Revisiting the structure-reactivity correlation in the reduction of trans-dichlorotetracyanoplatinate(IV) by a large series of alterable thiols

Two important bioinorganic chemistry aspects of the Pt(IV) complex trans -[PtCl 2 (CN) 4 ] 2− ( 1 ) were found previously: it was firstly used as a model complex for Pt(IV) antitumor prodrugs to elucidate the activation mechanism for the prodrug activations and as a reagent for efficient disulfide bond generation in peptides. Kinetically, reduction of 1 by 14 important thiols has been investigated at 25.0 °C and an ionic strength of 1.0 M. Second-order kinetics were precisely followed by all the reduction reactions, and the pH-dependent second-order rate constants k ′ were measured in a pH range as wide as possible. Reaction mechanisms were elucidated in which a few rate-controlling steps are encompassed. For each thiol, rate constants of the rate-controlling steps including k RS - (a particular thiolate species towards reduction of 1 ) were calculated. An excellent linear Brønsted correlation (log k RS - = 0.42·p K RSH ± 3.94) is re-defined by wide changes in both p K RSH and steric hindrance, where K RSH is the dissociation constant of the thiol group. The correlation is discussed in terms of the proposed transition state, strongly substantiating a Cl + transfer from one of two the coordinated chlorides in 1 to the sulfur atom. Interestingly, the Cl + transfer mode resembles to the reduction reactions of HOCl, a critical reactive oxygen species (ROS) in human body. Since the reduction rates of HOCl by many biologically-important reductants are very fast, they were difficult to measure directly. In this work, 1 is also demonstrated to be a good model oxidant for HOCl, possessing some advantages in the rate measurements; this could be another bioinorganic chemistry aspect of 1 . • Reductions of [PtCl 2 (CN) 4 ] 2− by a large series of thiols have been studied kinetically. • An excellent linear Brønsted correlation between log k RS - and p K RSH is re-defined in this work. • Mechanistically, reductions of [PtCl 2 (CN) 4 ] 2− and HOCl by sulfhydryl compounds are very similar. • [PtCl 2 (CN) 4 ] 2− cis a good model oxidant for HOCl possessing some advantages in rate measurements.