Alkyl Radical Geometry Controls Geminate Cage Recombination in Alkylcobalamins

摘要

The radical pair that results from photolysis of adenosylcob(Ⅲ)alamin (AdoCbl~Ⅲ) undergoes primary geminate recombination with a first-order rate constant of 1 x 10~9 s~(-1). In contrast, methylcob(Ⅲ)alamin (CH_3Cbl~Ⅲ) and aristeromicylcob(Ⅲ)alamin (AriCbl~Ⅲ, the carbocyclic analogue of AdoCbl~Ⅲ in which the ribofuranose ring oxygen has been replaced with a methylene group) does not undergo primary geminate recombination. The ribofuranose group enables a high rate of geminate recombination in the [Ado~· Cbl~Ⅲ] radical pair. This may be due to a stereoelectronic (β-anomeric) effect that maintains a pyramidal geometry at the 5′-carbon of the 5′-deoxyadenosyl radical, or it may be due to hindered rotation about the C_4′-C_5′ bond such that β-elimination to the olefin is prevented. Recombination in the geminate singlet radical pair is in competition with diffusive escape to form a solvent-separated radical pair. Hyperfine coupling from Co~Ⅱ promotes intersystem crossing to the triplet radical pair (Chagovetz, A. M.; Grissom, C. B. J. Am. Chem. Soc. 1993, 775, 12152). Recombination of the [CH_3 · Cbl~Ⅱ] radical pair is not prevented by a lack of intersystem crossing, as neither unlabeled or ~(13)C-labeled CH_3Cbl~Ⅲ undergoes geminate recombination. There is only a small difference in the rate of diffusive recombination in the solvent cage for AdoCbl~Ⅲ, AriCbl~Ⅲ, and CH_3Cbl~Ⅲ following photolysis: 2.01 x 10~4 s~(-4) 2.20 x 10~4 s~(-1), and 1.16 x 10~4 s~(-1) The rate of diffusive recombination is limited by productive collisions and not by radical geometry or intersystem crossing. The CF_3~· radical that results from photolysis of (trifluoromethyl)cob(Ⅲ)alamin (CF_3Cbl~Ⅲ) maintains its pyramidal geometry and undergoes faster diffusive recombination in the solvent cage at 51 x 10~4 s~(-1). The C-Co bond dissociation enthalpy in AriCbl~Ⅲ is 37 ± 1.4 kcal/mol. The profound difference in geminate recombination rates for AdoCbl~Ⅲ and CH_3Cbl~Ⅲ is consistent with their different biological roles as enzymatic cofactors: AdoCbl~Ⅲ is an initiator of radical chain chemistry in the active site, whereas CH_3Cbl~Ⅲ is a methyl group donor in an SN2-type process.