Epimerization of cyanocobalamin. Improved synthesis of cyano-8-epicobalamin and its characterization by x-ray crystallography, and 1H, 13C, and 15N NMR

Heteronuclear NMR Studies of Cobalt Corrinoids. 18. Correlation of Structure and Magnetic Resonance Parameters in Base-On Cobalamins1

“…Glusker 38 has attempted to quantitate this fold as the angle between the normals to a "northern" plane, defined by N21, C4, C5, C6, N22, C9, and C10, and a "southern" plane, defined by N24, C16, C15, C14, N23, C11, and C10. The Glusker fold angle for CN-13-epiCbl is 23.7°, almost identical to that for CN-8-epiCbl (23.8°) 15 but significantly larger than those for CNCbl (18.0°) and H 2 OCbl + (18.7°) (Table 2). However, there is also a significant twist between the two Glusker planes, roughly about the C15‚‚‚C5 line.…”

“…A comparison of the 13 C chemical shifts of CN-13-epiCbl and CNCbl is shown in structure 1, which gives all significant chemical shift differences (∆δ > 0.25 ppm) with large chemical shift differences (∆δ > 0.5 ppm) in boldface. This comparison shows that, unlike CN-8-epiCbl, 15 where chemical shift differences are almost completely confined to the region near the site of epimerization, CN-13-epiCbl has significant chemical shift differences quite remote from the site of epimerization. This gives rise to the conjecture that these remote chemical shift differences must be due to differences in conformation between CNCbl and CN-13-epiCbl since the similarity of the inner spheres of these two complexes makes it unlikely that either electronic or anisotropic differences contribute to the chemical shift differentials significantly.…”

“…For such comparisons, carbon atoms close to the site of epimerization must be avoided since the change in configuration will alter the magnetic environments in which these carbons find themselves. For CN-8-epiCbl, almost all of the carbons with chemical shifts significantly different from those in CNCbl occur at or near the site of epimerization . However, 15 carbons remote from the epimerization site in CN-13-epiCbl ( 1 ) have chemical shifts significantly different from those of their counterparts in CNCbl.…”

Heteronuclear NMR Studies of Cobalt Corrinoids. 18. Correlation of Structure and Magnetic Resonance Parameters in Base-On Cobalamins1

“…Glusker 38 has attempted to quantitate this fold as the angle between the normals to a "northern" plane, defined by N21, C4, C5, C6, N22, C9, and C10, and a "southern" plane, defined by N24, C16, C15, C14, N23, C11, and C10. The Glusker fold angle for CN-13-epiCbl is 23.7°, almost identical to that for CN-8-epiCbl (23.8°) 15 but significantly larger than those for CNCbl (18.0°) and H 2 OCbl + (18.7°) (Table 2). However, there is also a significant twist between the two Glusker planes, roughly about the C15‚‚‚C5 line.…”

“…A comparison of the 13 C chemical shifts of CN-13-epiCbl and CNCbl is shown in structure 1, which gives all significant chemical shift differences (∆δ > 0.25 ppm) with large chemical shift differences (∆δ > 0.5 ppm) in boldface. This comparison shows that, unlike CN-8-epiCbl, 15 where chemical shift differences are almost completely confined to the region near the site of epimerization, CN-13-epiCbl has significant chemical shift differences quite remote from the site of epimerization. This gives rise to the conjecture that these remote chemical shift differences must be due to differences in conformation between CNCbl and CN-13-epiCbl since the similarity of the inner spheres of these two complexes makes it unlikely that either electronic or anisotropic differences contribute to the chemical shift differentials significantly.…”

“…For such comparisons, carbon atoms close to the site of epimerization must be avoided since the change in configuration will alter the magnetic environments in which these carbons find themselves. For CN-8-epiCbl, almost all of the carbons with chemical shifts significantly different from those in CNCbl occur at or near the site of epimerization . However, 15 carbons remote from the epimerization site in CN-13-epiCbl ( 1 ) have chemical shifts significantly different from those of their counterparts in CNCbl.…”

