Temperature Dependence of Molecular Conformation, Dynamics, and Chemical Shift Anisotropy of α,α-Trehalose in D₂O by NMR Relaxation

Abstract

A molecular dynamics study and solution-phase 1 H and 13 C chemical shift anisotropy determination of a symmetric cryogenic disaccharide, R,R-trehalose, has been performed in a temperature range between 264 and 350 K. Negligible temperature dependence of proton-carbon couplings of the asymmetrically [1-13 C]-labeled trehalose suggest that the averaged conformation of the interglycosidic linkage is centered around dihedral angles φ ) ψ ) -41°with (5°uncertainty. Homonuclear NOE-s in the labeled trehalose support the dominance of similar conformation. Close to the slow and fast motional regime, R,R-trehalose can be considered as a spherical top, and global correlation times can be determined easily at extreme temperatures. This allows the construction of an Arrhenius plot for the whole range of temperature. The approach, which we call "trouble-free", yields E a ) 28.2 kJ/mol for the activation energy of molecular reorientation. The model-free analysis of 13 C T 1 , T 2 , and NOE data showed a local maximum of the generalized order parameters with S 2 ) 0.9 around 273 K. Monte-Carlo error analysis corroborated that this effect could be real; however, effective correlation times have relatively high error limits. Thermodynamically, the S 2 data can be interpreted in terms of changes in the Gibbs free energy due to increased or diminished spatial restriction of rapid CH fluctuations. Liquid state 1 H and 13 C chemical shift anisotropies were determined from the interference of dipole-dipole and chemical shift anisotropy relaxation. In solution, chemical shift anisotropies cannot be separated from an inherent geometrical factor, so a combined CSA g factor was used. Cross-correlated spectral densities could be well fitted for the C-1,H-1 vector over the entire temperature range with the "trouble-free" global correlation times. The resulting numerical values for CSA g were smaller compared to the model-free evaluation, due to the omission of internal fluctuations. The measured shift anisotropies were found to be independent from the selection of isotropic or anisotropic dynamical models. Apparent CSA g factors were nearly constant in the entire temperature range except C-3, H-2, and H-3. Comparison with deuterium labeled [2,4,6-2 H]-trehalose proved that temperature-induced changes of the ABX-type strong coupling pattern (caused by the change of differential chemical shift of vicinal H-2 and H-3 protons) interfere with asymmetric multiplet relaxation and potentially lead to misinterpretation of CSA/DD relaxation rates.

NMR relaxation interference effects and internal dynamics in γ-cyclodextrin

“…Since the three angles H CHC , u CH À u Z and h Z are interrelated, they were in the course of the fitting fixed at the tetrahedral values, and only Dr was adjusted. The values of Dr = 57.9 ± 1.5 at 323 K and Dr = 56.7 ± 1.5 at 343 K are in reasonable agreement with each other and in the range of the Dr value obtained for carbon-13 in other sugars [52][53][54]. The value of Dr is very sensitive to the value of h Z .…”

A new GROMOS force field for hexopyranose‐based carbohydrates

“…The testing of the force field for a more extensive set of mono-and disaccharides is in progress, and the results (including possible further refinement of the parameter set) will be reported in a forthcoming article. For trehalose: from X-ray crystallography (I: trehalose dihydrate; 91,92 II: anhydrous trehalose 93 ) and three independent NMR experiments (I, 94 II, 95 Note, finally, that two studies relying on of the present 45A4 carbohydrate force field have been reported. 87,88 In the first article, an early version of the force field was used to investigate the influence of methylation at specific hydroxyl groups on the stability of amylose and cellulose fragments.…”

Internal dynamics of hydroxymethyl rotation from CH2 cross-correlated dipolar relaxation in methyl-β-d-glucopyranoside

“…The plot is reasonably linear and the derived activation energy, E a ¼ 24 AE 4 kJ mol À1 , is in good agreement with ab initio calculation by Tvaroska et al [48], who obtained the rotational barrier for methyl 2,3-dideoxy-b-D D -glucopyranoside of about 25-30 kJ mol À1 . For the sake of comparison, we show in the same diagram also the corresponding plot for the global correlation time, which for sugar solutions is known to follow the Arrhenius relation [27,51].…”