Labíková Magdaléna, Svoboda Jiří, Tůma Jiří, Lindner Wolfgang, Kohout Michal
Department of Organic Chemistry, University of Chemistry and Technology Prague, Technická 5, 166 28 Prague, Czech Republic.
Institute of Analytical Chemistry, University of Vienna, Währinger Strasse 38, 1090 Vienna, Austria.
J Chromatogr A. 2024 Mar 29;1719:464729. doi: 10.1016/j.chroma.2024.464729. Epub 2024 Feb 16.
Current state-of-the-art chiral stationary phases (CSPs) enable chiral resolution of almost any racemic mixture of choice. The exceptions represent ionizable and ionized substances that fail at any attempts to resolve on commercially available CSPs. These compounds, however, can be efficiently separated on chiral ion exchangers. Commercially available Cinchona alkaloids-based chiral weak ion-exchangers are typically used for chiral resolution of organic acids, while zwitterion ion-exchangers are efficient in the resolution of acids, bases, and zwitterions. The latter possess in their structure a cation exchange unit, which alone can serve as a cornerstone of chiral strong cation exchangers facilitating chiral separation of various basic racemic mixtures. Although chiral strong cation exchangers (cSCX) are efficient CSPs, their structural variations have not been thoroughly studied so far. It was assumed that the mechanism of chiral recognition of basic compounds by cSCX is based predominantly on π-π-interactions, hydrogen bonding and steric interactions (CSP I). To verify this assumption, we aimed in our study on the design and synthesis of cSCX first lacking lateral polar substituents on the aromatic unit in the selector's structure (CSP II), and second, to replace the aromatic unit by a cyclohexane ring (CSP III and IV), thereby to omit completely the π-π-interactions. We hypothesized that this structural change should lead to a partial or complete loss of enantiorecognition power of the selectors. Surprisingly, the non-aromatic cSCXs have shown chiral recognition capability comparable to that of previously described chiral cation exchange-type CSPs: from 16 analytes screened, 11 analytes were baseline resolved and 5 partially resolved on CSP I, while non-aromatic CSP III resolved 10 analytes baseline and 6 partially. We discuss the structural motifs of the known cSCX and the novel non-aromatic selectors in a relationship with their chromatographic performance using a set of basic analytes. Moreover, we present a theory of an effective chiral recognition mechanism by two novel non-aromatic cSCXs based on the chromatographic results and quantum mechanical calculations.
当前最先进的手性固定相（CSP）能够实现几乎任何所需外消旋混合物的手性拆分。例外情况是那些可电离和已电离的物质，它们无法在市售的CSP上进行拆分。然而，这些化合物可以在手性离子交换剂上有效分离。市售的基于金鸡纳生物碱的手性弱离子交换剂通常用于有机酸的手性拆分，而两性离子交换剂在拆分酸、碱和两性离子方面效率较高。后者在其结构中具有阳离子交换单元，该单元本身可作为手性强阳离子交换剂的基石，促进各种碱性外消旋混合物的手性分离。尽管手性强阳离子交换剂（cSCX）是高效的CSP，但到目前为止，它们的结构变体尚未得到充分研究。据推测，cSCX对碱性化合物的手性识别机制主要基于π-π相互作用、氢键和空间相互作用（CSP I）。为了验证这一假设，我们在研究中设计并合成了cSCX，首先是在选择剂结构的芳香单元上缺少侧向极性取代基（CSP II），其次是用环己烷环取代芳香单元（CSP III和IV），从而完全消除π-π相互作用。我们假设这种结构变化会导致选择剂的对映体识别能力部分或完全丧失。令人惊讶的是，非芳香族cSCX显示出与先前描述的手性阳离子交换型CSP相当的手性识别能力：在筛选的16种分析物中，11种分析物在CSP I上实现基线分离，5种部分分离，而非芳香族CSP III基线分离了10种分析物，部分分离了6种。我们使用一组碱性分析物，讨论了已知cSCX和新型非芳香族选择剂的结构基序与其色谱性能之间的关系。此外，基于色谱结果和量子力学计算，我们提出了两种新型非芳香族cSCX的有效手性识别机制理论。
