252
M. J. Toda et al.
sensus on the character of transitions giving rise to the cob(I)alamin Abs spectra
using TD-DFT. The Abs spectra were simulated with CAM-B3LYP and BP86 and
were compared to the experimental spectrum. BP86 performed better than the hybrid
in exhibiting good agreement with experimentally determined Abs, CD, and MCD
spectra. It was concluded that the lowest energy band was MLCT in characterand
not a single π →π
∗ transition followed by a vibrational progression as was previously thought [49]. In addition, the idea that the α/β region arises from a vibrational
progression was not supported in this study rather both functionals indicated that
multiple electronic transitions are involved in this region.
10 Summary and Future Directions
In sum, Abs spectroscopy is an important tool to probe the electronically excited
states of cobalamins. It is evident that Abs spectra can be used as a diagnostic
tool to distinguish cobalamins from each other based on oxidation state and the
nature of the upper axial ligand. While experimental Abs spectroscopy is of critical
importance to understand the light sensitivity of B 12 derivatives, this alone is not
enough to understand the nature of the transitions that give rise to the distinctive
spectral features. TD-DFT is an appropriate computational tool to elucidate the nature
of the excitations responsible for a particular B 12 Abs spectrum. However, proper
functional choice is paramount in predicting these transitions and simulating the full
spectrum reliably. At this juncture in the field of B 12 chemistry, it is indisputable that
the BP86 functional are the proper functional for the assessment of the electronically
excited states of the cobalamins. The specific stories for each of the cobalamins
discussed in this chapter certainly corroborate the use of BP86. This GGA-type
functional is especially dependable in accounting for the contributions from Co.
Now that details of the electronically excited states of the cobalamins are widely
understood through the lens of Abs spectroscopy, it is time to look ahead to see how
this tool can be harnessed to solve practical problems in the field of B 12 chemistry.
Abs spectroscopy could be an important tool to understand light-induced RP formation. This has applications across various disciplines, but recent attention has
been given to the generation of OH radicals, drug delivery, antivitamins B 12 , the
transcription regulator CarH, and mimicking enzymatic catalysis. It has been shown
that hydroxyl radicals can be generated in situ from the aerobic photolysis of hydroxocobalamin (HOCbl), and this can be used to study DNA structure and binding [35].
Cobalamins can also be synthetically altered to be used as scaffolds for the targeted
release of therapeutics via light [80, 81]. Recently, two synthetic antivitamins B 12 ,
namely EtPhCbl and PhEtyCbl, have been studied and represent an interesting group
of derivatives that can counteract the physiological effects of the biologically relevant forms of B 12 by inhibition [60]. EtPhCbl has been used to induce B 12 -deficiency
in laboratory animals in studies of pernicious anemia [62]. It is expected that these
compounds can be used to investigate various aspects of B 12 pathophysiology that
remain poorly understood. EtPhCbl and PhEtyCbl also represent an important step
M. J. Toda et al.
sensus on the character of transitions giving rise to the cob(I)alamin Abs spectra
using TD-DFT. The Abs spectra were simulated with CAM-B3LYP and BP86 and
were compared to the experimental spectrum. BP86 performed better than the hybrid
in exhibiting good agreement with experimentally determined Abs, CD, and MCD
spectra. It was concluded that the lowest energy band was MLCT in characterand
not a single π →π
∗ transition followed by a vibrational progression as was previously thought [49]. In addition, the idea that the α/β region arises from a vibrational
progression was not supported in this study rather both functionals indicated that
multiple electronic transitions are involved in this region.
10 Summary and Future Directions
In sum, Abs spectroscopy is an important tool to probe the electronically excited
states of cobalamins. It is evident that Abs spectra can be used as a diagnostic
tool to distinguish cobalamins from each other based on oxidation state and the
nature of the upper axial ligand. While experimental Abs spectroscopy is of critical
importance to understand the light sensitivity of B 12 derivatives, this alone is not
enough to understand the nature of the transitions that give rise to the distinctive
spectral features. TD-DFT is an appropriate computational tool to elucidate the nature
of the excitations responsible for a particular B 12 Abs spectrum. However, proper
functional choice is paramount in predicting these transitions and simulating the full
spectrum reliably. At this juncture in the field of B 12 chemistry, it is indisputable that
the BP86 functional are the proper functional for the assessment of the electronically
excited states of the cobalamins. The specific stories for each of the cobalamins
discussed in this chapter certainly corroborate the use of BP86. This GGA-type
functional is especially dependable in accounting for the contributions from Co.
Now that details of the electronically excited states of the cobalamins are widely
understood through the lens of Abs spectroscopy, it is time to look ahead to see how
this tool can be harnessed to solve practical problems in the field of B 12 chemistry.
Abs spectroscopy could be an important tool to understand light-induced RP formation. This has applications across various disciplines, but recent attention has
been given to the generation of OH radicals, drug delivery, antivitamins B 12 , the
transcription regulator CarH, and mimicking enzymatic catalysis. It has been shown
that hydroxyl radicals can be generated in situ from the aerobic photolysis of hydroxocobalamin (HOCbl), and this can be used to study DNA structure and binding [35].
Cobalamins can also be synthetically altered to be used as scaffolds for the targeted
release of therapeutics via light [80, 81]. Recently, two synthetic antivitamins B 12 ,
namely EtPhCbl and PhEtyCbl, have been studied and represent an interesting group
of derivatives that can counteract the physiological effects of the biologically relevant forms of B 12 by inhibition [60]. EtPhCbl has been used to induce B 12 -deficiency
in laboratory animals in studies of pernicious anemia [62]. It is expected that these
compounds can be used to investigate various aspects of B 12 pathophysiology that
remain poorly understood. EtPhCbl and PhEtyCbl also represent an important step