Trifluoracetic Acid-Assisted Crystallization of Vitamin B12 Results in Protonation of the Phosphate Group of the Nucleotide Loop: Insight into the Influence of Crystal Packing Forces on Vitamin B12 Structures

“…In Figure a, the two groups are shown still separated according to Randaccio et al, who first showed cluster IV being characterized by two distinctive intramolecular H-bonds involving (i) the amide N40 nitrogen atom (chain c ) and the β-axial X group and (ii) the ribose O8R and the carbonyl O51 (chain e ) oxygen atoms . However, if a list of known modified CNCbls − or CNCbl-conjugates is included in the plot (Figure b), exceptions to this “rule” can be noted for cluster IV. In general, a discrete number of exceptions to general H-bonds motifs can be also found either in cluster I or II, as shown in Figure a.…”

Structural and Enzymatic Studies of a New Analogue of Coenzyme B12 with an α-Adenosyl Upper Axial Ligand

“…NMR Spectra of (R-ribo)AdoCbl. The 1 H and 13 C NMR spectra of (R-ribo)AdoCbl in aqueous solution were completely assigned using the now standard battery of homonuclear and heteronuclear 2D NMR experiments and assignment strategies (17,(56)(57)(58). A NMR correlation table and the 1 H and 13 C assignments are available as Supporting Information.…”

Heteronuclear NMR Studies of Cobalt Corrinoids. 18. Correlation of Structure and Magnetic Resonance Parameters in Base-On Cobalamins1

“…Glusker 38 has attempted to quantitate this fold as the angle between the normals to a "northern" plane, defined by N21, C4, C5, C6, N22, C9, and C10, and a "southern" plane, defined by N24, C16, C15, C14, N23, C11, and C10. The Glusker fold angle for CN-13-epiCbl is 23.7°, almost identical to that for CN-8-epiCbl (23.8°) 15 but significantly larger than those for CNCbl (18.0°) and H 2 OCbl + (18.7°) (Table 2). However, there is also a significant twist between the two Glusker planes, roughly about the C15‚‚‚C5 line.…”

“…A comparison of the 13 C chemical shifts of CN-13-epiCbl and CNCbl is shown in structure 1, which gives all significant chemical shift differences (∆δ > 0.25 ppm) with large chemical shift differences (∆δ > 0.5 ppm) in boldface. This comparison shows that, unlike CN-8-epiCbl, 15 where chemical shift differences are almost completely confined to the region near the site of epimerization, CN-13-epiCbl has significant chemical shift differences quite remote from the site of epimerization. This gives rise to the conjecture that these remote chemical shift differences must be due to differences in conformation between CNCbl and CN-13-epiCbl since the similarity of the inner spheres of these two complexes makes it unlikely that either electronic or anisotropic differences contribute to the chemical shift differentials significantly.…”

“…For such comparisons, carbon atoms close to the site of epimerization must be avoided since the change in configuration will alter the magnetic environments in which these carbons find themselves. For CN-8-epiCbl, almost all of the carbons with chemical shifts significantly different from those in CNCbl occur at or near the site of epimerization . However, 15 carbons remote from the epimerization site in CN-13-epiCbl ( 1 ) have chemical shifts significantly different from those of their counterparts in CNCbl.…”

Trifluoracetic Acid-Assisted Crystallization of Vitamin B12 Results in Protonation of the Phosphate Group of the Nucleotide Loop: Insight into the Influence of Crystal Packing Forces on Vitamin B12 Structures

“…In Figure a, the two groups are shown still separated according to Randaccio et al, who first showed cluster IV being characterized by two distinctive intramolecular H-bonds involving (i) the amide N40 nitrogen atom (chain c ) and the β-axial X group and (ii) the ribose O8R and the carbonyl O51 (chain e ) oxygen atoms . However, if a list of known modified CNCbls − or CNCbl-conjugates is included in the plot (Figure b), exceptions to this “rule” can be noted for cluster IV. In general, a discrete number of exceptions to general H-bonds motifs can be also found either in cluster I or II, as shown in Figure a.…”

