Dissertation/Thesis Abstract

Hydride Tunneling in the Reduction of an Organic Carbocation with NADH Models
by Maharjan, Binita, M.S., Southern Illinois University at Edwardsville, 2014, 82; 1566481
Abstract (Summary)

Kinetics of the hydride transfer reactions from 10-methyl-9,10-dihydroacridan (MAH) and 9,10-dimethylacridan(DMAH) to tropylium ion in acetonitrile were determined. The reactions are model reactions for enzymes that use NADH as hydride donor and catalyze hydride transfer between two carbons. The observed temperature over dependence of the primary kinetic isotope effects (KIEs) suggests H-tunneling. Within the Marcus-like H-tunneling model, the results can also be explained in terms of a loosely associated tunneling ready state (TRS) in a less restrictive solution medium, which requires the sampling of short donor acceptor distance (DAD) for H-tunneling, thereby resulting in a strong temperature dependence of primary KIEs. This is in contrary to the observed temperature independence of primary KIEs in the wild-type enzymes but similar to the situation in mutants, suggesting the reaction coordinate is well organized for H-tunneling in wild-type enzyme environment where sampling of DAD for tunneling is not needed. The secondary KIE at the 9-H/D position of MAH (1.09) is normal, consistent with the hybridization change from sp 3 to sp2. But it is close to EIE of 1.12 and far from unity, inconsistent with the exothermic nature of the reaction. This inflated KIE can be explained by 1o/2o H-coupled motion. Within Marcus like H-tunneling model, the secondary KIE reflects the effect of difference in the reorganization of the secondary isotope on the rates of reaction. The β-secondary KIE at 9-CH3/CD3 position is inverse (0.96), which is inconsistent with the hybridization change from sp3 to sp2. This inverse secondary KIE can be explained in terms of steric hindrance effect of N-CH3/CD3 with the neighbouring 4,5-H's,, which is higher for 9-CH3 than 9-CD3. The secondary KIE is more inverse for D-transfer (0.91) than H-transfer (0.96) due to the short donor acceptor distance requirement for D- tunneling than H-tunneling. The secondary KIEs at the 10-N-CH3/CD3 positions of both MAH (0.90) and DMAH (0.93) are inverse, which is inconsistent with the hybridization change from sp3 to sp2. This result can be explained by both in terms of nitrogen lone pair basicity, which is higher for CD3-NH2 compared to CH3-NH 2; and and the steric isotope effect, which is caused by their interactions with the neighboring 1,8-H's.

Indexing (document details)
Advisor: Lu, Yun
Commitee: Dixon, Robert P., O'Brien, Leah C.
School: Southern Illinois University at Edwardsville
Department: Chemistry
School Location: United States -- Illinois
Source: MAI 53/06M(E), Masters Abstracts International
Subjects: Organic chemistry
Publication Number: 1566481
ISBN: 9781321243086
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