An integrated approach to NMR spin relaxation in flexible biomolecules: Application to Β-D-glucopyranosyl-(1→6)-α-D -mannopyranosyl-OMe

The description of the reorientational dynamics of flexible molecules is a challenging task, in particular when the rates of internal and global motions are comparable. The commonly used simple mode-decoupling models are based on the assumption of statistical independence between these motions. This assumption is not valid when the time scale separation between their rates is small, a situation that was found to arise in oligosaccharides in the context of certain internal motions. To make possible the interpretation of NMR spin relaxation data from such molecules, we developed a comprehensive approach generally applicable to flexible rotators with one internal degree of freedom. This approach integrates a stochastic description of coupled global tumbling and internal torsional motion, quantum chemical calculations of the local potential and the local geometry at the site of the restricted torsion, and hydrodynamics-based calculations of the diffusive properties. The method is applied to the disaccharide Β-D-Glcp-(1→6)-α-D-[6- ¹³C]-Manp-OMe dissolved in a DMSO-d₆/D₂O cryosolvent. The experimental NMR relaxation parameters, associated with the ¹³CH₂ probe residing at the glycosidic linkage, include ¹³CT₁ and T₂ and ¹³C-{¹H} nuclear Overhauser enhancement (NOE) as well as longitudinal and transverse dipole-dipole cross-correlated relaxation rates, acquired in the temperature range of 253-293 K. These data are predicted successfully by the new theory with only the H-C-H angle allowed to vary. Previous attempts to fit these data using mode-decoupling models failed.