Sanii Rana, Patyk-Kaźmierczak Ewa, Hua Carol, Darwish Shaza, Pham Tony, Forrest Katherine A, Space Brian, Zaworotko Michael J
Department of Chemical Sciences and Bernal Institute, University of Limerick, Co. Limerick Y94T9PX, Ireland.
Department of Materials Chemistry, Faculty of Chemistry, Adam Mickiewicz University, Uniwerystetu Poznańskiego 8, 61-614, Poznań, Poland.
Cryst Growth Des. 2021 Sep 1;21(9):4927-4939. doi: 10.1021/acs.cgd.1c00353. Epub 2021 Jul 30.
The propensity of molecular organic compounds to form stoichiometric or nonstoichiometric crystalline hydrates remains a challenging aspect of crystal engineering and is of practical relevance to fields such as pharmaceutical science. In this work, we address the propensity for hydrate formation of a library of eight compounds comprised of 5- and 6-membered -heterocyclic aromatics classified into three subgroups: linear dipyridyls, substituted Schiff bases, and tripodal molecules. Each molecular compound studied possesses strong hydrogen bond acceptors and is devoid of strong hydrogen bond donors. Four methods were used to screen for hydrate propensity using the anhydrate forms of the molecular compounds in our library: water slurry under ambient conditions, exposure to humidity, aqueous solvent drop grinding (SDG), and dynamic water vapor sorption (DVS). In addition, crystallization from mixed solvents was studied. Water slurry, aqueous SDG, and exposure to humidity were found to be the most effective methods for hydrate screening. Our study also involved a structural analysis using the Cambridge Structural Database, electrostatic potential (ESP) maps, full interaction maps (FIMs), and crystal packing motifs. The hydrate propensity of each compound studied was compared to a compound of the same type known to form a hydrate through a previous study of ours. Out of the eight newly studied compounds (herein numbered -), three Schiff bases were observed to form hydrates. Three crystal structures (two hydrates and one anhydrate) were determined. Compound crystallized as an isolated site hydrate in the monoclinic space group 2/, while and crystallized in the monoclinic space group 2/ as a channel tetrahydrate and an anhydrate, respectively. Whereas we did not find any direct correlation between the number of H-bond acceptors and either hydrate propensity or the stoichiometry of the resulting hydrates, analysis of FIMs suggested that hydrates tend to form when the corresponding anhydrate structure does not facilitate intermolecular interactions.
分子有机化合物形成化学计量或非化学计量结晶水合物的倾向仍然是晶体工程中一个具有挑战性的方面，并且在药物科学等领域具有实际意义。在这项工作中，我们研究了由5元和6元杂环芳烃组成的8种化合物库形成水合物的倾向，这些化合物分为三个亚组：线性联吡啶、取代席夫碱和三脚架分子。所研究的每种分子化合物都具有强氢键受体，且没有强氢键供体。我们使用库中分子化合物的无水形式，通过四种方法筛选水合物形成倾向：环境条件下的水浆法、湿度暴露法、水相溶剂滴磨法（SDG）和动态水蒸气吸附法（DVS）。此外，还研究了混合溶剂中的结晶过程。发现水浆法、水相SDG法和湿度暴露法是筛选水合物最有效的方法。我们的研究还涉及使用剑桥结构数据库、静电势（ESP）图、全相互作用图（FIMs）和晶体堆积模式进行结构分析。通过我们之前的一项研究，将所研究的每种化合物的水合物形成倾向与已知形成水合物的同类型化合物进行了比较。在所研究的8种新化合物（此处编号为-）中，观察到3种席夫碱形成了水合物。确定了三种晶体结构（两种水合物和一种无水物）。化合物以单斜空间群2/中的孤立位点水合物形式结晶，而和分别以单斜空间群2/中的通道四水合物和无水物形式结晶。虽然我们没有发现氢键受体的数量与水合物形成倾向或所得水合物的化学计量之间存在任何直接关联，但对FIMs的分析表明，当相应的无水物结构不利于分子间相互作用时，水合物倾向于形成。
