Gaweda Karolina, Plazinski Wojciech
Jerzy Haber Institute of Catalysis and Surface Chemistry, Polish Academy of Sciences, ul. Niezapominajek 8, 30-239 Cracow, Poland.
Phys Chem Chem Phys. 2017 Aug 9;19(31):20760-20772. doi: 10.1039/c7cp02920a.
Among the descriptors of the molecular structure of carbohydrates, the conformation of the pyranose ring is usually the most problematic one to tackle. We present the results of a systematic study oriented at determining the ring-inversion properties of all d-hexopyranoses in the form of monosaccharides, O-methylated monosaccharides and homotrisaccharides. Contrary to the existing studies, based either on molecular mechanics force fields or on conformational search within ab initio potentials, we combine the structural information from molecular dynamics simulations performed within the GROMOS 56a6 force field and use it in a subsequent geometry optimization procedure, performed at the DFT level of theory. This two-step procedure allows avoiding errors resulting from overestimating the contribution of the hydrogen bond-rich, low-energy structures that are not abundant in aqueous solutions. The calculated anomeric ratios and the populations of staggered conformers of the hydroxymethyl group are in satisfactory agreement with the experimental data. Regarding the ring-inversion properties, for the first time, we achieved good agreement of the ab initio-derived data for all hexopyranoses with the experimentally inferred Angyal scheme and with the NMR-inferred populations of ring conformers. The same computational methodology allows determination of the influence of functionalization (methylation or glycosylation) on the ring-inversion properties which includes the influence of the anomeric effect, enhanced upon O-functionalization. In general, the correlation between ring-inversion properties of unfunctionalized monomers and those of O-methylated, O-glycosylated, O-glycosylated and O,O-diglycosylated monomers is qualitatively (but not quantitatively) compatible with that predicted by the classical force fields.
在碳水化合物分子结构的描述符中，吡喃糖环的构象通常是最难处理的一个。我们展示了一项系统性研究的结果，该研究旨在确定所有D-己吡喃糖以单糖、O-甲基化单糖和同三糖形式存在时的环翻转性质。与现有的基于分子力学力场或从头算势内构象搜索的研究不同，我们将在GROMOS 56a6力场中进行的分子动力学模拟得到的结构信息结合起来，并将其用于随后在密度泛函理论水平上进行的几何优化过程。这个两步过程可以避免因高估富含氢键、低能量结构（在水溶液中不丰富）的贡献而产生的误差。计算得到的异头物比例和羟甲基交错构象的布居与实验数据吻合良好。关于环翻转性质，我们首次实现了所有己吡喃糖的从头算数据与实验推断的安贾尔方案以及核磁共振推断的环构象布居的良好吻合。相同的计算方法可以确定功能化（甲基化或糖基化）对环翻转性质的影响，其中包括异头效应的影响，这种影响在O-功能化时会增强。一般来说，未功能化单体与O-甲基化、O-糖基化、O-糖基化和O,O-二糖基化单体的环翻转性质之间的相关性在定性上（但不是定量上）与经典力场预测的相关性相符。
