Reactivity of rescue agents for cisplatin induced nephrotoxicity with Pt-2 (2,2'-bipyridine)(2)(mu-N-acetyl-L-cysteinato-S)(2)

The reactivity of Pt-2(2,2'-bipyridine)(2)(mu-N-acetyl-L-cysteinato-S)(2) (1) with a variety of rescue agents for cisplatin induced nephrotoxicity was determined at 25 degrees C in aqueous solution. The observed relative reactivities were: sodium diethyldithiocarbamate > 2-mercaptopyrimidine, cysteine, 2-mercaptopyridine > 3-hydroxy-2-mercaptopyridine, 4-methyl-2-mercaptopyrimidine, thiourea > penicillamine, 2-aminoethane- thiol. No reaction was observed between complex 1 and either potassium thiocyanate or glycine within 3 h. The reaction products: Pt(ddtc)(2), Pt(2,2'-bipyridine) (eta(2)-D-cysteinato-N,S), Pt(2,2'-bipyridine) (eta(1)-thiourea-S)(2), Pt(2,2'-bipyridine) (eta(2)-D-penicillamine-N,S) and [Pt(2,2'-bipyridine) (eta(2)-2-aminoethanethiolate-N,S)](+) were identified by H-1 and C-13 NMR spectroscopy. The reaction of 1 and the 2-mercaptohetrocycles gave a complex mixture of products which were not identified. In view of 2-mercaptopyrimidine's relatively high reactivity, low toxicity and formation of a water soluble product, it appears to have the greatest potential as a therapeutic for cisplatin nephrotoxicity among the tested rescue agents. (C) 1997 Elsevier Science S.A.