A combination strategy of HPLC and boric acid modified β-CD polymer for super-efficiently separating chiral substances with O/N atoms in chiral and/or adjacent carbons

IF 6 2区化学 Q1 CHEMISTRY, ANALYTICAL

Analytica Chimica Acta Pub Date : 2025-09-23 DOI:10.1016/j.aca.2025.344687

Xiaoqian Yuan , Yuchen Cui , Yaqin Nan , Ruijun Tang , Xinru Wang , Yanmei Xu , Xinghua Jin , Yiwen Wang , Ding Cheng , Youxin Li

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引用次数: 0

Abstract

Background

Cyclodextrins (CDs) and their derivatives have been widely used as chiral selectors in HPLC. However, many derivatized CDs lack specificity for certain drugs and often exhibit limited resolution. Furthermore, their synthesis typically involves complex multi-step procedures, hindering scalability and cost-efficiency. To overcome these limitations, this study aims to develop a simple and scalable boric acid-modified β-cyclodextrin polymer (BA-β-CDP), targeting chiral substances with O/N atoms in chiral and/or adjacent carbons.

Results

BA-β-CDP was synthesized on a large scale using inexpensive reagents and a random substitution strategy, avoiding tedious protection-purification steps. Structural and chromatographic compatibility was confirmed by nine characterization techniques. In HPLC using the chiral mobile-phase additive (CMPA) method, BA-β-CDP enabled the efficient separation of 25 racemates. Among them, 24 achieved complete or baseline separation, and 10 exhibited resolution (Rs) values > 10. Typical cases included bisoprolol (Rs = 48.19), propranolol (Rs = 45.50), chlorpheniramine (Rs = 38.36), and metoprolol (Rs = 20.26). Additionally, the material demonstrated excellent batch-to-batch reproducibility, recyclability, and reusability.

Significance and novelty

This work presents a practical and cost-effective chiral selector. The synergistic mechanism offers strong and specific recognition toward chiral substances with O/N atoms in chiral and/or adjacent carbons. This approach represents a novel strategy for efficient and economical HPLC-based enantioseparation using widely accessible materials and methods.

Abstract Image

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高效液相色谱与硼酸修饰β-CD聚合物的结合策略用于超高效分离手性和/或邻碳上带有O/N原子的手性物质

环糊精及其衍生物作为手性选择剂在HPLC中得到了广泛的应用。然而，许多衍生cd缺乏对某些药物的特异性，并且通常表现出有限的分辨率。此外，它们的合成通常涉及复杂的多步骤过程，阻碍了可扩展性和成本效率。为了克服这些限制，本研究旨在开发一种简单且可扩展的硼酸修饰β-环糊精聚合物（BA-β-CDP），针对手性和/或相邻碳上具有O/N原子的手性物质。结果ba -β-CDP的大规模合成采用了廉价的试剂和随机替代策略，避免了繁琐的保护-纯化步骤。通过9种表征技术确定了结构和色谱相容性。采用手性流动相添加剂（CMPA）法，BA-β-CDP对25种外消旋物进行了高效分离。其中24个达到完全分离或基线分离，10个具有分辨率（Rs）值>；10。典型病例包括比索洛尔（Rs = 48.19）、心得安（Rs = 45.50）、氯苯那敏（Rs = 38.36）、美托洛尔（Rs = 20.26）。此外，该材料表现出优异的批对批再现性、可回收性和可重复使用性。本文提出了一种实用、经济的手性选择剂。这种协同机制对手性和/或相邻碳上含有O/N原子的手性物质具有很强的特异性识别能力。这种方法代表了一种高效、经济的基于高效液相色谱的对映体分离的新策略，使用了广泛可获得的材料和方法。

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来源期刊

Analytica Chimica Acta 化学-分析化学

CiteScore

10.40

自引率

6.50%

发文量

1081

审稿时长

38 days

期刊介绍： Analytica Chimica Acta has an open access mirror journal Analytica Chimica Acta: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. Analytica Chimica Acta provides a forum for the rapid publication of original research, and critical, comprehensive reviews dealing with all aspects of fundamental and applied modern analytical chemistry. The journal welcomes the submission of research papers which report studies concerning the development of new and significant analytical methodologies. In determining the suitability of submitted articles for publication, particular scrutiny will be placed on the degree of novelty and impact of the research and the extent to which it adds to the existing body of knowledge in analytical chemistry.