Anomeric effect torsional angles

Another anomeric effect is that acetal C-0 bonds, and to a lesser extent, the bonds between acetal carbons and ether oxygens, are shortened or elongated as a function of their associated torsional angles. Jeffrey and Taylor modified MMl to account for these anomeric effects (17) and similar additions were put in the standard 1985 version of MM2 (11). The parameterization of MM3 for anomeric effects is preliminary, with recent (18-20) results being monitored. 

It is to be emphasized that, in the absence of elements of symmetry, as is the case for carbohydrates, determination of the molecular structure should be based on both the experimental, vibrational spectra and the calculated frequencies. In order to minimize the differences between experimental and calculated results, the structure factors utilized in the calculation should take into account the previous conformational studies. The peculiarities of carbohydrate structures, such as anomeric and exo-anomeric effects, are revealed by bond shortening and torsion-angle modifications. These modifications are accompanied by a change in the vibrational-energy level, and hence, by the corresponding information in their infrared or Raman spectra. 

In MM3 a cross term involving torsional angles is also used[75] but in other programs it is neglected (exceptions are anomeric effects, e.g., with sugars). In other programs[52,5gJ, 1,3-interactions can be selectively included, e.g., to model the geometry of the chromophore of metal complexes. In these cases, an additional correction via a stretch-bend cross term is probably redundant. 

The bases are in syn or anti orientation. The orientation of the base relative to the sugar moiety is defined by torsion angle x which is constrained by steric interactions, and by the anomeric effect. The main conformations are referred to as syn and anti (see Fig. 17.5). In syn, j X is close to 0° (sp for torsion angle definition, see Box 13.3 Fig. 13.12), and the base is I oriented "above the ribose ring causing steric interactions which in the anti conformation with x close to 180° (ap) are avoided. The anti conformation is therefore preferred and is the j only form observed in double-helical DNA and RNA. An exception is the left-handed Z-DNA with alternating purine/pyrimidine nucleotide sequence where the purines are in the syn conformation. 

Definitions based on Eqs. 1,3, and 4 should, in principle, also apply for the exo-anomeric and reverse anomeric effects. There are, however, some problems with the practical application of Eq. 1 in the case of the exo-anomeric effect, because the AG values are largely not available. For the exo-anomeric effect, the conformational equiUbrium is specified by two dihedral angles, 6 and d>, and the value of AG° is needed for all six individual con-formers shown in Fig. 3. Because rotation around the exocychc bond by angle O is much less restricted in comparison with rotation by angle 6, a mixture of conformers was experimentally observed, with a difficult resolution of AG2 into individual components. If the exo-anomeric effect is treated by Eq. 3, the extra term AE(AE2) should be redefined for the whole range of values of the torsional angle O. Due to the lack of experimental data on AG or AE , for each conformer in Fig. 3, the energy values calculated correctly , for example by some molecular orbital method, are used, instead of... 

Additional evidence on the selection of conformations by the exo-ano-meric effect is derived from the solid-state structures of saccharides. It was earlier observed that the actual orientation of the anomeric alkoxyl group in pyranosides in the solid state corresponds to the (+sc, +sc) or ap, —sc) conformer, and thus proved that these conformers respectively represent the most stable axial and equatorial forms. As already noted, a particularly clear illustration of the operation of the exo-anomeric effect comes from the nonreducing disaccharide 0 ,a-trehalose, in which the most stable orientation about both exocyclic, C-0 bonds corresponds to the (+sc, +sc) conformer. Analyses of carbohydrate structures - revealed regularities in the distribution of the torsional angle O that are consistent with a restriction of rotation about the exocyclic C-O bond. The torsional angle for equatorial isomers varies from — 50° to — 110 , with a mean value of—79.4°. For the axial isomers, the range is 30-130°, with a mean value of 84.5 ° (see Ref. 29). 

Some 111 carbohydrate derivatives have been statistically treated, and coupling of the C-O bond-lengths and C-O-C bond angles to the orientation about the exocyclic C-1 -0-1 bond (exo-anomeric effect) was demonstrated. These results are given in Table IX. The differences in bond angles and bond lengths show a small but significant variation with the torsion... 

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