Where does computational chemistry overlap with organic chemistry?

I was wondering what research exists that combines computational chemistry and organic chemistry.

For the past three years, I've been using Amber and Gaussian (in hopes) to identify and understand trends in intramolecular interactions. This really just serves as an example of my past research which incorporated both physical chemistry and computational chemistry.

I would like to know what kind of research could be done that combines both organic chemistry with computational chemistry.

I've Googled computational research in organic chemistry, but haven't found much information. What are some examples of projects that have been done in organic chemistry that rely heavily on the computational side of things?

• Drug screening is pretty lucrative and mostly organic chemistry. ncbi.nlm.nih.gov/pmc/articles/PMC3880464 Or you could also work in creating force fields. There are many solvents whose force fields are not available, or accurate. Or in the spirit of this year's Nobel prize, you could look at the dynamics/simulation of molecular machines. – CoffeeIsLife Oct 11 '16 at 3:56
• You could also try research in transition state/intermediate states. IRC, they have trouble determining them because of optimization problems (global vs. local). Since determining intermediates and transition states is important in Ochem, I suppose it's related, . Although computational chemistry is still not very good at this, you could research this since it is a rather important subject. – CoffeeIsLife Oct 11 '16 at 3:59
• @QuantumCAPUCCINO Drug screening is also usually pretty computationally intensive, is it not? Worth looking into, but it might require more resources than you've got, Melanie. – hBy2Py Oct 11 '16 at 4:13
• the absolute coolest field of research right at the centre of chemistry is catalyst design. Using computational chemistry to design inorganic products with the end goal of doing fancy organic transformations, then scaling them up to the kilo level to make drugs and save the environment! and all along you continue to do computations, make predictions, perform experiments, and improve your understanding of the chemistry. imo the cat-chem/compchem/process chem area of chemistry is nested perfectly in the nexus of all scientific thought. It's like the perfect field. – gannex Oct 11 '16 at 5:45
• honestly though, chemistry is all about getting wet. Having a good basis in compchem as an undergrad is ideal. Working full time on computational is painfully boring and bad for your back, plus calculations take long enough that you might as well be setting up reactions while you're waiting. The cool thing about comp-chem is that it takes an often empirical science and brings the scientific method front & centre. You go Theory>prediction>experiment>theory until you make better chemistry and save the world one kcal at a time!! The future is interdisciplinary. You've got to have both. – gannex Oct 11 '16 at 5:55

The first thing that comes to mind: read the backlist of Henry Rzepa's and (especially) Steven Bachrach's blogs. Depending exactly on what resources you have available, there are lots of things they do on the computational side of organic chemistry that you could at first imitate and then use as a springboard to innovate.

In particular, I've found Bachrach's posts on reaction dynamics to be especially fascinating. This is the phenomenon where the topography of the potential energy surface near a transition state is such that the reactions don't always follow the minimum-energy path due, effectively, to the inertia of the nuclei as they cross the TS.

I also have a personal interest in Bader's Quantum Theory of Atoms in Molecules, which uses the topology of the electron density to divide molecules up into atoms, where each atomic volume is enclosed by a 'zero-flux surface' in the electron density. (There's some ongoing controversy over the theory, but it makes good sense to me, for whatever that's worth.) Bader's book is a good place to start; or, you can search the journal literature for Richard Bader and a whole bunch of examples will surely turn up. I engaged with Dr. Rzepa last year in the comment thread of a post of his about electrides that touched on QTAIM, the electron localization function (ELF), non-covalent interactions (NCI), etc.

Finally, I've been very curious lately about 'charge-shift bonding', a relatively newly described class of bond where the nuclear framework tries to cram so many electrons into a small space that in the end Pauli repulsion drives them apart, causing what might otherwise appear to be a covalent bond to instead take the form of a resonance between two ionic structures. (The electronic structure of $\ce{F_2},$ for example, is better described as a balanced resonance between $\ce{F- \!- F+}$ and $\ce{F+ \!- F-}$ overlaid atop a very weak covalent interaction, than as a purely covalent $\ce{F\!-F}$ species.) Search the literature for Sason Shaik's work for more information and examples.

Other things that I've come across that have seemed interesting include carbenes, cyclic alkynes, unusual Diels-Alder reactions, and fullerene systems.

I would also subscribe to, e.g., Computational Chemistry Highlights, CCL, and Jan Jensen's Computational Chemistry Daily -- the posts and/or questions that come across there might give you some inspiration.

I have complemented most of my organic chemistry ("wet chemistry") work with computational chemistry, and it's, in fact, quite common to do so today. I would say it pretty much depends on your interests. There are probably other members in the group of your professor. Maybe they face some problem where computational chemistry can assist in. One example is the possibility to simulate NMR, IR, UV-VIS or (V)CD spectra. Another is the calculation of ground states, intermediates and transition states of catalytic cycles in case the group is doing catalysis. Actually, I would say there definitely should be the possibility to apply computational chemistry in any chemistry group, the remaining question being how good the support will be and if your professor will appreciate what you are doing. There are many good books about (organic) computational chemistry out there. I particularly liked

• Computational organic chemistry by Steven M. Bachrach
• A Chemist’s Guide to Density functional theory by the authors Wolfram Koch, Max C. Holthausen
• Exploring Chemistry with Electronic Structure Methods by James B. Foresman
• Essentials of Computational Chemistry by Christopher J. Cramer
• Introduction to Computational Chemistry by Frank Jensen

more or less in that order. But there are lots of other good books of course. Another book for you, being interested in both physical and organic chemistry, is

• Modern Physical Organic Chemistry by Eric V. Anslyn, Dennis A. Dougherty

which by the way has a nice treatment of some organic computational chemistry topics as well.

• Ahh, yep, I realized after I went to bed that I forgot to mention spectroscopy. Frank Neese's pubs list and ORCA are a good place to start looking into that. – hBy2Py Oct 11 '16 at 11:47

One thing that would be interesting to tie together is the relationship between chiral resolution and resolving agent structure. Looking at the Dutch resolution on a molecular level would be cool. Relating Fogassy parameters with what happens at the molecular level is another aspect of the same area of work.