022-0222148-2822 Transition Metal Complexes with Bioligands: Modelling and Interaction


Principal Investigator: Jasmina Sabolović

Low-molecular-weight transition metal complexes with amino acids, peptides and proteins are supposed to be a part of exchangeable physiological pool for the storage and transport of essential metals for most tissues in living organisms. The binding affinity between a metal and a ligand affects the biological, chemical and toxicological properties of the metal. Redox potential, the metal-ligand bonding reversibility, ionic species distribution and stability constants in solutions can be measured by voltammetry, whereas the structural properties can be predicted and reproduced with theoretical molecular modelling methods. The Cu(II) complexes with Gly, Ala, Val, Leu, Ile show two-electron and quasi-reversible redox electrochemical behaviour in aqueous solution under physiological conditions. The changes between the vacuum geometries (calculated using quantum chemical methods) and experimental X-ray crystalline geometries of 7 Cu(II) amino acid complexes were revealed and attributed to the ligand-based strain and crystal lattice effects. These geometry changes can be simulated with our original molecular mechanics (MM) model and force field (named FFW) developed to reliably reproduce the experimental crystal and ab initio vacuum structures by geometry optimisation of a molecule in simulated crystalline surroundings and as an isolated system, respectively. By now FFW has been parametrised for bis-Cu(II) complexes with Gly, Ala, Val, Leu, Ile and their alkyl derivatives. The project goals are to gain new experimental and theoretical evidence of the physico-chemical properties of essential Cu and Zn and toxic Pb and Cd metal complexes with bioligands (amino acids, peptides) using theoretical methods (MM, molecular dynamics, quantum chemistry) and experimental methods (voltammetry, X-ray diffraction), and to predict and simulate the complexes’ properties in crystal, vacuum, and solution. Method development and the interplay of the experimental and theoretical results will contribute to the understanding of the metal-bioligand interactions and properties in different physico-chemical conditions. We expect that FFW enlarged with new empirical parameters for the Cu(II) and Zn(II) amino acidates will reliably predict the complexes” properties in a solution. The force field efficacy will be validated by the ability to reproduce experimental results. The proposed studies may lead to get new drugs for prevention of disturbed transition-metal metabolism effects in vivo.