A combined d. functional theory/continuum electrostatics approach was used to est. the pKa values of metal-based compds. and their hydrolysis products. Specifically, the protonation states and abs. pKa values of [M(h6-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) were studied by this approach and supplemented with exptl. pKa detns. using 31P NMR spectroscopy. Compds. of this type were recently used as anticancer agents and also to catalyze CO2 redn. The calcns. show that pta binding to a Ru center significantly reduces the basicity of the ligand. The exptl. obsd. pH-dependent DNA binding is rationalized by the hydroxo/aqua ligand equil. in [Ru(h6-benzene)Cl(OH2)(pta)]+. The applied computational scheme predicts that pKa tuning can be done most effectively by modifications of the arene ligand.