Semi-classical transitional state theory and Bell model with a H-tunneling correction are the traditional basis for the understanding of the hydrogen kinetic isotope effects (KIEs). However, they fail to explain many observations in H-transfer reactions. The major reason is that they do not consider the role of the heavy atom motions in the H-transfer chemistry. Marcus-like model is a phenomenological model which treats H as a wave between vibrational donor and acceptor and can explain the observations from temperature independence of KIEs for the wild-type enzymes (∆Ea = EaD - EaH = 0) and temperature dependence of KIE’s in mutated enzymes (∆Ea > 0). Within this new model, KIE originates from different H/D wave-function overlap between activated reactant and product at all possible donor-acceptor distances (DAD’s) sampled by the heavy atom motions. In this work, two hypotheses were recognized from this model, which link structure/DAD to KIEs and the temperature dependency of the KIEs. They are, (1) a shorter DAD is required for D-tunneling than for H-tunneling, and (2) the more rigid the reaction centers the weaker will be the temperature dependence of the 1° KIEs, i.e. a smaller ∆Ea. A series of hydride transfer reactions of NADH/NAD+ analogs in acetonitrile were designed to systematically investigate the hypotheses. Experiments studied electronic, steric, and temperature effects on kinetics and produced rate constants ranging from 105 to 1.0 M-1s-1, KIE’s from 2.5 to 5.31, and ∆Ea’s from nearly 0 to 1.19 kcal/mol. It was found that H- and D-tunneling processes use different tunneling-ready state electronic structures. It was also found that the ∆Ea increases as the rigidity of the donor-acceptor centers decreases. The latter results replicate the trend of ∆Ea’s observed from enzymes to mutated enzymes and have opened a new research direction that studies structure – ∆Ea relationship. Results support the two hypotheses, and thus are consistent with the Marcus-like H-tunneling model.
|Commitee:||Luesse, Sarah, Dong, Jie|
|School:||Southern Illinois University at Edwardsville|
|School Location:||United States -- Illinois|
|Source:||MAI 82/3(E), Masters Abstracts International|
|Keywords:||Donor-acceptor distances (DADs), H-tunneling, Marcus-like H-tunneling model, Temperature dependence of KIEs|
Copyright in each Dissertation and Thesis is retained by the author. All Rights Reserved
The supplemental file or files you are about to download were provided to ProQuest by the author as part of a
dissertation or thesis. The supplemental files are provided "AS IS" without warranty. ProQuest is not responsible for the
content, format or impact on the supplemental file(s) on our system. in some cases, the file type may be unknown or
may be a .exe file. We recommend caution as you open such files.
Copyright of the original materials contained in the supplemental file is retained by the author and your access to the
supplemental files is subject to the ProQuest Terms and Conditions of use.
Depending on the size of the file(s) you are downloading, the system may take some time to download them. Please be