The mechanism of the formation of dinuclear platinum(II) mu-hydroxo complexes from cisplatin hydrolysis products, their interconversion, decomposition, and reactions with biomolecules has been explored using a combined DFT/CDM approach. All activation barriers for the formation of [cis-{Pt(NH3)(2)(X)}-(mu-OH)-cis-{Pt(NH3)(2)(Y)}](n+) (X, Y = Cl, OH2, OH) via nucleophilic attack of a hydroxo complex on an aqua complex are lower than the activation barriers for cisplatin hydrolysis. Considering therapeutic Pt(II) concentrations in tumors, however, only the reaction between two molecules of cis-[Pt(NH3)(2)(OH2)(OH)](+) (E) yielding [cis-{Pt(NH3)(2)(OH2)}-(mu-OH)-cis-{Pt(NH3)(2)(OH)}](2+) (5) remains kinetically superior to cisplatin hydrolysis. 5 is strongly stabilized by intramolecular hydrogen bonding between the terminal aqua and hydroxo ligands, resulting in an unusually high pK(a) of 5 and a low pKa of its conjugate acid. Unimolecular cyclization of 5 yields the dimers [cis-{Pt(NH3)(2)}(mu-OH)](2)(2+) (7a with antiperiplanar OH groups and 7b with synperiplanar OH groups). The electronic structure of several diplatinum(II) complexes has been analyzed to clarify whether there are metal-metal interactions. The overall reactivity to guanine (Gua) and dimethyl sulfide (Met, representing the thioether functional group of methionine) increases in the order 5 < 7a approximate to 7b < mononuclear complexes, whereas the kinetic selectivity to Gua relative to Met increases in the order 7 approximate to 5 < 7b approximate to monocationic mononuclear complexes < dicationic mononuclear complex. The results of this work (i) help assess whether dinuclear metabolites play a role in cisplatin chemotherapy, (ii) elucidate the toxicity and pharmacological inactivity of [cis-{Pt(NH3)(2)}(mu-OH)](2)(2+), and (iii) suggest future investigations of dinuclear anticancer complexes that contain one mu-hydroxo ligand.