RESEARCH & DISCOVERY
The Hirschi group investigates reaction mechanisms in organic and enzymatic catalysis using state-of-the-art computational and NMR analysis. The development of novel catalyst architectures is driven by automated in-silico analysis of key interactions present at the transition state of these reactions.
DFT INVESTIGATIONS OF ENANTIOSELECTIVE AND BIOORTHOGONAL REACTIONS
We are interested in investigating the origin of enantioselectivity of contemporary reactions in asymmetric organocatalysis including bifunctional urea/thiourea catalysis, Brønsted acid/base catalysis. The computational models for enantioselectivity are validated using experimental isotope effect measurement. Our work in this area has led to the understanding of new reactivity/activation modes in these traditional areas of asymmetric catalysis. We are also interested in exploring the mechanism of bioorthogonal reactions with the goal of improving its application in biological settings.
KINETIC ISOTOPE EFFECT AS A TOOL TO PROBE HIGH-TALENT ORGANOMETALLIC INTERMEDIATES IN CATALYSIS
Our lab investigates organometallic reactions proceeding via intermediates with high-valent metal centers such as Cu(III), Pd(IV), Ni(IV), that are highly unstable and are therefore not easily isolated or characterized. As a result, there is little to no mechanistic information about the fine details of the catalytic cycles of these reactions. These reactions represent the frontier of contemporary transition metal catalysis and the future of organic synthesis. We are interested in exploring these reaction mechanisms since traditional approaches of studying reactivity of isolated, putative intermediates cannot be easily applied to these reactions.
PROBING THE ENERGY SURFACE OF PHOTOREDOX REACTIONS
A combination of kinetic isotope effects and computational modeling is utilized to gain mechanistic insights into interesting photochemical transformations.
IN-SILICO INHIBITOR DESIGN BY ANALYSIS OF ENZYMATIC TRANSITION STATES
A combined experimental and theoretical approach is applied to solving the chemical mechanisms of enzymatic reactions that are important drug targets. Computations are used to analyze the electronic attributes of the transition structure and provide guidelines for inhibitor design. These rationally designed 'transition state analogues' are evaluated in-silico and scored based on its similarity to the enzymatic transition state. The top candidates are then synthesized, and inhibition studies performed to test efficacy.