MOLECULAR RELAXATION OF SUCROSE IN AQUEOUS-SOLUTION - HOW A NANOSECOND MOLECULAR-DYNAMICS SIMULATION HELPS TO RECONCILE NMR DATA

The dynamical conformational behavior of sucrose in water was assessed through the combined use of molecular dynamics simulations and high-r esolution NMR spectroscopy. Molecular dynamics simulations were perfor med in vacuum and in aqueous solution for 1 and 1.2 ns, respectively. Carbon relaxation data were established at 62.9 and 100.6 MHz; three-b ond heteronuclear coupling constants were also determined. Two sets of phase-sensitive NOESY spectra were acquired. The presence of explicit water molecules in the simulation induces significant changes in the molecular potential. An important percentage of the glycosidic conform ational space is populated, exemplifying the inherent conformational f lexibility of sucrose. Hydration is inducing some conformational shift s, both in the glycosidic space acid in the conformational space of th e five-membered ring. The sucrose molecule is found to be extensively hydrogen bonded to water molecules. All of the potential intramolecula r hydrogen bonds are exchanged to surrounding water molecules; of part icular interest is the observation of a 25% populated water bridging c onformation: O2-g ... Ow ... O3-f. However, neither of the two crystal lographic intramolecular hydrogen bonds (O2-g ... HO-1f and O5-g ... H O-6f) persists durably in aqueous solution. A strong damping effect on high frequency motions is observed, but root-mean-square fluctuations are larger than those of the vacuum simulations. The softening of the molecular potential allows the crystal conformation of the sucrosyl r affinose to appear in a highly populated area of the conformational sp ace. The radius of gyration, overall molecular tumbling time, and self diffusion coefficient of the sucrose in aqueous solution were establi shed from the molecular dynamics simulations; they compare extremely w ell with the corresponding experimental values. Equally satisfactory i s the good agreement obtained with the glycosidic heteronuclear coupli ng constant. The molecular dynamics simulation shows that the high-fre quency oscillations of sucrose are severely damped by the presence of explicit water and that internal motions occur on the same time scale as the overall tumbling. For such a motional regime the second term in the model-free spectral densities cannot be ignored. Theoretical carb on longitudinal relaxation were fitted to experimental ones with the m olecular dynamics model by adjusting the correlation times for interna l motions. This model is very different from that previously proposed for sucrose in which internal motions are considered to be extremely r apid. The motional model was shown to be very satisfactory for calcula ting the NOESY volumes. Thus, the MD simulations were able to distingu ish between two otherwise equally good motional models based on NMR re laxation data. The selected model would appear to be a fairly universa l motional model for small carbohydrate molecules consistent with both proton and carbon relaxation data.