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

Abstract

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 [PtCl 2(SmecysH)], and the resultant chloro-aqua species have been determined by NMR, potentiometric, and spectrophotometric methods. Though hydrolysis constants, K h, for the two chlorides are similar (p K h = 4–5), the rate of hydrolysis of the chloride trans to coordinated S, k h = 3.4 × 10 −3 s −1, is 2–3 orders of magnitude faster than the k h for the other chloride, 2.3 × 10 −6 s −1, and for the cancer drug cisplatin, cis-[PtCl 2(NH 3) 2], 5.2 × 10 −5 s −1. Relative rates of hydrolysis determined under three different experimental conditions (pH ∼ 1 in 0.10 M HNO 3, 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 p K a values of all aqua species, which are comparable to values reported for corresponding aqua species derived from cisplatin.