芬那酸及烟酸类晶体中氢键和π-π作用的角色及相关机制

Fenamic acid, nicotinic acid and their derivatives have attracted great interest due to their significant pharmacological effects, and the investigations of their crystal structures are of considerable importance in the design and development of new drug. Hydrogen bond and π-π interaction are the main driving forces which combine the molecules together in the crystallization process. Understanding the significance of hydrogen bond and π-π interaction as well as their correlation in the crystal formation would be very helpful for researchers because they can synthesize a certain crystal structure by tuning the intermolecular interactions. Hence, the roles and correlation of hydrogen bond and π-π interaction in the crystals of fenamic acid, nicotinic acid and their derivatives will be systematically investigated by using the methods and analytical technology of quantum chemistry. The ability of the molecule in the formation of hydrogen bond π-π interaction will be analyzed based on its structural feature. Then the models of hydrogen bond and π-π interaction will be constructed, and their interplay and contributions will be discussed. After the optimization of the crystal structure, the analyses of crystallization force, Hirshfeld surface and fingerprint plot will be performed to determine the way of the interplay between hydrogen bond and π-π interaction and their contributions in the crystal. According to the above results, the formations of hydrogen bond and π-π interaction between molecules in the crystallization process and the mechanism of the effective combination between hydrogen bond and π-π interaction will be elaborated, and the rules will be summarized. They will provide theoretical guidance for the structural design and modification of drug molecule as well as the development of new drug.

芬那酸、烟酸及衍生物因其重要的药理特性受到广泛关注，研究这些分子的晶体结构对新药设计和开发具有重要意义。氢键和π-π作用是结晶过程中分子之间结合的主要作用力，了解它们对晶体形成的重要性及它们之间的相关机制有助于人们通过调控结晶过程中分子间的相互作用来实现特定晶体结构的合成。基于此，本项目拟采用量子化学的计算方法和分析手段对芬那酸和烟酸类晶体中氢键和π-π作用的角色和相关机制进行系统研究。根据分子结构分析其形成氢键和π-π作用的能力。然后构建氢键和π-π作用的模型并计算，讨论它们之间的相互影响和贡献。最后通过优化晶体结构，进行晶体力、Hirshfeld表面分析和指纹图分析，确定氢键和π-π作用的方式和贡献。综合这些结果分析在晶体形成过程中分子之间相互作用形成氢键和π-π作用的方式，以及氢键和π-π作用进行有效组合的机制，对其中的规律进行总结，为药物分子的结构设计和改造及新药研发提供理论指导。

芬那酸、烟酸及衍生物因其重要的药理特性受到广泛关注，研究这些分子的晶体结构对新药设计和开发具有重要意义。氢键和π-π作用是结晶过程中分子之间结合的主要作用力，了解它们对晶体形成的重要性及它们之间的相关机制有助于人们通过调控结晶过程中分子间的相互作用来实现特定晶体结构的合成。本项目选取芬那酸、烟酸及衍生物为研究对象，详细研究了五种烟酸的衍生物(2-羟基烟酸，卤代异烟酸，4-羟基烟酸，2-苯胺烟酸衍生物，氯胺烟酸)和4-氯芬那酸的晶型，它们的固体存在形式及热力学行为，从理论计算上研究了它们的分子构象的灵活多变性对晶体结构的影响，通过优化晶体结构计算晶格能比较各种晶型的稳定性，通过Hirshfeld表面分析和指纹图分析确定晶体内部各种弱相互作用的贡献。对于芬那酸晶体，从理论计算的角度对它的晶体中有两个不对称单元而不是一个的原因进行了详细解释。通过对这些晶体的分析和讨论，我们对晶体形成过程中分子间弱相互作用之间的有效组合机制得到了较为明确的认识，同时在对氢键，π-π，卤键等分子间弱相互作用体系的理论研究中我们对弱相互作用本质的研究也有助于理解它们在晶体结构中所扮演的角色。这些结果将为药物分子的结构设计和改造及新药研发提供理论指导。