Theoretical studies on the influence of exo-anomeric effect,geometry of sugar linkage on the unperturbed dimensions of polysaccharides

Abstract

Recently, application of conformational energy calculations in the field of carbohydrates has led to a number of interesting and important results. A few attempts have also been made to compute the unperturbed dimensions of a number of polysaccharides by applying the statistical method developed by Flory and compared with experimental data. Though these theoretical studies explained qualitatively the behaviour of these polysaccharides in solution, the quantitative agreement between theoretical and experimental results is poor. Some attempts have also been made to get agreement with the experimental values of cellulose by incorporating a small percentage of ?-D-glucose residues in boat and twist-boat conformations. However, there is no experimental or theoretical support for such an assumption. In all the earlier conformational energy calculations, the total potential energy was calculated by taking into account the nonbonded, electrostatic and torsional contributions. But it has been shown from both theoretical and experimental studies on simple sugars and their derivatives that the exo-anomeric effect plays a dominant role in deciding the favoured conformations in both solid state and in solution. However, this effect has not been taken into account in the study of polysaccharides or nucleic acids. Recently, it has also been shown by theory that the ^4C?(D) conformation of sugars is not as ‘rigid’ as believed earlier, but is found to be slightly flexible. The theory predicts, in agreement with experiment, that variations up to 10° and 5° in ring torsional angles and bond angles respectively are possible with very little change in energy. Such deformations in the pyranose ring may also be possible in solution. However, in all the earlier work, no attempt has been made to study the effect of the flexibility of the pyranose ring on the unperturbed dimensions. Hence, the disagreement between the earlier theoretical studies and experiment may be due to:

The neglect of the contribution of the exo-anomeric effect to the total potential energy, and Use of fixed geometry for the sugar ring.

In the present study, an attempt has been made to incorporate the exo-anomeric effect in the total potential energy function and study its effect on the unperturbed dimensions of 1–4 and 1–3 linked polysaccharides. An attempt has also been made to study the effect of the flexibility of the pyranose ring on the unperturbed dimensions of cellulose and amylose. Two methods, namely, the average matrix method of Flory and the Monte Carlo method have been used to compute the unperturbed dimensions of polysaccharides. The thesis consists of six chapters. A brief review of the theoretical and experimental studies on the average properties of polysaccharides and the conformation of pyranose sugar is presented in Chapter I. The factors that determine the chain conformation in solution are also discussed. A brief description of the average matrix method and the Monte Carlo method is also given. The various potential energy functions used in the study of the conformational analysis of sugars are briefly summarised. In Chapter II, general and specific expressions (for ? and ? linked polysaccharides) have been proposed for the variation of the exo-anomeric effect with the dihedral angle. The validity of the general expression has been tested using the X-ray crystal structure data of yeast tRNA. Chapter III deals with the conformational studies on cellulose. A brief description of the earlier experimental and theoretical studies on the unperturbed dimensions of cellulose and cellulose derivatives is given. The values of cellulose have been calculated for different ring geometries for two different bridge angles. The calculated C? values are found to be sensitive to the exo-anomeric effect, ring geometry and the bond angle at the bridge oxygen. The results suggest that the agreement between the calculated and experimental C? values could be improved by introducing small deformations in the pyranose ring conformation rather than invoking unrealistic boat and twist-boat conformations for the sugar residue or assuming unusual bond angles at the bridge oxygen. The C? values obtained for amylose with and without the exo-anomeric effect for different ring geometries of the pyranose ring have been described in Chapter IV. These results suggest that the inclusion of the exo-anomeric effect to the total potential energy leads to higher values.