This thesis focuses on the study of time-resolved mechanism of organic reactions with molecular reaction dynamics simulations. Gas-phase trajectory simulations were performed on (1) dimethyldioxirane C-H oxidation, which show how polar acetone solvation favors diradical recombination, leading to the retention of stereospecificity; (2) dehydro-Diels-Alder reactions, which reveal intrinsic dynamic features for concerted and stepwise pathways, where concerted pathway involves a vibrational excitation, while stepwise pathway involves a rotational excitation; (3) cyclopentadiene dimerization, in which two-stage pathway, as originally proposed by Woodward and Katz, is involved in 13% of the reactive trajectories, presenting a typical “dynamically stepwise” feature with time gap between formation of two bonds longer than 60 fs; and (4) sixteen reactions with potential energy surface bifurcation, where a linear correlation was found between TS bond lengths and the product ratio, serving as an empirical model to assist the discovery of new bifurcating reactions, and estimate product ratio without the expense of MD simulations.
The thesis reports the development of a new computational method, environment-perturbed transition state sampling, (EPTSS) to enable the study of reaction dynamics in solvent and in enzyme. EPTSS integrates the conformational sampling of solvent/enzyme and quasi-classical sampling of reacting molecules, which was inspired by Truhlar and Gao’s ensemble-average variational transition state theory. The method has been applied to (1) water-accelerated Diels-Alder reaction, which shows how water molecules dynamically participate the reaction and forms enhanced hydrogen bonds; (2) phosphoric acid-catalyzed allylboration reactions, in which an intrinsic synergy of enhancement between the CHï¿½ï¿½ï¿½O and OHï¿½ï¿½ï¿½O hydrogen bonds were observed, and the enhancement is diminished in toluene solvent; and (3) SpnF-catalyzed Diels-Alder reaction, which first demonstrates how enzyme dynamically control the product ratio of bifurcating reactions.