Kinetico-mechanistic study on the reduction/complexation sequence of PtIV/PtII organometallic complexes by thiol-containing biological molecules

Abstract

The kinetics of the reaction of [PtIV(4X-Cph,N,N')Cl(Y)2] complexes (2-X-Y) (X=Cl or F and Y=OH or Cl) with biological thiols (glutathione, cysteine, thiolactic acid) and methionine, has been monitored by UV-Vis spectrophotometry. The reactions have been followed at varying pHs and chloride concentrations (within the physiological range) and different temperatures and pressures. The bis-chlorido derivatives, 2-X-Cl, have been found to react with cysteine, glutathione and thiolactic acid, while the bis-hydroxido 2-X-OH derivatives are not reduced due to the high potential of the PtIV/PtII pair, as measured in aqueous solution. The lack of reactivity of methionine is related with its tioether nature preventing deprotonation of the S donor. In all remaining cases, two consecutive reaction steps have been found to occur. For cysteine the two steps can be kinetically resolved, the first step being neatly related to a PtIV to PtII reduction and the second step corresponding to the substitution of the remaining Cl− ligand by cysteine. The nature of the second step has been also confirmed by ESI-MS, as well as by the associative character of the activation parameters determined (low ΔH╪ and very negative ΔS╪ and ΔV╪). For glutathione and thiolactic acid, the rate and thermal and pressure activation parameters for the reduction step has been found similar to that obtained for the reaction with cysteine, but the substitution step could not be resolved kinetically. The substitution step, as measured from the reduced [PtII(4X-Cph,N,N')Cl] complex, is faster than the reduction process, and also much faster than that observed for the reaction with cysteine. In both cases the final product resulting for the reduction reactions corresponds thus to the final substituted complex as found for the reaction with cysteine.