Anisotropic Reorientation of 9-Methylpurine and 7-Methylpurine Molecules in Methanol Solution Studied by Combining ¹³C and ¹⁴N Nuclear Spin Relaxation Data and Quantum Chemical Calculations

Reorientation of 9-(trideuteromethyl)purine and 7-(trideuteromethyl)purine molecules in methanol-d4 solutions has been investigated on the basis of the interpretation of the nuclear spin relaxation rates of their 14N (or 1H) and 13C nuclei. The transverse quadrupole relaxation rates of 14N nuclei have been obtained from the line shape analysis of their 14N NMR spectra. Alternatively, the information on the longitudinal 14N relaxation rates has been obtained via the scalar relaxation of the second kind of protons coupled to 14N. The longitudinal dipolar relaxation rates of the protonated 13C nuclei in the investigated molecules have been determined by measuring their overall relaxation rates and NOE enhancement factors. The molecular geometries, scalar coupling constants, and EFG tensors needed for quantitative interpretation of the above data have been calculated theoretically [DFT B3LYP/6-311++G(2d,p) or B3PW91/6-311+G(df,pd)] including the impact of the solvent by using discrete solvation and the polarizable continuum model. The reorientation of the investigated purines has been described as rotational diffusion of an asymmetrical top. It has been found that to get a fully consistent interpretation of the relaxation data, effective C−H bond lengths being 3% longer than the calculated ones had to be used in analysis to compensate for the ground-state vibrations. The obtained rotational diffusion coefficients and orientations of the principal diffusion axes show that the investigated molecules reorient anisotropically and that the mode of their solvation is remarkably different, in spite of their structural similarity

Stochastic Modeling of Flexible Biomolecules Applied to NMR Relaxation. I. Internal Dynamics of Cyclodextrins: γ‑Cyclodextrin as a Case Study

In this work, we address the description of the dynamics of cyclodextrins in relation with nuclear magnetic resonance (NMR) relaxation data collected for hydroxymethyl groups. We define an integrated computational approach based on the definition and parametrization of a stochastic equation able to describe the relevant degrees of freedom affecting the NMR observables. The computational protocol merges molecular dynamics simulations and hydrodynamics approaches for the evaluation of most of the molecular parameters entering the stochastic description of the system. We apply the method to the interpretation of the 13C NMR relaxation of the −CH2OH group of cyclodextrins. We use γ-cyclodextrin as a case study. Results are in agreement with quantitative and qualitative analyses performed in the past with simpler models and molecular dynamics simulations. The element of novelty in our approach is in the treatment of the coupling of the relevant internal (glucopyranose ring twisting/tilting and hydroxymethyl group jumps) and global (molecular tumbling) degrees of freedom

Stochastic Modeling of Flexible Biomolecules Applied to NMR Relaxation. 2. Interpretation of Complex Dynamics in Linear Oligosaccharides

A computational stochastic approach is applied to the description of flexible molecules. By combining (i) molecular dynamics simulations, (ii) hydrodynamics approaches, and (iii) a multidimensional diffusive description for internal and global dynamics, it is possible to build an efficient integrated approach to the interpretation of relaxation processes in flexible systems. In particular, the model is applied to the interpretation of nuclear magnetic relaxation measurements of linear oligosaccharides, namely a mannose-containing trisaccharide and the pentasaccharide LNF-1. Experimental data are reproduced with sufficient accuracy without free model parameters