Self-association of organocobalamins in aqueous solution

Abstract

The ¹H n.m.r. spectrum of base-on methylcobalamin (CH₃–B₁₂, base = terminal 5,6-dimethylbenz-imidazole of a side chain) in neutral aqueous solution shows concentration-dependent shifts which conform to a monomer–dimer equilibrium. The shift changes on dimerization are characteristic of ring-current effects and support a structure in which the corrin rings are adjacent and roughly parallel-planar. This is also supported by the apparent steric effect of the organo-group on the equilibrium constant: CH_3^– > CH₃CH₂–B₁₂, and K= 0 for n-C₃H_7^– and 5′-deoxyadenosyl–B₁₂. The CH₃–B₁₂ dimer is favoured by increasing [NaCl](but not [NaClO₄]), and disfavoured by added miscible organic solvents. The temperature dependence of K yields ΔH=–13 kcal mol^–1 and ΔS=–33 cal K^–1 mol^–1 at [NaCl]= 0. The energy of association originates at least in part in π–π interactions between corrin rings. Base-off CH₃–B₁₂ in 1 mol dm^–3 DCI gives a K value ca. 100-fold smaller than for the base-on form. The n.m.r. shifts indicate π–π bonding involving both 5,6-dimethylbenzimidazolium and corrin rings. The cobalamins H₂O–B₁₂⁺ and CN–B₁₂ show no observable tendency to self-associate, and H₂O–B₁₂⁺, CN–B₁₂, n-C₃H₇–B₁₂, and 5′-deoxyadenosyl–B₁₂ show no tendency to associate with base-on CH₃–B₁₂.