Department of Pharmacognosy and Phytochemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, ul. Jagiellońska 4, 41-200 Sosnowiec, Poland.
Phys Chem Chem Phys. 2020 Dec 23;22(48):28202-28212. doi: 10.1039/d0cp02332a.
In this paper, we have analyzed structural, thermal, and dynamical properties of four azole antifungals: itraconazole (ITZ), posaconazole (POS), terconazole (TER) and ketoconazole (KET), differing mainly in the length of the rod-like backbone and slightly in side groups. Our investigations clearly demonstrated that the changes in the chemical structure result in a different ability to form the medium-range order (MRO) and variation in thermal and dynamical properties of these pharmaceuticals. Direct comparison of the diffractograms collected for glassy and crystalline materials indicated that the MRO observed in the former phases is related to maintaining the local molecular arrangement of the crystal structure. Moreover, it was shown that once the MRO-related diffraction peaks appear, additional mobility (δ- or α' relaxation), slower than the structural (α)-process, is also detected in dielectric spectra. This new mode is connected to the motions within supramolecular nanoaggregates. Detailed analysis of dielectric and calorimetric data also revealed that the variation in the internal structure and MRO of the examined pharmaceuticals have an impact on the glass transition temperature (Tg) shape of the α-process, isobaric fragility, molecular dynamics in the glassy state and number of dynamically correlated molecules. These findings could be helpful in an understanding the influence of different types of intermolecular MRO on the properties of substances having a similar chemical backbone.
伊曲康唑（ITZ）、泊沙康唑（POS）、特康唑（TER）和酮康唑（KET）的结构、热和动力学性质。它们主要在棒状主链的长度上有所不同，在侧基上略有差异。我们的研究清楚地表明，化学结构的变化导致了中程有序（MRO）形成能力的不同，并改变了这些药物的热和动力学性质。对玻璃态和晶态材料收集的衍射图的直接比较表明，前相中观察到的 MRO 与维持晶体结构的局部分子排列有关。此外，还表明，一旦出现与 MRO 相关的衍射峰，介电谱中还会检测到比结构（α）过程更慢的额外流动性（δ 或α'弛豫）。这种新的模式与超分子纳米聚集体中的运动有关。对介电和量热数据的详细分析还揭示了所研究药物的内部结构和 MRO 的变化对α过程玻璃化转变温度（Tg）形状、等压脆性、玻璃态分子动力学和动态相关分子数量的影响。这些发现有助于理解不同类型的分子间 MRO 对具有相似化学主链的物质性质的影响。
