The prime objectives of contrast agents in Magnetic Resonance Imaging(MRI) is to accelerate the relaxation rate of the solvent water protons in the surrounding tissue. Paramagnetic relaxation originates from dipole-dipole interactions between the nuclear spins and the fluctuating magnetic field induced by unpaired electrons. Currently Gadolinium(III) chelates are the most widely used contrast agents in MRI, and therefore it is incumbent to extend the fundamental theoretical understanding of parameters that drive the relaxation mechanism in these complexes. Traditionally the Solomon-Bloembergen-Morgan equations have been utilized to describe relaxation times in terms, primarily of the Zeeman interaction, which is the splitting of degenerate energy levels due to an applied magnetic field. However, in compounds such as Gadolinium(III) complexes with total electron spins higher than 1 (in this case S=7/2) other interactions such as the Zero-Field Splitting(ZFS) play a significant role. ZFS is the splitting of degenerate energy levels in the absence of an external magnetic field. For this purpose, the current research delves into an understanding of the relaxation process, focusing on ZFS in various complexes of interest, using quantum chemical methods as well as molecular dynamic simulations.

This thesis work deals with different aspects of the chemistry of La(III) and Gd(III) complexes, their interaction with DNA and proteins, photo-induced cleavage of double-stranded DNA, photocytotoxic effect on cancer cells, cell death mechanism and cellular localization behaviour. Chapter I gives an introduction to the metal-based anticancer agents with special emphasis on clinically used drugs and the growing field of lanthanide therapeutics. An overview of the current strategies of cancer treatment, especially photodynamic therapy (PDT), is presented. Mode of small molecule-DNA interactions and the mechanistic aspects associated with DNA photodamage reactions and PDT effect are discussed with selected examples of compounds that are known to photocleave DNA on exposure to light of different wavelengths. A brief discussion on the various therapeutic applications of the lanthanide compounds is also made. Chapter II presents the synthesis, characterization, DNA binding, BSA binding, photo-induced DNA cleavage activity and photocytotoxicity of La(III) and Gd(III) complexes of phenanthroline bases to explore the UV-A light-induced DNA cleavage activity and photocytotoxicity of the complexes. Chapter III describes the synthesis, characterization, DNA binding, photo-induced DNA cleavage activity and photocytotoxicity of La(III) and Gd(III) complexes of phenanthroline bases with an aim to improve the design of the complexes to achieve better solution stability and DNA binding of the complexes. Chapter IV presents the synthesis, characterization, DNA binding, and UV-A light-induced DNA photocleavage activity and photocytotoxicity of La(III) and Gd(III) complexes of pyridyl phenanthroline bases with an objective to improve the photoactivity of the complexes by introducing an additional pyridyl group. Cell death mechanism and confocal microscopic studies are also carried out to gain more insight into the PDT effect caused by light in the presence of the complex. Chapter V describes the synthesis and characterization of La(III) and Gd(III) complexes of terpyridine bases and acetylacetonate to study the complexes as a new class of photosensitizers to explore their DNA photocleavage activity and photocytotoxicity in HeLa cells. Effect of attaching a glucose moiety to the acetyl acetone (Hacac) ligand has been studied. The cellular uptake behaviour of the La(III) pyrenyl-terpyridine complexes has also been investigated. Finally, Chapter VI presents the synthesis and characterization of curcumin and glycosylated curcumin La(III) and Gd(III) complexes having terpyridine base with an objective to study the photoactivated anticancer activity of the complexes in visible light. This chapter describes the visible light-induced DNA cleavage activity and photocytotoxicity of the complexes by exploiting curcumin and glycosylated curcumin as the photosensitizer ligands. Study on the cellular uptake behavior of curcumin La(III) complexes having pyrenyl terpyridine ligand is also presented. The references have been assembled 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 which are characterized structurally by single crystal X-ray crystallography are provided 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 unintentional omission that might have happened due to oversight or mistake is sincerely regretted.