Molecular Design and Synthesis of d- (V and Ni) and p- (Sn) block Metal Complexes with Dibasic Ligands: Biological, and Catalytic Relevance

Abstract

The magnificent roles of cisplatin as a DNA-reactive therapeutic and gadolinium complexes as MRI diagnostics enthused the progress of metal-based therapeutics or diagnostic agents in the modern era. In such inorganic pharmaceuticals or probes, coordination chemistry in the biological environment or at the target site reclines at the heart of their modes of action. Therefore, molecular designing of new metal-based drugs or imaging probes by tuning the coordination environments, provides the opening in the alteration and improvement of such agents, thus raising metal-based compounds as promising pharmacological candidates. Keeping the importance of metal complexes in the biological aspect, this dissertation deliberately outlines the molecular design, synthetic methodology, characterization, and thorough investigation of the chemical properties of the transition metals (V, and Ni) and main group metal (Sn) complexes containing a variety of ONNO, and ONO donating salan, unsymmetrical-salen, aroylhydrazone, and Schiff base ligands with preference to their pharmacological activity. Characterization of all the new compounds has been done through numerous physicochemical (elemental analysis), spectroscopic (UV-vis, IR, and NMR), and spectrometric (ESI‒MS/ HR-ESI-MS) techniques. Solid-state structures of the complexes have been determined through single-crystal X-ray diffraction analysis. The photophysical characterization of some of the complexes has also been examined through UV-vis and fluorescence spectroscopy. The solution behavior of complexes in aqueous or biological media has been checked before studying them for any biological assay, in order to comprehend their transformation, interconversion, variations in coordination geometry, and change in nuclearity taking place, if there is any, in the solution phase. This will ultimately help to find out the actual species responsible for the overall observed biological activities. Furthermore, a detailed biological study of these complexes has been done by evaluating their interaction with biomolecules such as CT-DNA and proteins (HSA and BSA) by using various spectroscopic techniques like UV-vis, fluorescence, and circular dichroism. Also, the in vitro cytotoxicity potential of the synthesized complexes has been assessed against various cancer [human lung carcinoma (A549), human cervical cancer (HeLa), human breast adenocarcinoma, (MCF-7), and human colorectal adenocarcinoma (HT-29)], and noncancerous cell lines [mouse embryonic fibroblast cell line (NIH-3T3)]. In addition, for highly toxic compounds, the mechanism of cell death has been evaluated by following various traditional procedures well-established in the literature i.e., DAPI nuclear staining, AO/EB staining, cell cycle analysis, Annexin V/PI double staining apoptotic assay, cellular uptake analysis through confocal and flow cytometer, ROS generation, etc. On the other hand, fluorescent active and low-toxic compounds have been studied for bioimaging applications. For this application, their photostability has been checked and live cell confocal images have been taken to find out their specific localization in cellular organelles. From the overall studies, the test compounds are found to be a good binder with DNA and proteins. Also, based on the ligand environments, the role of the chosen metal, cellular uptake capacity, lipophilicity, and cytotoxicity, the synthesized complexes are defined as better cytotoxic agents for killing cancer cells or bioimaging probes for effectively tracking cellular organelles. The obtained results herein showed parallel, or in some cases even better in vitro cytotoxicity in contrast to many clinically testified chemotherapeutic drugs and some of the complexes might be used as an equal or better organelle tracking agent as compared to commercially available organelle trackers. Apart from this, considering the high catalytic importance of Ni and salen ligands, here some Ni(II)-unsymmetricalsalen complexes have been studied as catalysts for the synthesis of 2-amino-3-cyano-4H-pyrans derivatives through multicomponent reactions.