The reductive metabolism of BrCCl3 by ferrous deoxymyoglobin leads to the formation of heme-derived products, including those that are covalently bound to the protein. BrCCl3 caused a decrease in the absorption of the oxidized myoglobin in the Soret region, suggesting that the prosthetic heme moiety had been modified. Examination of the total reaction mixture by HPLC revealed the presence of three major soluble heme-derived products and a protein-bound heme adduct. The soluble products were unequivocally identified by electronic absorption, FAB mass spectrometry, and 2D NOESY and COSY NMR as β-carboxyvinyl, α-hydroxy-β-(trichloromethyl)ethyl, and α,β-bis(trichloromethyl)ethyl derivatives of the heme prosthetic group and are believed to result from the initial regiospecific attack of the trichloromethyl radical at the ring I vinyl substituent. As might be expected from the bulk of the trichloromethyl group and the crowded environment of the heme, the α,β-bis-(trichloromethyl)ethyl moiety was held in a rigid conformation about the heme. A similar approach utilizing cytochrome P-450 instead of myoglobin may be used to study the mechanism of inactivation of the P-450 enzyme by the trichloromethyl radical.
ASJC Scopus subject areas
- Colloid and Surface Chemistry