Vitamin B₁₂ Catalysis: Probing the Structure/Efficacy Relationship

Abstract

Vitamin B is a cofactor for many enzymes, but it also functions as a catalyst in C-C bond-forming reactions. Herein, the impact of corrin structural modifications on their catalytic efficacy was examined. Derivatives with various substituents at c-, d-, and meso-positions were synthesised by using traditional and new microwave methodologies, and then tested in the model reaction of 1,1-diphenylethylene with ethyl diazoacetate. To complement the experimental data, cyclic voltammetry and DFT calculations were performed. Mainly alterations at the c- or d-positions influence both the reaction yield and selectivity.

Reversal of Regioselectivity in Reactions of Donor-Acceptor Cyclopropanes with Eelectrophilic Olefins

“…Our previous studies indicated that the rate of reactions catalyzed by HME (2) are significantly higher than those catalyzed by native vitamin B12. [15] Indeed, kinetic studies performed for the HME-catalyzed formation of products 5a indicated a significant acceleration of the reaction rate compared to (CN)Cbl-catalyzed transformations (Figure 1). Indeed, the change of a catalyst from vitamin 1 to HME (2) enabled the formation of product 5f in a satisfactory yield (63%).…”

meso‐Modified Cobalamins: Synthesis, Structure, and Properties

“…To calculate the activation energy required for rotation around the torsion angles C9‐C10‐N‐C(O) and C10‐N‐C(O)‐CH 3 in the meso substituent, we use the truncated form of 1 as a model, as previously reported for computational analysis of cobalamins (Figure ) . The model lacks the peripheral amide chains and possesses the acetamide group as a meso substituent.…”

“…[15,16] The reduction potentials of Co III / Co II and Co II /Co I pairs mostlyd epend on the coordination state of the cobalt ion and on the natureo fa xial and equatorial ligands (trans and cis effect/influence). [17,18] The impact of axial ligandso nt he electronic characteristics of the cobalt ion is readily determined by meanso fl igand exchange. [2,[19][20][21][22][23] Conversely, exploring the effects of the uniquec orrin ligand on the properties of cobalamin requires its selective modification.…”

“…All biological functions of vitamin B 12 , as well as its catalytic properties, involve oxidation or reduction of the central cobalt ion as the main feature . The reduction potentials of Co III /Co II and Co II /Co I pairs mostly depend on the coordination state of the cobalt ion and on the nature of axial and equatorial ligands ( trans and cis effect/influence) . The impact of axial ligands on the electronic characteristics of the cobalt ion is readily determined by means of ligand exchange .…”

First and Second Sphere Interactions Accelerate Non-Native N-Alkylation Catalysis by the Thermostable, Methanol-Tolerant B12-Dependent Enzyme MtaC

“…Vitamin B12 catalyzes a wide range of chemical transformations, including dehalogenations, alkyl halide and alkene coupling reactions, cyclopropanation, and double bond addition reactions that are not known for B12-dependent enzymes in nature. 1 B12 is poorly soluble in most organic solvents, and a pendant dimethylbenzimidazole coordinates to its cobalt center in the +2 or +3 oxidation state in solution, 2 which complicates the use of synthetic ligands to tune B12 reactivity 3 . To address these limitations, chemists have developed organic-soluble derivatives of B12 and other synthetic model complexes that can be more readily used as catalysts for organic transformations.…”