Reactions of L-cysteine (CySH) and glutathione (GSH) with PtI(dien)(+) and Pt(dien)(H2O)(2+) were carried out in the presence and absence of guanosine 5’-monophosphate (GMP) at neutral pH. In the absence of GMP, reactions with the iodo complex afforded monomeric (thiolato)(dien)platinum(III) complexes initially. The platinum-195 chemical shifts of the cysteine and glutathione complexes are -3155 and -3217 ppm. The products are formed predominantly through direct reaction between the starting platinum complex and the ligands. The aquation pathway contributed insignificantly. The second-order rate constants for the cysteine and glutathione reactions were evaluated to be 1.3 +/- 0.1 and 0.66 +/- 0.08 M(-1) s(-1) at 40 degrees C. Reactions of Pt(dien)(H2O)(2+) with CySH and GSH lead to the formation of the same products. The second-order rate constants for the formation of the platinum-cysteine complex lie in the range 1.9 to 114 M(-1) s(-1) within the pH range 1.5 to 7.9 at 25 degrees C. HPLC and C-13 NMR data indicate that a bis(cysteine) complex is formed by slow secondary reactions through complete deligation of dien. Reactions of the thiols in the presence of excess GMP did not yield any GMP coordinated products at neutral pH. The products were the same as observed in the absence of the nucleotide. The kinetic preference of the aquaplatinum complex at neutral pH is unequivocally toward thiols, but not toward the nucleotide. The higher reactivity of thiols at neutral pH is presumably due to an efficient proton transfer from the thiols to the coordinated hydroxo-Pt(dien) complex.