FREE-RADICAL REPAIR BY A NOVEL PERTHIOL - REVERSIBLE HYDROGEN-TRANSFER AND PERTHIYL RADICAL FORMATION

2-(3-Aminopropyl-amino) ethaneperthiol (RSSH, the perthiol analogue of the thiol radioprotector, WR-1065) reacts with the alpha-hydroxy alky l radical (CH3)(2)(COH)-O-. by donating a hydrogen atom as indicated b y the characterization of perthiyl radicals (RSS(.); lambda(max) appro ximate to 374 nm, epsilon(374) approximate to 1680 +/- 20 dm(3) mol(-1 ) cm(-1)) by pulse radiolysis. The perthiyl radical abstracts a hydrog en from the alcohol to establish a reversible hydrogen-transfer equili brium. This equilibrium lies predominantly on the side of radical repa ir since the rate constants for the forward and reverse reactions at p H 4 are: k(RSSH + (CH3)(2)(COH)-O-.) = (2.4 +/- 0.1) x 10(9) dm(3) mol (-1) s(-1) and k(RSS(.) + (CH3)(2)CHOH) = (3.8 +/- 0.3) x 10(3) dm(3) mol(-1) s(-1) respectively. The pK(a) (RSSH reversible arrow RSS(-) H+) = 6.2 +/- 0.1 was determined from the pH dependence of the rate of perthiol repair. Identical experiments have been performed with WR-10 65 allowing a direct comparison of free-radical repair reactivity to b e made with the parthiol analogue. At pH approximate to 7.4 the reacti vities of the thiol and perthiol were similar, both repairing the alco hol radical with a rate constant of similar to (2.4 +/- 0.1) x 10(8) d m(3) mol(-1) s(-1). However, at pH 5 whilst the hydrogen-donation rate of the thiol was 15-20% higher than at pH 7.4, the perthiol reactivit y was over an order of magnitude higher. The thermodynamic driving for ce for the observed enhanced free-radical repair reactivity of RSSH co mpared to RSH is attributed to the resonance stabilization energy of 8 .8 kJ mol(-1) within the RSS(.) radical. These results indicate a poss ible application of RSSH/RSS(-) as DNA-targeted antioxidants or chemop rotectors.