bottom of [http://www.gaussian.com/g_tech/g_ur/k_scrf.htm this page])
<pre># mpw1pw91/6-31(d,p) NMR scrf(cpcm,solvent=chloroform)

NMR calculation for literature compound

0 1
atom1_symbol 0 optimized-x-cooordinate of atom1 optimized-cooordinate of atom2 optimized-cooordinate of atom3</pre>
Resubmit this new input file for calculation as described above. This will take much less time to calculate than before. Whilst it is possible to catenate the two jobs you have run (the optimization and the NMR calculation), this requires a great deal more editing of the .gjf file, and hence scope for errors.

==== Analyzing the NMR Chemical Shift calculation ====
#[[Image:scan4.jpg|right|thumb]] When this second calculation is finished, download this time the Gaussian Log file (instead of the checkpoint file). Open this in Gaussview and from that program, select '''Results/NMR''' (if the NMR keyword is greyed out, it means the calculations was not in fact successful).
# From the Spectral display that appears, select the '''C''' nucleus, and the appropriate Reference Value. Click on any peak to find out what its chemical shift is, and compare with the spectrumreported in the literature.
# You should note that carbons attached to "heavy" elements (particularly eg halogens) have shifts which need correction for so-called Spin-orbit coupling errors. Typically, C-Cl needs correcting by -3 ppm, C-Br by -12 ppm, and C-I by about -28 ppm. First row transition metals are around -3ppm. Other elements to be determined!2. Another systematic error present is that the carbonyl of esters, amides etc tends to be out by about 5ppm. Use the following simple correction for such carbons only: δcorr = 0.96δcalc + 12.2.
# You can probably use your calculation to actually assign the 13C shifts to the carbons of your molecule. If you spot one or more carbons out by more than about 5ppm, its quite likely that you have the wrong conformation of your molecule in that region (i.e. the method can actually be used for conformational analysis), or of course that the original assigment in the literature is wrong. This actually happens quite often!
# The method should work for other nuclei (except hydrogen, which requires much greater accuracies to be really useful). First row transition metals (organometallics) appear to be reasonably handled.
# Complete this section by returning to [https://scanweb.cc.imperial.ac.uk/uportal2/ the SCAN portal] and click on the '''publish''' link next to the job that carries the NMR prediction. This will deposit your calculation into a so-called '''Digital repository'''. Quote the entry in your Wiki pages as <nowiki>{{DOI|10042/to-xyz}}</nowiki> where xyz is the entry generated by the previous operation.

====References====

# S. D. Rychnovsky, ''Org. Lett.,'' '''2006''', ''13'', 2895-2898. {{DOI|10.1021/ol0611346}}
# C. Braddock and H. S. Rzepa, ''J. Nat. Prod.,'' '''2008''', ''71'', 728-730. {{DOI|10.1021/np0705918}}
# A recent development is an enhanced technique for accurately computing 1H chemical shifts: {{DOI|10.1021/jo900482q}}
# Goodman has produced some interesting tools for aiding NMR analysis.
## {{DOI|10.1021/jo900408d}}
##[http://www-jmg.ch.cam.ac.uk/tools/nmr/ Applet]
## {{DOI|10.1021/ja105035r}}
## [http://www.spectroscopynow.com/coi/cda/detail.cda?id=24215&type=Feature&chId=5&page=1 Blog commentary]

===Predicting the 3J H-H couplings of your compound===

The above technique is reliable for 13C shifts, but less so for 1H shifts. However, three-bond couplings can be predicted reasonably well using a very rapid and simple method based on the Karplus equations. To do this, you will need to have a 3D model of your unknown, which should emerge out of your 13C prediction in the preceeding section. The start point should be to use Chem3D to save an MDL Molfile of your final coordinates. This can then be read into [http://www.ch.ic.ac.uk/local/organic/janocchio/index.html Janocchio,] to provide the coupling constants.

It is also possible to compute J couplings using quantum mechanical methods (Gaussian keyword '''NMR(spinspin)''') but these calculations are '''highly''' time consuming if accurate results are to be obtained.

====Reference ====

D. A. Evans, M. J. Bodkin, S. R. Baker, G. J. Sharman, ''J. Magn. Reson,'', '''2007'''. * {{DOI|10.1002/mrc.2016}}

=== Predicting the IR Spectrum of a compound ===

Calculating the vibrational normal modes of a molecule is simpler than NMR since it can be done in a single job, but it may also be more time consuming. Only try this for smaller molecules (<25 non hydrogen atoms, including the first row transition metal series).
==== Procedure ====
Create an initial .gjf file, and modify it thus;
<pre># b3lyp/6-31G(d,p) opt freq

Geometry optimization and vibrational frequencies for literature compound

0 1
atom1-symbol 0 x-cooordinate of atom1 2-cooordinate of atom2 -cooordinate of atom3
atom2-symbol 0 x-cooordinate of atom1 2-cooordinate of atom2 -cooordinate of atom3
... ... ...</pre>
In the resulting output, <pre>Sum of electronic and thermal Free Energies= -3170.440313</pre>
gives you in effect ΔG = ΔH - T.ΔS. You can use this term to compare the '''difference''' in free energies between two molecules, remembering that it is expressed in Hartrees; 1 Hartree = 627.5 kcal/mol.
==== Analyzing the Vibrational Spectrum ====

Download the.fchk file from the SCAN page, and by double-clicking, open it in Gaussview. From '''Results/Vibrations''', select the '''Save normal modes''' from the '''Run FreqChk''' pop-up box and inspect the normal modes and their predicted intensities, using the animation feature to help describe them. Errors in the predicted wavenumbers are systematically too high for stretches (which means they can be corrected using empirical factors) by around 8%; bending and lower frequency modes are normally about right. Pay particular attention to the predicted intensities, which may help you to assign the vibrations. If you get any apparently negative modes, you will have in fact obtained a transition state (or higher order) stationary point.

==== Reference ====

R. Janoschek, ''Pure and Applied Chemistry'', '''2001''', ''73'', 1521-1553. {{DOI|10.1351/pac200173091521}}

=== Predicting the Optical Rotation (OR) and the Electronic Circular Dichroism (CD/UV-Visible) Spectrum of a compound ===
Measuring optical rotations is one of the oldest spectroscopic techniques, dating back well into the 19th century, and a mainstay of organic chemistry until IR/NMR etc came along mid 20th century. Although the theory of how molecules interact with polarized light has been known for a long time, it is only in the last 5 years or so that computers have become sufficiently fast to solve the problem to the required accuracy, which in fact comes in two parts. The simpler is to see if the absolute sign of the optical rotation predicted for a given absolute configuration of a molecule corresponds to that measured. Because the sign can easily change as a result of apparently minor changes to the structure of the molecule (or even in extreme cases, its conformation), there is little ''intuition'' that can be applied, or indeed simple rules. A full quantum mechanical calculation is pretty much the only reliable method for predicting the absolute sign of the OR. The second aspect is predicting the magnitude of the rotation. This again can vary from close to zero, to many thousands! It is generally accepted that only compounds with ORs of magnitude >|100| (or at a pinch >50) can be successfully used to predict absolute configurations with near total confidence. So you should only attempt to predict the OR of an asymmetric molecule if it fulfills these criteria. Another chiro-optical property is the CD spectrum. This is essentially the UV spectrum of the molecule, with the difference that it is recorded with '''chiral''' light. The two enantiomers of a disymmetric molecule interact differently with this light (think of it as opto-electronic diastereomers), and particularly the sign of the intensity of each electron transition can be either positive or negative. The resulting CD spectra are exact mirror images of each other for each enantiomer of the molecule, which means that distinguishing between them is trivial. The crucial difference between CD and OR is that the former is very much less sensitive to conformation, and hence the answer so much more definitive. There are other types of '''chiro-optical''' spectroscopies (Vibrational circular dichroism, Raman Optical Activity) which can be even more definitive, but these are still rarely used.

Proceed as follows:
==== Procedure for Optical Rotation====
Take the output of the previous frequency or NMR calculation (i.e. the optimized geometry), and run a job of the following type:

<pre>
# cam-b3lyp/ 6-311G(d,p) polar(optrot) scrf(IEFPCM,solvent=chloroform) CPHF=RdFreq
This is a blank line; put no text in it
Optical rotation for literature compound
This is a blank line; put no text in it
0 1
firstatom-symbol 0 x-cooordinate of atom1 2-cooordinate of atom1 -cooordinate of atom1
...
lastatom-symbol 0 x-cooordinate of lastatom 2-cooordinate of lastatom -cooordinate of lastatom
This is a blank line; put no text in it
589nm
This is a blank line; put no text in it
</pre>
The Cambridge variation on the B3LYP density functional method is used, which improves the prediction of chiro-optical properties compared to the normal B3LYP version. The keyword '''aug-cc-pvdz''' invokes an augmented (i.e. with additional diffuse basis functions), correlation-consistent double-ζ valence polarization basis set suitable for optical rotation calculations and polar(optrot) calculates the [alpha]D optical rotation components of an asymmetric mol. The i wavelength of the incident light (589nm is the sodium D line) is read in using the keyword CPHF=RdFreq and the line appended as 589nm after a blank line following the coordinates. A final blank line follows the frequency line. Specify the appropriate solvent in the SCRF keyword. If this recipe fails to converge (it can do occasionally), try instead a faster and simpler basis set to replace the aug-cc-pvdz one: '''6-31G(d,p)'''.

In the resulting output, e.g. [ALPHA] ( 5890.0 A) = -324.5 deg gives the estimated optical rotation for the exact enantiomer that you built (try submitting the other enantiomer and see if you get the opposite rotation). The value given by [Alpha]D is misleading, it being the non-frequency dependent approximation to this parameter (and regarded as less accurate than the frequency dependent value at 589nm which follows). The method will reliably predict whether the optical rotation corresponds to the enantiomer you have built if [Alpha]D > 100°, but becomes increasingly unreliable for lower values. The OR is also highly sensitive to conformation; even a 60° rotation of an OH group can alter its value by a factor of two! Turned on its head, predicting OR could be regarded as a highly sensitive method for conformational analysis! You should be aware that this calculation an be quite time consuming, and molecules with > 20 non hydrogen atoms should not be attempted.

==== Procedure for the CD (Circular Dichroism) Spectrum ====

Use the following keywords, which invokes the so-called time-dependent DFT method, where the first 20 electronic singlet excitations are included (you can reduce this to a much smaller value, eg 3 or 5, or a much higher one if you want to simulate the high energy/UV region of the spectrum).

<pre># cam-b3lyp/6-311G(d,p) td(NStates=20) scrf(IEFPCM,solvent=chloroform)

Circular dichroism for literature compound

0 1
atom1-symbol 0 x-cooordinate of atom1 2-cooordinate of atom2 -cooordinate of atom3
atom2-symbol 0 x-cooordinate of atom1 2-cooordinate of atom2 -cooordinate of atom3
... ... ...</pre>

The spectrum can be viewed using the ''Results/UV-Vis'' option in Gaussview 3 or 5. The regular UV spectrum is shown first, followed by the CD version.

