Density functional theory (DFT) calculations (BP86/6-31+G(d,p)) and an analysis of the electron density using Bader's quantum theory of atoms in molecules (QTAIM) are used to explore factors that influence the bond dissociation energy (BDE) of the Co-C bond in models for the cofactor in the coenzyme B12-dependent enzymes. An increase in the basicity of L in [L-Co(III)(corrin)-CH3](n+), L = NH3, NH2(-), and NH(2-), causes an elongation of the trans Co-C bond, but this does not necessarily cause the BDE to decrease. The bond between the metal and the N-donor of L, Co-Nα, usually becomes shorter after Co-C homolysis as the resulting five-coordinate product permits the metal ion to move toward L. This contraction increases with the basicity of L and stabilizes the five-coordinate product. The BDE is found to correlate well with two variables, the basicity of L and the difference in the Co-Nα bond length between the five-coordinate product and the six-coordinate ground state. When L is a naturally occurring amino acid or a model for its metal-coordinating side chain, the BDE is found to be moderately dependent on L and decrease with an increase in the softness of the donor atom of L. Sulfides produce a BDE