O-Methylation in Carbohydrates: An NMR and MD Simulation Study with Application to Methylcellulose.

Alessandro Ruda,Göran Widmalm,Jakob Wohlert

doi:10.1021/acs.jpcb.1c07293

Abstract

Methylated carbohydrates are important from both biological and technical perspectives. Specifically, methylcellulose is an interesting cellulose derivative that has applications in foods, materials, cosmetics, and many other fields. While the molecular dynamics simulation technique has the potential for both advancing the fundamental understanding of this polymer and aiding in the development of specific applications, a general drawback is the lack of experimentally validated interaction potentials for the methylated moieties. In the present study, simulations using the GROMOS 56 carbohydrate force field are compared to NMR spin–spin coupling constants related to the conformation of the exocyclic torsion angle ω in d-glucopyranose and derivatives containing a 6-O-methyl substituent and a 13C-isotopologue thereof. A 3JCC Karplus-type relationship is proposed for the C5–C6–O6–CMe torsion angle. Moreover, solvation free energies are compared to experimental data for small model compounds. Alkylation in the form of 6-O-methylation affects exocyclic torsion only marginally. Computed solvation free energies between nonmethylated and methylated molecules were internally consistent, which validates the application of these interaction potentials for more specialized purposes.

Highlights

Methylation in carbohydrates is found in many places in nature such as bacteria, fungi, worms, mollusks, algae, and plants, but it is still rare compared to other modifications.[1]
It provides variation in chemical properties by rendering the carbohydrate more hydrophobic, and by modulating the conformational space.[8]. This is exploited in methylcellulose (MC) which is synthesized from cellulose by O-methylation in positions 2, 3, and/or 6 of the glucose units (Figure 1a)
The chemical shifts were referenced to internal sodium 3-trimethylsilyl(2,2,3,3-2H4)-propanoate (TSP) in D2O and external 10% 1,4-dioxane in D2O. 1H and 13C NMR experiments were recorded at 298 K, unless otherwise stated, with a digital resolution of 0.2 and 0.5 Hz/point, respectively, and zero-filled prior to Fourier transformation of the FIDs. nJHH and 3JCH coupling constants were extracted by lineshape analysis using the NMR spin-simulation software PERCH;[26] the experimental error for nJHH is estimated to be ≤0.2 Hz

Summary

■ INTRODUCTION

Methylation in carbohydrates is found in many places in nature such as bacteria, fungi, worms, mollusks, algae, and plants, but it is still rare compared to other modifications.[1]. A new 3JCC Karplus-type relation for the exo-cyclic θ torsion is parameterized This equation is used to validate simulations using the GROMOS carbohydrate force field.[20] Simulations are further extended to include selectively methylated cellooligomers with the purpose of studying the effect on the free energy of hydration. The difference between the free energies obtained in this way from simulations in both solvent and vacuum corresponds to ΔΔGsbetween the original and the methylated solute, ΔΔGs = ΔGsOMe − ΔGsOH = ΔGmwautt − ΔGmvauct, due to that the thermodynamic cycle must add up to zero (Figure 1c), and is a measure of the effect of methylation itself For these simulations, 25 λ-points were used, each simulated for 2 ns, employing temperature replica exchange as described above. This protocol was recently used for simulations of acetylated cellooligomers and cellulose nanocrystals.[52]

■ RESULTS AND DISCUSSION

■ CONCLUSIONS

■ ACKNOWLEDGMENTS

■ REFERENCES