Understanding the bio-activity of salicylaldehyde related complexes.

In this thesis, we studied the conformational stability of the salicylaldehyde-N,N-disubstituted semicarbazones (H2ssc) and their interaction with copper using density functional theory (DFT) method. Our results revealed that three stable conformers are available for the H2ssc and their conformers’ stability are highly sensitive to the steric hindrance of the N-substituents. Our NBO analysis revealed copper interact with H2ssc through ionic interaction and strong covalent bond interaction by n(H2ssc atom) → 4s (copper) donor acceptor interaction. The anti-cancer mechanism of action for Cu(II) complexes of H2ssc were studied through synthesis, cytotoxicity evaluation, DNA binding and DNA cleavage studies. Our results showed significant enhanced activity for Cu(II) complexes as compared to H2ssc. DNA interaction studies suggested the mechanism of action of anti-cancer activity of Cu(II) complexes involves the binding of the complexes to the DNA and their subsequent generation of hydroxyl radicals on site to cleave the DNA strands which then lead to cancer cell apoptosis. We also performed QSAR analysis on salicylaldehyde benzoylhydrazones and its copper(II) complexes to demonstrate the applicability of QSAR on metal complexes using electro-topological state atom indices and DFT-derived descriptors. Our QSAR models demonstrated high statistical qualities and provide important information about the structural requirements for the design of next generation of anti-cancer metallodrugs.Doctor of Philosophy (SCBE