Probing the Effect of Fluorine on Hydrogen Bonding Interactions in a Pharmaceutical Hydrate Using Advanced Solid-State NMR

IF 4.5 2区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Molecular Pharmaceutics Pub Date : 2025-03-05 DOI:10.1021/acs.molpharmaceut.4c0105510.1021/acs.molpharmaceut.4c01055

Chaithanya Hareendran, and , T.G. Ajithkumar*,

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Abstract

Structural studies of pharmaceutical hydrates are essential to understanding stability-related issues, especially during the heating process of formulation. A thorough understanding of the hydration and dehydration behavior of active pharmaceutical ingredient (API) hydrate is also important since phase transitions can occur during the formulation process. This is because dehydration could result in a considerable rearrangement in the structure if water–API hydrogen bonding is present. We perform advanced solid-state NMR experiments on regorafenib monohydrate to investigate the role of fluorine in hydrogen bonding interaction, and the results are compared to its anhydrous form and its structural analogue, namely, sorafenib. Our results show that significant structural changes could not be observed on dehydration. Based on our study, it can be concluded that the introduction of fluorine restricts the intramolecular hydrogen bonding and the asymmetry in the structure of regorafenib monohydrate is absent, in comparison to sorafenib.

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利用先进固体核磁共振探测氟对药物水合物氢键相互作用的影响

药物水合物的结构研究对于理解稳定性相关问题至关重要，特别是在配方加热过程中。全面了解活性药物成分（API）水合物的水合和脱水行为也很重要，因为在配方过程中可能发生相变。这是因为如果水- api氢键存在，脱水会导致相当大的结构重排。我们对reorafenib进行了先进的固态核磁共振实验，以研究氟在氢键相互作用中的作用，并将结果与reorafenib的无水形式及其结构类似物索拉非尼进行了比较。我们的研究结果表明，脱水不能观察到明显的结构变化。根据我们的研究，可以得出结论，氟的引入限制了分子内氢键，与索拉非尼相比，regorafenib一水化合物的结构不对称。

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来源期刊

Molecular Pharmaceutics 医学-药学

CiteScore

8.00

自引率

6.10%

发文量

391

审稿时长

2 months

期刊介绍： Molecular Pharmaceutics publishes the results of original research that contributes significantly to the molecular mechanistic understanding of drug delivery and drug delivery systems. The journal encourages contributions describing research at the interface of drug discovery and drug development. Scientific areas within the scope of the journal include physical and pharmaceutical chemistry, biochemistry and biophysics, molecular and cellular biology, and polymer and materials science as they relate to drug and drug delivery system efficacy. Mechanistic Drug Delivery and Drug Targeting research on modulating activity and efficacy of a drug or drug product is within the scope of Molecular Pharmaceutics. Theoretical and experimental peer-reviewed research articles, communications, reviews, and perspectives are welcomed.