Aspects Of The Chemistry Of Iron Complexes Showing DNA Photo-cleavage Activity

Abstract

The present thesis deals with different aspects of the chemistry of iron complexes, their interaction with DNA and photo-induced cleavage of double-stranded DNA. Chapter I presents a general introduction on metal-based drugs in cancer therapy and the evolution of the transition metal complexes capable of targeting DNA leading to DNA strand scission, emphasizing particularly the photo-induced DNA cleavage activities for their potential utility in PDT. The mechanistic pathways associated with the DNA cleavage are discussed citing selected examples of compounds that are known to be efficient DNA photo-cleavers on irradiation with light of different wavelengths. Objective of the present investigation is dealt in this chapter. Chapter II deals with the synthesis, crystal structure, DNA binding and oxidative DNA cleavage activity of ternary iron(II) complexes of phenanthroline bases to explore the chemistry of iron(II) complexes towards the metal-assisted photo-induced DNA cleavage activity. Chapter III presents the synthesis and characterization of a cationic imidazo[1,5-a]pyridine derivative to explore the role of imidazopyridine moiety in the photo-induced DNA cleavage activity of the compound. Its cytotoxic effect to the HeLa cancer cell has also been studied using UV-A light of 365 nm. Chapter IV presents the synthesis and characterization of dipyridoquinoxaline (dpq) complexes of bivalent 3d-metal ions such as d6-iron(II), d7-cobalt(II), d8-nickel(II), d9-copper(II) and d10-zinc(II) to explore any specific role that is played by the transition-metal ions in exhibiting visible light-induced DNA cleavage activity. Chapter V deals with the synthesis, characterization of oxo-bridged diiron(III) complexes of phenanthrolne bases having a structural motif found in many iron-containing metalloproteins with a diiron core in the active site. DNA binding and photo-induced DNA cleavage activity of the complexes is studied. Finally, Chapter VI deals with the synthesis and characterization of oxo-bridged diiron(III) complexes having L-histidine (L-his) and N,N-donor heterocyclic bases. This chapter describes the double-strand DNA cleavage activity of [{Fe(L-his)(dpq)}2(μ-O)](ClO4)2. Rationalization of the DNA double strand break (dsb) has been made using molecular docking calculations. This chapter also deals with the site-specific protein (bovine serum albumin, BSA) cleavage activity of the complexes on UV-A light irradiation. The references have been compiled at the end of each chapter and indicated as superscript numbers in the text. The complexes presented in this thesis are represented by bold-faced numbers. Crystallographic data of the complexes, characterized structurally by single crystal X-ray crystallography, are given in CIF format in the enclosed CD (Appendix-I). Due acknowledgements have been made wherever the work described is based on the findings of other investigators. Any omission that might have happened due to oversight or mistake is regretted.