Publication Date:
2016-10-15
Description:
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 6 physical solvents (H2O, DMSO, CH3OH, 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 oxygen-hydrogen 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. This article is protected by copyright. All rights reserved.
Print ISSN:
0018-019X
Electronic ISSN:
1522-2675
Topics:
Chemistry and Pharmacology
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