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Published June 20, 2019 | Version peer-reviewed
Journal article Open

Conformational behavior of d-lyxose in gas and solution phases by rotational and NMR spectroscopies.

Description

Understanding the conformational preferences and intramolecular dynamics of carbohydrates is crucial to explain the interactions with their biological targets and, in turn, to improve their use as therapeutic agents. Herein, we present experimental evidence that resolves the conformational analysis of the monosaccharide D‑lyxose, for which quantum mechanical (QM) calculations offered model‑dependent results. The study compares the structural preferences in the gas phase, determined by rotational spectroscopy, with the solution, resolved by combining NMR and molecular dynamics (MD) simulations. Rotational results show that D‑lyxose adopts only pyranose forms in the gas phase. The α‑anomer exhibits both the 4C1 and 1C4 chairs with a ratio of 60:40, while the β‑anomer, whose effective structure at atomic resolution was determined by (13C, 2H and 18O) monoisotopic enriched samples, displays exclusively 4C1 form. Conversely, in water solution, the most populated conformation is the α‑anomer, which features a 1C4 chair. Moreover, the thorough solvation studies indicate that the β‑anomer is poorly solvated. This result, together with the larger dipole moment exhibited by the 1C4 form of the α‑anomer, may explain the preferences observed in solution, proving the active role of water in the conformational preferences of this monosaccharide. Markedly, the main conformers found in the gas phase (β‑anomer in a 4C1 chair) and in solution (α‑anomer in a 1C4 form) are characterized by the lack of the stabilizing anomeric effect. From a mechanism perspective, rotational spectroscopy together with solid‑state NMR experiments, corroborates that α«β or furanose«pyranose interconversions are prevented in gas phase. The multidisciplinary strategy presented here provides a powerful way of unravelling the role of water in the conformational preferences of challenging molecules, such as flexible monosaccharides.

Notes

We thank MINECO (projects CTQ2017 89150 R, CTQ2015 68148 C2 2P, CTQ2015 67727 R), Basque Government (PIBA 2018 11), Universidad de La Rioja (UNLR13 4E 1931), the UPV/EHU (PPG17/10), Fundación BBVA, the EU (Marie Sklodowska Curie ITN, ProteinConjugates, grant agreement No. 675007) for the financial support. C.C. thanks MINECO for a Juan de la Cierva contract. I.C. thanks Universidad de La Rioja for the FPI grant. Computational, laser and NMR resources of the UPV/EHU were used in this work. We thank Dr. Imanol Usabiaga (Università di Bologna) for his help with theoretical calculations.

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