Metal complexes of environmental and biological interest

This work reports on the research activities that I’ve carried out during these three years, which covered the following topics: i) Fluorescent probes for environmental and biological applications; ii) Bioactive ligands and metal complexes. As regards the first research line (Part 1 of the present work) I’ve prepared a series substituted derivatives of 3-(pyridin-2-yl)coumarin and evaluated their potential application as fluorescent chemosensors for the recognition and quantitation of environmentally and biologically relevant analytes. Interestingly, I’ve found out how these compounds show a “ratiometric” and “turn-on” fluorescent behaviour towards Fe(III), a paramagnetic metal ion that usually quenches the fluorescence of organic molecules. The most promising ligand of the series shows selectivity towards this metal ion, with a limit of detection in the micromolar concentration range and a fluorescent response that has been observed both in solution and on cellulose paper strip. These results suggest a potential application of this chemosensor for the determination of Fe(III) in liquid samples. As regards the second research line (Part 2 of this PhD thesis), I’ve designed, synthesized, and characterized a series of ternary Cu(II) bis-phenanthroline complexes bearing different classes of organic auxiliary ligands, (e.g., imidazolidine-2-thiones, coumarin-based oxylacetic acids, ER-stress modulators) with the aim of obtaining novel potential anticancer metallodrugs that might overcome currently approved Pt(II)-based chemotherapeutics. These studies were carried out in collaboration with Prof. Vanhara’s Group, Masaryk University, Brno (CZ). These complexes show high anticancer potency (at micromolar/sub-micromolar) level in-vitro on different cancer cell lines. Interestingly, these compounds induce cell death by activating the pro-apoptotic branch of the Unfolded Protein Response (UPR), a signalling pathway that is activated in cells that undergo to a prolonged or severe condition of Endoplasmic Reticulum (ER) stress. I’ve also prepared a series of hydroxylated derivatives of 3-(pyridin-2-yl)coumarin and evaluated their antioxidant and inhibitory activity towards lipoxygenases, a class of enzymes that are commonly known to be involved in the pathogenesis of several inflammatory disorders and cancers. These compounds have proved to possess potent lipoxygenase inhibitory activity, with tuneable antioxidant properties according to the number and relative position of the hydroxyl groups in the coumarinic backbone. In addition, I’ve evaluated the potential sites of absorption and distribution properties of these molecules by merging the protonation constants, determined experimentally, with selected in-silico molecular descriptors. Finally, I’ll report on the preliminary data regarding the antioxidant and anti-tyrosinase activity of a panel of thiosemicarbazones of 3-acetylcoumarin that I’ve prepared and characterized (in collaboration with Prof. Fais’s Group, University of Cagliari). These compounds show promising anti-tyrosinase activity, with variable antioxidant properties according to the substituents in the coumarinic skeleton.