title: Theoretical calculations of stability constants and pKa values of metal complexes in solution: application to pyridoxamine-copper(II) complexes and their biological implications in AGE inhibition.
abstract: Accurate prediction of thermodynamic constants of chemical reactions in solution is one of the current challenges in computational chemistry. We report a scheme for predicting stability constants (log β) and pKa values of metal complexes in solution by means of calculating free energies of ligand- and proton-exchange reactions using Density Functional Theory calculations in combination with a continuum solvent model. The accuracy of the predicted log β and pKa values (mean absolute deviations of 1.4 and 0.2 units respectively) is equivalent to the experimental uncertainties. This theoretical methodology provides direct knowledge of log β and pKa values of major and minor species, so it is of potential use in combination with experimental techniques to obtain a detailed description of the microscopic equilibria. In particular, the proposed methodology is shown to be especially useful for obtaining the real acidity constants of those chelates where the metal-ligand coordination changes as a result of ligand deprotonation. The stability and acidity constants of pyridoxamine-Cu(2+) chelates calculated with the proposed methodology show that pyridoxamine is an efficient scavenging agent of Cu(2+) under physiological pH conditions. This is of special interest as Cu(2+) overload is involved in the formation of advanced glycation end-products (AGEs) and their associated degenerative medical conditions.
authors.affiliation: Institut d'Investigació en Ciències de la Salut (IUNICS), Departament de Química, Universitat de les Illes Balears, E-07122 Palma de Mallorca, Spain. juan.frau@uib.es.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Casasnovas
authors.forename: Joaquín
authors.initials: J
authors.lastname: Ortega-Castro
authors.forename: Josefa
authors.initials: J
authors.lastname: Donoso
authors.forename: Juan
authors.initials: J
authors.lastname: Frau
authors.forename: Francisco
authors.initials: F
authors.lastname: Muñoz
mesh_terms: D056831:Coordination Complexes / Q000737:chemistry* / Q000378:metabolism; D003300:Copper / Q000737:chemistry*; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008958:Models, Molecular; D011733:Pyridoxamine / Q000737:chemistry*
chemical_list: D056831:Coordination Complexes; D017127:Glycation End Products, Advanced; D011733:Pyridoxamine; D003300:Copper