Geometric analyses of three mylonite zones, including two metamorphic-core-complex SC-mylonite zones, show that the mylonitic foliation surfaces (S-surfaces) are consistently discordant to the margins of the shear zones. Finite-strain analyses show that the foliation surfaces in each zone are consistently oriented parallel to the XY-plane of the finite strain ellipsoid. The shear bands within the mylonites (C-surfaces, C'-surfaces, extensional crenulations, and shear-band cleavages) are uniformly oriented subparallel to the margins of the shear zones. The finite lengths and discontinuous natures of the shear bands require that the displacement along them be accommodated by the S-surfaces at the tips of the shear bands. Thus the S-surface elongations and orientations represent the total bulk rock strain, rather than some minimum measure of inter-C-surface strain. General stress and strain considerations indicate that the shear bands are planes of maximum shear stress, and that they are not only simple-shear slip planes. This interpretation implies that in simple-shear deformation, a single, irrotational set of shear bands will develop parallel to the shear-zone boundaries. In deformations involving significant components of coaxial strain, however, shear bands may develop in other orientations or in conjugate sets and rotate with progressive deformation.

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The overexpression and phosphorylation of the wild type Anaplastic Lymphoma Kinase (ALK) receptor in neuroblastoma has been associated with a worse prognosis for patients suffering from high risk neuroblastoma. Recent evidence has shown that truncated forms of the ALK receptor may be capable of promoting downstream pathways associated with ALK activation and increased cellular proliferation. ALK has been shown to cleave into 220kDa and 140kDa bands in vivo, but the exact location of the cleavage site within the ALK protein has not yet been characterized. By generating amino acid substitutions around the putative cleavage site of ALK, we sought to determine if we could inhibit ALK cleavage. We were able to significantly inhibit cleavage through substitutions in amino acids L655 and F656 surrounding our predicted cleavage site. These amino acids may potentially play a critical role in enzymatic identification of the ALK cleavage site and mediating ALK cleavage. Future studies are necessary in order to determine if ALK constructs with three amino acid substitutions around the cleavage site will show complete ALK cleavage inhibition and determine the relationship between ALK cleavage and activation of downstream pathways.

Selective ester bond cleavage using lithium and zinc halides was attempted in a select group of phospholipids, namely phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylserine (PS). Several reaction parameters including catalyst (lithium chloride, lithium bromide, lithium iodide, zinc chloride, zinc bromide and zinc iodide), reaction temperature (21, 30, 50 and 60 oC), and reaction time (2 and 4 hours) were varied and the effects on cleavage studied. Reacted phospholipid samples were characterized by attenuated total reflectance (ATR) and transmission FTIR spectroscopy. The FTIR spectra of pure (unreacted) and reacted PC, PE and PE were analyzed qualitatively and quantitatively (Peak Height Ratio). The appearance of asymmetric carboxylate anion stretch (1577 cm-1) and symmetric phosphonyl dianion stretch (1006 cm-1) in the reacted phospholipid spectra reveals cleavage of ester bonds in carbonyl and phosphonyl. Reaction temperature and time did not significantly influence the cleavage results over the temperature and time range tested.

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.

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