==== References ====

# P. J. Stephens et al, ''Chirality'', '''2008''', ''20'', 454-470. {{DOI|10.1002/chir.20466}} {{DOI|10.1063/1.1477925}} {{DOI|10.1063/1.1436466}}
# B. Mennucci, M. Claps, A. Evidente, and C. Rosini, ''J. Org. Chem.,'' '''2007''', ''72'', 6680-6691. {{DOI|10.1021/jo070806i}}
# For an example of a calculation, see that for pentahelicene ([alpha]D 2061°) {{DOI|10042/to-888}} If you really want to entertain yourself, try something larger such as decahelicene!
# For a recent application to another type of highly chiral molecule, see {{DOI|10.1021/ol901172g}}

===Using the SCAN for Density functional MO calculations===

You can use the '''SCAN''' to run a Gaussian calculation. Using ChemBio3D, pre-optimise the structure using a fast method such as Molecular mechanics before submitting the DFT calculation. If you do not do this, the latter will take much longer! Create a Gaussian input file (a '''.gjf''' file) as [[mod:chem3d|described]] in the instructions, and then
# Go to [https://scanweb.cc.imperial.ac.uk/uportal2/ https://scanweb.cc.imperial.ac.uk/uportal2/] and log in.
# Select '''Projects''' and '''create a project name''' suitable for your needs.
# Select '''New Job''', then:
##'''Chemistry lab 1''' (a queue of width 8 which runs during the day)

# Then enter your project, and upload the .gjf or .com file. Put in a descriptive title to help remind you of the purpose of the calculation, and click on submit. The Job will show as either pending (for all overnight jobs) or running (for the first 8 jobs on Chemistry Lab 1). When complete, it can be collected from the same web page. In particular, if you select the '''Formatted checkpoint file''' from output list, and download it, Gaussview will open it and display the result of your calculation. You can also open this file with ChemBio3D.
# The SCAN is powerful enough that if you wished, all the molecules in this section could be submitted using the Gaussian program. You can submit multiple jobs, one after another using this technique. You could also increase the level of theory. In this case, change the basis set from 6-31G(d) to e.g. cc-pVTZ, or you could e.g. include a vibrational analysis ('''freq''' keyword) which in fact will result in an entropy correction to the energy, to give in effect a ΔG for your energy (this energy is labelled <tt>Sum of electronic and thermal Free Energies=</tt>)

==== Troubleshooting the SCAN outputs ====

The following lists some of the things that might go wrong, and what to do about them. If you identify a reproducible cause of failure yourself, please feel free to add to the list below!
* A job is finished but it returns no formatted checkpoint file. It is likely that there was an error in the input .gjf file. A common error is the positioning or omission of blank lines in this file or that one of the keywords is mis-typed. Another error is that a keyword may be repeated (thus Gaussian does not much like repetition of the '''opt''' keyword). Download the log file (if it exists) and open it with eg '''Wordpad'''. Check that blanks lines are all correctly present and positioned and for keyword errors or duplication. The output may give a clue of sorts, but the presence or absence of blank lines often confuse it. The below is an example of how an unrecognized keyword is flagged.
<pre>
# b3lyp/6-31G(d) nopt
---------------------
QPERR --- A SYNTAX ERROR WAS DETECTED IN THE INPUT LINE.
# b3lyp/6-31G(d) nopt
^</pre>
*If you cannot get a log file from the finished job, it is likely it ran out of time (each job has a limit of 48 hours). Put simply, your molecule (or the property you are trying to calculate) is a tad too big/demanding!
*It is important if a job fails, to provide as much evidence as you can to demonstrators. Thus at a minimum, you should have to hand the input file (.gjf), and ascertain if running it produces any output. Do also remember that computers are relatively reproducible. If a job fails, resubmitting it will most likely produce a second failure. Rather than simply resubmitting a job, you '''must''' resolve the undoubted error the input contains. Remember that errors can be caused by what is called '''white space''' (which of course since it consists of nothing much, is easily disregarded), and that often even experienced demonstrators might fail to spot that extra bit of white space that is causing the error. If nothing obvious strikes you about an input, it might be easier to throw it away and start again rather than wait eg 24 hours to find it has (reproducibly) failed again!
*It is also a good idea to '''run Gaussian on your laptop for a few seconds at least, this being better than waiting up to 24 hours to find that a trivial error stopped the calculation.''' You can run a Gaussian input either from ChemBio3D, or Gaussview (by now you will appreciate that Gaussian itself is really not very good at handling and describing errors).

= Help =

#In addition to demonstrators and staff, you may wish to keep an eye out on the [[Mod:latebreak|late breaking news]] page for general updates, and the discussion areas for [[Talk:Mod:organic|Module 1]], [[Talk:Mod:inorganic|module 2]] and [[Talk:Mod:physical|module 3]] where people document their experiences, suggest bug fixes etc.

= General References =

<references/>

= Module 1 Marking =

The marks for this module are split 60% for the four components of part '''1.2''' and '''1.3''' (15% each) and 40% for the miniproject part '''2'''. You will be assessed not simply on whether you got the ''right'' answer, but on your analysis of the problem, how you might have designed control calculations, or e.g. worked out ways of making the modelling more efficient. The project is at least as much about how you go about organising your '''workflows''' in the time you have decided to spend on it, as it is about getting the right answer. Marks for each individual component will also be awarded for how you cite and quote the literature (in particular for citing any relevant references that we do '''not''' give you in the notes). Remember, being critical is more important than merely reproducing quotes from an article. After all, the original people who reported the chemistry may have not understood what happened themselves, and it is perfectly possible that you may actually be able to critically improve that understanding!

Your grade will be recorded in Blackboard and comments on your experiment will appear in the discussion section of your Wiki report. If you want to discuss your experiment and its grade, please contact Prof Alan Armstrong directly or Dr Bao Nguyen directly.

----
See also: [[Mod:timetable|Timetable]],[[Mod:lectures|Intro lecture]],[[mod:laptop|Laptop use]], [[mod:programs|Programs]], [[mod:organic|Module 1]], [[Mod:inorganic|Module 2]], [[Mod:phys3|Module 3]],[[Mod:writeup|Writing up]]

Mod:dont panic

2011-11-01T08:42:14Z

Bnguyen: Created page with "800px 200px So you've done your calculations as instructed, and got your optimised structures with a whol..."

[[Image:A_beginners_guide.jpg|center|800px]]
[[Image:dont_panic.jpg|center|200px]]

So you've done your calculations as instructed, and got your optimised structures with a whole lot of properties to boot. What else is expected of you? What does analysis exactly mean, anyway? Don't panic! Here you'll find most of what you need to know to survive Module 1 and beyond.

==Analysis==

"How much analysis is expected from us?", I hear you ask. The answer is: AS MUCH AS 60% OF YOUR MARK! Getting the lowest in energy conformers is quite a challenge which will test your chemical knowledge and patience to the limit, but it wouldn't do you much good if you can't extract chemical information from the exercise. There are several types of information which can be discussed from the calculated structures of compounds or transition states in organic chemistry. The most common ones are listed below:

*Energies
*Bond angles and dihedral angles
*Molecular orbitals
*Bond strength, bond lengths and vibrational frequencies

====Energies====

Energies show how stable your structure is and when it comes to energy, the lower the better. Watch out when you compare energies of different structures, unless the number and types of atoms involved are the same, the comparison isn't valid. Under equilibrium, species of different energies will follow the same relationship as that between Gibbs free energy and equilibrium constant.

Comparing absolute energies between different computational methods is impossible, as they are calculated as the sum of different factors. However, the difference in energy between isomeric transition states calculated by different methods has often been compared with experimentally measured selectivity to judge the accuracy of computational methods.

====Bond angles and dihedral angels====

These values are very useful in intepreting the breakdown components of energy from Molecular Mechanics calculation. They're still useful in quantum mechanics, although there won't be any tangible result you can directly relate them to. A strained structure is a strained structure regardless of how you calculate it.

====Bond strength, bond lengths and vibrational frequencies====

A bond is defined and displayed differently by Molecular Mechanics and quantum mechanics techniques. Be mindful as what you see in the visualisation doesn't necessarily be what your calculation results mean. The strength of a bond, and to some extent its multiplicity, is best judged by examining the bond length and its vibrational frequencies.

====Molecular orbitals====

MOs are only accessible via quantum mechanics. In organic chemistry, we're mostly concerned with the frontier orbitals. Examining their position, shape and symmetry often gives clues about the nature of the MOs (bonding vs antibonding, σ-π interaction, etc.), and more importantly the reactivity and selectivity of the molecule in reactions.

==Data presentation==

So you aren't as good at writing wikis as the geeks who live in a garage, who shower once a month and are on a permanent supplement course of caffeine. Neither are we!

There is no doctor-ordered style for your report and marks won't be given for visual effects or creative designs of your wiki pages. Instead, we want clear, concise communication from you so that we can fully appreciate your work. One golden rule must be remembered: IF WE CAN'T SEE IT (CLEARLY), WE CAN'T MARK IT. The same goes for your analysis. If your visual aid helps the readers understand your points, by all means include it.

Another issue, which is most relevant with the mini projects, is the context of your work. Tell us why and how. More importantly, tell us EXACTLY WHAT QUESTION ARE YOU TRYING TO ANSWER WITH YOUR CALCULATION, other than for getting marks, of course.

Occasionally, we'll contact you during the marking for your original files if we find some of your results interesting, or if we feel there wasn't enough information in your wiki page. Remember to keep your files, and name them in a way that the future you won't struggle to comprehend.

==Methods of calculation==

====Molecular Mechanics====

An excellent description of molecular mechanics has already been included at [[Mod:molecular_mechanics|this page]]. Here we'll simply summarise that it's basically balls and sophisticated springs. It's fast, cheap to compute but has to rely on carefully developed force field information (the anharmonic oscillator parameters). Thus, molecular mechanics can only handle structures it has been taught to handle and those unfortunately don't include organometallic compounds.

Of particular note, bonds are treated as springs and have to be specified in the starting structure. As a results, molecular mechanics performs poorly when it comes to electronic interactions, or bond forming-breaking processes. In these cases, molecular mechanics is often employed to clean up the structure, before a more appropriate method is applied.

====Semi-empirical methods====

To cut computational cost in quantum mechanics, approximations were made to simplify the Schrödinger equation. Semi-empricial molecular orbitals methods were born. They're still fast, albeit at the cost of accuracy, compared to ''ab initio'' methods. Semi-quantitative description of electronic distribution, molecular structure, MOs and energies can be quickly derived using these methods. They're also capable of calculations for organometallic compounds.

