Evidence for the Unexpected Associative Displacement of Adenosyl by Cyanide in Coenzyme B₁₂

Abstract

The reaction of coenzyme B(12) (adenosylcobalamin) with cyanide has been reinvestigated in detail using spectroscopic and kinetic techniques. It has been shown that this reaction proceeds in one kinetically observable step, contradicting previous findings, with rate-determining attack of the first cyanide (k = (7.4 +/- 0.1) x 10(-3) M(-1) s(-1), 25.0 degrees C, I = 1.0 M (NaClO(4))). The activation parameters were found to be DeltaH() = 53.0 +/- 0.6 kJ mol(-1), DeltaS() = -127 +/- 3 J mol(-1) K(-1) and DeltaV() = -10.0 +/- 0.4 cm(3) mol(-1), suggesting an associative displacement mechanism. It is postulated that attack of the first cyanide occurs at the beta-(5'-deoxy-5'-adenosyl) site rather than at the alpha-dimethylbenzimidazole site.

Kinetic and thermodynamic studies on the cyanation reactions and base-on/base-off equilibria of alkyl-13-epicobalamins

“…In this work, the fascinating influence of a single cobalt-carbon bond in tuning the reactivity of the Co() center was clearly demonstrated. [25][26][27][28][29] We found that the reaction of XCbl with CN Ϫ , where X = NCCH 2 , CF 3 and CN Ϫ , proceeded via the formation of an intermediate X(CN)Cbl, which subsequently reacts, in the presence of CN Ϫ , to give (CN) 2 Cbl Ϫ . 26 We also found that the mechanism of substituting the axial DMBz trans to the X group in a series of XCbl by CN Ϫ occurred via a dissociative mechanism.…”

Electronically and sterically tuned trans labilization controls the substitution behaviour of cobaloximes

“…Application of high pressure techniques have been successfully applied to the chemistry of vitamin B 12 and its derivatives. [18][19][20][21][22] Recently some of us studied the reaction of a series of alkylcobalamins (RCbls) with cyanide and found that the kinetic trans effect increases in the order CN Ϫ < CF 3 < NCCH 2 < CF 2 H < CF 3 CH 2 < Me < n-Pr. The mechanism of the reaction of RCbls with cyanide was found to be limiting dissociative (D) in the case of R = NCCH 2 , CF 3 , CN Ϫ .…”

Equilibrium, Kinetic and Leaving Group Effect Studies on Ligand Substitution Reactions of a Simple Model for Coenzyme B12

“…[22Ϫ36] In the case of the coenzyme, however, evidence for an associative substitution mode was reported. [37] In order to gain further insight into the reasons for this unexpected mechanistic changeover, we have now investigated substitution reactions of trans-[Co(en) 2 (Me)H 2 O] 2ϩ and trans-[Co(en) 2 (Me)NH 3 ] 2ϩ to study the effect of the leaving group on the axial ligand substitution mechanism of these model complexes that include a cobaltϪcarbon σ-bond. These complexes allow us to mimic the active site of the coenzyme since the ammine ligand trans to the CoϪMe bond represents the dimethylbenzimidazole moiety in the coenzyme.…”