Belinostat is a histone deacetylase inhibitor for the treatment of refractory T-cell lymphoma. Our study found that the tendency to form solvates of belinostat with hydrogen-bond acceptor type solvents was obvious based on the COSMO-RS model. Motivated by the prediction results, we investigated eight novel solvates, with 1,4-dioxane, tetrahydrofuran, furan, 3-picoline, cyclopentanone, 1-methyl-2-pyrrolidinone, and dimethyl sulfoxide/water as guest molecules, obtained by different crystallization methods. The obtained solid forms were thoroughly characterized with various analytical techniques, namely, powder X-ray diffraction, Fourier transform infrared spectroscopy, and thermal analysis. The thermal stability order of solvates was S_3PC > S′_Diox > S_NMP > S_CP > S_Furan > S_THF > S_Diox > S_DMSO/H2O, and a strong correlation between the boiling points of solvents and the crystal lattice energy with the thermal stability of solvates was observed. Additionally, six crystal structures of five solvates and the reported Form I were successfully determined from single-crystal X-ray diffraction data. The results revealed that the belinostat molecule adopted flexible conformations in different crystal structures; meanwhile, the formation of belinostat solvate was mainly driven by the belinostat–solvent intermolecular interactions and the improved packing efficiency due to the introduction of solvent molecules.

中文翻译：

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通过实验筛选和计算预测合理化 Belinostat 溶剂化物的形成

Belinostat 是一种组蛋白去乙酰化酶抑制剂，用于治疗难治性 T 细胞淋巴瘤。我们的研究发现，基于 COSMO-RS 模型，belinostat 与氢键受体型溶剂形成溶剂化物的趋势是明显的。受预测结果的启发，我们研究了以 1,4-二恶烷、四氢呋喃、呋喃、3-甲基吡啶、环戊酮、1-甲基-2-吡咯烷酮和二甲亚砜/水为客体分子，通过不同结晶法获得的 8 种新型溶剂化物方法。用各种分析技术，即粉末 X 射线衍射、傅里叶变换红外光谱和热分析对获得的固体形式进行彻底表征。溶剂化物的热稳定性顺序为 S _3PC > S' _Diox > S _NMP > S_CP > S _Furan > S _THF > S _Diox > S _{DMSO/H 2 O}，并且观察到溶剂沸点和晶格能与溶剂化物热稳定性之间的强相关性。此外，从单晶 X 射线衍射数据成功确定了五种溶剂化物的六种晶体结构和报告的 I 型。结果表明，belinostat分子在不同的晶体结构中采用灵活的构象；同时，belinostat溶剂化物的形成主要是由belinostat-溶剂分子间相互作用和由于溶剂分子的引入而提高的填充效率驱动的。