Being quantum mechanic techniques, they can model electronic effect, orbital interactions or hydrogen bondings, bond formation/breaking, and transition states (all the things Molecular Mechanics can't do!).

====''Ab initio'' calculations====

These fully-fledged quantum mechanic techniques are the current last words, if not the only words, in computational chemistry. They can also handle every chemical structure you can come up with, given an infinite amount of time. The price is that you'll need a supercomputer with 'brain the size of a planet', and the geeks, who write wikis for breakfast, to run it. Users are protected by a web-based or a console-based submission system. Submitted jobs will join queue and occasionally get trapped in an endless loop when you will have to contact the aforementioned IT experts to intervene.

One can optimise structure (can be quite time consumming, depending on how many electrons you have in your structure), calculate energy (enthalpy, entropy) in gas and liquid phases. Recent advances allow fairly accurate prediction of NMR chemical shifts, CD spetrum and optical rotation, as well as IR vibrational frequencies. Bewarned: optical rotation and IR vibrational frequencies calculations are time consumming and shouldn't be carried out unless there's good justification (the submission deadline on Friday is infinitesimally close compared to infinity!).

==Starting structure==

Just as in life, your starting point affects your destination in molecular modelling. A poor starting structure will give you a poorly optimised end-product. Your software doesn't come with an AI (yet!) and so your chemical intuition will have to suffice. Crystal structures, if found, are good places to start as they are at least real minima in solid phase. Most of your calculations, however, will be in gas phase or in solvents.

==Thermodynamics vs kinetics==

Reactions under equilibrium are under thermodynamic control and the more stable product will be formed predominantly, hence the term 'thermodynamic product'. When the reaction is one-way, the distribution of products, i.e. the selectivity, is dictated by the relative energies of the corresponding transition states, which also means the relative rates of different pathways (Arrhenius equation), and not that of the products. The major product in this case is called 'kinetic product'. 'Thermodynamic product' and 'kinetic product' refers to the energy of different species (products and transition states), and therefore, are not mutually exclusive. In many reactions, both of these are the same.

==Other things==

If you have questions about anything not covered on this page, talk to us. In fact, talk to us in any case. Mini project, especially, shouldn't even be attempted before some interaction with us. Computational chemistry can get extremely complicated very quickly and a chat with us would prevent you from realising you've bitten up more than you can chew the night before submission. This of course in theory can't happen because you've been following our advice to start your mini project as early as Monday of the second week.

Rep:Mod:bnguyen

2011-11-01T08:26:58Z

Bnguyen: /* Thermodynamics vs kinetics */

[[Image:A_beginners_guide.jpg|center|800px]]
[[Image:dont_panic.jpg|center|200px]]

So you've done your calculations as instructed, and got your optimised structures with a whole lot of properties to boot. What else is expected of you? What does analysis exactly mean, anyway? Don't panic! Here you'll find most of what you need to know to survive Module 1 and beyond.

==Analysis==

"How much analysis is expected from us?", I hear you ask. The answer is: AS MUCH AS 60% OF YOUR MARK! Getting the lowest in energy conformers is quite a challenge which will test your chemical knowledge and patience to the limit, but it wouldn't do you much good if you can't extract chemical information from the exercise. There are several types of information which can be discussed from the calculated structures of compounds or transition states in organic chemistry. The most common ones are listed below:

*Energies
*Bond angles and dihedral angles
*Molecular orbitals
*Bond strength, bond lengths and vibrational frequencies

====Energies====

Energies show how stable your structure is and when it comes to energy, the lower the better. Watch out when you compare energies of different structures, unless the number and types of atoms involved are the same, the comparison isn't valid. Under equilibrium, species of different energies will follow the same relationship as that between Gibbs free energy and equilibrium constant.

Comparing absolute energies between different computational methods is impossible, as they are calculated as the sum of different factors. However, the difference in energy between isomeric transition states calculated by different methods has often been compared with experimentally measured selectivity to judge the accuracy of computational methods.

====Bond angles and dihedral angels====

These values are very useful in intepreting the breakdown components of energy from Molecular Mechanics calculation. They're still useful in quantum mechanics, although there won't be any tangible result you can directly relate them to. A strained structure is a strained structure regardless of how you calculate it.

====Bond strength, bond lengths and vibrational frequencies====

A bond is defined and displayed differently by Molecular Mechanics and quantum mechanics techniques. Be mindful as what you see in the visualisation doesn't necessarily be what your calculation results mean. The strength of a bond, and to some extent its multiplicity, is best judged by examining the bond length and its vibrational frequencies.

====Molecular orbitals====

MOs are only accessible via quantum mechanics. In organic chemistry, we're mostly concerned with the frontier orbitals. Examining their position, shape and symmetry often gives clues about the nature of the MOs (bonding vs antibonding, σ-π interaction, etc.), and more importantly the reactivity and selectivity of the molecule in reactions.

==Data presentation==

So you aren't as good at writing wikis as the geeks who live in a garage, who shower once a month and are on a permanent supplement course of caffeine. Neither are we!

There is no doctor-ordered style for your report and marks won't be given for visual effects or creative designs of your wiki pages. Instead, we want clear, concise communication from you so that we can fully appreciate your work. One golden rule must be remembered: IF WE CAN'T SEE IT (CLEARLY), WE CAN'T MARK IT. The same goes for your analysis. If your visual aid helps the readers understand your points, by all means include it.

Another issue, which is most relevant with the mini projects, is the context of your work. Tell us why and how. More importantly, tell us EXACTLY WHAT QUESTION ARE YOU TRYING TO ANSWER WITH YOUR CALCULATION, other than for getting marks, of course.

Occasionally, we'll contact you during the marking for your original files if we find some of your results interesting, or if we feel there wasn't enough information in your wiki page. Remember to keep your files, and name them in a way that the future you won't struggle to comprehend.

==Methods of calculation==

====Molecular Mechanics====

An excellent description of molecular mechanics has already been included at [[Mod:molecular_mechanics|this page]]. Here we'll simply summarise that it's basically balls and sophisticated springs. It's fast, cheap to compute but has to rely on carefully developed force field information (the anharmonic oscillator parameters). Thus, molecular mechanics can only handle structures it has been taught to handle and those unfortunately don't include organometallic compounds.

Of particular note, bonds are treated as springs and have to be specified in the starting structure. As a results, molecular mechanics performs poorly when it comes to electronic interactions, or bond forming-breaking processes. In these cases, molecular mechanics is often employed to clean up the structure, before a more appropriate method is applied.

====Semi-empirical methods====

To cut computational cost in quantum mechanics, approximations were made to simplify the Schrödinger equation. Semi-empricial molecular orbitals methods were born. They're still fast, albeit at the cost of accuracy, compared to ''ab initio'' methods. Semi-quantitative description of electronic distribution, molecular structure, MOs and energies can be quickly derived using these methods. They're also capable of calculations for organometallic compounds.

Being quantum mechanic techniques, they can model electronic effect, orbital interactions or hydrogen bondings, bond formation/breaking, and transition states (all the things Molecular Mechanics can't do!).

====''Ab initio'' calculations====

These fully-fledged quantum mechanic techniques are the current last words, if not the only words, in computational chemistry. They can also handle every chemical structure you can come up with, given an infinite amount of time. The price is that you'll need a supercomputer with 'brain the size of a planet', and the geeks, who write wikis for breakfast, to run it. Users are protected by a web-based or a console-based submission system. Submitted jobs will join queue and occasionally get trapped in an endless loop when you will have to contact the aforementioned IT experts to intervene.

One can optimise structure (can be quite time consumming, depending on how many electrons you have in your structure), calculate energy (enthalpy, entropy) in gas and liquid phases. Recent advances allow fairly accurate prediction of NMR chemical shifts, CD spetrum and optical rotation, as well as IR vibrational frequencies. Bewarned: optical rotation and IR vibrational frequencies calculations are time consumming and shouldn't be carried out unless there's good justification (the submission deadline on Friday is infinitesimally close compared to infinity!).

==Starting structure==

Just as in life, your starting point affects your destination in molecular modelling. A poor starting structure will give you a poorly optimised end-product. Your software doesn't come with an AI (yet!) and so your chemical intuition will have to suffice. Crystal structures, if found, are good places to start as they are at least real minima in solid phase. Most of your calculations, however, will be in gas phase or in solvents.

==Thermodynamics vs kinetics==

Reactions under equilibrium are under thermodynamic control and the more stable product will be formed predominantly, hence the term 'thermodynamic product'. When the reaction is one-way, the distribution of products, i.e. the selectivity, is dictated by the relative energies of the corresponding transition states, which also means the relative rates of different pathways (Arrhenius equation), and not that of the products. The major product in this case is called 'kinetic product'. 'Thermodynamic product' and 'kinetic product' refers to the energy of different species (products and transition states), and therefore, are not mutually exclusive. In many reactions, both of these are the same.

==Other things==

If you have questions about anything not covered on this page, talk to us. In fact, talk to us in any case. Mini project, especially, shouldn't even be attempted before some interaction with us. Computational chemistry can get extremely complicated very quickly and a chat with us would prevent you from realising you've bitten up more than you can chew the night before submission. This of course in theory can't happen because you've been following our advice to start your mini project as early as Monday of the second week.

Rep:Mod:bnguyen

2011-10-28T18:49:30Z

Bnguyen: /* Other things */

[[Image:A_beginners_guide.jpg|center|800px]]
[[Image:dont_panic.jpg|center|200px]]

So you've done your calculations as instructed, and got your optimised structures with a whole lot of properties to boot. What else is expected of you? What does analysis exactly mean, anyway? Don't panic! Here you'll find most of what you need to know to survive Module 1 and beyond.

==Analysis==

"How much analysis is expected from us?", I hear you ask. The answer is: AS MUCH AS 60% OF YOUR MARK! Getting the lowest in energy conformers is quite a challenge which will test your chemical knowledge and patience to the limit, but it wouldn't do you much good if you can't extract chemical information from the exercise. There are several types of information which can be discussed from the calculated structures of compounds or transition states in organic chemistry. The most common ones are listed below:

*Energies
*Bond angles and dihedral angles
*Molecular orbitals
*Bond strength, bond lengths and vibrational frequencies

====Energies====

Energies show how stable your structure is and when it comes to energy, the lower the better. Watch out when you compare energies of different structures, unless the number and types of atoms involved are the same, the comparison isn't valid. Under equilibrium, species of different energies will follow the same relationship as that between Gibbs free energy and equilibrium constant.

Comparing absolute energies between different computational methods is impossible, as they are calculated as the sum of different factors. However, the difference in energy between isomeric transition states calculated by different methods has often been compared with experimentally measured selectivity to judge the accuracy of computational methods.

