The Potential Utility of Predicted One Bond Carbon-Proton Coupling Constants in the Structure Elucidation of Small Organic Molecules by NMR Spectroscopy

NMR spectroscopy is the most popular technique used for structure elucidation of small organic molecules in solution, but incorrect structures are regularly reported. One-bond proton-carbon J-couplings provide additional information about chemical structure because they are determined by different features of molecular structure than are proton and carbon chemical shifts. However, these couplings are not routinely used to validate proposed structures because few software tools exist to predict them. This study assesses the accuracy of Density Functional Theory for predicting them using 396 published experimental observations from a diverse range of small organic molecules. With the B3LYP functional and the TZVP basis set, Density Functional Theory calculations using the open-source software package NWChem can predict one-bond CH J-couplings with good accuracy for most classes of small organic molecule. The root-mean-square deviation after correction is 1.5 Hz for most sp3 CH pairs and 1.9 Hz for sp2 pairs; larger errors are observed for sp3 pairs with multiple electronegative substituents and for sp pairs. These results suggest that prediction of one-bond CH J-couplings by Density Functional Theory is sufficiently accurate for structure validation. This will be of particular use in strained ring systems and heterocycles which have characteristic couplings and which pose challenges for structure elucidation.

核磁共振波谱法（NMR spectroscopy）是当前用于解析溶液中小型有机分子结构的最常用技术，但错误的分子结构仍时有报道。一键质子-碳J耦合（one-bond proton-carbon J-couplings）能够提供额外的化学结构信息，因为其由分子结构的不同特征所决定，与质子和碳的化学位移的决定因素存在差异。然而，这类耦合常数尚未被常规用于验证所提出的分子结构，原因是目前可用于预测这类耦合的软件工具较为匮乏。本研究基于涵盖多种不同类型小型有机分子的396个已发表实验观测值，评估了密度泛函理论（Density Functional Theory）在预测一键质子-碳J耦合时的准确性。采用B3LYP泛函与TZVP基组，通过开源软件包NWChem进行的密度泛函理论计算，能够对绝大多数类别的小型有机分子的一键CH J耦合进行良好精度的预测。校正后的均方根偏差（root-mean-square deviation）对于多数sp3杂化的CH键对为1.5 Hz，对于sp2杂化的CH键对为1.9 Hz；而对于带有多个电负性取代基的sp3杂化CH键对以及sp杂化CH键对，则观测到了更大的预测误差。上述结果表明，通过密度泛函理论预测一键CH J耦合的精度足以满足结构验证的需求，这对于具备特征耦合常数且在结构解析中颇具挑战的张力环体系与杂环化合物而言，将具有尤为重要的应用价值。