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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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.
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.