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Spectral and electronic properties of nitrosylcobalamin.

Pallares IG, Brunold TC - Inorg Chem (2014)

Bottom Line: Previous studies revealed that among the known biologically relevant cobalamin species, NOCbl possesses the longest bond between the Co ion and the axially bound 5,6-dimethylbenzimidazole base, which was postulated to result from a strong trans influence exerted by the NO ligand.Collectively, our results indicate that the formally unoccupied Co 3dz(2) orbital engages in a highly covalent bonding interaction with the filled NO π* orbital and that the Co-NO bond is strengthened further by sizable π-backbonding interactions that are not present in any other Co(III)Cbl characterized to date.The implications of our results with respect to the unusual structural features and thermochromism of NOCbl and the proposed inhibition mechanisms of B12-dependent enzymes by NOCbl are discussed.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, University of Wisconsin-Madison , Madison, Wisconsin 53706, United States.

ABSTRACT
Nitrosylcobalamin (NOCbl) is readily formed when Co(II)balamin reacts with nitric oxide (NO) gas. NOCbl has been implicated in the inhibition of various B12-dependent enzymes, as well as in the modulation of blood pressure and of the immunological response. Previous studies revealed that among the known biologically relevant cobalamin species, NOCbl possesses the longest bond between the Co ion and the axially bound 5,6-dimethylbenzimidazole base, which was postulated to result from a strong trans influence exerted by the NO ligand. In this study, various spectroscopic (electronic absorption, circular dichroism, magnetic circular dichroism, and resonance Raman) and computational (density functional theory (DFT) and time-dependent DFT) techniques were used to generate experimentally validated electronic structure descriptions for the "base-on" and "base-off" forms of NOCbl. Further insights into the principal Co-ligand bonding interactions were obtained by carrying out natural bond orbital analyses. Collectively, our results indicate that the formally unoccupied Co 3dz(2) orbital engages in a highly covalent bonding interaction with the filled NO π* orbital and that the Co-NO bond is strengthened further by sizable π-backbonding interactions that are not present in any other Co(III)Cbl characterized to date. Because of the substantial NO(-) to Co(III) charge donation, NOCbl is best described as a hybrid of Co(III)-NO(-) and Co(II)-NO(•) resonance structures. In contrast, our analogous computational characterization of a related species, superoxocobalamin, reveals that in this case a Co(III)-O2(-) description is adequate due to the larger oxidizing power of O2 versus NO. The implications of our results with respect to the unusual structural features and thermochromism of NOCbl and the proposed inhibition mechanisms of B12-dependent enzymes by NOCbl are discussed.

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Abs (top), CD (center),and 7 T MCD (bottom) spectra at various temperatures of NOCbi+, a spectroscopic model of base-off NOCbl.
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fig3: Abs (top), CD (center),and 7 T MCD (bottom) spectra at various temperatures of NOCbi+, a spectroscopic model of base-off NOCbl.

Mentions: Upon substitution of the DMB ligandof NOCbl with a more weakly σ-donating water molecule in NOCbi+, a ∼1000 cm–1 blue shift of theα/β bands is observed (Figures 3, top). Additionally, a positively signed feature at 18 500cm–1 appears in the CD spectrum of NOCbi+ that has no counterpart in the NOCbl spectrum, while the prominentnegative feature at 19 000 cm–1 decreasesin intensity and shifts to higher energy (Figure 3, middle). Because the MCD spectra of NOCbl and NOCbi+ are essentially temperature-independent in the 4.5 to 50K range (Supporting Information, Figures S4 andS5), it can be concluded that both species possess diamagnetic(S = 0) ground states, consistent with a Co(III)/NO– oxidation state assignment. Previous studies of otherCo(III) corrinoids have revealed that the spectral changes in theα/β region that occur in response to a DMB → H2O lower ligand substitution reflect a stabilization of theHOMO relative to the LUMO, the extent of which depends on the σ-donatingstrength of the upper axial ligand.20 Asthe blue shift of the α/β bands from NOCbl to NOCbi+ (∼1000 cm–1) is considerably smallerthan the shift observed from MeCbl to MeCbi+ (∼2500cm–1),4 NO may appearto be a weaker σ-donating ligand than a methyl group. However,since the α/β bands of NOCbl occur at higher energiesthan those of MeCbl and all other alkylcobalamins,4 their small blue shifts from NOCbl to NOCbi+ could also be due to the fact that the DMB moiety is only weaklyinteracting with the Co ion in the former species, as suggested bythe unusually long Co–N(DMB) bond observed in the crystal structureof NOCbl.16


Spectral and electronic properties of nitrosylcobalamin.

