Monitoring the Switching from Base-on to Base-off Forms of Vitamin B12 by Natural and Magnetic Circular Dichroism Spectroscopies

TL;DR

This paper shows how combining two spectroscopy techniques helps detect structural changes in vitamin B12 molecules, which is important for understanding their biological functions.

Contribution

The study is the first to use MCD and ECD together to distinguish between base-on and base-off forms of cobalamins in different pH conditions.

Findings

MCD and ECD can differentiate between base-on and base-off Cbls in aqueous and acidic environments.

The techniques are sensitive to structural modifications at the corrin macrocycle or axial ligands of Cbls.

Quantum mechanics calculations support the spectroscopic differentiation of Cbl forms.

Abstract

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 meso position of the corrin macrocycle or
in the axial upper ligands.

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