Klepach Thomas, Zhao Hongqiu, Hu Xiaosong, Zhang Wenhui, Stenutz Roland, Hadad Matthew J, Carmichael Ian, Serianni Anthony S
Department of Chemistry and Biochemistry, University of Notre Dame, 251 Nieuwland Science Hall, Notre Dame, IN, 46556-5670, USA.
Methods Mol Biol. 2015;1273:289-331. doi: 10.1007/978-1-4939-2343-4_20.
Density functional theory (DFT) is a powerful computational tool to enable structural interpretations of NMR spin-spin coupling constants ( J-couplings) in saccharides, including the abundant (1)H-(1)H ( JHH), (13)C-(1)H ( JCH), and (13)C-(13)C ( JCC) values that exist for coupling pathways comprised of 1-4 bonds. The multiple hydroxyl groups in saccharides, with their attendant lone-pair orbitals, exert significant effects on J-couplings that can be difficult to decipher and quantify without input from theory. Oxygen substituent effects are configurational and conformational in origin (e.g., axial/equatorial orientation of an OH group in an aldopyranosyl ring; C-O bond conformation involving an exocyclic OH group). DFT studies shed light on these effects, and if conducted properly, yield quantitative relationships between a specific J-coupling and one or more conformational elements in the target molecule. These relationships assist studies of saccharide structure and conformation in solution, which are often challenged by the presence of conformational averaging. Redundant J-couplings, defined as an ensemble of J-couplings sensitive to the same conformational element, are particularly helpful when the element is flexible in solution (i.e., samples multiple conformational states on the NMR time scale), provided that algorithms are available to convert redundant J-values into meaningful conformational models. If the latter conversion is achievable, the data can serve as a means of testing, validating, and refining theoretical methods like molecular dynamics (MD) simulations, which are currently relied upon heavily to assign conformational models of saccharides in solution despite a paucity of experimental data needed to independently validate the method.
密度泛函理论（DFT）是一种强大的计算工具，可用于对糖类中的核磁共振自旋 - 自旋耦合常数（J耦合）进行结构解释，包括由1 - 4键组成的耦合途径中存在的丰富的（1）H - （1）H（JHH）、（13）C - （1）H（JCH）和（13）C - （13）C（JCC）值。糖类中的多个羟基及其伴随的孤对轨道对J耦合有显著影响，如果没有理论输入，这些影响可能难以解读和量化。氧取代基效应源于构型和构象（例如，吡喃醛糖环中OH基团的轴向/赤道取向；涉及环外OH基团的C - O键构象）。DFT研究揭示了这些效应，如果进行得当，可得出特定J耦合与目标分子中一个或多个构象元素之间的定量关系。这些关系有助于研究溶液中糖类的结构和构象，而构象平均化的存在常常给这些研究带来挑战。冗余J耦合定义为对同一构象元素敏感的J耦合集合，当该元素在溶液中具有灵活性时（即在NMR时间尺度上呈现多种构象状态）特别有用，前提是有算法可将冗余J值转换为有意义的构象模型。如果能够实现后者的转换，这些数据可作为测试、验证和完善分子动力学（MD）模拟等理论方法的手段，尽管目前严重依赖MD模拟来确定溶液中糖类的构象模型，但独立验证该方法所需的实验数据却很少。
