Conformational behavior of sucrose and its deoxy analog in water as determined by NMR and molecular modeling

Abstract

The conformational behavior of aqueous sucrose and its 2-deoxy analogue were studied by NMR and computerized molecular modeling. 'H steady-state NOE and NOESY data are reported along with long-range W-'H coupling constants. In modeling calculations, a full force field energy minimization was used to obtain the initial residue geometry, followed by a rigid residue approximation in which the glycosidic dihedral angles and the methoxyl group orientations are varied. Theoretical steady-state NOEs are calculated by a full spin relaxation matrix method, and 3JC-H data are correlated with the glycosidic torsional angle. The data do not support a single conformation model, and only conformational averaging can give a good agreement between theoretical and experimental data. The inclusion of hydrogen bonding in the force field does not affect the statistical weights of calculated NOEs, and the similar values of observed NOEs for sucrose and the 2-deoxy analogue argue against the importance of hydrogen bonding in sucrose conformation. Introduction The molecular conformation in crystalline sucrose is known unambiguously through X-ray' and neutron diffraction2 studies. However, the conformational behavior of sucrose in aqueous solution is still controversial, despite numerous experimentalf and model i r~g~r '~ studies. In most of those e f f o r t ~ , ~ J ~ ' ~ sucrose was assumed to be nearly spherical, similar to its shape in crystalline sucrose, and quite rigid. However, when the crystal structures of sucrase,'J sucrose-salt comple~es , '~J~ and oligosaccharides that contain sucrosyl residueslbZ are examined, the (1 2) glycosidic linkages between a-glucopyranose and 0-fructofuranose exhibit wide ranges (see Table I). Recent molecular mechanics and dynamics s t ~ d i e s ~ ~ v ~ ~ identified three low-energy conformations for sucrose, providing further support for the concept of flexible linkages in this disaccharide. Besides the flexibility of sucrose, another controversy is the persistence in solution of the 0-2g-O-If and 0-5g-O-6f hydrogen bonds found in the crystal. Mathlouti et al.3-S interpreted X-ray and Raman data to show that the number of intramolecular hydrogen bonds depends on the concentration of sucrose, with no hydrogen bonding at low concentrations. Bock and LemieuxJ2 argued, supported by modeling and detailed I3C TI and NOE measurements, that dilute aqueous sucrose has one intramolecular hydrogen bond. Finally, based on their N M R study of sucrose in DMSO, Christofides and Davies6v7 suggested that two intramolecular hydrogen bonds, namely 0-2g-0-1 f and 0-2g-0-3f, compete with each other. Because of these observations and a report that the crystalline conformation cannot account for all of the N M R data,I0 we decided that further study was needed. Interpreting the solution behavior of sucrose from N M R data without an assumption of rigid conformation is an ambitious task, since NMR parameters reflect only a virtual conformat i~n .~~ Recently, Cumming and Carverz6 combined N M R data with results from computerized molecular modeling that accommodates conformational flexibility. Further analyses of various diand trisaccharides have mostly used NOE value^^'-^^ although constants from coupling through the glycosidic linkage were also This modeling procedure is used in the present work. The extent of intramolecular hydrogen bonding is probed in a parallel study of 2-deoxysucrose, a compound that cannot form the 0-1f-O-2g hydrogen bond. Also, the 'Service RMN du DEpartement de Chimie. * Laboratoire de Physicochimie des MacromolEcules. 1 Laboratoire Beghin-Say. E.S.C.I.L. 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