UBC Theses and Dissertations
Hydrogen atom transfer reactions and the effects of non-redox active metal cations van Santen, Jeffrey A.
Hydrogen atom transfer (HAT) reactions are a fundamental step in many biological processes, but can initiate the free-radical induced oxidation of cellular components. Although HAT reactions appear fundamentally elementary, there are many poorly understood factors that influence HAT. In this thesis, three aspects of HAT reactivity are investigated using quantum chemical techniques. First, the importance of pre-reaction complex formation in considering the kinetics of HAT reactions were investigated. For a set of nearly-thermoneutral HAT reactions involving oxygen-centred radicals, the relationship between pre-reaction complex non-covalent binding energies and Arrhenius pre-exponential factors (A-factors) was investigated. It is demonstrated that for HAT reactions that take place through similar mechanisms, there is a strong correlation between pre-reaction complex binding energies and A-factors. This suggests that non-covalent interactions may directly affect the kinetics of certain HAT reactions. Next, the relationship between bond dissociation energies (BDEs) and reaction rates for abstraction of a hydrogen from a C-H bond by the CumO radical are investigated in the context of the Bell-Evans-Polanyi (BEP) principle. The applicability of the BEP principle is examined by exploring a hypothesis: If the BEP principle is a valid linear free-energy relationship, there should exist two linear relationships for BDE against the logarithm of HAT rate constant, one for incipient radicals that are allylic or benzylic, and one for alkyl radicals. It is demonstrated that there is a reasonably strong correlation for allylic/benzylic C-H bonds, but not for alkyl ones. The BEP principle should not be used for quantitative prediction, but remains useful as a conceptual framework. Finally, the effect of non-redox active metal cations on HAT reactions involving small models for proteins and oxygen-centred radicals is studied. Previous experimental evidence demonstrated that Lewis acid-base interactions between metal cations and substrates can inhibit HAT reactions, and that the cations may serve as a form of chemo-protection in biological systems. The results herein demonstrate that metal-substrate interactions can deactivate certain C-H bonds. Metal-radical interactions may promote HAT reactions. On the basis of these limited results, non-redox active metal cations might not act as natural chemo-protective agents.
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