====Bond angles and dihedral angels====

These values are very useful in intepreting the breakdown components of energy from Molecular Mechanics calculation. They're still useful in quantum mechanics, although there won't be any tangible result you can directly relate them to. A strained structure is a strained structure regardless of how you calculate it.

====Bond strength, bond lengths and vibrational frequencies====

A bond is defined and displayed differently by Molecular Mechanics and quantum mechanics techniques. Be mindful as what you see in the visualisation doesn't necessarily be what your calculation results mean. The strength of a bond, and to some extent its multiplicity, is best judged by examining the bond length and its vibrational frequencies.

====Molecular orbitals====

MOs are only accessible via quantum mechanics. In organic chemistry, we're mostly concerned with the frontier orbitals. Examining their position, shape and symmetry often gives clues about the nature of the MOs (bonding vs antibonding, σ-π interaction, etc.), and more importantly the reactivity and selectivity of the molecule in reactions.

==Data presentation==

So you aren't as good at writing wikis as the geeks who live in a garage, who shower once a month and are on a permanent supplement course of caffeine. Neither are we!

There is no doctor-ordered style for your report and marks won't be given for visual effects or creative designs of your wiki pages. Instead, we want clear, concise communication from you so that we can fully appreciate your work. One golden rule must be remembered: IF WE CAN'T SEE IT (CLEARLY), WE CAN'T MARK IT. The same goes for your analysis. If your visual aid helps the readers understand your points, by all means include it.

Another issue, which is most relevant with the mini projects, is the context of your work. Tell us why and how. More importantly, tell us EXACTLY WHAT QUESTION ARE YOU TRYING TO ANSWER WITH YOUR CALCULATION, other than for getting marks, of course.

Occasionally, we'll contact you during the marking for your original files if we find some of your results interesting, or if we feel there wasn't enough information in your wiki page. Remember to keep your files, and name them in a way that the future you won't struggle to comprehend.

==Methods of calculation==

====Molecular Mechanics====

An excellent description of molecular mechanics has already been included at [[Mod:molecular_mechanics|this page]]. Here we'll simply summarise that it's basically balls and sophisticated springs. It's fast, cheap to compute but has to rely on carefully developed force field information (the anharmonic oscillator parameters). Thus, molecular mechanics can only handle structures it has been taught to handle and those unfortunately don't include organometallic compounds.

Of particular note, bonds are treated as springs and have to be specified in the starting structure. As a results, molecular mechanics performs poorly when it comes to electronic interactions, or bond forming-breaking processes. In these cases, molecular mechanics is often employed to clean up the structure, before a more appropriate method is applied.

====Semi-empirical methods====

To cut computational cost in quantum mechanics, approximations were made to simplify the Schrödinger equation. Semi-empricial molecular orbitals methods were born. They're still fast, albeit at the cost of accuracy, compared to ''ab initio'' methods. Semi-quantitative description of electronic distribution, molecular structure, MOs and energies can be quickly derived using these methods. They're also capable of calculations for organometallic compounds.

Being quantum mechanic techniques, they can model electronic effect, orbital interactions or hydrogen bondings, bond formation/breaking, and transition states (all the things Molecular Mechanics can't do!).

====''Ab initio'' calculations====

These fully-fledged quantum mechanic techniques are the current last words, if not the only words, in computational chemistry. They can also handle every chemical structure you can come up with, given an infinite amount of time. The price is that you'll need a supercomputer with 'brain the size of a planet', and the geeks, who write wikis for breakfast, to run it. Users are protected by a web-based or a console-based submission system. Submitted jobs will join queue and occasionally get trapped in an endless loop when you will have to contact the aforementioned IT experts to intervene.

One can optimise structure (can be quite time consumming, depending on how many electrons you have in your structure), calculate energy (enthalpy, entropy) in gas and liquid phases. Recent advances allow fairly accurate prediction of NMR chemical shifts, CD spetrum and optical rotation, as well as IR vibrational frequencies. Bewarned: optical rotation and IR vibrational frequencies calculations are time consumming and shouldn't be carried out unless there's good justification (the submission deadline on Friday is infinitesimally close compared to infinity!).

==Starting structure==

Just as in life, your starting point affects your destination in molecular modelling. A poor starting structure will give you a poorly optimised end-product. Your software doesn't come with an AI (yet!) and so your chemical intuition will have to suffice. Crystal structures, if found, are good places to start as they are at least real minima in solid phase. Most of your calculations, however, will be in gas phase or in solvents.

==Thermodynamics vs kinetics==

==Other things==

If you have questions about anything not covered on this page, talk to us. In fact, talk to us in any case. Mini project, especially, shouldn't even be attempted before some interaction with us. Computational chemistry can get extremely complicated very quickly and a chat with us would prevent you from realising you've bitten up more than you can chew the night before submission. This of course in theory can't happen because you've been following our advice to start your mini project as early as Monday of the second week.

Rep:Mod:bnguyen

2011-10-28T18:48:35Z

Bnguyen: /* Ab initio calculations */

[[Image:A_beginners_guide.jpg|center|800px]]
[[Image:dont_panic.jpg|center|200px]]

So you've done your calculations as instructed, and got your optimised structures with a whole lot of properties to boot. What else is expected of you? What does analysis exactly mean, anyway? Don't panic! Here you'll find most of what you need to know to survive Module 1 and beyond.

==Analysis==

"How much analysis is expected from us?", I hear you ask. The answer is: AS MUCH AS 60% OF YOUR MARK! Getting the lowest in energy conformers is quite a challenge which will test your chemical knowledge and patience to the limit, but it wouldn't do you much good if you can't extract chemical information from the exercise. There are several types of information which can be discussed from the calculated structures of compounds or transition states in organic chemistry. The most common ones are listed below:

*Energies
*Bond angles and dihedral angles
*Molecular orbitals
*Bond strength, bond lengths and vibrational frequencies

====Energies====

Energies show how stable your structure is and when it comes to energy, the lower the better. Watch out when you compare energies of different structures, unless the number and types of atoms involved are the same, the comparison isn't valid. Under equilibrium, species of different energies will follow the same relationship as that between Gibbs free energy and equilibrium constant.

Comparing absolute energies between different computational methods is impossible, as they are calculated as the sum of different factors. However, the difference in energy between isomeric transition states calculated by different methods has often been compared with experimentally measured selectivity to judge the accuracy of computational methods.

====Bond angles and dihedral angels====

These values are very useful in intepreting the breakdown components of energy from Molecular Mechanics calculation. They're still useful in quantum mechanics, although there won't be any tangible result you can directly relate them to. A strained structure is a strained structure regardless of how you calculate it.

====Bond strength, bond lengths and vibrational frequencies====

A bond is defined and displayed differently by Molecular Mechanics and quantum mechanics techniques. Be mindful as what you see in the visualisation doesn't necessarily be what your calculation results mean. The strength of a bond, and to some extent its multiplicity, is best judged by examining the bond length and its vibrational frequencies.

====Molecular orbitals====

MOs are only accessible via quantum mechanics. In organic chemistry, we're mostly concerned with the frontier orbitals. Examining their position, shape and symmetry often gives clues about the nature of the MOs (bonding vs antibonding, σ-π interaction, etc.), and more importantly the reactivity and selectivity of the molecule in reactions.

==Data presentation==

So you aren't as good at writing wikis as the geeks who live in a garage, who shower once a month and are on a permanent supplement course of caffeine. Neither are we!

There is no doctor-ordered style for your report and marks won't be given for visual effects or creative designs of your wiki pages. Instead, we want clear, concise communication from you so that we can fully appreciate your work. One golden rule must be remembered: IF WE CAN'T SEE IT (CLEARLY), WE CAN'T MARK IT. The same goes for your analysis. If your visual aid helps the readers understand your points, by all means include it.

Another issue, which is most relevant with the mini projects, is the context of your work. Tell us why and how. More importantly, tell us EXACTLY WHAT QUESTION ARE YOU TRYING TO ANSWER WITH YOUR CALCULATION, other than for getting marks, of course.

Occasionally, we'll contact you during the marking for your original files if we find some of your results interesting, or if we feel there wasn't enough information in your wiki page. Remember to keep your files, and name them in a way that the future you won't struggle to comprehend.

==Methods of calculation==

====Molecular Mechanics====

An excellent description of molecular mechanics has already been included at [[Mod:molecular_mechanics|this page]]. Here we'll simply summarise that it's basically balls and sophisticated springs. It's fast, cheap to compute but has to rely on carefully developed force field information (the anharmonic oscillator parameters). Thus, molecular mechanics can only handle structures it has been taught to handle and those unfortunately don't include organometallic compounds.

Of particular note, bonds are treated as springs and have to be specified in the starting structure. As a results, molecular mechanics performs poorly when it comes to electronic interactions, or bond forming-breaking processes. In these cases, molecular mechanics is often employed to clean up the structure, before a more appropriate method is applied.

====Semi-empirical methods====

To cut computational cost in quantum mechanics, approximations were made to simplify the Schrödinger equation. Semi-empricial molecular orbitals methods were born. They're still fast, albeit at the cost of accuracy, compared to ''ab initio'' methods. Semi-quantitative description of electronic distribution, molecular structure, MOs and energies can be quickly derived using these methods. They're also capable of calculations for organometallic compounds.

Being quantum mechanic techniques, they can model electronic effect, orbital interactions or hydrogen bondings, bond formation/breaking, and transition states (all the things Molecular Mechanics can't do!).

====''Ab initio'' calculations====

These fully-fledged quantum mechanic techniques are the current last words, if not the only words, in computational chemistry. They can also handle every chemical structure you can come up with, given an infinite amount of time. The price is that you'll need a supercomputer with 'brain the size of a planet', and the geeks, who write wikis for breakfast, to run it. Users are protected by a web-based or a console-based submission system. Submitted jobs will join queue and occasionally get trapped in an endless loop when you will have to contact the aforementioned IT experts to intervene.

One can optimise structure (can be quite time consumming, depending on how many electrons you have in your structure), calculate energy (enthalpy, entropy) in gas and liquid phases. Recent advances allow fairly accurate prediction of NMR chemical shifts, CD spetrum and optical rotation, as well as IR vibrational frequencies. Bewarned: optical rotation and IR vibrational frequencies calculations are time consumming and shouldn't be carried out unless there's good justification (the submission deadline on Friday is infinitesimally close compared to infinity!).

==Starting structure==

Just as in life, your starting point affects your destination in molecular modelling. A poor starting structure will give you a poorly optimised end-product. Your software doesn't come with an AI (yet!) and so your chemical intuition will have to suffice. Crystal structures, if found, are good places to start as they are at least real minima in solid phase. Most of your calculations, however, will be in gas phase or in solvents.

==Thermodynamics vs kinetics==

==Other things==

If you have questions about anything not covered on this page, talk to us. In fact, talk to us in any case. Mini project, especially, shouldn't even be attempted before some interaction with us. Computational chemistry can get extremely complicated very quickly and a chat with us would prevent you from realising you've bitten up more than you can chew the night before submission. This of course in theory can't happen because you've been following our advice to start your mini project as early as Monday on the second week.

