A. Medek et L. Frydman, A multinuclear solid-state NMR analysis of vitamin B-12 in its different polymorphic forms, J AM CHEM S, 122(4), 2000, pp. 684-691
Multinuclear solid-state nuclear magnetic resonance methods (Co-59, C-13, N
-15, and P-31 NMR) were applied at natural abundance to the structural and
dynamic analysis of cyanocobalamin ( vitamin B-12) polymorphs. These studie
s involved recrystallizing a series of samples under different conditions a
nd from various solvents, and subsequently recording their powder NMR spect
ra at different temperature. Two pofq morphs could be identified in these s
tudies, in correspondence with the two structures described by Hodgkin and
co-workers in their seminal vitamin B-12 crystallographic analyses, Most in
formative about the molecular differences characterizing these two forms we
re the C-13 NMR data, which showed sharp and well-resolved resonances indic
ative of high sample crystallinity. Diagnostic differences between these tw
o forms could be observed in the chemical shifts of particular resonances,
many of which could be assigned to their molecular sites on the basis of so
lution-state Literature and of solid-state spectral editing procedures. The
se shifts indicated a conformational variability that involved a few specif
ic sites in the corrinoid ring and which was not entirely evident from diff
erences among the X-ray structures previously reported for the forms. Furth
er evidence about the conformational flexibility of these sites in the soli
d is furnished by C-13 spectral shifts observed upon changing temperatures.
The relevance of these observations within the context of the extensive st
ructure/ activity relation studies that have been carried out on this class
of systems is briefly addressed.