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In this study, we developed an efficient approach for disulfide bond formation in peptides utilizing the Pt(IV) complex

Ormaplatin ([Pt(dach)Cl4]) represents one of the three primary structural prototypes of Pt(iv) anticancer-active prodrugs. The reduction of ormaplatin by an extended series of thiols has been studied kinetically in a broad pH range. A novel and remarkable correlation between log kRS- and the thiol dissociation constants pKRSH is disclosed: log kRS- = (0.50 ± 0.02)pKRSH + (0.68 ± 0.13), where kRS- denotes the second-order rate constant of each thiolate towards the reduction of ormaplatin.

Sodium thiosulfate has been utilized as a rescuing agent for relief of the toxic effects of cisplatin and carboplatin. In this work, we characterized the kinetics of reactions of the trans-dichloro-platinum(IV) complexes cis-[Pt(NH3)2Cl4], ormaplatin [Pt(dach)Cl4] and trans-[PtCl2(CN)4]2− (anticancer prodrugs and a model compound) with thiosulfate at biologically important pH. An overall second-order rate law was established for the reduction of trans-[PtCl2(CN)4]2− by thiosulfate, and varying the pH from 4.45 to 7.90 had virtually no influence on the reaction rate. In the reactions of thiosulfate with cis-[Pt(NH3)2Cl4] and with [Pt(dach)Cl4], the kinetic traces displayed a fast reduction step followed by a slow substitution involving the intermediate Pt(II) complexes. The reduction step also followed second-order kinetics. Reductions of cis-[Pt(NH3)2Cl4] and [Pt(dach)Cl4] by thiosulfate proceeded with similar rates, presumably due to their similar configurations, whereas the reduction of trans-[PtCl2(CN)4]2− was about 1,000 times faster. A common reduction mechanism is suggested, and the transition state for the rate-determining step has been delineated. The activation parameters are consistent with transfer of Cl+ from the platinum(IV) center to the attacking thiosulfate in the rate-determining step.

The kinetics and mechanism of the reduction of chromium(VI) by lactic acid (Lac) in aqueous acidic medium was studied with spectrophotometry in a temperature range of 298.15 K~313.15 K. Under the conditions of the pseudo-first order , the observed rate constant increased with the increase in [Lac] and . There is no salt effect. Based on the experimental results, a probable reaction mechanism of oxidation was proposed. The rate equation derived from the mechanism could explain all the experimental phenomena. Activation parameters along with rate constant of the rate-determining step have been evaluated.

Kinetics and mechanism of oxidation of leucine and alanine by Ag(III) complex were studied spectrophotometrically in alkaline medium at constant ion strength. The reaction was in first order with respect to Ag(III) complex and amino acids (leucine, alanine). The second-order rate constant, k−, decreased with the increasing in [OH−] and [IO4−]. A plausible mechanism was proposed from the kinetics study, and the rate equations derived from mechanism can explain all experimental phenomena. The activation parameters were calculated at 298.2 K.

The kinetics and mechanism of oxidation of aspartic acid by the bis(hydrogen periodato) complex of Cu(III), [Cu(HIO6)2]5−, is studied in an alkaline medium. The reaction rate is first order with respect to Cu(III) and fractional order with respect to aspartic acid. The value of the observed rate constant is found to decrease with the increase in concentrations of either OH− or IO4 −. There is a positive salt effect, and the free radical has been determined. In view of these kinetics phenomena, a plausible mechanism is proposed and the rate equations derived from the mechanism can explain all experimental results. The activation parameters along with the rate constants of the rate-determining step are calculated.

Kinetics and mechanism of oxidation of 1,4-butanediamine by a Ag(III) complex were studied spectrophotometrically in alkaline medium at constant ion strength. The reaction shows first order with respect to the Ag(III) complex and 1,4-butanediamine respectively. The second order rate constant, k′, increased with the increasing in [OH−], and decreased with the increasing in [IO4−]. A plausible mechanism was proposed from the kinetics study. The rate equations derived from the mechanism can explain all experimental phenomena. The activation parameters were calculated.

The oxidation of leucine, isoleucine and valine by bis(dihydrogen tellurate)argentate(III) ion was studied by stopped-flow technique. It was both first order with respect to Ag(III) complex and amino acids. A plausible mechanism was proposed form the kinetics study. And the rate equations derived from mechanism can explain all experimental phenomena. The activation parameters along with the second order rate constants were calculated.

The oxidation of 6-Aminocaproic acid by Ag(III) complex, dihydroxydiperiodatoargentate(III) (DPA), was studied in alkaline medium. The reaction was first order with respect to Ag(III) complex, and the order with respect to 6-aminocaproic acid was from one to two. A plausible mechanism involving a pre-equilibrium of adduct formation between the complex and reductant was proposed form the kinetics study. The rate equations derived from mechanism can explain all experimental phenomena, and the activation parameters along with rate constants of the rate-determining step were calculated

Captopril, the first pharmaceutical drug designed, synthesized, and used primarily for the treatment of hypertension and congestive heart failure, is an angiotensin-converting-enzyme inhibitor and is also an antioxidant. On the other hand, the kinetic and mechanistic aspects for the oxidation of captopril are not well understood. The oxidation of captopril by cisplatin prodrug and a model compound, cis-[Pt(NH3)2Cl4] and trans-[PtCl2(CN)4]2−, was thus investigated in this work. A stopped-flow spectrometer was employed to follow the oxidation kinetics over a wide pH-range under the pseudo first-order conditions of [captopril] ≫ [Pt(IV)]. The oxidation by the Pt(IV) complexes displayed a second-order character, first-order each in [Pt(IV)] and in [captopril], whereas the metal-ion-catalyzed autooxidation made a very minor contribution to the overall kinetics in acidic media and was negligible in neutral media. Captopril was oxidized to form the captopril-disulfide as identified by ESI mass spectrometry under the conditions of the kinetic measurements. In the proposed reaction mechanism, the Pt(IV) complexes are reduced by the three protolytic captopril species in parallel as rate-determining steps, generating reactive species of chlorothiol and/or sulfenylchloride. The reactive species will be rapidly trapped, either directly or indirectly, by another molecule of captopril to form captopril-disulfide. The rate constants for the rate-determining steps have been derived, demonstrating that the fully deprotonated captopril is about 105 to 106 times more reactive than its corresponding thiol form toward the Pt(IV) complexes.