Stereoelectronic and Solvation Effects Determine Hydroxymethyl Conformational Preferences in Monosaccharides
Journal Article
2008
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J. Phys. Chem. B.
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American Chemical Society
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University of Cape Town
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Abstract
Although the conformational preferences in glucose and galactose have been studied since the early 1970s, only recently have the glucose and galactose hydroxymethyl populations been resolved by combining 3JHH and 2JHH NMR coupling data using a modified Karplus equation. A preference for gauche conformations is observed in monosaccharides, but the reasons for this are not understood. We calculated the free energy of rotation profiles for glucose and galactose primary alcohols using a semiempirical description of the monosaccharides in QM/MM simulations. From this we observed excellent agreement between our simulated population distributions for glucose gg/gt/tg = 35:57:3 and galactose gg/gt/tg = 4:86:7 with those measured from NMR. A stereoelectronic analysis of the minimum energy conformations using natural bond orbitals provides a clear description of the stabilizing contribution to the gauche conformers stemming from the C−H bonding and the C−O antibonding orbital interactions, specifically σC6−H → σ*C5−O5 and σC5−H → σ*C6−O6. Analysis of the solution trajectories reveals that persistent intramolecular hydrogen bonds and intermolecular bridging hydrogen bonds formed by water molecules between the ring oxygen and the hydroxymethyl group further stabilizes the gt conformation making it the preferred rotamer in both hydrated glucose and galactose. The hydroxymethyl quantum mechanics/molecular mechanics molecular dynamics trajectories and derived rotational free energies for these monosaccharides in water solutions explain that the experimental observations are due to a combination of competing stereoelectronic (gauche), electronic (intramolecular hydrogen bonding), and electrostatic (solvent-saccharide hydrogen bonding) factors.
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Reference:
Barnett, C. B., & Naidoo, K. J. (2008). Stereoelectronic and solvation effects determine hydroxymethyl conformational preferences in monosaccharides. The Journal of Physical Chemistry B, 112(48), 15450-15459.