pKa Estimation of Ruthenium(II)−Arene PTA Complexes and their Hydrolysis Products via a DFT/Continuum Electrostatics Approach

A combined density functional theory/continuum electrostatics approach has been used to estimate the p K a values of a series of metal-based compounds and their hydrolysis products. Specifically, the protonation states and absolute p K a values of the complexes [M(η 6 -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, H 2 O, OH, guanine; pta = 1,3,5-triaza-7-phosphaadamantane) have been investigated by this approach and supplemented with experimental p K a determinations using 31 P NMR spectroscopy. Compounds of this type have been recently used as anticancer agents and also to catalyze CO 2 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(η 6 -benzene)Cl(OH 2 )(pta)] + . The applied computational scheme predicts that p K a tuning can be done most effectively by modifications of the arene ligand.