UC Davis

This dissertation covers a range of computational studies on noncovalent interactions in biological systems and mechanistic investigations of synthetically and biosynthetically relevant reactions. Chapter 1 introduces the main concepts (i.e., basics of quantum mechanics, analysis of noncovalent interactions, and modeling organic reactions) behind quantum chemical calculations discussed (in the order they appear) in this report.Chapter 2 details the roles of noncovalent interactions involving sulfur atoms in biological systems, where computational approaches for modeling noncovalent interactions were described and examples of their applications were provided. Chapter 3 homes elucidation of organic reaction mechanisms involving sulfur atoms: (1) a collaborative effort with the research groups of Prof. John P. Toscano, Prof. Adrian J. Hobbs, and Prof. Jon M. Fukuto which explored the reaction mechanism of hydropersulfides with S-nitrosothiols, and revealed that S-nitrosothiols can be degraded by hydropersulfides to release nitric oxide which results in the regulation of vascular tone; (2) mechanistic investigation of the formation of zwiebelanes which are bioactive natural products isolated from onion extracts (ongoing). Chapter 4 details a collaboration with Prof. Uttam K. Tambar’s group. Our study discussed the catalyst-controlled regiodivergence in rearrangements of indole-based onium ylides and the mechanistic investigation of rhodium- and copper-catalyzed reactions showed divergent pathways favoring [2,3]-rearrangement involving a metal-free ylide and [1,2]-rearrangement involving a metal-coordinated ion pair in a solvent-cage. Lastly, Chapter 5 of this dissertation (in collaboration with the groups of Prof. Ikuro Abe, Prof. John A. Porco Jr., and Prof. Makoto Fujita) focuses on the evaluation of the potential of meroterpenoid cyclases to expand the chemical space of fungal meroterpenoids. Our study shed light on their catalytic activity and could pave the way to create unnatural pathways towards second generation meroterpenoids.