Experimental and Theoretical Conformational Analysis: From Atoms to Proteins

Molecular conformation plays an important role in many aspects of chemistry and at all scales. Studying conformation dynamically typically requires considerable interplay between theoretical and experimental approaches. This thesis presents two such studies. The first examines a fundamental stereoelectronic effect in a series of 1,3- diheterocyclohexane systems, which serve as efficient probes of orbital interactions at the atomic scale. The results of spectroscopy and ab initio computational studies of these compounds reveal the nature of the conformational deuterium isotope effect and its underlying origins in terms of hyperconjugation. The second study is of a vastly different scale, examining the dynamic conformations of influenza neuraminidases in complex with a new class of inhibitors, which are potential lead compounds for novel pharmaceuticals. This work employs molecular dynamics simulations in conjunction with an improved analysis technique. The results reveal the highly dynamic nature of this new class of inhibitors and the implications for rational drug design.