Performance of DFT in modeling electronic and structural properties of cobalamins

Abstract

Computational modeling of the enzymatic activity of B 12 -dependent enzymes requires a detailed understanding of the factors that influence the strength of the CoAC bond and the limits associated with a particular level of theory. To address this issue, a systematic analysis of the electronic and structural properties of coenzyme B 12 models has been performed to establish the performance of three different functionals including B3LYP, BP86, and revPBE. In particular the cobalt-carbon bond dissociation energies, axial bond lengths, and selected stretching frequencies have been analyzed in detail. Current analysis shows that widely used B3LYP functional significantly underestimates the strength of the CoAC bond while the nonhybrid BP86 functional produces very consistent results in comparison to experimental data. To explain such different performance of these functionals molecular orbital analysis associated with axial bonds has been performed to show differences in axial bonding provided by hybrid and nonhybrid functionals.

On the Importance of Ribose Orientation in the Substrate Activation of the Coenzyme B12‐Dependent Mutases

“…Apart from the fact that this model (hereafter denoted RibCorIm) was used in the previous study that supported the conductor hypothesis, [18] it has also been shown by several groups [20,21] that similar models capture the essential structural and electronic features of AdoCbl. In our calculations, the substrate (Glu-H) is included in its entirety, and is made neutral to account for the electrostatic influence of the GM active site.…”

“…Other studies involving analogous model systems have observed a similar trend, though the use of BP86 is encouraged over B3-LYP for cobalamins on the basis of yielding results that are more consistent with experiment for www.chemeurj.org a variety of organometallic systems. [21] The overall homolysis-abstraction process (see Figure 2) is found to be endothermic by 105.0 (BP86) and 54.2 (B3-LYP) kJ mol…”

DFT Analysis of Co−Alkyl and Co−Adenosyl Vibrational Modes in B12-Cofactors

“…Furthermore, the hybrid B3LYP functional does not perform as well as nonhybrid BP86, as has been recently demonstrated. 45,46 For both functionals, the frequencies for the Co-C bond stretch are overestimated and the force constants have to be scaled in order to obtain reasonable agreement with experiment. While the BP86 value is closer to experiment, the overall performance from a statistical point of view is better for B3LYP.…”

Theoretical investigations of photophysics and spectroscopic properties in B12 cofactors.

“…100,155,156,163 For this reason, the electronically excited states of B 12 cofactors 105,106,118,119 have also been investigated using generalized-gradient-approximation-type (GGA-type) functionals, such as BP86. 123,124 It has been deduced that if one is interested in a larger number of MeCbl excited states, the utilization of at least two functionals (i.e., B3LYP and BP86) was required.…”

“…Full geometry optimization was carried out employing the BP86/6-31G(d) (5d) level of theory, which has been found to be appropriate for structural analysis of cobalt corrinoids. 100,155,164 For each optimized geometry harmonic frequencies were calculated to verify that the optimized structure corresponds to a stable minimum. The geometry optimization and frequency calculations have been carried out using the Gaussian 03 suite of programs for the electronic structure calculations.…”