Department of Chemistry, Federal University of Lavras, Lavras, Minas Gerais, Brazil.
J Phys Chem A. 2011 Nov 24;115(46):13504-12. doi: 10.1021/jp201576u. Epub 2011 Nov 1.
NMR J-couplings across hydrogen bonds reflect the static and dynamic character of hydrogen bonding. They are affected by thermal and solvent effects and can therefore be used to probe such effects. We have applied density functional theory (DFT) to compute the NMR (n)J(N,H) scalar couplings of a prototypical Chagas disease drug (metronidazole). The calculations were done for the molecule in vacuo, in microsolvated cluster models with one or few water molecules, in snapshots obtained from molecular dynamics simulations with explicit water solvent, and in a polarizable dielectric continuum. Hyperconjugative and electrostatic effects on spin-spin coupling constants were assessed through DFT calculations using natural bond orbital (NBO) analysis and atoms in molecules (AIM) theory. In the calculations with explicit solvent molecules, special attention was given to the nature of the hydrogen bonds formed with the solvent molecules. The results highlight the importance of properly incorporating thermal and solvent effects into NMR calculations in the condensed phase.
NMR 偶合常数反映了氢键的静态和动态特征。它们受到热效应和溶剂效应的影响，因此可以用来探测这些效应。我们应用密度泛函理论（DFT）计算了一种典型的恰加斯病药物（甲硝唑）的 NMR（n）J（N，H）标量偶合。这些计算是在真空状态下、在带有一个或几个水分子的微溶剂化团簇模型中、在具有显式溶剂水分子的分子动力学模拟快照中以及在极化介电连续体中进行的。通过使用自然键轨道（NBO）分析和分子中的原子（AIM）理论的 DFT 计算，评估了超共轭和静电效应对自旋-自旋偶合常数的影响。在带有显式溶剂分子的计算中，特别关注了与溶剂分子形成的氢键的性质。结果强调了在凝聚相的 NMR 计算中正确纳入热效应和溶剂效应的重要性。