Rep:Mod:bnguyen

2011-10-28T18:46:44Z

Bnguyen: /* Analysis */

[[Image:A_beginners_guide.jpg|center|800px]]
[[Image:dont_panic.jpg|center|200px]]

So you've done your calculations as instructed, and got your optimised structures with a whole lot of properties to boot. What else is expected of you? What does analysis exactly mean, anyway? Don't panic! Here you'll find most of what you need to know to survive Module 1 and beyond.

==Analysis==

"How much analysis is expected from us?", I hear you ask. The answer is: AS MUCH AS 60% OF YOUR MARK! Getting the lowest in energy conformers is quite a challenge which will test your chemical knowledge and patience to the limit, but it wouldn't do you much good if you can't extract chemical information from the exercise. There are several types of information which can be discussed from the calculated structures of compounds or transition states in organic chemistry. The most common ones are listed below:

*Energies
*Bond angles and dihedral angles
*Molecular orbitals
*Bond strength, bond lengths and vibrational frequencies

====Energies====

Energies show how stable your structure is and when it comes to energy, the lower the better. Watch out when you compare energies of different structures, unless the number and types of atoms involved are the same, the comparison isn't valid. Under equilibrium, species of different energies will follow the same relationship as that between Gibbs free energy and equilibrium constant.

Comparing absolute energies between different computational methods is impossible, as they are calculated as the sum of different factors. However, the difference in energy between isomeric transition states calculated by different methods has often been compared with experimentally measured selectivity to judge the accuracy of computational methods.

====Bond angles and dihedral angels====

These values are very useful in intepreting the breakdown components of energy from Molecular Mechanics calculation. They're still useful in quantum mechanics, although there won't be any tangible result you can directly relate them to. A strained structure is a strained structure regardless of how you calculate it.

====Bond strength, bond lengths and vibrational frequencies====

A bond is defined and displayed differently by Molecular Mechanics and quantum mechanics techniques. Be mindful as what you see in the visualisation doesn't necessarily be what your calculation results mean. The strength of a bond, and to some extent its multiplicity, is best judged by examining the bond length and its vibrational frequencies.

====Molecular orbitals====

MOs are only accessible via quantum mechanics. In organic chemistry, we're mostly concerned with the frontier orbitals. Examining their position, shape and symmetry often gives clues about the nature of the MOs (bonding vs antibonding, σ-π interaction, etc.), and more importantly the reactivity and selectivity of the molecule in reactions.

==Data presentation==

So you aren't as good at writing wikis as the geeks who live in a garage, who shower once a month and are on a permanent supplement course of caffeine. Neither are we!

There is no doctor-ordered style for your report and marks won't be given for visual effects or creative designs of your wiki pages. Instead, we want clear, concise communication from you so that we can fully appreciate your work. One golden rule must be remembered: IF WE CAN'T SEE IT (CLEARLY), WE CAN'T MARK IT. The same goes for your analysis. If your visual aid helps the readers understand your points, by all means include it.

Another issue, which is most relevant with the mini projects, is the context of your work. Tell us why and how. More importantly, tell us EXACTLY WHAT QUESTION ARE YOU TRYING TO ANSWER WITH YOUR CALCULATION, other than for getting marks, of course.

Occasionally, we'll contact you during the marking for your original files if we find some of your results interesting, or if we feel there wasn't enough information in your wiki page. Remember to keep your files, and name them in a way that the future you won't struggle to comprehend.

==Methods of calculation==

====Molecular Mechanics====

An excellent description of molecular mechanics has already been included at [[Mod:molecular_mechanics|this page]]. Here we'll simply summarise that it's basically balls and sophisticated springs. It's fast, cheap to compute but has to rely on carefully developed force field information (the anharmonic oscillator parameters). Thus, molecular mechanics can only handle structures it has been taught to handle and those unfortunately don't include organometallic compounds.

Of particular note, bonds are treated as springs and have to be specified in the starting structure. As a results, molecular mechanics performs poorly when it comes to electronic interactions, or bond forming-breaking processes. In these cases, molecular mechanics is often employed to clean up the structure, before a more appropriate method is applied.

====Semi-empirical methods====

To cut computational cost in quantum mechanics, approximations were made to simplify the Schrödinger equation. Semi-empricial molecular orbitals methods were born. They're still fast, albeit at the cost of accuracy, compared to ''ab initio'' methods. Semi-quantitative description of electronic distribution, molecular structure, MOs and energies can be quickly derived using these methods. They're also capable of calculations for organometallic compounds.

Being quantum mechanic techniques, they can model electronic effect, orbital interactions or hydrogen bondings, bond formation/breaking, and transition states (all the things Molecular Mechanics can't do!).

====''Ab initio'' calculations====

These full-fledged quantum mechanic techniques are the current last words, if not the only words, in computational chemistry. They can also handle every chemical structures you can come up with, given an infinite amount of time. The price is that you'll need a supercomputer with 'brain the size of a planet', and the geeks, who write wikis for breakfast, to run it. Users are protected by web-based or console-based submission system. Submitted jobs will join queue and occasionally get trapped in endless loop when you have to contact the aforementioned IT experts to intervene.

One can optimise structure (can be quite time consumming, depending on how many electrons you have in your structure), calculate energy (enthalpy, entropy) in gas and liquid phases. Recent advances allow fairly accurate prediction of NMR chemical shifts, CD spetrum and optical rotation, as well as IR vibrational frequencies. Bewarned: optical rotation and IR vibrational frequencies calculations are time consumming and shouldn't be carried out unless there's good justification (the submission deadline on Friday is infinitesimally close compared to infinity!).

==Starting structure==

Just as in life, your starting point affects your destination in molecular modelling. A poor starting structure will give you a poorly optimised end-product. Your software doesn't come with an AI (yet!) and so your chemical intuition will have to suffice. Crystal structures, if found, are good places to start as they are at least real minima in solid phase. Most of your calculations, however, will be in gas phase or in solvents.

==Thermodynamics vs kinetics==

==Other things==

If you have questions about anything not covered on this page, talk to us. In fact, talk to us in any case. Mini project, especially, shouldn't even be attempted before some interaction with us. Computational chemistry can get extremely complicated very quickly and a chat with us would prevent you from realising you've bitten up more than you can chew the night before submission. This of course in theory can't happen because you've been following our advice to start your mini project as early as Monday on the second week.

Rep:Mod:bnguyen

2011-10-28T10:16:05Z

Bnguyen: /* Molecular Mechanics */

[[Image:A_beginners_guide.jpg|center|800px]]
[[Image:dont_panic.jpg|center|200px]]

So you've done your calculations as instructed, and got your optimised structures with a whole lot of properties to boot. What else is expected of you? What does analysis exactly mean, anyway? Don't panic! Here you'll find most of what you need to know to survive Module 1 and beyond.

==Analysis==

"How much analysis is expected from us?", I hear you ask. The answer is: AS MUCH AS 60% OF YOUR MARK! Getting the lowest in energy conformers is quite a challenge which will test your chemical knowledge and patience to the limit, but it wouldn't do you much good if you can extract chemical information from the exercise. There are several types of information which can be discussed from the calculated structures of compounds or transition states in organic chemistry. The most common ones are listed below:

*Energies
*Bond angles and dihedral angles
*Molecular orbitals
*Bond strength, bond lengths and vibrational frequencies

====Energies====

Energies show how stable your structure is and when it comes to energy, the lower the better. Watch out when you compare energies of different structures, unless the number and types of atoms involved are the same, the comparison isn't valid. Under equilibrium, species of different energies will follow the same relationship as that between Gibbs free energy and equilibrium constant.

Comparing absolute energies between different computational methods is impossible, as they are calculated as the sum of different factors. However, the difference in energy between isomeric transition states calculated by different methods has often been compared with experimentally measured selectivity to judge the accuracy of computational methods.

====Bond angles and dihedral angels====

These values are very useful in intepreting the breakdown components of energy from Molecular Mechanics calculation. They're still useful in quantum mechanics, although there won't be any tangible result you can directly relate them to. A strained structure is a strained structure regardless of how you calculate it.

====Bond strength, bond lengths and vibrational frequencies====

A bond is defined and displayed differently by Molecular Mechanics and quantum mechanics techniques. Be mindful as what you see in the visualisation doesn't necessarily be what your calculation results mean. The strength of a bond, and to some extent its multiplicity, is best judged by examining the bond length and its vibrational frequencies.

====Molecular orbitals====

MOs are only accessible via quantum mechanics. In organic chemistry, we're mostly concerned with the frontier orbitals. Examining their position, shape and symmetry often gives clues about the nature of the MOs (bonding vs antibonding, σ-π interaction, etc.), and more importantly the reactivity and selectivity of the molecule in reactions.

==Data presentation==

So you aren't as good at writing wikis as the geeks who live in a garage, who shower once a month and are on a permanent supplement course of caffeine. Neither are we!

There is no doctor-ordered style for your report and marks won't be given for visual effects or creative designs of your wiki pages. Instead, we want clear, concise communication from you so that we can fully appreciate your work. One golden rule must be remembered: IF WE CAN'T SEE IT (CLEARLY), WE CAN'T MARK IT. The same goes for your analysis. If your visual aid helps the readers understand your points, by all means include it.

Another issue, which is most relevant with the mini projects, is the context of your work. Tell us why and how. More importantly, tell us EXACTLY WHAT QUESTION ARE YOU TRYING TO ANSWER WITH YOUR CALCULATION, other than for getting marks, of course.

Occasionally, we'll contact you during the marking for your original files if we find some of your results interesting, or if we feel there wasn't enough information in your wiki page. Remember to keep your files, and name them in a way that the future you won't struggle to comprehend.

==Methods of calculation==

====Molecular Mechanics====

An excellent description of molecular mechanics has already been included at [[Mod:molecular_mechanics|this page]]. Here we'll simply summarise that it's basically balls and sophisticated springs. It's fast, cheap to compute but has to rely on carefully developed force field information (the anharmonic oscillator parameters). Thus, molecular mechanics can only handle structures it has been taught to handle and those unfortunately don't include organometallic compounds.

Of particular note, bonds are treated as springs and have to be specified in the starting structure. As a results, molecular mechanics performs poorly when it comes to electronic interactions, or bond forming-breaking processes. In these cases, molecular mechanics is often employed to clean up the structure, before a more appropriate method is applied.

====Semi-empirical methods====

To cut computational cost in quantum mechanics, approximations were made to simplify the Schrödinger equation. Semi-empricial molecular orbitals methods were born. They're still fast, albeit at the cost of accuracy, compared to ''ab initio'' methods. Semi-quantitative description of electronic distribution, molecular structure, MOs and energies can be quickly derived using these methods. They're also capable of calculations for organometallic compounds.

