Alkyl transfer reactions involving cobalamin and other transition metal complexes have been considered as one of the most important biologically relevant reactions.Cobalamins are ubiquitous cobalt containing organometallic compounds, plausibly the most complex biological cofactor, in which the central cobalt atom is coordinated by four equatorial nitrogen atoms of the corrin ring.Under nonreducing conditions, the cobalt atom in cobalamin exists in the +3 oxidation state where two axial ligands are appended from the periphery of the corrin macrocycle.The lower axial ligand is coordinated by the intramolecular 5,6-dimethylbenzimidazole base (DBI) and the upper axial ligand can be coordinated by various ligands.The super-reduced form of cob(III)alamin found in abiotic systems is reduced to 4-coordinated cob(I)alamin.Cobalamin in which the upper axial ligand is coordinated by cyanide ligand is called cyanocobalamin, also known as Vitamin B12.Vitamin B12 and its derivatives are cofactors for methyltransferases and dehalogenases class of enzymes.Cobalamin-dependent methyltransferases play a vital role in amino acid metabolism in many organisms, whereas the dehalogenases class of enzyme is well reputed for their involvement in detoxification of chlorinated organic compound.These widespread biological applications of cobalt corrinoid compound make such reaction is of great biochemically interested. Within the acetyl-CoA (Ljungdahl-Wood) pathway of autotrophic carbon fixation in various bacteria and archaea a unique methyl transfer reaction was found, where the metal atom acts as a donor and an acceptor of the methyl group.The vital step of this reaction is the transfer of the methyl group from the methyl-cob(III)alamin to the adjacent Ni atom situated at the active site cluster A of acetyl-CoA synthase (ACS).We have investigated a series of alkylation reaction of cob(I)almin by methyl, isopropyl and tertbutyl halides (I,Cl). Density functional theory (DFT/BP86) and Polarizable Continuum Model (PCM/water) for solvation have been applied to study those alkyl transfer reaction.The alkyl transfer reactions can proceed via two mechanisms i.e. SN2 type nucleophilic displacement and inner N or outer sphere electron transfer.Due to ample biological significance of the methyl transfer reaction involving transition metals, a systematic and comprehensive mechanistic study using quantum chemical methods is of immense importance to elucidate this intricate reaction mechanism.

Mechanism of Alkyl transfer reaction involving Cob(I)Alamin by Alkyl halide: SN2 or radical mechanism?

255th National Meeting (2018)

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