Models of chemical structure and dynamics via nuclear magnetic resonance and ab initio computational chemistry

The combination of nuclear magnetic resonance (NMR) and ab initio calculations has become one of the most powerful tools to solve important structural and energetic problems in the field of chemistry. Chemical shifts observed in NMR present detailed information about local electronic structure while dynamic NMR allows us to extract kinetic and thermodynamic properties without perturbing equilibrium. Ab initio calculations are able to interpret the chemical shifts in terms of the chemical structure and provide detailed analysis of the energetic components that make up the process probed by dynamic NMR. This work involves three important applications of this powerful combination tool.;First, we present a combined X-ray, solid-state NMR, and ab initio study of the 140 kDa enzyme tryptophan synthase that allows for the determination of chemical structure for the key enzymatic intermediates in the enzyme cycle. The results support the ketoenamine and dipolar forms that are in fast exchange with each other in the quionoid intermediate, a result that we believe has mechanistic implications. The structural characterization of this enzymatic intermediate provides insight into the energetic and chemical transformations responsible for biological function.;Second, the combination of NMR and ab initio calculations has been applied to the field of catalysis. We find that specific position of the peripheral substitutions outside the central chiral pocket accounts for most of the discrepancies in fundamental physicochemical properties among related cinchona alkaloids via a combination of energetic and entropic effects. These differences in physicochemical properties are ultimately responsible for the differences in chemical reactivity that make each molecule so unique.;Finally, we make use of dynamic NMR and ab initio calculations to investigate the rotational barriers of a series of pyridine thiocarboxamides, and identify different electronic and structural factors that contribute to changes in the energetic processes. Comparison between thiocarboxamides and their corresponding amide analogues highlights the important role of the resonance interaction proposed by the canonical amide resonance model.