Barnett Christopher B, Naidoo Kevin J
Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa.
J Phys Chem B. 2008 Dec 4;112(48):15450-9. doi: 10.1021/jp8067409.
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 (3)J(HH) and (2)J(HH) 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 sigma(C6-H) --> sigma*(C5-O5) and sigma(C5-H) --> sigma*(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.
尽管自20世纪70年代初以来就对葡萄糖和半乳糖的构象偏好进行了研究，但直到最近，才通过使用修正的Karplus方程结合（3）J（HH）和（2）J（HH）核磁共振耦合数据，解析出葡萄糖和半乳糖羟甲基的分布情况。在单糖中观察到对gauche构象的偏好，但其原因尚不清楚。我们在QM/MM模拟中使用单糖的半经验描述，计算了葡萄糖和半乳糖伯醇的旋转自由能曲线。由此我们观察到，模拟得到的葡萄糖gg/gt/tg = 35:57:3和半乳糖gg/gt/tg = 4:86:7的分布情况与核磁共振测量结果非常吻合。使用自然键轨道对最低能量构象进行立体电子分析，清晰地描述了C-H键和C-O反键轨道相互作用，特别是sigma（C6-H）→sigma*（C5-O5）和sigma（C5-H）→sigma*（C6-O6）对gauche构象的稳定作用。对溶液轨迹的分析表明，由水分子在环氧和羟甲基之间形成的持续分子内氢键和分子间桥连氢键进一步稳定了gt构象，使其成为水合葡萄糖和半乳糖中首选的旋转异构体。这些单糖在水溶液中的羟甲基量子力学/分子力学分子动力学轨迹和推导的旋转自由能解释了实验观察结果是由于竞争的立体电子（gauche）、电子（分子内氢键）和静电（溶剂-糖氢键）因素共同作用的结果。
