Thermodynamic study of first-row transition metal ions complexes of biomedical interests

First-row transition metal ions are often regarded as essential, or nearly essential, for life. Both deficiency and excess of these metals are associated with pathological conditions. Owing to their biological relevance, complexes of first-row transition metals have attracted considerable interest as potential therapeutic agents, either as alternatives to more toxic and less selective metal-based drugs (e.g., platinum-based compounds) or as platforms for novel targeting strategies. The biological behaviour of these metals is strictly related to their chemical form and oxidation state, as metal ions are typically bound to natural or synthetic ligands. Metal–ligand interactions profoundly modify the chemical properties of both partners and play a key role in metal transport, bioavailability, and sequestration, ultimately modulating the involvement of metal ions in biological processes. The chemistry of first-row transition metals in biological media is governed by complex equilibria involving protonation, coordination, and redox processes, which are strongly influenced by solution conditions. Understanding these phenomena is therefore essential for rationalizing the behaviour of metal-based systems in analytical and bioinorganic chemistry. This thesis is devoted to the investigation of first-row transition metal–ligand systems in solution, with particular emphasis on vanadium(IV/V), copper(II), and zinc(II) complexes formed with oxygen- and nitrogen-donor ligands of biological and chemical relevance. The main objective is to elucidate the speciation, stability, structural features, and electronic properties of these systems under controlled experimental conditions, employing a multi-technique approach. An integrated analytical strategy combining electrochemical and spectroscopic techniques was adopted to correlate thermodynamic data with structural and electronic information. The ligands considered belong to the classes of 8-hydroxyquinolines and o-diphenols. 8- Hydroxyquinolin-2-carboxylic acid and 2-aminomethylquinolin-8-ol were selected as representative derivatives, featuring different functionalization at the 2-position and enabling potential tridentate coordination. The solution speciation of vanadium(IV/V) and copper(II) complexes with 8- hydroxyquinolin-2-carboxylic acid, as well as copper(II) complexes with 2-aminomethylquinolin-8- ol, is described together with a multi-technique characterization of the formed species. Preliminary results on iron(III) systems are also reported, confirming the relevant coordination capability of this ligand. Comparison with literature data highlights the role of the additional donor atom, which depends strongly on the nature of the metal ion. Several o-diphenolic compounds and related ligands were also investigated in combination with metal ions characterized by different redox properties. These ligands act not only as chelators but also as redox non-innocent ligands, potentially displaying antioxidant or pro-oxidant behaviour. The chemical speciation of vanadium(IV/V), copper(II), and zinc(II) in the presence of o-diphenols, such Abstract 9 as 6,7-dihydroxycoumarin and ethyl-3,4-dihydroxybenzoate, was systematically studied. Particular attention was devoted to the redox properties of these systems, which were found to be strongly dependent on the nature of the metal ion. Overall, this work provides detailed insights into the solution chemistry of vanadium, copper, and zinc complexes, emphasizing the central role of ligand design, redox activity, and solution effects in governing metal–ligand interactions. The results demonstrate the effectiveness of combining equilibrium analysis with spectroscopic techniques for the investigation of complex metal-based systems