Kinetics and mechanism of the interaction of cis-diamminediaquaplatinum(II) with organocobalamins

Abstract

The stoicheiometries and kinetics of the reactions of cis-diamminediaquaplatinum(II) with adenosylcobalamin and a series of alkylcobalamins have been examined. The reactions proceed with a 1.3 : 1 and a 1 : 1 stoicheiometry (Pt^II : cobalamin) for the interaction between cis-[Pt(NH₃)₂(OH₂)₂]²⁺ and adenosylcobalamin and the alkylcobalamins, respectively. In all cases the interactions generate the ‘base-off’ form of the organocobalamins. Our kinetic studies indicate that the reactions are first order in organocobalamin and first order in cis-[Pt(NH₃)₂(OH₂)₂]²⁺ at low concentrations of Pt^II, but that they approach zero order as the Pt^II concentration is increased. The kinetic data are interpreted in terms of a fast equilibrium between the alkylcobalamin and cis-[Pt(NH₃)₂(OH₂)₂]²⁺ followed by a rate-determining ligand exchange between N³ of the 5,6-dimethylbenzimidazole ligand and a co-ordinated H₂O of the platinum complex. The mechanism of the ‘base-on’→‘base-off’ conversion for the adenosylcobalamin–diamminediaquaplatinum(II) complex is different from that for the alkylcobalamin–diamminediaquaplatinum(II) complexes. The interaction between adenosylcobalamin and cis-[Pt(NH₃)₂(OH₂)₂]²⁺ dramatically reduces the light sensitivity of the carbon–cobalt bond. Prolonged exposure of the adenosylcobalamin–diamminediaquaplatinum(II) complex to visible light in the presence of air yields 5′-deoxy-5′-oxoadenosine as the only nucleoside product. No photolysis occurs in the absence of air. These observations suggest that even in the presence of only stoicheiometric amounts of cis-[Pt(NH₃)₂(OH₂)₂]²⁺, the platinum complex interacts with the 5′-deoxyadenosyl ligand of the coenzyme. Carbon-13 and ³¹P n.m.r. spectroscopy studies using [5′-¹³C]adenosylcobalamin show that the adenosylcobalamin–diamminediaquaplatinum(II) complex consists of at least four ‘base-off’ conformers. These ‘base-off’conformers are probably the consequence of a downward distortion of the corrin ring resulting from the interaction between the 5′-deoxyadenosyl ligand, the corrin ring, and the cis-[Pt(NH₃)₂(OH₂)₂]²⁺ ion.