Department of Chemistry, University College London, London, United Kingdom.
J Phys Chem A. 2012 Jan 26;116(3):1093-109. doi: 10.1021/jp211083f. Epub 2012 Jan 18.
The potential of an approach combining nuclear magnetic resonance (NMR) spectroscopy, molecular dynamics (MD) simulations, and quantum mechanical (QM) calculations for full structural characterizations in solution is assessed using cyclic organic compounds, namely, benzazocinone derivatives 1-3 with fused five- and eight-membered aliphatic rings, camphoric anhydride 4, and bullvalene 5. Various MD simulations were considered, using force field and semiempirical QM treatments, implicit and explicit solvation, and high-temperature MD calculations for selecting plausible molecular geometries for subsequent QM geometry optimizations using mainly B3LYP, M062X, and MP2 methods. The QM-predicted values of NMR parameters were compared to their experimental values for verification of the final structures derived from the MD/QM analysis. From these comparisons, initial estimates of quality thresholds (calculated as rms deviations) were 0.7-0.9 Hz for (3)J(HH) couplings, 0.07-0.11 Å for interproton distances, 0.05-0.08 ppm for (1)H chemical shifts, and 1.0-2.1 ppm for (13)C chemical shifts. The obtained results suggest that the accuracy of the MD analysis in predicting geometries and relative conformational energies is not critical and that the final geometry refinements of the structures selected from the MD simulations using QM methods are sufficient for correcting for the expected inaccuracy of the MD analysis. A unique example of C(sp(3))-H···N(sp(3)) intramolecular noncovalent interaction is also identified using the NMR/MD/QM and the natural bond orbital analyses. As the NMR/MD/QM approach relies on the final QM geometry optimization, comparisons of geometric characteristics predicted by different QM methods and those from X-ray and neutron diffraction measurements were undertaken using rigid and flexible cyclic systems. The joint analysis shows that intermolecular noncovalent interactions present in the solid state alter molecular geometries significantly compared to the geometries of isolated molecules from QM calculations.
采用核磁共振（NMR）光谱、分子动力学（MD）模拟和量子力学（QM）计算相结合的方法，对具有融合五元脂环和八元脂环的苯并氮杂环酮衍生物 1-3、樟脑酸酐 4 和 bullvalene 5 等环状有机化合物进行了全结构特征评估。考虑了各种 MD 模拟，包括使用力场和半经验 QM 处理、隐式和显式溶剂化以及高温 MD 计算，以选择合理的分子几何形状，随后使用主要的 B3LYP、M062X 和 MP2 方法进行 QM 几何优化。将 QM 预测的 NMR 参数值与实验值进行比较，以验证从 MD/QM 分析得出的最终结构。通过这些比较，（3）J（HH）偶合的初始质量阈值（计算为均方根偏差）估计值为 0.7-0.9 Hz，质子间距离为 0.07-0.11 Å，（1）H 化学位移为 0.05-0.08 ppm，（13）C 化学位移为 1.0-2.1 ppm。结果表明，MD 分析在预测几何形状和相对构象能方面的准确性并不关键，并且从 MD 模拟中使用 QM 方法选择的结构的最终几何精修足以纠正 MD 分析的预期误差。还使用 NMR/MD/QM 和自然键轨道分析确定了一个独特的 C(sp(3))-H···N(sp(3)) 分子内非共价相互作用的例子。由于 NMR/MD/QM 方法依赖于最终的 QM 几何优化，因此使用刚性和柔性环状系统对不同 QM 方法预测的几何特征与 X 射线和中子衍射测量值进行了比较。联合分析表明，与从 QM 计算得出的孤立分子的几何形状相比，固态中非共价相互作用会显著改变分子的几何形状。
