64806-05-9Relevant articles and documents
Kinetics and mechanism of oxidation of captopril by diperiodatocuprate(III) in aqueous alkaline medium
Angadi, Mahantesh A.,Tuwar, Suresh M.
, p. 219 - 229 (2015/02/19)
Captopril is a sulfur containing drug which inhibits angiotensin-converting enzyme. Its kinetics of oxidation were studied spectrophotometrically using diperiodatocuprate(III) in aqueous alkali. Major oxidative product of captopril was identified as captopril disulfide along with trace amount of the hydrolyzed product, l-proline. Kinetics of oxidation was found to be first order each in [oxidant] and [reductant]. Rate of reaction was decreased by increasing [OH-], whereas added periodate retarded the rate. Other kinetic parameters viz., ionic strength, dielectric constant, temperature effect, and intervention of free radical were also studied. Activation parameters like EA, ΔH#, ΔS#, ΔG #, and log A were calculated. A suitable mechanism was proposed. Rate law for proposed mechanism was derived and verified. Reaction constants involved in various steps of mechanism were evaluated and used to regenerate first-order experimental rate constants at various experimental conditions.
Thiol/disulfide exchange reactions of captopril and penicillamine with arginine vasopressin and oxytocin
Rabenstein, Dallas L.,Yeo, Pauline L.
, p. 109 - 118 (2007/10/02)
The kinetics and equilibria of the reaction of the thiol-containing drugs captopril (D-3-mercapto-2-methylpropanoyl-L-proline, CpSH) and penicillamine (β, β-dimethylcysteine, PSH) with the disulfide bonds of the neurohypophyseal peptide hormones arginine vasopressin (AVP) and oxytocin (OT) have been characterized. CpSH reacts with AVP and OT by thiol/disulfide interchange to form two peptide-CpSH mixed disulfides, which in turn react with another molecule of CpSH to form the reduced peptide and CpSSCp. Forward and reverse rate constants and the equilibrium constant are reported for both steps in the reaction of CpSH with AVP and OT at pH 7.00. The rate constant for the first step (k1) is much larger than that for the second step (k2). Also, once formed, the peptide-CpSH mixed disulfides rapidly undergo intramolecular thiol/disulfide interchange with reformation of the cyclic peptide and CpSH. PSH reacts with AVP and OT by the same two-step reaction sequence; however, the rate of the second step is very slow due to steric hindrance from the methyl groups of PSH and the PSH moiety of the peptide-PSH mixed disulfides. Using rate constants determined in this study and PSH levels in the plasma of patients on PSH therapy, it is predicted that in vivo reduction of the disulfide bonds of AVP and OT by PSH and CpSH has little effect on the plasma half-lives of AVP or OT.
