基于太赫兹光谱和DFT计算的甲氨蝶呤和组氨酸共晶研究

IF 3.1 3区 化学 Q3 CHEMISTRY, PHYSICAL
Zhongxin Zhang , Shuhan Li , Huan An , Reyihanguli Tudi , XinTian Song , Minjie Zhou , Fan Zhang , Wuyang Shi , Ao Li , Zhiqiang Li , Mei Xiang , Bumaliya Abulimiti , Bing Jin
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引用次数: 0

摘要

药物共晶是一种很有前途的策略,可以调节活性药物成分(api)的物理化学性质,改善药物的传递。甲氨蝶呤(Methotrexate, MTX)是一种广泛应用的抗肿瘤药物,但由于其水溶性差、毒性大,临床应用受到限制。在这里,我们通过使用实验和计算相结合的方法合成和表征MTX-His共晶来解决这些限制。时域太赫兹光谱(THz-TDS)是一种对分子间相互作用高度敏感的技术,它揭示了MTX-His共晶独特的低频振动模式,与母体材料和物理混合物相比,提供了分子间相互作用改变的直接光谱证据。还进行了互补拉曼光谱分析。密度泛函理论(DFT)的计算证实了太赫兹- tds的发现,阐明了特定的分子间相互作用,特别是氢键,对共晶稳定性的能量贡献。这些综合结果证明了太赫兹- tds与DFT计算相结合的能力,可以表征药物共晶中的分子间相互作用,并为合理设计具有定制特性的共晶以改善药物传递提供了见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Research on the cocrystal of methotrexate and histidine based on terahertz spectroscopy and DFT calculations

Research on the cocrystal of methotrexate and histidine based on terahertz spectroscopy and DFT calculations
Pharmaceutical cocrystals represent a promising strategy to modulate the physicochemical properties of active pharmaceutical ingredients (APIs) and improve drug delivery. Methotrexate (MTX), a widely used anti-tumor drug, suffers from limited clinical utility due to poor aqueous solubility and high toxicity. Here, we address these limitations by synthesizing and characterizing MTX-His cocrystals using a combined experimental and computational approach. Time-domain terahertz spectroscopy (THz-TDS), a technique highly sensitive to intermolecular interactions, revealed distinct low-frequency vibrational modes unique to the MTX-His cocrystal, providing direct spectroscopic evidence of altered intermolecular interactions compared to the parent materials and physical mixtures. Complementary Raman spectroscopy was also performed. Density functional theory (DFT) calculations corroborated the THz-TDS findings, elucidating the energetic contributions of specific intermolecular interactions, particularly hydrogen bonds, to the cocrystal's stability. These combined results demonstrate the power of THz-TDS, in conjunction with DFT calculations, to characterize intermolecular interactions in pharmaceutical cocrystals and provide insights into the rational design of cocrystals with tailored properties for improved drug delivery.
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来源期刊
Chemical Physics Letters
Chemical Physics Letters 化学-物理:原子、分子和化学物理
CiteScore
5.70
自引率
3.60%
发文量
798
审稿时长
33 days
期刊介绍: Chemical Physics Letters has an open access mirror journal, Chemical Physics Letters: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. Chemical Physics Letters publishes brief reports on molecules, interfaces, condensed phases, nanomaterials and nanostructures, polymers, biomolecular systems, and energy conversion and storage. Criteria for publication are quality, urgency and impact. Further, experimental results reported in the journal have direct relevance for theory, and theoretical developments or non-routine computations relate directly to experiment. Manuscripts must satisfy these criteria and should not be minor extensions of previous work.
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