Solvent-Modulated Influence of Intramolecular Hydrogen-Bonding on the Conformational Properties of the Hydroxymethyl Group in Glucose and Galactose: A Molecular Dynamics Simulation Study

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• 作者：Alice Lonardi ; Pavel Oborský ; and Philippe H. Hü ; nenberger
• 刊名：Helvetica Chimica Acta
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：100
• 期：1
• 全文大小：18156K
• ISSN：1522-2675

文摘

Intramolecular hydrogen-bonding (H-bonding) is commonly regarded as a major determinant of the conformation of (bio)molecules. However, in an aqueous environment, solvent-exposed H-bonds are likely to represent only a marginal (possibly adverse) conformational driving as well as steering force. For example, the hydroxymethyl rotamers of glucose and galactose permitting the formation of an intramolecular H-bond with the adjacent hydroxyl group are not favored in water but, in the opposite, least populated. This is because the solvent-exposed H-bond is dielectrically screened as well as subject to intense H-bonding competition by the water molecules. In the present study, the effect of a decrease in the solvent polarity on this rotameric equilibrium is probed using molecular dynamics simulation. This is done by considering six physical solvents (H₂O, DMSO, MeOH, CHCl₃, CCl₄, and vacuum), along with 19 artificial water-like solvent models for which the dielectric permittivity and H-bonding capacity can be modulated independently via a scaling of the O–H distance and of the atomic partial charges. In the high polarity solvents, the intramolecular H-bond is observed, but arises as an opportunistic consequence of the proximity of the H-bonding partners in a given rotameric state. Only when the polarity of the solvent is decreased does the intramolecular H-bond start to induce a conformational pressure on the rotameric equilibrium. The artificial solvent series also reveals that the effects of the solvent permittivity and of its H-bonding capacity mutually enhance each other, with a slightly larger influence of the permittivity. The hydroxymethyl conformation in hexopyranoses appears to be particularly sensitive to solvent-polarity effects because the H-bond involving the hydroxymethyl group is only one out of up to five H-bonds capable of forming a network around the ring.