Cobalamins are a ubiquitous family of corrinoid metabolites whose roles in biological systems, particularly as cofactors, are far reaching and critical. Cobalamin specifically refers to vitamin B12 but other derivatives of note include methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl). In addition to these cobalamins, are a new class of derivatives known as antivitamins B12. Understanding the complexities of the photochemical properties of these systems has tangible applications in light activated drug design. Antivitamins B12 exhibit this potential for light-induced medicinal applications and have been studied experimentally with several spectroscopic techniques but with limited theoretical insight. Thus, the first theoretical analysis of antivitamins B12 is provided in the form of ground and excited state potential energy surfaces that explain the mechanism of photodissociation of the upper axial ligand and corroborate recent experimental findings. Also included are such results for thiolato-cobalamins, another type of cobalamin derivative. Density functional theory as well as time dependent density functional theory are employed to describe these isolated cofactors in solution, following the successes of several bench mark studies on various members of the vitamin B12 family. Lambda diagnostic calculations, thorough orbital analysis, and agreement with experiment further solidify the choice of method. The enzymatic environment is a crucial factor in considering the properties of cobalamins. As a result, in concert with the TD-DFT calculations for the isolated cofactors, QM/MM calculations are provided for methylmalonyl-CoA mutase, an AdoCbl dependent enzyme. These theoretical insights have implications not only for medicinal applications but also show tractable ways to study transition metal systems and their photochemistry computationally.

Photochemical properties of vitamin B12 derivatives: Implications from TD-DFT calculations

255th National Meeting (2018)

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