Being quantum mechanic techniques, they can model electronic effect, orbital interactions or hydrogen bondings, bond formation/breaking, and transition states (all the things Molecular Mechanics can't do!).

====''Ab initio'' calculations====

These full-fledged quantum mechanic techniques are the current last words, if not the only words, in computational chemistry. They can also handle every chemical structures you can come up with, given an infinite amount of time. The price is that you'll need a supercomputer with 'brain the size of a planet', and the geeks, who write wikis for breakfast, to run it. Users are protected by web-based or console-based submission system. Submitted jobs will join queue and occasionally get trapped in endless loop when you have to contact the aforementioned IT experts to intervene.

One can optimise structure (can be quite time consumming, depending on how many electrons you have in your structure), calculate energy (enthalpy, entropy) in gas and liquid phases. Recent advances allow fairly accurate prediction of NMR chemical shifts, CD spetrum and optical rotation, as well as IR vibrational frequencies. Bewarned: optical rotation and IR vibrational frequencies calculations are time consumming and shouldn't be carried out unless there's good justification (the submission deadline on Friday is infinitesimally close compared to infinity!).

==Starting structure==

Just as in life, your starting point affects your destination in molecular modelling. A poor starting structure will give you a poorly optimised end-product. Your software doesn't come with an AI (yet!) and so your chemical intuition will have to suffice. Crystal structures, if found, are good places to start as they are at least real minima in solid phase. Most of your calculations, however, will be in gas phase or in solvents.

==Thermodynamics vs kinetics==

==Other things==

If you have questions about anything not covered on this page, talk to us. In fact, talk to us in any case. Mini project, especially, shouldn't even be attempted before some interaction with us. Computational chemistry can get extremely complicated very quickly and a chat with us would prevent you from realising you've bitten up more than you can chew the night before submission. This of course in theory can't happen because you've been following our advice to start your mini project as early as Monday on the second week.

Rep:Mod:bnguyen

2011-10-28T10:07:09Z

Bnguyen: /* Ab initio calculations */

[[Image:A_beginners_guide.jpg|center|800px]]
[[Image:dont_panic.jpg|center|200px]]

So you've done your calculations as instructed, and got your optimised structures with a whole lot of properties to boot. What else is expected of you? What does analysis exactly mean, anyway? Don't panic! Here you'll find most of what you need to know to survive Module 1 and beyond.

==Analysis==

"How much analysis is expected from us?", I hear you ask. The answer is: AS MUCH AS 60% OF YOUR MARK! Getting the lowest in energy conformers is quite a challenge which will test your chemical knowledge and patience to the limit, but it wouldn't do you much good if you can extract chemical information from the exercise. There are several types of information which can be discussed from the calculated structures of compounds or transition states in organic chemistry. The most common ones are listed below:

*Energies
*Bond angles and dihedral angles
*Molecular orbitals
*Bond strength, bond lengths and vibrational frequencies

====Energies====

Energies show how stable your structure is and when it comes to energy, the lower the better. Watch out when you compare energies of different structures, unless the number and types of atoms involved are the same, the comparison isn't valid. Under equilibrium, species of different energies will follow the same relationship as that between Gibbs free energy and equilibrium constant.

Comparing absolute energies between different computational methods is impossible, as they are calculated as the sum of different factors. However, the difference in energy between isomeric transition states calculated by different methods has often been compared with experimentally measured selectivity to judge the accuracy of computational methods.

====Bond angles and dihedral angels====

These values are very useful in intepreting the breakdown components of energy from Molecular Mechanics calculation. They're still useful in quantum mechanics, although there won't be any tangible result you can directly relate them to. A strained structure is a strained structure regardless of how you calculate it.

====Bond strength, bond lengths and vibrational frequencies====

A bond is defined and displayed differently by Molecular Mechanics and quantum mechanics techniques. Be mindful as what you see in the visualisation doesn't necessarily be what your calculation results mean. The strength of a bond, and to some extent its multiplicity, is best judged by examining the bond length and its vibrational frequencies.

====Molecular orbitals====

MOs are only accessible via quantum mechanics. In organic chemistry, we're mostly concerned with the frontier orbitals. Examining their position, shape and symmetry often gives clues about the nature of the MOs (bonding vs antibonding, σ-π interaction, etc.), and more importantly the reactivity and selectivity of the molecule in reactions.

==Data presentation==

So you aren't as good at writing wikis as the geeks who live in a garage, who shower once a month and are on a permanent supplement course of caffeine. Neither are we!

There is no doctor-ordered style for your report and marks won't be given for visual effects or creative designs of your wiki pages. Instead, we want clear, concise communication from you so that we can fully appreciate your work. One golden rule must be remembered: IF WE CAN'T SEE IT (CLEARLY), WE CAN'T MARK IT. The same goes for your analysis. If your visual aid helps the readers understand your points, by all means include it.

Another issue, which is most relevant with the mini projects, is the context of your work. Tell us why and how. More importantly, tell us EXACTLY WHAT QUESTION ARE YOU TRYING TO ANSWER WITH YOUR CALCULATION, other than for getting marks, of course.

Occasionally, we'll contact you during the marking for your original files if we find some of your results interesting, or if we feel there wasn't enough information in your wiki page. Remember to keep your files, and name them in a way that the future you won't struggle to comprehend.

==Methods of calculation==

====Molecular Mechanics====

An excellent description of molecular mechanics has already been included at [[Mod:molecular_mechanics|this page]]. Here we'll simply summarise that it's basically balls and sophisticated springs. It's fast, cheap to compute but has to rely on carefully developed force field information (the anharmonic oscillator parameters). Thus, molecular mechanics can only handle structures it has been taught to handle and those unfortunately don't include organometallic compounds.

Of particular note, bonds are treated as springs and have to be specified in the starting structure. As a results, molecular mechanics performs poorly when it comes to electronic interactions, or bond forming-breaking processes.

====Semi-empirical methods====

To cut computational cost in quantum mechanics, approximations were made to simplify the Schrödinger equation. Semi-empricial molecular orbitals methods were born. They're still fast, albeit at the cost of accuracy, compared to ''ab initio'' methods. Semi-quantitative description of electronic distribution, molecular structure, MOs and energies can be quickly derived using these methods. They're also capable of calculations for organometallic compounds.

Being quantum mechanic techniques, they can model electronic effect, orbital interactions or hydrogen bondings, bond formation/breaking, and transition states (all the things Molecular Mechanics can't do!).

====''Ab initio'' calculations====

These full-fledged quantum mechanic techniques are the current last words, if not the only words, in computational chemistry. They can also handle every chemical structures you can come up with, given an infinite amount of time. The price is that you'll need a supercomputer with 'brain the size of a planet', and the geeks, who write wikis for breakfast, to run it. Users are protected by web-based or console-based submission system. Submitted jobs will join queue and occasionally get trapped in endless loop when you have to contact the aforementioned IT experts to intervene.

One can optimise structure (can be quite time consumming, depending on how many electrons you have in your structure), calculate energy (enthalpy, entropy) in gas and liquid phases. Recent advances allow fairly accurate prediction of NMR chemical shifts, CD spetrum and optical rotation, as well as IR vibrational frequencies. Bewarned: optical rotation and IR vibrational frequencies calculations are time consumming and shouldn't be carried out unless there's good justification (the submission deadline on Friday is infinitesimally close compared to infinity!).

==Starting structure==

Just as in life, your starting point affects your destination in molecular modelling. A poor starting structure will give you a poorly optimised end-product. Your software doesn't come with an AI (yet!) and so your chemical intuition will have to suffice. Crystal structures, if found, are good places to start as they are at least real minima in solid phase. Most of your calculations, however, will be in gas phase or in solvents.

==Thermodynamics vs kinetics==

==Other things==

If you have questions about anything not covered on this page, talk to us. In fact, talk to us in any case. Mini project, especially, shouldn't even be attempted before some interaction with us. Computational chemistry can get extremely complicated very quickly and a chat with us would prevent you from realising you've bitten up more than you can chew the night before submission. This of course in theory can't happen because you've been following our advice to start your mini project as early as Monday on the second week.

Rep:Mod:bnguyen

2011-10-28T10:04:42Z

Bnguyen: /* Ab initio calculations */

[[Image:A_beginners_guide.jpg|center|800px]]
[[Image:dont_panic.jpg|center|200px]]

So you've done your calculations as instructed, and got your optimised structures with a whole lot of properties to boot. What else is expected of you? What does analysis exactly mean, anyway? Don't panic! Here you'll find most of what you need to know to survive Module 1 and beyond.

==Analysis==

"How much analysis is expected from us?", I hear you ask. The answer is: AS MUCH AS 60% OF YOUR MARK! Getting the lowest in energy conformers is quite a challenge which will test your chemical knowledge and patience to the limit, but it wouldn't do you much good if you can extract chemical information from the exercise. There are several types of information which can be discussed from the calculated structures of compounds or transition states in organic chemistry. The most common ones are listed below:

*Energies
*Bond angles and dihedral angles
*Molecular orbitals
*Bond strength, bond lengths and vibrational frequencies

====Energies====

Energies show how stable your structure is and when it comes to energy, the lower the better. Watch out when you compare energies of different structures, unless the number and types of atoms involved are the same, the comparison isn't valid. Under equilibrium, species of different energies will follow the same relationship as that between Gibbs free energy and equilibrium constant.

Comparing absolute energies between different computational methods is impossible, as they are calculated as the sum of different factors. However, the difference in energy between isomeric transition states calculated by different methods has often been compared with experimentally measured selectivity to judge the accuracy of computational methods.

====Bond angles and dihedral angels====

These values are very useful in intepreting the breakdown components of energy from Molecular Mechanics calculation. They're still useful in quantum mechanics, although there won't be any tangible result you can directly relate them to. A strained structure is a strained structure regardless of how you calculate it.

====Bond strength, bond lengths and vibrational frequencies====

A bond is defined and displayed differently by Molecular Mechanics and quantum mechanics techniques. Be mindful as what you see in the visualisation doesn't necessarily be what your calculation results mean. The strength of a bond, and to some extent its multiplicity, is best judged by examining the bond length and its vibrational frequencies.

====Molecular orbitals====

MOs are only accessible via quantum mechanics. In organic chemistry, we're mostly concerned with the frontier orbitals. Examining their position, shape and symmetry often gives clues about the nature of the MOs (bonding vs antibonding, σ-π interaction, etc.), and more importantly the reactivity and selectivity of the molecule in reactions.

==Data presentation==

So you aren't as good at writing wikis as the geeks who live in a garage, who shower once a month and are on a permanent supplement course of caffeine. Neither are we!

