Li Yuhui, Yang Xinlang, Yu Yuanqin, Zhou Xiaoguo, Zhang Rui, Sun Jin, Liu Shilin
School of Physics and Optoelectronic Engineering, Anhui University, Hefei 230601, China.
Hefei National Laboratory for Physical Sciences at the Microscale, iChEM (Collaborative Innovation Center of Chemistry for Energy Materials), Department of Chemical Physics, University of Science and Technology of China, Hefei 230026, China.
J Phys Chem A. 2023 Nov 2;127(43):9013-9021. doi: 10.1021/acs.jpca.3c04674. Epub 2023 Oct 24.
Intramolecular hydrogen bonds (H-bonds) are abundant in physicochemical and biological processes. The strength of such interaction is governed by a subtle balance between conformational flexibility and steric effect that are often hard to predict. Herein, using linear aminoalcohols NH(CH)OH ( = 2-5) as a model system, we demonstrated the dependence of intramolecular H-bond on the backbone chain length. With sensitive photoacoustic Raman spectroscopy (PARS), the gas-phase Raman spectra of aminoalcohols were measured in both N-H and O-H stretching regions at 298 and 338 K and explained with the aid of quantum chemistry calculations. For = 2-4, two conformers corresponding to the O-H···N intramolecular H-bond and free OH were identified, whereas for = 5, only the free-OH conformer was identified. Compared to free OH, a striking spectral dependence was observed for the intramolecular H-bonded conformer. According to the red shift of the OH-bonded band, the strongest intramolecular H-bond yields in = 4, but the favorable chain length to form an intramolecular hydrogen bond at room temperature was observed in = 3, which corresponds to a six-membered-ring in 3-aminopropanol. This is in good agreement with statistical analysis from the Cambridge Structural Database (CSD) that the intramolecular hydrogen bond is preferred when the six-membered ring is formed. Furthermore, combined with the calculated thermodynamic data at the MP2/aug-cc-pVTZ//M062/6-311++G(d,p) level, the origin of decrease in intramolecular hydrogen-bond formation was ascribed to an unfavorable negative entropy contribution when the backbone chain is further getting longer, which results in the calculated Gibbs free energy optimum changing with increasing temperature from = 4 (0-200 K) to = 3 (200-400 K) and to = 2 (above 400 K). These results will provide new insight into the nature of intramolecular hydrogen bonds at the molecular level and the application of intramolecular hydrogen bonds in rational drug design and supramolecular assembly.
分子内氢键在物理化学和生物过程中广泛存在。这种相互作用的强度由构象灵活性和空间效应之间的微妙平衡决定，而这往往难以预测。在此，我们以直链氨基醇NH(CH)OH（n = 2 - 5）作为模型体系，证明了分子内氢键对主链链长的依赖性。利用灵敏的光声拉曼光谱（PARS），在298 K和338 K下测量了氨基醇在N - H和O - H伸缩区域的气相拉曼光谱，并借助量子化学计算进行了解释。对于n = 2 - 4，鉴定出了对应于O - H···N分子内氢键和游离OH的两种构象，而对于n = 5，仅鉴定出了游离OH构象。与游离OH相比，分子内氢键构象表现出显著的光谱依赖性。根据OH键合带的红移，最强的分子内氢键出现在n = 4时，但在室温下形成分子内氢键的有利链长出现在n = 3时，这对应于3 - 氨基丙醇中的六元环。这与剑桥结构数据库（CSD）的统计分析结果高度一致，即形成六元环时分子内氢键更受青睐。此外，结合在MP2/aug - cc - pVTZ//M062/6 - 311++G(d,p)水平下计算得到的热力学数据，分子内氢键形成减少的原因归因于主链链长进一步增加时不利的负熵贡献，这导致计算得到的吉布斯自由能最优值随温度升高从n = 4（0 - 200 K）变为n = 3（200 - 400 K），再变为n = 2（高于400 K）。这些结果将在分子水平上为分子内氢键的本质以及分子内氢键在合理药物设计和超分子组装中的应用提供新的见解。