Pallares IG, Brunold TC - Inorg Chem (2014)

Abs (top), CD (center),and 7 T MCD (bottom) spectra at various temperatures of NOCbi+, a spectroscopic model of base-off NOCbl.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4334241&req=5

fig3: Abs (top), CD (center),and 7 T MCD (bottom) spectra at various temperatures of NOCbi+, a spectroscopic model of base-off NOCbl.
Mentions: Upon substitution of the DMB ligandof NOCbl with a more weakly σ-donating water molecule in NOCbi+, a ∼1000 cm–1 blue shift of theα/β bands is observed (Figures 3, top). Additionally, a positively signed feature at 18 500cm–1 appears in the CD spectrum of NOCbi+ that has no counterpart in the NOCbl spectrum, while the prominentnegative feature at 19 000 cm–1 decreasesin intensity and shifts to higher energy (Figure 3, middle). Because the MCD spectra of NOCbl and NOCbi+ are essentially temperature-independent in the 4.5 to 50K range (Supporting Information, Figures S4 andS5), it can be concluded that both species possess diamagnetic(S = 0) ground states, consistent with a Co(III)/NO– oxidation state assignment. Previous studies of otherCo(III) corrinoids have revealed that the spectral changes in theα/β region that occur in response to a DMB → H2O lower ligand substitution reflect a stabilization of theHOMO relative to the LUMO, the extent of which depends on the σ-donatingstrength of the upper axial ligand.20 Asthe blue shift of the α/β bands from NOCbl to NOCbi+ (∼1000 cm–1) is considerably smallerthan the shift observed from MeCbl to MeCbi+ (∼2500cm–1),4 NO may appearto be a weaker σ-donating ligand than a methyl group. However,since the α/β bands of NOCbl occur at higher energiesthan those of MeCbl and all other alkylcobalamins,4 their small blue shifts from NOCbl to NOCbi+ could also be due to the fact that the DMB moiety is only weaklyinteracting with the Co ion in the former species, as suggested bythe unusually long Co–N(DMB) bond observed in the crystal structureof NOCbl.16

Bottom Line: Previous studies revealed that among the known biologically relevant cobalamin species, NOCbl possesses the longest bond between the Co ion and the axially bound 5,6-dimethylbenzimidazole base, which was postulated to result from a strong trans influence exerted by the NO ligand.Collectively, our results indicate that the formally unoccupied Co 3dz(2) orbital engages in a highly covalent bonding interaction with the filled NO π* orbital and that the Co-NO bond is strengthened further by sizable π-backbonding interactions that are not present in any other Co(III)Cbl characterized to date.The implications of our results with respect to the unusual structural features and thermochromism of NOCbl and the proposed inhibition mechanisms of B12-dependent enzymes by NOCbl are discussed.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, University of Wisconsin-Madison , Madison, Wisconsin 53706, United States.

ABSTRACT
Nitrosylcobalamin (NOCbl) is readily formed when Co(II)balamin reacts with nitric oxide (NO) gas. NOCbl has been implicated in the inhibition of various B12-dependent enzymes, as well as in the modulation of blood pressure and of the immunological response. Previous studies revealed that among the known biologically relevant cobalamin species, NOCbl possesses the longest bond between the Co ion and the axially bound 5,6-dimethylbenzimidazole base, which was postulated to result from a strong trans influence exerted by the NO ligand. In this study, various spectroscopic (electronic absorption, circular dichroism, magnetic circular dichroism, and resonance Raman) and computational (density functional theory (DFT) and time-dependent DFT) techniques were used to generate experimentally validated electronic structure descriptions for the "base-on" and "base-off" forms of NOCbl. Further insights into the principal Co-ligand bonding interactions were obtained by carrying out natural bond orbital analyses. Collectively, our results indicate that the formally unoccupied Co 3dz(2) orbital engages in a highly covalent bonding interaction with the filled NO π* orbital and that the Co-NO bond is strengthened further by sizable π-backbonding interactions that are not present in any other Co(III)Cbl characterized to date. Because of the substantial NO(-) to Co(III) charge donation, NOCbl is best described as a hybrid of Co(III)-NO(-) and Co(II)-NO(•) resonance structures. In contrast, our analogous computational characterization of a related species, superoxocobalamin, reveals that in this case a Co(III)-O2(-) description is adequate due to the larger oxidizing power of O2 versus NO. The implications of our results with respect to the unusual structural features and thermochromism of NOCbl and the proposed inhibition mechanisms of B12-dependent enzymes by NOCbl are discussed.

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