REGIOSELECTIVE PORPHYRIN BRIDGE CLEAVAGE CONTROLLED BY ELECTRONIC EFFECTS - COUPLED OXIDATION OF 3-DEMETHYL-3-(TRIFLUOROMETHYL)MESOHEMIN-IXAND IDENTIFICATION OF ITS 4 BILIVERDIN DERIVATIVES

This report describes the nonenzymatic oxidative cleavage of the title porphyrin (2) performed with oxygen and ascorbic acid in aqueous pyri dine at 37 degrees C (coupled oxidation), via hydrolysis of the corres ponding verdoheme intermediates, followed by esterification of the res ulting free acid mesobiliverdin analogues to their dimethyl esters 4 ( alpha isomer), 5 (beta isomer), 6 (gamma isomer), and 7 (delta isomer) . The four biliverdin derivatives were purified by HPLC, and their str uctures were confirmed by FAB MS and also by UV-vis and H-1 NMR spectr oscopies. The purity of each compound was checked by F-19 NMR, and the four regioisomers were assigned through their 2D-NMR ROESY spectra an d confirmed by UV-vis spectroscopy. The ratio of regioisomers was dete rmined by F-19 NMR spectroscopy before any purification of single comp ounds was attempted: alpha:beta:gamma:delta 11:6:26:57 (%). This unusu ally high regioselectivity was attributed to the electron-withdrawing effect of the CF3 group on the electronic structure of porphyrin as sh own considering the ab initio calculations of an iron(II) beta-substit uted (trifluoromethyl)porphyrin used as a model compound. In porphyrin 2, the oxidation clearly takes place at the electron richest meso pos itions, the order of reactivity strictly following that of electron de nsity, pointing out that the regiospecificity of the bridge cleavage c an be effectively controlled by the electronic effects of some strateg ic substituents in the chromophore. The relevance of all these results in the study of the mechanism of the reactions involved in the natura l catabolism of heme, catalyzed by heme oxygenase, is discussed. The a dvantages of 2 derived from this work, which make it a suitable model compound for the enzymatic reaction, are also discussed.