Faculty of Chemistry, University of Wrocław, ul. F. Joliot-Curie 14, 50-383 Wrocław, Poland.
Molecules. 2022 Apr 1;27(7):2299. doi: 10.3390/molecules27072299.
The intra- and intermolecular interactions of selected quinolone carboxylic acid derivatives were studied in monomers, dimers and crystals. The investigated compounds are well-recognized as medicines or as bases for further studies in drug design. We employed density functional theory (DFT) in its classical formulation to develop gas-phase and solvent reaction field (PCM) models describing geometric, energetic and electronic structure parameters for monomers and dimers. The electronic structure was investigated based on the atoms in molecules (AIM) and natural bond orbital (NBO) theories. Special attention was devoted to the intramolecular hydrogen bonds (HB) present in the investigated compounds. The characterization of energy components was performed using symmetry-adapted perturbation theory (SAPT). Finally, the time-evolution methods of Car-Parrinello molecular dynamics (CPMD) and path integral molecular dynamics (PIMD) were employed to describe the hydrogen bond dynamics as well as the spectroscopic signatures. The vibrational features of the O-H stretching were studied using Fourier transformation of the autocorrelation function of atomic velocity. The inclusion of quantum nuclear effects provided an accurate depiction of the bridged proton delocalization. The CPMD and PIMD simulations were carried out in the gas and crystalline phases. It was found that the polar environment enhances the strength of the intramolecular hydrogen bonds. The SAPT analysis revealed that the dispersive forces are decisive factors in the intermolecular interactions. In the electronic ground state, the proton-transfer phenomena are not favourable. The CPMD results showed generally that the bridged proton is localized at the donor side, with possible proton-sharing events in the solid-phase simulation of stronger hydrogen bridges. However, the PIMD enabled the quantitative estimation of the quantum effects inclusion-the proton position was moved towards the bridge midpoint, but no qualitative changes were detected. It was found that the interatomic distance between the donor and acceptor atoms was shortened and that the bridged proton was strongly delocalized.
本研究以选定的喹诺酮羧酸衍生物为研究对象，对其单体、二聚体和晶体中的分子内和分子间相互作用进行了研究。这些被研究的化合物是公认的药物或药物设计进一步研究的基础。我们采用经典形式的密度泛函理论（DFT）来建立气相和溶剂反应场（PCM）模型，以描述单体和二聚体的几何、能量和电子结构参数。电子结构是基于原子在分子中的理论（AIM）和自然键轨道（NBO）理论进行研究的。特别关注了研究化合物中存在的分子内氢键（HB）。采用对称适应微扰理论（SAPT）对能量成分进行了表征。最后，采用 Car-Parrinello 分子动力学（CPMD）和路径积分分子动力学（PIMD）时间演化方法来描述氢键动力学和光谱特征。通过原子速度自相关函数的傅里叶变换研究了 O-H 伸缩振动的振动特征。量子核效应的包含提供了对桥接质子离域的准确描述。CPMD 和 PIMD 模拟分别在气相和晶体相中进行。结果表明，极性环境增强了分子内氢键的强度。SAPT 分析表明，色散力是分子间相互作用的决定性因素。在电子基态下，质子转移现象不利于发生。CPMD 结果表明，在供体侧通常存在桥接质子的局域化，在更强氢键的固态模拟中可能存在质子共享事件。然而，PIMD 使包括质子位置向桥中点移动的量子效应定量估计成为可能，但没有检测到定性变化。结果发现，供体和受体原子之间的原子间距离缩短，桥接质子强烈离域。
