Computational Simulation of Solution Phase NADH/NAD + Model Reaction

Kinetic isotope effects (KIEs) for the hydride transfer reactions from 10-methylacridan (MAH) and 9,10-dimethylacridan (DMAH) to Tropylium ion (Tr+) in acetonitrile were determined in Lu's group. They include 1° KIEs and 2° KIEs at the 9-&agr;-H/D and 10-CH3/CD3 positions of the MAH and 9-beta-CH3/CD3 and 10-CH3/CD 3 positions of the DMAH. The results indicate that the reactions take place by H-tunneling mechanism. In this thesis, structures of the tunneling ready states (TRS's) of different donor-acceptor distance (DAD) for the two reactions were found via a calculation following the Marcus-like H-tunneling model.;A theoretical study was conducted in an attempt to model experimentally measured 2° KIEs. This method is based on Marcus-like H-tunneling model. It employs a number of software and DFT/B3LYP/6-31G+(d) level of theory. A procedure was followed to find the double degenerate potential well which is necessary for tunneling and the corresponding tunneling ready state structure.;The calculated inverse beta-CH3/CD3 2° KIEs become more inverse with decreasing DAD but the calculated normal &agr;-H/D 2° KIEs do not show the apparent dependence upon DAD. These are consistent with the experimental observations and can be explained in terms of the steric isotope effect of the beta-CH3/CD3, which is more significant in D-tunneling. D-tunneling requires a shorter DAD and hence has a crowded reaction environment.;The calculated 10-CH3/CD3 inverse 2° KIEs for both systems are also consistent with the experiments. This is explained in terms of the stronger basicity of the N-CD3 base than the N-CH 3. The reactions use the hydride tunneling mechanism following the Marcus-like H-tunneling model which involves heavy atom reorganization along with the reaction.