2014-03-21T19:00:11Z

Js6511:

== 3rd Year Organic Computational Chemistry Lab ==

James Spreadborough
00690768

== Introduction ==

Molecular mechanics is a way of modeling chemical structures to predict certain properties they have, such as their potential energy and preferred configuration in space. NMR spectra of different active atoms in these molecules can also be predicted and compared to actual spectra. With these calculations a force field is used, a group mathematical equations that determine the different energies of the molecule. In this experiment molecular mechanics was used to predict the energies, structures and spectra of a number of different compounds, some of which were molecules synthesised in the 1S synthesis experiment. Specifically, the MMFF94s force field was used in these calculations, a non-specific force field used for many different types of molecules.<ref name="Molecular_mechanics" /> <ref name="Molecular" />

Different programs were used for different parts of this experiment. Chemdraw was used to initially draw the molecules, and these were opened in Avogadro to optimise their geometry directly and then set up the input file to submit to the HPC portal for their energy and predicted NMRs be determined.<ref name="HPC" /> The output file was then opened in Gaussview to analyse the results from the calculation.

== Initial Optimisations ==

=== The Hydrogenation of Cyclopentadiene Dimer ===

Cyclopentadiene can react with itself in a Diels-Alder addition to create a dimer. One of the double bonds of the first cyclopentadiene molecules forms bonds with the second as the closest part of the molecule (exo) or on the other side, with the two molecules on top of each other (endo), giving two possible products.<ref name="dimer" /> The endo product is formed preferentially from research, so the calculations should explain whether this is the thermodynamic or kinetic product. <ref name="cyclo_dimer" />

[[File:CYCLO1.png|thumb|250px|left|The 1st cyclopentadiene molecule (exo).]]

[[File:CYCLO2.png|thumb|250px|center|The 2nd cyclopentadiene molecule (endo).]]

Avogadro was first used to calculate the optimised molecule of the cyclopentadiene dimer, and then used to calculate the different energies of the molecules. For these molecules it was fairly simple to obtain the lowest energy geometry because they are fairly small and the geometry optimisation always reverses the molecule to either 1 or 2.

<jmolFile text="Jmol file for Cyclopentadiene 1">Cyclo_1.mol</jmolFile>

<jmolFile text="Jmol file for Cyclopentadiene 2">Cyclo_2_(2).mol</jmolFile>

The energies of the different isomers were then calculated and compared in the table below:

{| class="wikitable"
|+ Energies of Optimised Cyclopentadiene Molecules
! Type of Energy
! 1 (kcal mol-1)
! 2 (kcal mol-1)
|-
| Total Energy || 55.39601 || 58.19073
|-
| Bond Stretching Energy || 3.54803 || 3.46682
|-
| Angle Bending Energy || 30.79924 || 33.19345
|-
| Torsional Energy || -2.79503 || -2.94976
|-
| van der Waals Energy || 12.85715 || 12.35564
|-
| Electrostatic Energy || 13.01460 || 14.18452
|}

The endo product, formed as the major product in literature, has the higher total energy in Avogadro's calculations. This suggests that the kinetic product is formed preferentially, and this is supported by evidence in the literature, describing the endo product as the higher energy isomer.<ref name="cyclo_dimer" />

The second cyclopentadiene molecule can then be hydrogenated at either double bond, forming either molecule 3 or 4.

[[File:CYCLO3.png|thumb|250px|left|The 3rd cyclopentadiene molecule, hydrogenated.]]

[[File:CYCLO4.png|thumb|250px|center|The 4th cyclopentadiene molecule, hydrogenated.]]

Avogadro was again used to calculate the optimised molecule of the cyclopentadiene dimer before calculating the different energies of the molecules. It was also similarly straightforward to obtain the lowest energy geometry because of their equal size and shape to the first and second molecules.

