EaStCHEM School of Chemistry, University of Edinburgh, Joseph Black Building, David Brewster Road, Edinburgh, EH9 3FJ, UK.
Syngenta, Jealott's Hill International Research Centre, Bracknell, Berkshire, RG42 6EY, UK.
Angew Chem Int Ed Engl. 2022 Jul 25;61(30):e202206604. doi: 10.1002/anie.202206604. Epub 2022 Jun 14.
The experimental isolation of H-bond energetics from the typically dominant influence of the solvent remains challenging. Here we use synthetic molecular balances to quantify amine/amide H-bonds in competitive solvents. Over 200 conformational free energy differences were determined using 24 H-bonding balances in 9 solvents spanning a wide polarity range. The correlations between experimental interaction energies and gas-phase computed energies exhibited wild solvent-dependent variation. However, excellent correlations were found between the same computed energies and the experimental data following empirical dissection of solvent effects using Hunter's α/β solvation model. In addition to facilitating the direct comparison of experimental and computational data, changes in the fitted donor and acceptor constants reveal the energetics of secondary local interactions such as competing H-bonds.
从通常占主导地位的溶剂影响中分离氢键能量仍然具有挑战性。在这里，我们使用合成分子天平来量化竞争性溶剂中的胺/酰胺氢键。在 9 种具有广泛极性范围的溶剂中使用 24 个氢键平衡，确定了 200 多个构象自由能差异。实验相互作用能与气相计算能之间的相关性表现出强烈的溶剂依赖性变化。然而，使用 Hunter 的 α/β 溶剂化模型对溶剂效应进行经验分解后，发现相同的计算能与实验数据之间存在极好的相关性。除了促进实验和计算数据的直接比较外，拟合供体和受体常数的变化还揭示了次级局部相互作用（如竞争氢键）的能量。
