In a search for new crystalline forms of linezolid with modified thermal properties five cocrystals of this wide range antibiotic with aromatic acids were obtained via mechanochemical grinding and analyzed with single crystal X‐ray diffraction, solid‐state NMR spectroscopy, powder X‐ray diffraction and DSC measurements. The coformers used in this study were benzoic acid, p‐hydroxybenzoic acid, protocatechuic acid, γ‐resorcylic acid and gallic acid. In each of the cocrystals distinct structural features have been found, including a variable amount of water and different heterosynthons, indicating that there is more than one type of intermolecular interaction preferred by the linezolid molecule. Basing on the frequency of the observed supramolecular synthons, the proposed hierarchy of the hydrogen‐bond acceptor sites of linezolid (LIN) is C=O_amide > C=O_oxazolidone > C—O—C_morpholine > C—N—C_morpholine > C—O—C_oxazolidone. In addition, aromatic–aromatic interactions were found to be important in the stabilization of the analyzed structures. The obtained cocrystals show modified thermal properties, with four of them having melting points lower than the temperature of the phase transition from linezolid form II to linezolid form III. Such a change in this physicochemical property allows for the future application of melting‐based techniques of introducing linezolid into drug delivery systems. In addition a change in water solubility of linezolid upon cocrystalization was evaluated, but only in the case of the cocrystal with protocatechuic acid was there a significant (43%) improvement in solubility in comparison with linezolid.

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改变热性能的利奈唑胺共晶体中杂合子的结构变化

为了寻找具有改进的热性能的利奈唑胺的新晶体形式，通过机械化学研磨获得了这种宽范围抗生素与芳香酸的五种共晶体，并通过单晶X射线衍射，固态NMR光谱，粉末X射线衍射和DSC测量。在此研究中使用的助形成物是苯甲酸，p-羟基苯甲酸，原儿茶酸，γ-间苯二酸和没食子酸。在每种共晶体中，已经发现了不同的结构特征，包括可变数量的水和不同的异合子，表明存在利奈唑烷分子优选的一种以上的分子间相互作用。根据观察到的超分子合成子的频率，拟议的利奈唑胺（LIN）氢键受体位点的层次结构为C = O_酰胺> C = O_恶唑烷酮> C-OC_吗啉> C- _NC吗啉> C-O-C_恶唑烷酮。此外，发现芳香族-芳香族的相互作用对于稳定所分析的结构也很重要。所获得的共晶体显示出改进的热性质，其中四个具有低于从利奈唑胺形式II到利奈唑胺形式III的相变温度的熔点。这种理化性质的这种变化使得将来可以应用基于熔融的技术将利奈唑胺引入药物输送系统。另外，评估了利奈唑胺在共结晶时水溶性的变化，但是仅在与原儿茶酸共结晶的情况下，与利奈唑胺相比溶解度有显着改善（43％）。