A Molecular Mechanics Force Field for Alkylcobaloximes, a Model of Vitamin B12 Coenzyme – Implications of Steric and Electronic Factors in the Co–C Bond Cleavage

Abstract

Molecular mechanics force field constants have been derived for alkylcobaloximes, (alkyl)Co(DH)2L (DH = monoanion of dimethylglyoxime and L = planar N‐donor ligand), implementing the AMBER force field. Atomic charges have been calculated by the semiempirical ZINDO/1 method. Stretching and bending constants have been calculated by the Badger and Halgren equations, with the introduction of simple functions for the description of the electronic influence of the axial ligands on the coordination geometry. 26 parameters have been optimized, by the Simplex method, to fit 4523 bond lengths and angles of 52 alkylcobaloxime accurate crystal structures. In spite of the oversimplification of the adopted method for the description of the electronic effects, this approach provides a good description of the metal coordination geometries. The root‐mean‐square deviations of the calculated bond lengths and angles from the experimental values average to 0.023 Å and 1.4°, respectively. The molecular mechanics results are discussed in terms of the steric properties of the axial ligands and correlated with their calculated cone angles. The force field has been used to analyse some conformational features of these compounds, such as the influence of the rotation of the axial ligands on their coordination geometry. The calculated energy for the Co–N rotational barrier agrees well with the experimetal ones derived from dynamic and saturation 1H‐NMR spectroscopy in (alkyl)Co(DH)2(2‐NH2‐py). In order to have more experimental data for this analysis, the crystal structures of two new cobaloximes, (CH2Cl)Co(DH)2L with L = py, 1, and 1‐Me‐Im, 2) have been determined. The results of a conformational analysis on ribosyl‐imidazole derivatives, taken as a suitable vitamin B12 coenzyme model, suggest that the 1‐Me‐imidazole‐like ligands have a significantly greater rotation freedom with respect to the benzimidazole‐like ones, but cause similar stretchings of the Co–C bond, and a significantly less stretching of the Co–N one. Implications for the recent findings on the binding mode of the coenzyme B12 in the enzyme active site are discussed.

New Alkyl−Cobalt(III) Complexes with Tridentate Amino−Oxime Ligands: Synthesis, Structure, and Reactivity

“…These structural features are in agreement with recent molecular mechanics calculations for LCo(DH) 2 Me (L is a planar N donor ligand) based on a new approach which also takes the contribution of the electronic trans influence into account. [5] These calculations have furnished profiles of the strain energy against the ϕ angle, which is characterised by a large maximum centred at ϕ ϭ 90°and a minimum at ϕ ϭ 0°, the difference in height ranging from 8 to 40 kJ/mol and increasing with the L bulk. [5] In addition, the large maximum at approximately ϕ ϭ 90°has a fine structure, consisting of two nearly equal maxima at about 55°and 145°, separated by a relative minimum at ϕ ϭ 90°.…”

“…[5] These calculations have furnished profiles of the strain energy against the ϕ angle, which is characterised by a large maximum centred at ϕ ϭ 90°and a minimum at ϕ ϭ 0°, the difference in height ranging from 8 to 40 kJ/mol and increasing with the L bulk. [5] In addition, the large maximum at approximately ϕ ϭ 90°has a fine structure, consisting of two nearly equal maxima at about 55°and 145°, separated by a relative minimum at ϕ ϭ 90°. This suggested that orientation C (Scheme 2) is energetically even less favoured than orientation B.…”

“…[2] This finding has renewed interest in the nature of the CoϪL bond in simple models. [3,4,5] The early hypothesis [1] that the CoϪL distance is influenced by the orientation of the planar L ligand, measured by the torsional angle ϕ around that bond, has been confirmed. [6Ϫ8] In orientation A (Scheme 2), when ϕ is close to 0, the CoϪL distance is found to be shorter by about 0.03 Å than in orientation B (Scheme 2), corresponding to ϕ close to 90°.…”

Syntheses, Structures and Antibacterial Activities of Two Nickel(II) Complexes with N‐Hexanoylsalicylhydrazide Ligand

“…The observed bond lengths in the octahedron of complex 2 can be slightly modified by the packing effects, which can force the molecule into a strained conformation. 29 At the same time, the axial DMF ligand was expected to have lower σ-donor ability in the structure of complex 2. So the bond lengths around the central Ni atom of complex 2 are all slightly shorter than the corresponding ones of compound 1.…”

Coenzyme B12 model studies: Equilibrium constants for the pH-dependent axial ligation of benzyl(aquo)cobaloxime by various N- and S-donor ligands

“…These studies were useful in understanding the mechanism of Co-C bond cleavage in the vitamin B 12 coenzyme. Marques et al 11 and Randaccio et al 12 studied the molecular mechanism of modelling of cobaloximes. Halpern et al 13 studied the hydrolytic dealkylation of organo-cobaloximes related to coenzyme B 12 .…”