Hydrophobic vitamin B₁₂. Part 15 ¹. Carbon-skeleton rearrangement reactions mediated by hydrophobic vitamin B₁₂ covalently bound to an anionic lipid species in aqueous media

A novel artificial vitamin B₁₂ holoenzyme was prepared in aqueous media by combination of a hydrophobic vitamin B_i2 covalently bound to an anionic lipid species and a bilayer matrix of sodium N,N-dihexadecyl-N^α-(6-sulfohexanoyl)-L-alaninamide. Microenvironmental properties around a hydrophobic vitamin B₁₂ placed in the bilayer membrane were examined by electronic spectroscopy and fluorescence polarization measurements. The hydrophobic vitamin B₁₂ was well separated from a bulk aqueous phase, and its molecular motion was markedly suppressed. A reaction mimicking catalytic functions of methylmalonyl-CoA mutase was carried out by using hydrophobic vitamin B₁₂ derivatives having a diethyl 2,2-bis(ethoxycarbonyl)propyl group at an axial site of the nuclear cobalt. A carbon-skeleton rearrangement of the alkyl ligand bound to a hydrophobic vitamin B₁₂ was markedly promoted in the bilayer matrix, relative to the reaction in methanol and benzene, via formation of a radical intermediate. A reaction simulating catalysis by α-methyleneglutarate mutase was also carried out. The cyanide ion enhanced a carbon-skeleton rearrangement of the 2,3-bis(ethoxycarbonyl)-l-butene moiety bound to hydrophobic vitamin B₁₂ derivatives in the bilayer membrane under photolysis conditions via formation of an anionic intermediate. As an extension of such mimicking reactions, a carbon-skeleton rearrangement reaction of diethyl 2-acetylamino-2-methylpropanedioate coordinated to a hydrophobic vitamin B₁₂ covalently bound to a lipid species, which afforded diethyl 2-acetylaminobutanedioate, was also examined in the bilayer membrane under photolysis conditions. The motional repression and desolvation effects operated on the substrate-bound hydrophobic vitamin B₁₂ were found to be responsible for enhancement of the rearrangement reactions of the substrate radicals formed under photolysis conditions.