Structural and Enzymatic Studies of a New Analogue of Coenzyme B12 with an α-Adenosyl Upper Axial Ligand

“…NMR Spectra of (R-ribo)AdoCbl. The 1 H and 13 C NMR spectra of (R-ribo)AdoCbl in aqueous solution were completely assigned using the now standard battery of homonuclear and heteronuclear 2D NMR experiments and assignment strategies (17,(56)(57)(58). A NMR correlation table and the 1 H and 13 C assignments are available as Supporting Information.…”

Heteronuclear NMR Studies of Cobalt Corrinoids. 18. Correlation of Structure and Magnetic Resonance Parameters in Base-On Cobalamins1

“…Glusker 38 has attempted to quantitate this fold as the angle between the normals to a "northern" plane, defined by N21, C4, C5, C6, N22, C9, and C10, and a "southern" plane, defined by N24, C16, C15, C14, N23, C11, and C10. The Glusker fold angle for CN-13-epiCbl is 23.7°, almost identical to that for CN-8-epiCbl (23.8°) 15 but significantly larger than those for CNCbl (18.0°) and H 2 OCbl + (18.7°) (Table 2). However, there is also a significant twist between the two Glusker planes, roughly about the C15‚‚‚C5 line.…”

“…A comparison of the 13 C chemical shifts of CN-13-epiCbl and CNCbl is shown in structure 1, which gives all significant chemical shift differences (∆δ > 0.25 ppm) with large chemical shift differences (∆δ > 0.5 ppm) in boldface. This comparison shows that, unlike CN-8-epiCbl, 15 where chemical shift differences are almost completely confined to the region near the site of epimerization, CN-13-epiCbl has significant chemical shift differences quite remote from the site of epimerization. This gives rise to the conjecture that these remote chemical shift differences must be due to differences in conformation between CNCbl and CN-13-epiCbl since the similarity of the inner spheres of these two complexes makes it unlikely that either electronic or anisotropic differences contribute to the chemical shift differentials significantly.…”

“…For such comparisons, carbon atoms close to the site of epimerization must be avoided since the change in configuration will alter the magnetic environments in which these carbons find themselves. For CN-8-epiCbl, almost all of the carbons with chemical shifts significantly different from those in CNCbl occur at or near the site of epimerization . However, 15 carbons remote from the epimerization site in CN-13-epiCbl ( 1 ) have chemical shifts significantly different from those of their counterparts in CNCbl.…”

Trifluoracetic Acid-Assisted Crystallization of Vitamin B12 Results in Protonation of the Phosphate Group of the Nucleotide Loop: Insight into the Influence of Crystal Packing Forces on Vitamin B12 Structures

“…In Figure a, the two groups are shown still separated according to Randaccio et al, who first showed cluster IV being characterized by two distinctive intramolecular H-bonds involving (i) the amide N40 nitrogen atom (chain c ) and the β-axial X group and (ii) the ribose O8R and the carbonyl O51 (chain e ) oxygen atoms . However, if a list of known modified CNCbls − or CNCbl-conjugates is included in the plot (Figure b), exceptions to this “rule” can be noted for cluster IV. In general, a discrete number of exceptions to general H-bonds motifs can be also found either in cluster I or II, as shown in Figure a.…”

Structural and Enzymatic Studies of a New Analogue of Coenzyme B12 with an α-Adenosyl Upper Axial Ligand

“…NMR Spectra of (R-ribo)AdoCbl. The 1 H and 13 C NMR spectra of (R-ribo)AdoCbl in aqueous solution were completely assigned using the now standard battery of homonuclear and heteronuclear 2D NMR experiments and assignment strategies (17,(56)(57)(58). A NMR correlation table and the 1 H and 13 C assignments are available as Supporting Information.…”