Computational study of the thermochemical aspects of hydrogen atom donating antioxidants using the ab initio Hartree-Fock method

Abstract

Despite the extensive and intensive investigations so far, there are still significant gaps in our knowledge and understanding of the chemical and biological mechanisms of antioxidants. For instance, studies aimed at prevention or intervention of diseases with common exogenous antioxidants have shown mixed outcomes. In relation to this also there does not seem to be a general consensus about the actual biological mechanisms of many compounds including dietary polyphenols, which have been classically considered as antioxidants. Even somewhat surprisingly, antioxidants in general and radical scavengers in particular were never properly described in thermodynamical terms. One of the most commonly studied aspects of antioxidants is their ability to neutralize free radicals by donating electrons or hydrogen atoms. However, upon perusal of the ever-increasing literature on the subject, it would not be long before one is confronted with the fact that the thermodynamics and kinetics of hydrogen atom transfer (HAT) reactions of antioxidants are often either confused with each other or lumped together in perplexity. A detailed understanding of the chemical aspects of antioxidant molecules is deemed crucial as it may enable unravelling some of the controversies and uncertainties surrounding them. The detailed chemical knowledge of antioxidants may also serve as a foundation upon which more complex and biologically relevant predictive models could be built. With this in mind and being inspired by a couple of intriguing observations from my related previous studies, I have attempted in the present PhD study to investigate the thermochemical aspects of the HAT reactions of common antioxidant molecules using quantum molecular computations. In summary, the thermodynamic basis of the radical scavenging activities of antioxidants was shown to be their abilities to donate two hydrogen atoms with relative enthalpy changes below 104.206 kcal mol1. The important kinetic parameters BDE and BDFE were reliably estimated as the relative energy changes accompanying the formation of suitable DSs. Depending on the class of compounds, DSs were proposed to be electronically and/or vibrationally excited species. Moreover, ab initio UHF method was shown to be remarkably adequate for the study of HAT reactions of antioxidants. The above findings may warrant further investigation as they may not only contribute to our general understanding of antioxidants but also have far-reaching implications on several fundamental aspects of antioxidants' HAT reactions and the computational tools recommended for their study. Furthermore, the findings of this PhD study can form the basis for robust and inclusive quantitative structure-activity relationships of antioxidants.

Date of Award	2014
Original language	English