Computational Methods for Selective Catalysis



 DESCRIPTION (provided by applicant): The overall objective of this research program is to develop and apply state-of-the-art computation methods to understand stereoselectivity, chemoselectivity, and reactivity at the molecular level with the aim of designing new, more effective reagents and catalysts. The control of selectivity and reactivity are essential features f efficient synthesis, yet our molecular level understanding of how fundamental interactions perturb these aspects is only rudimentary. This program seeks to quantitate these fundamental interactions to explain the observed results and to build on this foundation. In addition to developing improved computational and analytical tools, a primer will be constructed tabulating the prevalence and strength of these widespread, fundamental interactions. We have identified three overall goals. In the first, transition state calculations will be used to probe mechanism, understand control elements, and quantitate fundamental interactions. In the second, empirical modeling tools will be developed and used to identify the key control factors governing reactivity and selectivity. This knowledge, in turn, focuses the studies in aim 1 to the most important elements. In the third, a new experimental measure of reactivity is outlined, which is an important component of the interaction primer that is being built. Relevance The fundamental hallmark of this proposal is the ability to design new reactions and catalysts via computation to construct important organic structures in an efficient and rational manner. New synthetic methods greatly increase access to untapped chemical space, leading to materials and pharmaceuticals that benefit society. To achieve this goal, investigations will focus on obtaining an improved understanding of the fundamental interactions governing reactivity and selectivity. These same interactions govern biological systems, and further understanding will enable the design of enzymatic inhibitors and agents targeting other biomolecules to disrupt biological functions. Invaluable training will be afforded to undergraduate students, graduate students, and postdoctoral researchers involved in this proposal.