Mechanistic insight from activation parameters for the reaction between co-enzyme B12 and cyanide: further evidence that heterolytic Co–C bond cleavage is solvent-assistedElectronic supplementary information (ESI) available: NMR and kinetic data. See http://www.rsc.org/suppdata/dt/b2/b210068a/

Abstract

The potential involvement of the solvent in heterolytic Co–C bond cleavage for vitamin B12 derivatives has been probed by measuring for the first time activation parameters for heterolytic Co–C bond cleavage. If a water molecule is part of the transition state, negative entropies and volumes of activation should be observed. Conversely, if Co–C bond cleavage is a purely dissociative process, these parameters will be positive. Activation parameters have been determined for the reactions of co-enzyme B12 (5′-deoxyadenosylcobalamin, AdoCbl) and the corresponding cobinamide, 5′-deoxyadenosylcobinamide (AdoCbi+), with cyanide, since previous studies have shown that these reactions proceed at convenient rates, Co–C heterolytic bond cleavage is rate-determining and the reaction proceeds cleanly (that is, negligible homolytic cleavage). In addition, the kinetics of the reaction of AdoCbl with cyanide in aqueous solution were re-investigated at high concentrations of sodium cyanide (up to 3.00 M) at pH 11.0 and I = 5.0 M (NaClO4) using UV-visible and 1H NMR spectroscopy. A significant kinetic saturation was obtained at high CN− concentrations and the limiting rate constant at 25.0 °C was found to be (2.21 ± 0.04) × 10−2 s−1, with an overall formation constant for the (β-Ado)(α-CN)Cbl− intermediate, KCN/KCo, of 0.259 ± 0.007 M−1. ΔH≠, ΔS≠ and ΔV≠ under these conditions were found to be 55 ± 1 kJ mol−1, −98 ± 3 J K−1 mol−1 and −5.7 ± 0.3 cm3 mol−1, respectively. ΔV≠ for the reaction of AdoCbi+ and CN− at pH 11.0 and 35.0 °C was found to be −4.5 ± 0.4 cm3 mol−1, while ΔV≠ for the reaction of AdoCbl and AdoCbi+ with tetrabutylammonium cyanide in 92%DMF–8%D2O at 35 °C was found to be −8.2 ± 0.3 and −8.8 ± 0.7 cm3 mol−1, respectively. The activation parameters data obtained in the present study support the earlier suggestion that the rate determining step for the reaction of AdoCbl and AdoCbi+ with CN− which involves heterolytic cleavage of the Co–C bond of the (β-Ado)(α-CN)Cbl− and (β-Ado)(α-CN)Cbi intermediates, respectively, is a solvent-assisted, β-elimination process, in which the solvent partially protonates the ribosyl oxygen of the intermediate.