2-Hydroxypropyl-β-cyclodextrin (HPBCD) is one of the most important cyclodextrin derivatives, finding extensive applications in the pharmaceutical sector. Beyond its role as an excipient, HPBCD achieved orphan drug status in 2015 for Niemann-Pick type C disease treatment, prompting research into its therapeutic potential for various disorders. However, the acceptance of HPBCD as an active pharmaceutical ingredient may be impeded by its complex nature. Indeed, HPBCD is not a single entity with a well-defined structure, instead, it is a complex mixture of isomers varying in substituent positions and the degree of hydroxypropylation, posing several challenges for unambiguous characterization. Pharmacopoeias' methods only address the average hydroxypropylation extent, lacking a rapid approach to characterize the substituent positions on the CD scaffold. Recognizing that the distribution of substituents significantly influences the complexation ability and overall activity of the derivative, primarily by altering cavity dimensions, we present a straightforward and non-destructive method based on liquid state NMR spectroscopy to analyze the positions of the hydroxypropyl sidechains. This method relies on a single set of routine experiments to establish quantitative assignment and it provides a simple yet effective tool to disclose the substitution pattern of this complex material, utilizing easily accessible (400 MHz NMR) instrumentation.

中文翻译：

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解决 2-羟丙基 β-环糊精之谜：通过 NMR 光谱详细分配取代基分布


2-羟丙基-β-环糊精（HPBCD）是最重要的环糊精衍生物之一，在制药领域有着广泛的应用。除了作为赋形剂的作用外，HPBCD 还于 2015 年获得了治疗 Niemann-Pick C 型疾病的孤儿药地位，促进了对其治疗各种疾病潜力的研究。然而，HPBCD 作为活性药物成分的接受可能因其复杂的性质而受到阻碍。事实上，HPBCD 并不是一个具有明确结构的单一实体，相反，它是取代基位置和羟丙基化程度不同的异构体的复杂混合物，这对明确的表征提出了一些挑战。药典方法仅涉及平均羟丙基化程度，缺乏快速表征 CD 支架上取代基位置的方法。认识到取代基的分布主要通过改变空腔尺寸来显着影响衍生物的络合能力和整体活性，我们提出了一种基于液态核磁共振波谱的简单且非破坏性的方法来分析羟丙基侧链的位置。该方法依赖于一组常规实验来建立定量分配，并且它提供了一种简单而有效的工具，利用易于访问的 (400 MHz NMR) 仪器来揭示这种复杂材料的替代模式。