Interaction of vanadium compounds with Cytochrome c

One of the most interesting application of vanadium compounds is their development as promising metallodrugs in the treatment of several diseases, such as diabetes and cancer. However, their mechanism of action and the active oxidation state in the organism remain unclear and biospeciation has not been completely ascertained. 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. 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. In this work, the interaction with Cyt of some V(IV) and V(V) coordination complexes with potential pharmacological activity, with composition [VIVOL2] or [VVO2L2]-, such as those formed by pyranones (i.e. maltol), pyridinones (i.e. deferiprone), acetylacetone and quinolone 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. 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. Preliminary data indicate that the binding of VIVO-L and VVO2-L moieties is possible and both covalent and non-covalent interactions occur.