Photodissociation of ethylphenylcobalamin antivitamin B₁₂

Biologically active forms of cobalamins are crucial cofactors in biochemical reactions and these metabolites can be inhibited by their structurally similar analogues known as antivitamins B₁₂. Phenylethynylcobalamin (PhEtyCbl) or 4-ethylphenylcobalamin (EtPhCbl) exemplify recently synthesized and structurally characterized antivitamins B₁₂. Herein, DFT and TD-DFT studies of EtPhCbl are provided to explore its photochemical behavior, which may lead to design of arylcobalamins that can be used as therapeutic agents in light activated drug applications. To understand the photolability of EtPhCbl, a potential energy surface (PES) for the photodissociation of the Co-C bond was constructed. The S₁ PES contains two energy minima, one being metal-to-ligand charge transfer (MLCT) and another the ligand-field (LF) state. There are two possible pathways for photodissociation: the first pathway (path A) involves initially lengthening the Co-C bond from the MLCT minimum and then elongation of Co-N_Im while the second pathway (path B) involves the lengthening of the Co-N_Im bond through the MLCT region followed by the lengthening of the Co-C bond through the LF region. It is shown that photodissociation involving path A is not energetically favorable whereas preferable photodissociation of the Co-C bond involves path B.