Assessing Electronically Excited States of Cobalamins …
221
compounds that remain constant across the entire family of derivatives. All B 12
derivatives contain a corrin macrocycle with a central cobalt (Co) ion that is equatorially ligated to four nitrogens of the corrin ring. There are several side chains attached
to the corrin ring that include methyl, acetamide, and propionamide groups. In the
Co(III) form, the metal center is axially ligated to an upper and lower ligand. The
lower ligand is a dimethylbenzimidazole (DBI) base in what is known as the base-on
form. The upper axial ligand is variable and can be used to distinguish cobalamins
from each other. For the case of vitamin B 12 (CNCbl), also known as cyanocobalamin, the upper ligand is a cyano group (CN). There are several other upper axial
ligands that are known to occur naturally as well as various synthetic derivatives.
Herein, we will focus on a few of them, such as the free base corrin (FBC) and
the biochemically relevant CNCbl, methylcobalamin (MeCbl), and adenosylcobalamin (AdoCbl). In addition, we will discuss some other unique derivatives including
antivitamins B 12 , non-alkyl cobalamins, as well as reduced and super-reduced forms.
These will all be discussed in later sections of this chapter.
The field of B 12 chemistry is diverse and has a long and rich history. The discovery
of vitamin B 12 , the elucidation of its role in metabolism, structural characterization,
total synthesis, as well as the discovery of B 12 -dependent enzymes occurred in distinct phases over more than 100 years. It was the subject of two separate Nobel Prizes.
Vitamin B 12 was discovered in 1926 by Georg R. Minot and William P. Murphy. In
1934, both scientists, as well as George Whipple, won a Nobel Prize for their work
in the treatment of pernicious anemia. Vitamin B 12 was not officially isolated until
1948. The vitamin was isolated by two groups simultaneously and was crystallized
and characterized in the laboratory of Dorothy Hodgkin in 1954–1955. Her contributions to X-ray crystallography, through the determination of the structures of
important biochemical substances, including vitamin B 12 , were recognized when she
was awarded the Nobel Prize in chemistry in 1964.
There have been a number of extensive reviews and a few books that summarize
various aspects of B 12 -related chemistry and biochemistry [4–9, 16, 25, 67, 69, 75,
77, 80, 89, 95]. However, a synopsis concerning the role of the methods of computational chemistry in advancing this field beyond the twentieth century has not yet been
completed. This book chapter aims to shed light on the use of density functional theory (DFT) and time-dependent density functional theory (TD-DFT) [10, 11, 74] in
understanding the electronically excited states of these compounds in the context of
absorption (Abs) spectroscopy. Herein, we will follow an overview of B 12 chemistry
with a discussion of the importance of electronically excited states and early efforts to
understand these states. For thorough discussions of the electronic spectra of B 12 , we
encourage the curious reader to refer to Giannotti [24] and Pratt’s [68] contributions.
We will also introduce DFT and TD-DFT and their application to electronic structure
calculations. Important conclusions from benchmark studies of various cobalamins
for both ground- and excited-state properties will be summarized. The bulk of this
chapter will be devoted to discussing specific cobalamins and what is known about
their Abs properties from both spectroscopic and computational point of views.
221
compounds that remain constant across the entire family of derivatives. All B 12
derivatives contain a corrin macrocycle with a central cobalt (Co) ion that is equatorially ligated to four nitrogens of the corrin ring. There are several side chains attached
to the corrin ring that include methyl, acetamide, and propionamide groups. In the
Co(III) form, the metal center is axially ligated to an upper and lower ligand. The
lower ligand is a dimethylbenzimidazole (DBI) base in what is known as the base-on
form. The upper axial ligand is variable and can be used to distinguish cobalamins
from each other. For the case of vitamin B 12 (CNCbl), also known as cyanocobalamin, the upper ligand is a cyano group (CN). There are several other upper axial
ligands that are known to occur naturally as well as various synthetic derivatives.
Herein, we will focus on a few of them, such as the free base corrin (FBC) and
the biochemically relevant CNCbl, methylcobalamin (MeCbl), and adenosylcobalamin (AdoCbl). In addition, we will discuss some other unique derivatives including
antivitamins B 12 , non-alkyl cobalamins, as well as reduced and super-reduced forms.
These will all be discussed in later sections of this chapter.
The field of B 12 chemistry is diverse and has a long and rich history. The discovery
of vitamin B 12 , the elucidation of its role in metabolism, structural characterization,
total synthesis, as well as the discovery of B 12 -dependent enzymes occurred in distinct phases over more than 100 years. It was the subject of two separate Nobel Prizes.
Vitamin B 12 was discovered in 1926 by Georg R. Minot and William P. Murphy. In
1934, both scientists, as well as George Whipple, won a Nobel Prize for their work
in the treatment of pernicious anemia. Vitamin B 12 was not officially isolated until
1948. The vitamin was isolated by two groups simultaneously and was crystallized
and characterized in the laboratory of Dorothy Hodgkin in 1954–1955. Her contributions to X-ray crystallography, through the determination of the structures of
important biochemical substances, including vitamin B 12 , were recognized when she
was awarded the Nobel Prize in chemistry in 1964.
There have been a number of extensive reviews and a few books that summarize
various aspects of B 12 -related chemistry and biochemistry [4–9, 16, 25, 67, 69, 75,
77, 80, 89, 95]. However, a synopsis concerning the role of the methods of computational chemistry in advancing this field beyond the twentieth century has not yet been
completed. This book chapter aims to shed light on the use of density functional theory (DFT) and time-dependent density functional theory (TD-DFT) [10, 11, 74] in
understanding the electronically excited states of these compounds in the context of
absorption (Abs) spectroscopy. Herein, we will follow an overview of B 12 chemistry
with a discussion of the importance of electronically excited states and early efforts to
understand these states. For thorough discussions of the electronic spectra of B 12 , we
encourage the curious reader to refer to Giannotti [24] and Pratt’s [68] contributions.
We will also introduce DFT and TD-DFT and their application to electronic structure
calculations. Important conclusions from benchmark studies of various cobalamins
for both ground- and excited-state properties will be summarized. The bulk of this
chapter will be devoted to discussing specific cobalamins and what is known about
their Abs properties from both spectroscopic and computational point of views.