There is no doctor-ordered style for your report and marks won't be given for visual effects or creative designs of your wiki pages. Instead, we want clear, concise communication from you so that we can fully appreciate your work. One golden rule must be remembered: IF WE CAN'T SEE IT (CLEARLY), WE CAN'T MARK IT. The same goes for your analysis. If your visual aid helps the readers understand your points, by all means include it.

Another issue, which is most relevant with the mini projects, is the context of your work. Tell us why and how. More importantly, tell us EXACTLY WHAT QUESTION ARE YOU TRYING TO ANSWER WITH YOUR CALCULATION, other than for getting marks, of course.

Occasionally, we'll contact you during the marking for your original files if we find some of your results interesting, or if we feel there wasn't enough information in your wiki page. Remember to keep your files, and name them in a way that the future you won't struggle to comprehend.

==Methods of calculation==

====Molecular Mechanics====

An excellent description of molecular mechanics has already been included at [[Mod:molecular_mechanics|this page]]. Here we'll simply summarise that it's basically balls and sophisticated springs. It's fast, cheap to compute but has to rely on carefully developed force field information (the anharmonic oscillator parameters). Thus, molecular mechanics can only handle structures it has been taught to handle and those unfortunately don't include organometallic compounds.

Of particular note, bonds are treated as springs and have to be specified in the starting structure. As a results, molecular mechanics performs poorly when it comes to electronic interactions, or bond forming-breaking processes.

====Semi-empirical methods====

To cut computational cost in quantum mechanics, approximations were made to simplify the Schrödinger equation. Semi-empricial molecular orbitals methods were born. They're still fast, albeit at the cost of accuracy, compared to ''ab initio'' methods. Semi-quantitative description of electronic distribution, molecular structure, MOs and energies can be quickly derived using these methods. They're also capable of calculations for organometallic compounds.

Being quantum mechanic techniques, they can model electronic effect, orbital interactions or hydrogen bondings, bond formation/breaking, and transition states (all the things Molecular Mechanics can't do!).

====''Ab initio'' calculations====

These full-fledged quantum mechanic techniques are the current last words, if not the only words, in computational chemistry. They can also handle every chemical structures you can come up with, given an infinite amount of time. The price is that you'll need a supercomputer, and the geeks, who write wikis for breakfast, to run it. Users are protected by web-based or console-based submission system. Submitted jobs will join queue and occasionally get trapped in endless loop when you have to contact the aforementioned IT experts to intervene.

One can optimise structure (can be quite time consumming, depending on how many electrons you have in your structure), calculate energy (enthalpy, entropy) in gas and liquid phases. Recent advances allow fairly accurate prediction of NMR chemical shifts, CD spetrum and optical rotation, as well as IR vibrational frequencies. Bewarned: optical rotation and IR vibrational frequencies calculations are time consumming and shouldn't be carried out unless there's good justification (the submission deadline on Friday is infinitesimally close compared to infinity!).

==Starting structure==

Just as in life, your starting point affects your destination in molecular modelling. A poor starting structure will give you a poorly optimised end-product. Your software doesn't come with an AI (yet!) and so your chemical intuition will have to suffice. Crystal structures, if found, are good places to start as they are at least real minima in solid phase. Most of your calculations, however, will be in gas phase or in solvents.

==Thermodynamics vs kinetics==

==Other things==

If you have questions about anything not covered on this page, talk to us. In fact, talk to us in any case. Mini project, especially, shouldn't even be attempted before some interaction with us. Computational chemistry can get extremely complicated very quickly and a chat with us would prevent you from realising you've bitten up more than you can chew the night before submission. This of course in theory can't happen because you've been following our advice to start your mini project as early as Monday on the second week.

Rep:Mod:bnguyen

2011-10-28T09:00:37Z

Bnguyen: /* Ab initio calculations */

[[Image:A_beginners_guide.jpg|center|800px]]
[[Image:dont_panic.jpg|center|200px]]

So you've done your calculations as instructed, and got your optimised structures with a whole lot of properties to boot. What else is expected of you? What does analysis exactly mean, anyway? Don't panic! Here you'll find most of what you need to know to survive Module 1 and beyond.

==Analysis==

"How much analysis is expected from us?", I hear you ask. The answer is: AS MUCH AS 60% OF YOUR MARK! Getting the lowest in energy conformers is quite a challenge which will test your chemical knowledge and patience to the limit, but it wouldn't do you much good if you can extract chemical information from the exercise. There are several types of information which can be discussed from the calculated structures of compounds or transition states in organic chemistry. The most common ones are listed below:

*Energies
*Bond angles and dihedral angles
*Molecular orbitals
*Bond strength, bond lengths and vibrational frequencies

====Energies====

Energies show how stable your structure is and when it comes to energy, the lower the better. Watch out when you compare energies of different structures, unless the number and types of atoms involved are the same, the comparison isn't valid. Under equilibrium, species of different energies will follow the same relationship as that between Gibbs free energy and equilibrium constant.

Comparing absolute energies between different computational methods is impossible, as they are calculated as the sum of different factors. However, the difference in energy between isomeric transition states calculated by different methods has often been compared with experimentally measured selectivity to judge the accuracy of computational methods.

====Bond angles and dihedral angels====

These values are very useful in intepreting the breakdown components of energy from Molecular Mechanics calculation. They're still useful in quantum mechanics, although there won't be any tangible result you can directly relate them to. A strained structure is a strained structure regardless of how you calculate it.

====Bond strength, bond lengths and vibrational frequencies====

A bond is defined and displayed differently by Molecular Mechanics and quantum mechanics techniques. Be mindful as what you see in the visualisation doesn't necessarily be what your calculation results mean. The strength of a bond, and to some extent its multiplicity, is best judged by examining the bond length and its vibrational frequencies.

====Molecular orbitals====

MOs are only accessible via quantum mechanics. In organic chemistry, we're mostly concerned with the frontier orbitals. Examining their position, shape and symmetry often gives clues about the nature of the MOs (bonding vs antibonding, σ-π interaction, etc.), and more importantly the reactivity and selectivity of the molecule in reactions.

==Data presentation==

So you aren't as good at writing wikis as the geeks who live in a garage, who shower once a month and are on a permanent supplement course of caffeine. Neither are we!

There is no doctor-ordered style for your report and marks won't be given for visual effects or creative designs of your wiki pages. Instead, we want clear, concise communication from you so that we can fully appreciate your work. One golden rule must be remembered: IF WE CAN'T SEE IT (CLEARLY), WE CAN'T MARK IT. The same goes for your analysis. If your visual aid helps the readers understand your points, by all means include it.

Another issue, which is most relevant with the mini projects, is the context of your work. Tell us why and how. More importantly, tell us EXACTLY WHAT QUESTION ARE YOU TRYING TO ANSWER WITH YOUR CALCULATION, other than for getting marks, of course.

Occasionally, we'll contact you during the marking for your original files if we find some of your results interesting, or if we feel there wasn't enough information in your wiki page. Remember to keep your files, and name them in a way that the future you won't struggle to comprehend.

==Methods of calculation==

====Molecular Mechanics====

An excellent description of molecular mechanics has already been included at [[Mod:molecular_mechanics|this page]]. Here we'll simply summarise that it's basically balls and sophisticated springs. It's fast, cheap to compute but has to rely on carefully developed force field information (the anharmonic oscillator parameters). Thus, molecular mechanics can only handle structures it has been taught to handle and those unfortunately don't include organometallic compounds.

Of particular note, bonds are treated as springs and have to be specified in the starting structure. As a results, molecular mechanics performs poorly when it comes to electronic interactions, or bond forming-breaking processes.

====Semi-empirical methods====

To cut computational cost in quantum mechanics, approximations were made to simplify the Schrödinger equation. Semi-empricial molecular orbitals methods were born. They're still fast, albeit at the cost of accuracy, compared to ''ab initio'' methods. Semi-quantitative description of electronic distribution, molecular structure, MOs and energies can be quickly derived using these methods. They're also capable of calculations for organometallic compounds.

Being quantum mechanic techniques, they can model electronic effect, orbital interactions or hydrogen bondings, bond formation/breaking, and transition states (all the things Molecular Mechanics can't do!).

====Ab initio calculations====

These are the current last words, if not the only words, in computational chemistry. They can also handle every chemical structures you can come up with, given an infinity of time. The price is that you'll need a supercomputer, and the geeks, who write wikis for breakfast, to run it. Users are protected by web-based or console-based submission system. Submitted jobs will join queue and occasionally get trapped in endless loop when you have to contact the aforementioned IT experts to intervene.

One can optimise structure (can be quite time consumming, depending on how many electrons you have in your structure), calculate energy (enthalpy, entropy) in gas and liquid phases. Recent advances allow fairly accurate prediction of NMR chemical shifts, CD spetrum and optical rotation, as well as IR vibrational frequencies. Bewarned: optical rotation and IR vibrational frequencies calculations are time consumming and shouldn't be carried out unless there's good justification.

==Starting structure==

Just as in life, your starting point affects your destination in molecular modelling. A poor starting structure will give you a poorly optimised end-product. Your software doesn't come with an AI (yet!) and so your chemical intuition will have to suffice. Crystal structures, if found, are good places to start as they are at least real minima in solid phase. Most of your calculations, however, will be in gas phase or in solvents.

==Thermodynamics vs kinetics==

==Other things==

If you have questions about anything not covered on this page, talk to us. In fact, talk to us in any case. Mini project, especially, shouldn't even be attempted before some interaction with us. Computational chemistry can get extremely complicated very quickly and a chat with us would prevent you from realising you've bitten up more than you can chew the night before submission. This of course in theory can't happen because you've been following our advice to start your mini project as early as Monday on the second week.

Rep:Mod:bnguyen

2011-10-28T08:50:05Z

Bnguyen: /* Semi-empirical methods */

[[Image:A_beginners_guide.jpg|center|800px]]
[[Image:dont_panic.jpg|center|200px]]

So you've done your calculations as instructed, and got your optimised structures with a whole lot of properties to boot. What else is expected of you? What does analysis exactly mean, anyway? Don't panic! Here you'll find most of what you need to know to survive Module 1 and beyond.

==Analysis==

"How much analysis is expected from us?", I hear you ask. The answer is: AS MUCH AS 60% OF YOUR MARK! Getting the lowest in energy conformers is quite a challenge which will test your chemical knowledge and patience to the limit, but it wouldn't do you much good if you can extract chemical information from the exercise. There are several types of information which can be discussed from the calculated structures of compounds or transition states in organic chemistry. The most common ones are listed below:

*Energies
*Bond angles and dihedral angles
*Molecular orbitals
*Bond strength, bond lengths and vibrational frequencies

====Energies====

Energies show how stable your structure is and when it comes to energy, the lower the better. Watch out when you compare energies of different structures, unless the number and types of atoms involved are the same, the comparison isn't valid. Under equilibrium, species of different energies will follow the same relationship as that between Gibbs free energy and equilibrium constant.

