p<i>K</i>_a Estimation of Ruthenium(II)−Arene PTA Complexes and their Hydrolysis Products via a DFT/Continuum Electrostatics Approach

Abstract

A combined density functional theory/continuum electrostatics approach has been used to estimate the pKa values of a series of metal-based compounds and their hydrolysis products. Specifically, the protonation states and absolute pKa values of the complexes [M(η6-arene)(X)(Y)(pta)]n+ (M = Ru or Os; arene = benzene, p-cymene, 1,3,5-trifluorobenzene, benzene-1,3,5-triamine; X, Y = halide, H2O, OH, guanine; pta = 1,3,5-triaza-7-phosphaadamantane) have been investigated by this approach and supplemented with experimental pKa determinations using 31P NMR spectroscopy. Compounds of this type have been recently used as anticancer agents and also to catalyze CO2 reduction. Our calculations show that pta binding to a ruthenium center significantly reduces the basicity of the ligand. The experimentally observed pH-dependent DNA binding is rationalized by the hydroxo/aqua ligand equilibrium in [Ru(η6-benzene)Cl(OH2)(pta)]+. The applied computational scheme predicts that pKa tuning can be done most effectively by modifications of the arene ligand.