HYDROPHOBIC VITAMIN-B-12 - PART 15 - CARBON-SKELETON REARRANGEMENT REACTIONS MEDIATED BY HYDROPHOBIC VITAMIN-B-12 COVALENTLY BOUND TO AN ANIONIC LIPID SPECIES IN AQUEOUS-MEDIA

A novel artificial vitamin B-12 holoenzyme was prepared in aqueous med ia by combination of a hydrophobic vitamin B-12 covalently bound to an anionic lipid species and a bilayer matrix of sodium hexadecyl-N-alph a-(6-sulfohexanoyl)-L-alaninamide. Microenvironmental properties aroun d a hydrophobic vitamin B-12 placed in the bilayer membrane were exami ned by electronic spectroscopy and fluorescence polarization measureme nts, The hydrophobic vitamin B-12 was well separated from a bulk aqueo us phase, and its molecular motion was markedly suppressed. A reaction mimicking catalytic functions of methylmalonyl-CoA mutase was carried out by using hydrophobic vitamin B-12 derivatives having a diethyl 2, 2-bis(ethoxycarbonyl)propyl group at an axial site of the nuclear coba lt. A carbon-skeleton rearrangement of the alkyl ligand bound to a hyd rophobic vitamin B-12 was markedly promoted in the bilayer matrix, rel ative to the reaction in methanol and benzene, via formation of a radi cal intermediate. A reaction simulating catalysis by alpha-methylenegl utarate mutase was also carried out. The cyanide ion enhanced a carbon -skeleton rearrangement of the 2,3-bis(ethoxycarbonyl)-1-butene moiety bound to hydrophobic vitamin B-12 derivatives in the bilayer membrane under photolysis conditions via formation of an anionic intermediate. As an extension of such mimicking reactions, a carbon-skeleton rearra ngement reaction of diethyl 2-acetylamino-2-methylpropanedioate coordi nated to a hydrophobic vitamin B-12 covalently bound to a lipid specie s, which afforded diethyl 2-acetylaminobutanedioate, was also examined in the bilayer membrane under photolysis conditions. The motional rep ression and desolvation effects operated on the substrate-bound hydrop hobic vitamin B-12 were found to be responsible for enhancement of the rearrangement reactions of the substrate radicals formed under photol ysis conditions. (C) 1998 Elsevier Science S.A. All rights reserved.