Mechanism of Co–C Bond Photolysis in Methylcobalamin: Influence of Axial Base

A mechanism of Co–C bond photolysis in the base-off form of the methylcobalamin cofactor (MeCbl) and the influence of its axial base on Co–C bond photodissociation has been investigated by time-dependent density functional theory (TD-DFT). At low pH, the MeCbl cofactor adopts the base-off form in which the axial nitrogenous ligand is replaced by a water molecule. Ultrafast excited-state dynamics and photolysis studies have revealed that a new channel for rapid nonradiative decay in base-off MeCbl is opened, which competes with bond dissociation. To explain these experimental findings, the corresponding potential energy surface of the S₁ state was constructed as a function of Co–C and Co–O bond distances, and the manifold of low-lying triplets was plotted as a function of Co–C bond length. In contrast to the base-on form of MeCbl in which two possible photodissociation pathways were identified on the basis of whether the Co–C bond (path A) or axial Co–N bond (path B) elongates first, only path B is active in base-off MeCbl. Specifically, path A is inactive because the energy barrier associated with direct dissociation of the methyl ligand is higher than the barrier of intersection between two different electronic states: a metal-to-ligand charge transfer state (MLCT), and a ligand field state (LF) along the Co–O coordinate of the S₁ PES. Path B initially involves displacement of the water molecule, followed by the formation of an LF-type intermediate, which possesses a very shallow energy minimum with respect to the Co–C coordinate. This LF-type intermediate on path B may result in either S₁/S₀ internal conversion or singlet radical pair generation. In addition, intersystem crossing (ISC) resulting in generation of a triplet radical pair is also feasible

Mechanism of Co–C Bond Photolysis in the Base-On Form of Methylcobalamin

A mechanism of Co–C bond photodissociation in the base-on form of the methylcobalamin cofactor (MeCbl) has been investigated employing time-dependent density functional theory (TD-DFT), in which the key step involves singlet radical pair generation from the first electronically excited state (S₁). The corresponding potential energy surface of the S₁ state was constructed as a function of Co–C and Co–N_axial bond distances, and two possible photodissociation pathways were identified on the basis of energetic grounds. These pathways are distinguished by whether the Co–C bond (path A) or Co–N_axial bond (path B) elongates first. Although the final intermediate of both pathways is the same (namely a ligand field (LF) state responsible for Co–C dissociation), the reaction coordinates associated with paths A and B are different. The photolysis of MeCbl is wavelength-dependent, and present TD-DFT analysis indicates that excitation in the visible α/β band (520 nm) can be associated with path A, whereas excitation in the near-UV region (400 nm) is associated with path B. The possibility of intersystem crossing, and internal conversion to the ground state along path B are also discussed. The mechanism proposed in this study reconciles existing experimental data with previous theoretical calculations addressing the possible involvement of a repulsive triplet state

The Cobalt–Methyl Bond Dissociation in Methylcobalamin: New Benchmark Analysis Based on Density Functional Theory and Completely Renormalized Coupled-Cluster Calculations

The Co–C_Me bond dissociation in methylcobalamin (MeCbl), modeled by the Im–[Co^IIIcorrin]–Me⁺ system consisting of 58 atoms, is examined using the coupled-cluster (CC), density-functional theory (DFT), complete-active-space self-consistent-field (CASSCF), and CASSCF-based second-order perturbation theory (CASPT2) approaches. The multilevel variant of the local cluster-in-molecule framework, employing the completely renormalized (CR) CC method with singles, doubles, and noniterative triples, termed CR-CC(2,3), to describe higher-order electron correlation effects in the region where the Co–C_Me bond breaking takes place, and the canonical CC approach with singles and doubles (CCSD) to capture the remaining correlation effects, abbreviated as CR-CC(2,3)/CCSD, is used to obtain the benchmark potential energy curve characterizing the Co–C_Me dissociation in the MeCbl cofactor. The Co–C_Me bond dissociation energy (BDE) resulting from the CR-CC(2,3)/CCSD calculations for the Im–[Co^IIIcorrin]–Me⁺ system using the 6-31G* basis set, corrected for the zero-point energies (ZPEs) and the effect of replacing the 6-31G* basis by 6-311++G**, is about 38 kcal/mol, in excellent agreement with the experimental values characterizing MeCbl of 37 ± 3 and 36 ± 4 kcal/mol. Of all DFT functionals examined, the best dissociation energies and the most accurate description of the Co–C_Me bond breaking in the Im–[Co^IIIcorrin]–Me⁺ system are provided by B97-D and BP86 corrected for dispersion using the D3 correction of Grimme et al., which give 35 and 40 kcal/mol, respectively, when the 6-311++G** basis set is employed and when the results are corrected for ZPEs and basis set superposition error. None of the other DFT approaches examined provide results that fall into the experimental range of the Co–C_Me dissociation energies in MeCbl of 32–40 kcal/mol. The hybrid DFT functionals with a substantial amount of the Hartree–Fock (HF) exchange, such as B3LYP, considerably underestimate the calculated dissociation energies, with the magnitude of the error being proportional to the percentage of the HF exchange in the functional. It is argued that the overstabilization of diradical structures that emerge as the Co–C_Me bond is broken and, to some extent, the neglect of dispersion interactions at shorter Co–C_Me distances, postulated in previous studies, are the main factors that explain the substantial underestimation of the Co–C_Me BDE by B3LYP and other hybrid functionals. Our calculations suggest that CASSCF and CASPT2 may have difficulties with providing a reliable description of the Co–C_Me bond breaking in MeCbl, since using adequate active spaces is prohibitively expensive