REACTIONS OF CAPTOPRIL AND EPICAPTOPRIL WITH TRANSITION-METAL IONS AND HYDROXYL RADICALS - AN EPR SPECTROSCOPY STUDY

In the present study, using the technique of EPR spin trapping with DM PO a spin trap, we demonstrated formation of thiyl radicals from thiol -containing angiotensin converting enzyme (ACE) inhibitor captopril (C AP) and from its stereoisomer epicaptopril (EPICAP), a non-ACE inhibit or, in the process of .OH radical scavenging. Splitting constants of D MPO/thiyl radical adducts were identical for both thiols and were a(N) = 15.3 G, and a(H) = 16.2 G. Bimolecular rate constants for the react ion of CAP and EPICAP with .OH radicals were close to a diffusion-cont rolled rate (almost-equal-to 2 x 10(10) M-1s-1). Our data also show th at both CAP and EPICAP reduce Fe(III) ions and that their respective t hiyl radicals are formed in this reaction. In the presence of Fe(III), H2O2, and CAP, or EPICAP, .OH radicals were produced by a thiol-drive n Fenton mechanism. Copper(II) ions were also reduced by these thiols, but no thiyl radicals could be detected in these reactions, and no .O H or other Fenton oxidants were observed in the presence of H2O2. Our data show direct evidence that thiol groups of CAP and EPICAP are invo lved in scavenging of .OH radicals. The direct .OH radical scavenging, together with the reductive ''repair'' of other sites of .OH radical attack, may contribute to the known protective effect of CAP against i schemia/reperfusion-induced arrhythmias. The formation of reactive thi yl radicals in the reactions of the studied compounds with .OH radical s and with Fe(III) ions may play a role in some of the known adverse e ffects of CAP.