Theoretical analysis of reactive intermediates and their consequent damages in DNA

Abstract

The DNA damages are caused sometime due to the generation of reactive intermediates under various conditions and also sometime during anticancer actions. Analysis of various reactive intermediates for understanding DAN damage may be essential to control the adverse effects of anticancer drugs and the result can be used for developing new anti cancer drugs with low cytotoxic effect. The thesis consists of eleven chapters, covering the analysis of energetics, geometries and DNA fragmentation pattern etc of different intermediates. Each chapter explains the objective of the work with the conclusion on the results of investigation. Chapter 1 The chapter discusses the general introduction on the projected research work such as the conditions of generating radicals and subsequent DNA fragmentation pathway. The possible secondary reactions are also highlighted. Under different environmental conditions, there are several free radicals detected in DNA, particularly on various sites of nucleobases and deoxyribose groups. The generation of those radicals in biological system due to ionization radiation has been known. During anticancer drug action, the strong binding of DNA by drug might be another reason of forming these radicals. Intranucleotidal and internucleotidal hydrogen abstraction has considered as another possible pathway of forming free radical. Chapter 2 The chapter explains different methodologies used to investigate the reactive intermediates. The applicability of different level of theories in the systems is thoroughly discussed. The importance of basis set and electron densities for obtaining the accurate result are explained. The uses of ab initio and DFT level of theories into particular molecular system are illustrated and the limitations of MP2 level of calculation based on molecular size are shown. Chapter 3 Initially the formation of sugar (deoxyribose) radicals in the nucleotide has been investigated. The studies on the energetics of sugar radicals in the nucleotides are reported in this chapter. The...