Interaction of vanadium(IV,V) coordination complexes with proteins

One of the most interesting applications of vanadium coordination compounds is their development as promising metallodrugs in the treatment of several diseases, such as diabetes and cancer.1 However, their mechanism of action and the active oxidation state in the organism remain unclear and biospeciation has not been completely ascertained.2 Once administrated, the metallodrug can undergo various biotransformations before reaching the target site (i.e. ligand exchange, complexation, redox reactions); in this context, the interaction with proteins plays a central role both for their large concentration in the biological environment and the high affinity toward specific metals.3 Cytochrome c (Cyt) is a small heme protein which has an important biological function since it is involved in the electron transport chain in mitochondria and play a crucial role in the apoptosis pathway.4 In this work, the interaction with Cyt of some V(IV) and V(V) coordination complexes with potential pharmacological activity, such as those formed by pyranones (i.e. maltol) and pyridinones (i.e. deferiprone) ligands, has been studied through the combined application of EPR (Electron Paramagnetic Resonance) and UV-Vis spectroscopy, ESI-MS (ElectroSpray Ionization - Mass Spectrometry), and computational (docking and DFT) methods.5 EPR helps to distinguish the type of amino acid residues involved in the coordination (Asp/Glu or His) and, together with UV-Vis studies, the variation in the oxidation state of the metal; ESI-MS allows the determination of stoichiometry of the V-protein adducts, and computational calculations predict the specific residues which can interact with V and provide the 3D structure of the binding site (see Figure, taken from ref. 5). In particular, the possibility of an electron transfer between Cyt and vanadium compounds with different geometry and stability has been investigated to understand if redox processes may occur in physiological conditions. References 1. Rehder, D. Future Med. Chem. 2016, 8, 325-338 2. Costa Pessoa, J.; Correia, I. Inorganics 2021, 9, 17 3. Ugone, V.; Sanna, D.; Sciortino, G.; Crans, D. C.; Garribba, E. Inorg. Chem. 2020, 59, 9739-9755 4. Jiang, X. Wang, X. Annu. Rev. Biochem. 2004, 73, 87-106 5. Ugone, V.; Pisanu, D.; Garribba, E. J. Inorg. Biochem. 2022, 234, 111876