<jmolFile text="Jmol file for Cyclopentadiene 3">Cyclo_3.mol</jmolFile>

<jmolFile text="Jmol file for Cyclopentadiene 4">Cyclo_4.mol</jmolFile>

The energies of the different isomers were then also calculated and compared in the table below:

{| class="wikitable"
|+ Energies of Optimised Cyclopentadiene Molecules
! Type of Energy
! 3 (kcal mol-1)
! 4 (kcal mol-1)
|-
| Total Energy || 50.44623 || 41.25751
|-
| Bond Stretching Energy || 3.31070 || 2.82259
|-
| Angle Bending Energy || 32.00089 || 24.68652
|-
| Torsional Energy || -1.52746 || -0.37723
|-
| van der Waals Energy || 13.63337 || 10.63515
|-
| Electrostatic Energy || 5.11940 || 5.14702
|}

The overall energy of the fourth molecule was calculated here to be lower than that of the third, indicating it was more stable. This then indicates that the fourth molecule would be simpler to synthesise than the third, which is supported by the literature. <ref name="cyclo_dimer_hydrod" /> Catalytic hydrogenation alone is enough to make the fourth molecule

=== Taxol Intermediate Optimisation (MMFF94s) ===

Avogadro was used to calculate the optimised molecule of a taxol intermediate:

{| class="wikitable"
|+ Energies of Optimised Taxol Intermediate Molecules
! Type of Energy
! 9 (kcal mol-1)
! 10 (kcal mol-1)
! 9 (altered, kcal mol-1)
! 10 (altered, kcal mol-1)
|-
| Total Energy || 147.25428 || 138.24808 || 127.14173 || 126.40225
|-
| Bond Stretching Energy || 14.66408 || 14.60783 || 12.64375 || 13.10797
|-
| Angle Bending Energy || 62.34485 || 48.74384 || 55.43813 || 51.70586
|-
| Torsional Energy || 16.22860 || 18.32473 || 8.35237 || 8.03288
|-
| van der Waals Energy || 49.42617 || 52.41845 || 46.67422 || 49.78176
|-
| Electrostatic Energy || 1.73013 || 1.86927 || 1.57516 || 1.94169
|}

<jmolFile text="Jmol file for Taxol Intermediate 9">Taxol_Intermediate_9.2.mol</jmolFile>

<jmolFile text="Jmol file for Taxol Intermediate 10">Taxol_Intermediate_10.2.mol</jmolFile>

<jmolFile text="Jmol file for Taxol Intermediate 9 (altered)">Taxol_Intermediate_9.mol</jmolFile>

<jmolFile text="Jmol file for Taxol Intermediate 10 (altered)">Taxol_Intermediate_100.mol</jmolFile>

== Spectroscopic Simulation using Quantum Mechanics ==

<jmolFile text="Jmol file for Taxol Intermediate 17">Taxol_17_Result.mol</jmolFile>

[[File:Taxol_Intermediate_17_NMR.png|center|1000px|]]

<jmolFile text="Jmol file for Taxol Intermediate 18">Taxol_18_Result.mol</jmolFile>

<jmolFile text="Jmol file for Shi Catalyst">Shi_Catalyst_Result.mol</jmolFile>

== Spectroscopic Simulation - Epoxides ==

<jmolFile text="Jmol file for Trans Stilbene Epoxide">Trans_Stilbene_Epoxide_Result.mol</jmolFile>

<jmolFile text="Jmol file for Trans Styrene Epoxide">Styrene_Epoxide_Result.mol</jmolFile>

== References ==

<references>
<ref name="Molecular_mechanics"> T. A. Halgren, ''Journal of Computational Chemistry'', 17, 5&6, '''1996''', 490-519.</ref>
<ref name="Molecular"> Overview to [[Mod:mechanics|molecular mechanics]] </ref>
<ref name="HPC"> Overview of [[Mod:scan|HPC submission]] </ref>
<ref name="dimer"> Overview of cyclopentadiene dimerisation. [http://www.ch.ic.ac.uk/motm/porphyrins/introDA.html#footnote] </ref>
<ref name="cyclo_dimer"> P. Caramella, P. Quadrella and L. Toma, ''J. Am. Chem. Soc.'' 124, 7, '''2002''', 1130-1. [http://pubs.acs.org/doi/pdf/10.1021/ja016622h] </ref>
<ref name="cyclo_dimer_hydrod"> T. J. A. Graham, T. H. Poole, C. N. Reese and B. C. Goess, ''Am. Chem. Soc.'' 76, '''2011''', 4132-8. [http://pubs.acs.org/doi/pdf/10.1021/jo200262r] </ref>
</references>

2014-03-21T12:12:52Z

Js6511: