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 1: DOI:10.1021/np0705918 Structural Reassignment of Obtusallenes V, VI, and VII by GIAO-Based Density Functional Prediction, with direct link to spectra.
- Example 2: DOI:10.1002/chem.201101129 On the determination of the stereochemistry of semi-synthetic natural product analogues using chiroptical spectroscopy: Desulfurization of epidithiodioxopiperazine fungal metabolites
Molecular orbital calculations – which allow calculation of energy levels and visualisation of key orbitals to improve our understanding of bonding and reactivity
- Example 3: DOI:10.1021/jp902176a The Geometry and Electronic Topology of Higher-Order Charged Möbius Annulenes, with direct link to orbitals.
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 4: DOI:10.1021/jo900840v Constrained β-Proline Analogues in Organocatalytic Aldol Reactions: The Influence of Acid Geometry
- Example 5: DOI:10.1021/ja905615a Heavier Group 2 Metals and Intermolecular Hydroamination: A Computational and Synthetic Assessment
- Example 6: DOI:10.1021/jo048213k An Experimental and Computational Investigation of the Diels−Alder Cycloadditions of Halogen-Substituted 2(H)-Pyran-2-ones
- Example 7: 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.

An alternative view in the form of slides is available here