Investigation of Biological and Magnetic Properties of Vanadium(IV/V) and Cobalt(II) Complexes Incorporating Mono and Dibasic Ligands

Abstract

Transition metals play a significant role in bio-inorganic chemistry. Transition metals can interact with several molecules that are negatively charged and display various oxidation states. Because of this activity, transition metal-based medicines have recently been developed and are being explored as good candidates for pharmacological and therapeutic uses. Among the transition metals, vanadium complexes have shown promising candidates as an alternative for the treatment of cancer. It is because these complexes exhibit a wide range of chemical properties and structures, which allows for the design of specific complexes tailored to target specific cancer cells. This versatility can potentially lead to more effective and targeted cancer therapies. Furthermore, targeting these particular metal ions is also justified by the fact that they are less toxic, and their toxicity can be further decreased when combined with ligands. Even though there are several ligands available, the chosen arylazo, aroylhydrazone, Schiff base, and N-heterocycles (1,10- phenanthroline, bipyridine) each offer a distinct advantage that is very helpful in designing an ideal drug. Additionally, the N-heterocycles' role as ligands alters the environment of the complex in a way that promotes their lipophilicity, which is a crucial aspect of drug design. Therefore, the emphasis of this dissertation is mostly on the study of a few pharmacological actions of the more accessible and less expensive first-row transition metal V(IV/V) complexes. To assess the biological activity of complexes, various analytical techniques are used to study the interactions of complexes with CT-DNA and a variety of proteins (HSA, BSA, and lysozyme). The findings of the investigations indicated that the test complexes were good DNA and protein binders. Additionally, the in vitro antiproliferative activity of the synthesized complexes were investigated against different cancer [human cervical cancer (HeLa), human colorectal adenocarcinoma (HT-29)], and noncancerous cell lines [human epidermal keratinocyte cells (HaCaT) and mouse embryonic fibroblast cell line (NIH-3T3)]. The complexes examined here showed noticeable in vitro cytotoxicity when compared to numerous clinically reported chemotherapeutic drugs which could provide the basis for the design of potentially effective target-specific drugs for the treatment of cancer. In addition to the pharmacological activity, the temperature-dependent magnetic susceptibility of di-nuclear oxidovanadium(IV) and mono-nuclear cobalt(II) complexes have been investigated to understand the structural influence on magnetic behavior. Further, I have explored their solid and solution state EPR spectra, FD-FT THz-EPR spectra, magnetization, dynamic magnetic behavior, slow magnetic relaxation behavior, and ab initio computational studies. For di-nuclear oxidovanadium(IV) complexes the temperature-dependent magnetic susceptibility measurements of 1 and 2 revealed the exchange between the two vanadium centres to be weak and antiferromagnetic. Theoretical calculations of 1 and 2 were carried out using broken-symmetry DFT, which shows good agreement with the experimental results. For cobalt(II) complexes the magnetic susceptibility and FD-FT THz-EPR measurements together with ab initio calculations reveal an easy-axis type of anisotropy for both 1 and 2, with a spin-reversal barrier of 58.9 and 60.5 cm–1 , respectively. For both compounds, frequency-dependent ac susceptibility measurements show an out-of-phase susceptibility under applied static fields of 40 and 100 mT, which can be analyzed in terms of Orbach and Raman processes within the observed temperature range. Finally, a detail of the structural influence on magnetic studies has also been discussed in detail. Keeping all these things in mind, in this dissertation the chemistry of a wide variety of new versatile oxido/dioxido vanadium(IV/V), dinuclear oxidovanadium(IV), and mononuclear cobalt(II) complexes of some bidentate uni-negative ON and tridentate bi-negative ONO donor arylazo, aroyl hydrazone, and Schiff base as main and an ancillary ligand (bipy and phen) as co-ligand are reported, with special emphasis on their solution behavior, pharmacological activity, and magnetic studies. A variety of physicochemical techniques, including elemental analysis (CHNS), spectroscopic (UV-vis, IR, NMR, and EPR), spectrometric (ESI-MS), and electrochemical (cyclic voltammetry), have been used to characterize all the synthesized ligands and their corresponding metal complexes. The structure of all the complexes was further confirmed by single-crystal X-ray diffraction analysis. Molecular structure and spectroscopic characteristics like EPR and magnetic data of some of the aforesaid compounds were simulated using DFT (density functional theory) methods to obtain more information. In summary, these findings have helped us to figure out the active species that are responsible for cytotoxic activity, which often remains elusive. The limited understanding of the active species' identification is an important aspect of the progress of clinical studies with vanadium-based drugs and industrial experimentation. So, these findings of the current investigation on the capabilities of recently synthesized vanadium(IV/V) complexes serve as a source of motivation for us to persist in the advancement of metal-based compounds for anti-cancer research. Further, the knowledge acquired from the examination of the magnetic properties of vanadium and cobalt complexes serves as a basis for visualizing a prospective scenario in which these elements assume a crucial function in the advancement of medical science. The range of prospective applications encompasses a wide spectrum, ranging from enhanced imaging diagnostics to novel cancer therapies and tailored drug delivery systems. This approach must take into consideration both the magnetic characteristics of the complexes as well as their interactions with biological systems.