Kinetic and thermodynamic studies on ligand substitution reactions and base-on/base-off equilibria of cyanoimidazolylcobamide, a vitamin B12 analog with an imidazole axial nucleoside

Abstract

Ligand substitution reactions of the vitamin B12 analog cyanoimidazolylcobamide, CN(Im)Cbl, with cyanide were studied. Cyanide substitutes imidazole (Im) in the alpha-position more slowly than it substitutes dimethylbenzimidazole in cyanocobalamin (vitamin B12). The kinetics of the displacement of Im by CN- showed saturation behaviour at high cyanide concentration; the limiting rate constant was found to be 0.0264 s(-1) at 25 degrees C and is characterized by the activation parameters: DeltaH(not =) = 111 +/- 2 kJ mol(-1), DeltaS(not =) = +97 +/- 6 J K(-1) mol(-1), and DeltaV(not =) = +9.3 +/- 0.3 cm3 mol(-1). These parameters are interpreted in terms of an I(d) mechanism. The equilibrium constant for the reaction of CN(Im)Cbl with CN- was found to be 861 +/- 75 M(-1), which is significantly less than that obtained for the reaction of cyanocobalamin with CN- (viz. 10(4) M(-1)). pKbase-off for the base-on/base-off equilibrium was determined spectrophotometrically and found to be 0.99 +/- 0.05, which is about 0.9 pH units higher than that obtained previously in the case of cyanocobalamin. In addition, the kinetics of the base-on/base-off reaction was studied using a pH-jump technique and the data obtained revealed evidence for an acid catalyzed reaction path. The results obtained in this study are discussed in reference to those reported previously for cyanocobalamin.

The reaction of HOCl and cyanocobalamin: Corrin destruction and the liberation of cyanogen chloride

“…Incubation of Cobl with lower concentration (100 μM) of HOCl for 2h caused a distinct shift in UV absorption peak (from 360 to 363 nm), and an additional shift in the visible absorption region from (550 to 590 nm). This distinct red shift of the absorbance spectra was indicative of α-axial ligand replacement, as reported earlier [29]. Incubation of Cobl with higher concentration (>100 μM) of HOCl caused decrease and flattening in the absorbance spectra indicating oxidative destruction of the corrin ring.…”

“…H 2 O, CH 3 , adenosyl and OH) [31–34] whereas a significant red shifted spectrum resulted upon the replacement of the dimethylbenzimidazole group attached to α-axial with different substituent (e.g. CN − ) [29]. Despite the high affinity of HOCl towards CN − ( k on = 1.22×10 9 M −1 s −1 , at 25° C) [15], the present results failed to demonstrate a direct CN − removal prior to the corrin ring destruction.…”

Application of High Pressure in the Elucidation of Inorganic and Bioinorganic Reaction Mechanisms

“…There were some surprising findings but these have been rationalized, with in many cases temperature and pressure derived activation parameters invoked in mechanistic explanations. This whole field of endeavor, including the portrayal of relevant volume profiles, has been described very recently 73,[250][251][252] and therefore the topic will not be repeated herein.…”

Chemoselective Deprotection of α-Indole and Imidazole Ribonucleosides

“…Semisynthesis of cobalamins [1][2][3][4][5][6] with altered axial nucleotide ligands requires cobyric acid [7] and an α-ribonucleotide [8] as precursors. Analogs of coenzyme B 12 (5 -deoxyadenosylcobalamin, AdoCbl) with altered axial nucleotide ligands, such as B3-deazaAdoCbl ( Figure 1) are of interest as probes of the function, if any, of the axial nucleotide in the enzymatic activation of AdoCbl for carbon-cobalt bond homolysis [9,10] .…”