Interaction Mode and Regioselectivity in Vitamin B₁₂-Dependent Dehalogenation of Aryl Halides by <i>Dehalococcoides mccartyi</i> Strain CBDB1

Abstract

The bacterium <i>Dehalococcoides</i>, strain CBDB1, transforms aromatic halides through reductive dehalogenation. So far, however, the structures of its vitamin B₁₂-containing dehalogenases are unknown, hampering clarification of the catalytic mechanism and substrate specificity as basis for targeted remediation strategies. This study employs a quantum chemical donor–acceptor approach for the Co­(I)-substrate electron transfer. Computational characterization of the substrate electron affinity at carbon–halogen bonds enables discriminating aromatic halides ready for dehalogenation by strain CBDB1 (active substrates) from nondehalogenated (inactive) counterparts with 92% accuracy, covering 86 of 93 bromobenzenes, chlorobenzenes, chlorophenols, chloroanilines, polychlorinated biphenyls, and dibenzo<i>-p-</i>dioxins. Moreover, experimental regioselectivity is predicted with 78% accuracy by a site-specific parameter encoding the overlap potential between the Co­(I) HOMO (highest occupied molecular orbital) and the lowest-energy unoccupied sigma-symmetry substrate MO (σ*), and the observed dehalogenation pathways are rationalized with a success rate of 81%. Molecular orbital analysis reveals that the most reactive unoccupied sigma-symmetry orbital of carbon-attached halogen X (σ_C–X^*) mediates its reductive cleavage. The discussion includes predictions for untested substrates, thus providing opportunities for targeted experimental investigations. Overall, the presently introduced orbital interaction model supports the view that with bacterial strain CBDB1, an inner-sphere electron transfer from the supernucleophile B₁₂ Co­(I) to the halogen substituent of the aromatic halide is likely to represent the rate-determining step of the reductive dehalogenation