| Abstract
| - The 4-coordinate, low-spin cob(I)alamin (Co1+Cbl) species, which can be obtained by heterolyticcleavage of the Co−C bond in methylcobalamin or the two-electron reduction of vitamin B12, is one of themost powerful nucleophiles known to date. The supernucleophilicity of Co1+Cbl has been harnessed by anumber of cobalamin-dependent enzymes, such as the B12-dependent methionine synthase, and by enzymesinvolved in the biosynthesis of B12, including the human adenosyltransferase. The nontoxic nature of theCo1+Cbl supernucleophile also makes it an attractive target for the in situ bioremediation of halogenatedwaste. To gain insight into the geometric, electronic, and vibrational properties of this highly reactive species,electronic absorption, circular dichroism (CD), magnetic CD, and resonance Raman (rR) spectroscopieshave been employed in conjunction with density functional theory (DFT), time-dependent DFT, and combinedquantum mechanics/molecular mechanics computations. Collectively, our results indicate that the supernucleophilicity of Co1+Cbl can be attributed to the large destabilization of the Co 3dz2-based HOMO and itsfavorable orientation with respect to the corrin macrocycle, which minimizes steric repulsion duringnucleophilic attack. An intense feature in the CD spectrum and a prominent peak in the rR spectra ofCo1+Cbl have been identified that may serve as excellent probes of the nucleophilic character, and thusthe reactivity, of Co1+Cbl in altered environments, including enzyme active sites. The implications of ourresults with respect to the enzymatic formation and reactivity of Co1+Cbl are discussed, and spectroscopictrends along the series from Co3+Cbls to Co2+Cbl and Co1+Cbl are explored.
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