Structure and Conformation of Carbohydrates
1.1
37
2 Physical Methods
2.1 Introduction
The physical methods used for the analysis of carbohydrate conformations are becoming
increasingly sophisticated as the molecules studied and the questions asked become larger
and more complicated. X-ray crystallography provides a reference point, the conformations
of compounds in the solid state. In solution, molecular modeling supplies a framework which
can be used to interpret the results of the vast array of NMR spectral observations and those
from other methods. For reviews, see [2,354].
2.2 X-Ray Crystallography
The determination of crystal structures of small molecules has now become routine provided that suitable crystals are available [362,363,364,365]. The advent of higher power X-ray
sources, more synchronized light, and better recording devices has meant that smaller and
smaller crystals can be solved by diffraction methods. At the same time, the analysis of patterns from larger and larger molecules has become easier so that the limit on the use of X-ray
crystallography is the production of crystals.
The crystal structures of a large number of carbohydrate derivatives have been solved [1,106,
366]. Crystal structures provide critical data on bond lengths, bond angles, torsional angles,
intramolecular distances, etc., and this data has played and is continuing to play an important role in the discussion of the factors that influence conformation. Consideration of conformations of individual molecules using X-ray data must take into account intermolecular
forces within the crystal lattice. Analysis of large sets of X-ray data from the Cambridge
Data File avoids this difficulty and this method has influenced discussion of the anomeric
effect [61,62,69]. Although most molecules crystallize in the conformation that is most highly
populated in solution, this is not always true. For instance, 3-ammonio-3-deoxy-1,6-anhydroβ-D-glucopyranose is present in solution mostly in a boat conformation [184,367] but crystallizes in a chair [367]. Of increasing use is the determination of crystal structures of carbohydrates bound to proteins [368,369]. This allows analysis of the conformation of the bound
carbohydrate and of the binding factors, both of which allow the synthesis of better binding
molecules that may have medicinal applications.
2.3 NMR Spectroscopy
NMR spectroscopy is the most important technique for the examination of structure and
conformation in solution [370,371,372,373]. Many aspects of NMR spectroscopy can be
employed for the study of carbohydrates [130,351,374,375,376,377]. Assignment techniques
are discussed in many books and will not be considered here. Chapters by Widmalm [354]
and Serianni [376] include sections on assignment of carbohydrate spectra.
1.1
37
2 Physical Methods
2.1 Introduction
The physical methods used for the analysis of carbohydrate conformations are becoming
increasingly sophisticated as the molecules studied and the questions asked become larger
and more complicated. X-ray crystallography provides a reference point, the conformations
of compounds in the solid state. In solution, molecular modeling supplies a framework which
can be used to interpret the results of the vast array of NMR spectral observations and those
from other methods. For reviews, see [2,354].
2.2 X-Ray Crystallography
The determination of crystal structures of small molecules has now become routine provided that suitable crystals are available [362,363,364,365]. The advent of higher power X-ray
sources, more synchronized light, and better recording devices has meant that smaller and
smaller crystals can be solved by diffraction methods. At the same time, the analysis of patterns from larger and larger molecules has become easier so that the limit on the use of X-ray
crystallography is the production of crystals.
The crystal structures of a large number of carbohydrate derivatives have been solved [1,106,
366]. Crystal structures provide critical data on bond lengths, bond angles, torsional angles,
intramolecular distances, etc., and this data has played and is continuing to play an important role in the discussion of the factors that influence conformation. Consideration of conformations of individual molecules using X-ray data must take into account intermolecular
forces within the crystal lattice. Analysis of large sets of X-ray data from the Cambridge
Data File avoids this difficulty and this method has influenced discussion of the anomeric
effect [61,62,69]. Although most molecules crystallize in the conformation that is most highly
populated in solution, this is not always true. For instance, 3-ammonio-3-deoxy-1,6-anhydroβ-D-glucopyranose is present in solution mostly in a boat conformation [184,367] but crystallizes in a chair [367]. Of increasing use is the determination of crystal structures of carbohydrates bound to proteins [368,369]. This allows analysis of the conformation of the bound
carbohydrate and of the binding factors, both of which allow the synthesis of better binding
molecules that may have medicinal applications.
2.3 NMR Spectroscopy
NMR spectroscopy is the most important technique for the examination of structure and
conformation in solution [370,371,372,373]. Many aspects of NMR spectroscopy can be
employed for the study of carbohydrates [130,351,374,375,376,377]. Assignment techniques
are discussed in many books and will not be considered here. Chapters by Widmalm [354]
and Serianni [376] include sections on assignment of carbohydrate spectra.