Aqueous solution chemistry of dichloro[S-methylcysteine(N,S)]platinum(II) isomers and their hydrolysis products

Rate and equilibrium constants at 25 °C, pH ∼ 1, and ionic strength 0.10 for hydrolysis of the two non-equivalent chlorides of dichloro[S-methyl-l-cysteine(N,S)]platinum(II) isomers, denoted [PtCl2(SmecysH)], and the resultant chloro-aqua species have been determined by NMR, potentiometric, and spectrophotometric methods. Though hydrolysis constants, Kh, for the two chlorides are similar (pKh = 4–5), the rate of hydrolysis of the chloride trans to coordinated S, kh = 3.4 × 10−3 s−1, is 2–3 orders of magnitude faster than the kh for the other chloride, 2.3 × 10−6 s−1, and for the cancer drug cisplatin, cis-[PtCl2(NH3)2], 5.2 × 10−5 s−1. Relative rates of hydrolysis determined under three different experimental conditions (pH ∼ 1 in 0.10 M HNO3, high pH in 0.10 M NaOH, and at low pH with Ag+ assistance) are consistent: the Cl trans to S is 100–1000 times more labile than the Cl cis to S. Potentiometric and NMR methods were also used to estimate pKa values of all aqua species, which are comparable to values reported for corresponding aqua species derived from cisplatin.

Equilibrium and rate constants, four Kh and four corresponding kh–ka pairs, for the stepwise reversible hydrolysis at low pH of the two non-equivalent chlorides of [PtCl2(S-methylcysteine)] are reported, along with hydrolysis rates at high pH and with Ag+ assistance and pKa values for the aqua species formed in the hydrolysis reactions.Figure optionsDownload as PowerPoint slide