Comparing absolute energies between different computational methods is impossible, as they are calculated as the sum of different factors. However, the difference in energy between isomeric transition states calculated by different methods has often been compared with experimentally measured selectivity to judge the accuracy of computational methods.

====Bond angles and dihedral angels====

These values are very useful in intepreting the breakdown components of energy from Molecular Mechanics calculation. They're still useful in quantum mechanics, although there won't be any tangible result you can directly relate them to. A strained structure is a strained structure regardless of how you calculate it.

====Bond strength, bond lengths and vibrational frequencies====

A bond is defined and displayed differently by Molecular Mechanics and quantum mechanics techniques. Be mindful as what you see in the visualisation doesn't necessarily be what your calculation results mean. The strength of a bond, and to some extent its multiplicity, is best judged by examining the bond length and its vibrational frequencies.

====Molecular orbitals====

MOs are only accessible via quantum mechanics. In organic chemistry, we're mostly concerned with the frontier orbitals. Examining their position, shape and symmetry often gives clues about the nature of the MOs (bonding vs antibonding, σ-π interaction, etc.), and more importantly the reactivity and selectivity of the molecule in reactions.

==Data presentation==

So you aren't as good at writing wikis as the geeks who live in a garage, who shower once a month and are on a permanent supplement course of caffeine. Neither are we!

There is no doctor-ordered style for your report and marks won't be given for visual effects or creative designs of your wiki pages. Instead, we want clear, concise communication from you so that we can fully appreciate your work. One golden rule must be remembered: IF WE CAN'T SEE IT (CLEARLY), WE CAN'T MARK IT. The same goes for your analysis. If your visual aid helps the readers understand your points, by all means include it.

Another issue, which is most relevant with the mini projects, is the context of your work. Tell us why and how. More importantly, tell us EXACTLY WHAT QUESTION ARE YOU TRYING TO ANSWER WITH YOUR CALCULATION, other than for getting marks, of course.

Occasionally, we'll contact you during the marking for your original files if we find some of your results interesting, or if we feel there wasn't enough information in your wiki page. Remember to keep your files, and name them in a way that the future you won't struggle to comprehend.

==Methods of calculation==

====Molecular Mechanics====

An excellent description of molecular mechanics has already been included at [[Mod:molecular_mechanics|this page]]. Here we'll simply summarise that it's basically balls and sophisticated springs. It's fast, cheap to compute but has to rely on carefully developed force field information (the anharmonic oscillator parameters). Thus, molecular mechanics can only handle structures it has been taught to handle and those unfortunately don't include organometallic compounds.

Of particular note, bonds are treated as springs and have to be specified in the starting structure. As a results, molecular mechanics performs poorly when it comes to electronic interactions, or bond forming-breaking processes.

====Semi-empirical methods====

To cut computational cost in quantum mechanics, approximations were made to simplify the Schrödinger equation. Semi-empricial molecular orbitals methods were born. They're still fast, albeit at the cost of accuracy, compared to ''ab initio'' methods. Semi-quantitative description of electronic distribution, molecular structure, MOs and energies can be quickly derived using these methods. They're also capable of calculations for organometallic compounds.

Being quantum mechanic techniques, they can model electronic effect, orbital interactions or hydrogen bondings, bond formation/breaking, and transition states (all the things Molecular Mechanics can't do!).

====Ab initio calculations====

==Starting structure==

Just as in life, your starting point affects your destination in molecular modelling. A poor starting structure will give you a poorly optimised end-product. Your software doesn't come with an AI (yet!) and so your chemical intuition will have to suffice. Crystal structures, if found, are good places to start as they are at least real minima in solid phase. Most of your calculations, however, will be in gas phase or in solvents.

==Thermodynamics vs kinetics==

==Other things==

If you have questions about anything not covered on this page, talk to us. In fact, talk to us in any case. Mini project, especially, shouldn't even be attempted before some interaction with us. Computational chemistry can get extremely complicated very quickly and a chat with us would prevent you from realising you've bitten up more than you can chew the night before submission. This of course in theory can't happen because you've been following our advice to start your mini project as early as Monday on the second week.

Rep:Mod:bnguyen

2011-10-28T08:49:11Z

Bnguyen: /* Semi-empirical methods */

[[Image:A_beginners_guide.jpg|center|800px]]
[[Image:dont_panic.jpg|center|200px]]

So you've done your calculations as instructed, and got your optimised structures with a whole lot of properties to boot. What else is expected of you? What does analysis exactly mean, anyway? Don't panic! Here you'll find most of what you need to know to survive Module 1 and beyond.

==Analysis==

"How much analysis is expected from us?", I hear you ask. The answer is: AS MUCH AS 60% OF YOUR MARK! Getting the lowest in energy conformers is quite a challenge which will test your chemical knowledge and patience to the limit, but it wouldn't do you much good if you can extract chemical information from the exercise. There are several types of information which can be discussed from the calculated structures of compounds or transition states in organic chemistry. The most common ones are listed below:

*Energies
*Bond angles and dihedral angles
*Molecular orbitals
*Bond strength, bond lengths and vibrational frequencies

====Energies====

Energies show how stable your structure is and when it comes to energy, the lower the better. Watch out when you compare energies of different structures, unless the number and types of atoms involved are the same, the comparison isn't valid. Under equilibrium, species of different energies will follow the same relationship as that between Gibbs free energy and equilibrium constant.

Comparing absolute energies between different computational methods is impossible, as they are calculated as the sum of different factors. However, the difference in energy between isomeric transition states calculated by different methods has often been compared with experimentally measured selectivity to judge the accuracy of computational methods.

====Bond angles and dihedral angels====

These values are very useful in intepreting the breakdown components of energy from Molecular Mechanics calculation. They're still useful in quantum mechanics, although there won't be any tangible result you can directly relate them to. A strained structure is a strained structure regardless of how you calculate it.

====Bond strength, bond lengths and vibrational frequencies====

A bond is defined and displayed differently by Molecular Mechanics and quantum mechanics techniques. Be mindful as what you see in the visualisation doesn't necessarily be what your calculation results mean. The strength of a bond, and to some extent its multiplicity, is best judged by examining the bond length and its vibrational frequencies.

====Molecular orbitals====

MOs are only accessible via quantum mechanics. In organic chemistry, we're mostly concerned with the frontier orbitals. Examining their position, shape and symmetry often gives clues about the nature of the MOs (bonding vs antibonding, σ-π interaction, etc.), and more importantly the reactivity and selectivity of the molecule in reactions.

==Data presentation==

So you aren't as good at writing wikis as the geeks who live in a garage, who shower once a month and are on a permanent supplement course of caffeine. Neither are we!

There is no doctor-ordered style for your report and marks won't be given for visual effects or creative designs of your wiki pages. Instead, we want clear, concise communication from you so that we can fully appreciate your work. One golden rule must be remembered: IF WE CAN'T SEE IT (CLEARLY), WE CAN'T MARK IT. The same goes for your analysis. If your visual aid helps the readers understand your points, by all means include it.

Another issue, which is most relevant with the mini projects, is the context of your work. Tell us why and how. More importantly, tell us EXACTLY WHAT QUESTION ARE YOU TRYING TO ANSWER WITH YOUR CALCULATION, other than for getting marks, of course.

Occasionally, we'll contact you during the marking for your original files if we find some of your results interesting, or if we feel there wasn't enough information in your wiki page. Remember to keep your files, and name them in a way that the future you won't struggle to comprehend.

==Methods of calculation==

====Molecular Mechanics====

An excellent description of molecular mechanics has already been included at [[Mod:molecular_mechanics|this page]]. Here we'll simply summarise that it's basically balls and sophisticated springs. It's fast, cheap to compute but has to rely on carefully developed force field information (the anharmonic oscillator parameters). Thus, molecular mechanics can only handle structures it has been taught to handle and those unfortunately don't include organometallic compounds.

Of particular note, bonds are treated as springs and have to be specified in the starting structure. As a results, molecular mechanics performs poorly when it comes to electronic interactions, or bond forming-breaking processes.

====Semi-empirical methods====

To cut computational cost in quantum mechanics, approximations were made to simplify the Schrödinger equation. Semi-empricial molecular orbitals methods were born. They're still fast, albeit at the cost of accuracy, compared to ''ab initio'' methods. Semi-quantitative description of electronic distribution, molecular structure, MOs and energies can be quickly derived using these methods. They're also capable of calculations for organometallic compounds.

Being quantum mechanic techniques, they can model electronic effect, orbital interactions or hydrogen bondings (all the things Molecular Mechanics can't do!).

====Ab initio calculations====

==Starting structure==

Just as in life, your starting point affects your destination in molecular modelling. A poor starting structure will give you a poorly optimised end-product. Your software doesn't come with an AI (yet!) and so your chemical intuition will have to suffice. Crystal structures, if found, are good places to start as they are at least real minima in solid phase. Most of your calculations, however, will be in gas phase or in solvents.

==Thermodynamics vs kinetics==

==Other things==

If you have questions about anything not covered on this page, talk to us. In fact, talk to us in any case. Mini project, especially, shouldn't even be attempted before some interaction with us. Computational chemistry can get extremely complicated very quickly and a chat with us would prevent you from realising you've bitten up more than you can chew the night before submission. This of course in theory can't happen because you've been following our advice to start your mini project as early as Monday on the second week.

Rep:Mod:bnguyen

2011-10-28T08:40:36Z

Bnguyen: /* Molecular Mechanics */

Rep:Mod:bnguyen

2011-10-28T08:00:09Z

Bnguyen: /* Other things */

Rep:Mod:bnguyen

2011-10-28T07:56:53Z

Bnguyen: /* Other things */

Rep:Mod:bnguyen

2011-10-28T07:56:11Z

Bnguyen: /* Thermodynamics vs kinetics */

Rep:Mod:bnguyen

2011-10-28T07:52:28Z

Bnguyen:

Rep:Mod:bnguyen

2011-10-28T07:48:14Z

Bnguyen: /* Bond angles and dihedral angels */

Rep:Mod:bnguyen

2011-10-28T07:42:38Z

Bnguyen: /* Analysis */

Rep:Mod:bnguyen

2011-10-28T07:41:50Z

Bnguyen: /* Starting point */

Rep:Mod:bnguyen

2011-10-28T07:41:12Z

Bnguyen: /* Molecular orbitals */

Rep:Mod:bnguyen

2011-10-28T07:35:54Z

Bnguyen: /* Energies */

Rep:Mod:bnguyen

2011-10-28T07:29:42Z

Bnguyen: /* Bond strength, bond lengths and vibrational frequencies */

Rep:Mod:bnguyen

2011-10-28T07:29:15Z

Bnguyen: /* Bond strength, bond lengths and vibrational frequencies */

Rep:Mod:bnguyen

2011-10-28T07:26:10Z

Bnguyen: /* Energies */