Conformational Analysis in Solution by NMR

In order to understand the molecular basis of oligosaccharide-mediated recognition phenomena, we need to have knowledge of the structure and dynamics of the free carbohydrate ligand in addition to the ligand-receptor complex. In this Chapter, I shall review current knowledge on the former. A discussion of ligand-receptor complexes can be foimd elsewhere in this volume. 

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R133 S. W. Homans, Conformational Analysis in Solution by NMR , p. 947 R134 J. F. G. Vliegenthart and H.-C. Siebert, Carbohydrate-Protein Interactions Use of the Laser Photo Chemically Induced Dynamic Nuclear Polarization (CIDNP) - NMR Technique , p. 1025... 

Conformational analysis of oligosaccharides in solution by NMR is mainly based on hydrogen-hydrogen distance information obtained from the nuclear Overhauser effect (n.O.e.) ( ). Other independent NMR... 

A trisaccharide fragment of the jV-type oligosaccharides (oc-D-Man-(l-3)-p-D-Man-(l-4)- 3-D-Glc.VAc) including the central P-D-Man has been obtained as single crystals. The dihedral angles of the glycosidic bonds which were obtained from an X-ray analysis are summarized in Fig. 9 [ 137]. This conformation is very closely related to the conformations calculated or determined experimentally in solution by NMR... 

This can be overcome by an analysis of chemical shifts, which also depend on conformation. A detailed case history, which provides an example of NMR conformational analysis in solution and the solid state, for glyconamides is given in Sec. 4.2. ... 

The conformational behaviour in solution of a dermatan-derived tetra-saccharide has been explored by means of NMR spectroscopy, especially by NOE-based conformational analysis. RDCs were also measured for the tetrasaccharide in a phage solution and interpreted in combination with restrained MD simulations. The RDC-derived data substantially confirmed the validity of the conformer distribution resulting from the NOE-derived simulations, but allowed an improved definition of the conformational behaviour of the oligosaccharides in solution, which show a moderate flexibility at the central glycosidic linkage. Differences in the shapes of the different species with the IdoA in skew and in chair conformations and in the distribution of the sulphate groups were also highlighted.28... 

Tnformation about the characteristics of keto-hexoses in solution has been - derived mainly from optical rotatory data (I, 2, 3, 4) and in recent years by application of the principles of conformational analysis (5, 6). In the current study an attempt is made to describe the conformation and composition of these sugars in solution by nuclear magnetic resonance (NMR) spectroscopy, a highly sensitive means for examining stereochemistry and for differentiating between isomeric species. 

NMR and UV-vis spectroscopic studies as well as molecular mechanics calculations have been performed for the trans and cis isomers of a series of chlorine substituted stilbenes. In a continuing study on the use of hydroxy protons in conformational analysis of saccharides in aqueous solution by NMR, a number of disaccharides with 1,3-, 1,4- and 1,6-hnkages were investigated. ... 

Similarly, the CC conformation was found for compounds 52 and 53 in the solid state (X-ray data) (50). Compound 52 was found by variable temperature H-NMR spectroscopy to undergo a rapid base-induced intramolecular 3,7-hydride shift (the associated activation energy is AG1 = 19.4 0.2kcal mol1 at 113°C)(51). The CC conformation of compounds 54 (52) and 55-58 (4) and the CB conformation of compound 59 (4) found in solution by analysis of 13C-NMR spectra are as expected. However, the preference for the CC conformation was discussed on the basis of 13C-NMR data for the... 

The 3,7-diazabicyclo[3.3.1]nonanes (bispidines) are among the most thoroughly investigated hetero analogs of bicyclo[3.3.1]nonane (1,2). Conformational studies of 3,7-dimethyl-3,7-diazabicyclo[3.3.1]nonane (147) in solution by the dipole moment method, and by H- and 13C-NMR spectroscopy (107,108), have shown a preference for the chair-chair conformation. Semiempirical calculations (EH, CNDO/2) (109) and analysis of the photoelectron spectrum of 147 in combination with three sets of other MO calculations (MINDO/3, MNDO, and ab initio at the STO-3G level) lead to the conclusion that, in the gas phase, 147 exists in the chair-chair conformation (108). 

The above discussion has dealt with reduction of F430 to the putative active form. Unfortunately, there is little structural information on Ni F430, except that regarding the direct coordination environment around Ni(I), as derived in solution by EXAFS, EPR, and related techniques (Sect. 5.4, 5.6, 5.7). In contrast, NMR and crystallographic studies have provided detailed information on the solution and solid-state conformation of isolated F430 and derivatives, as well as of numerous model compounds (Sects. 5.1,5.2). This information has provided the basis for several studies using conformational analysis, both of F430 [99,100, 40] and of model compounds [101,102],... 

A similar structural study was made with angustifoline. The H and l3C NMR spectra of the alkaloid in four different solvents were fully assigned by resorting to 2D H- H and H-I3C COSY and 2D J resolved spectra. Conformational analysis in the solid state and in solution is presented [201]. More recently other studies of the conformational equilibrium of diazatricyclic systems based on one- and two- dimensional H, 3C and 15N NMR experiments were published [202,203]. 

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