Monitoring the Switching from Base-on to Base-off Forms of Vitamin B ₁₂ by Natural and Magnetic Circular Dichroism Spectroscopies

This work demonstrates that an approach which makes use of magnetic circular dichroism (MCD) together with electronic circular dichroism (ECD) brings one to a rapid, sensitive, nondestructive, and inexpensive determination of the electronic structure of diamagnetic, chiral, and flexible molecular systems. The subject of this study is cobalamins (Cbls), including vitamin B₁₂, the unique and intricate structure of which determines their selective and strong protein binding. Their existence in two forms (base-on and base-off) not only causes significant structural changes but also influences the reactivity of B₁₂ derivatives in biologically important organometallic reactions. Therefore, recognizing the Cbl forms and understanding how they switch between them is essential. Notably, this study is the first to show that combining MCD and ECD, supported by quantum mechanics calculations, allows differentiation between base-on and base-off Cbls in aqueous environment at pH 7.4 and in acidic conditions, respectively. Furthermore, these techniques are sensitive to Cbl modifications at the <i>meso</i> position of the corrin macrocycle or in the axial upper ligands.