Armstrong Daniel W, Aslani Saba, Nafie Jordan, Wu Yong, Stoddart J Fraser
University of Texas at Arlington, Arlington, Texas 76019, United States.
AZYP, LLC, Arlington, Texas 76019, United States.
JACS Au. 2024 Dec 19;5(2):693-701. doi: 10.1021/jacsau.4c00962. eCollection 2025 Feb 24.
Cyclodextrins (CDs) were the first identified molecules and arguably the most consequential molecules in the areas of macrocyclic science and technology. As carbohydrates, their intrinsic architecture and chirality have played a fundamental role in their response to and effect on guest molecules. Indeed, the nature of inclusion complexation was formalized with CD-based hosts. A recent report on the first synthesis of unnatural mirror-image l-cyclodextrins foreshadows a new era of stereochemical research involving macrocyclic entities. Here, we show the inherently difficult, but rapid and sensitive, separation of enantiomeric CDs. The absolute configurations of CD antipodes have been investigated and distinguished by vibrational circular dichroism (VCD). Results indicated that the most intense VCD band at 1150 cm arises from the C-O stretching of the glucosidic bonds lining the CD torus. It follows that chiroptical radiation can excite either d- or l-CD selectively. The enzymatic susceptibilities of mirror-image CDs are vastly different, suggesting the possibility of different biochemical and medicinal uses. The electrophoretic migration of small chiral molecules, e.g., amino acids is easily and predictably reversed with d- and l-CDs.
环糊精（CDs）是大环科学与技术领域中最早被鉴定出的分子，也可以说是该领域中最重要的分子。作为碳水化合物，它们的内在结构和手性在其对客体分子的响应和作用中发挥了基础性作用。事实上，包合络合的本质是通过基于CD的主体得以形式化的。最近一篇关于首次合成非天然镜像L-环糊精的报道预示着涉及大环实体的立体化学研究的新时代。在此，我们展示了对映体CDs固有困难但快速且灵敏的分离方法。通过振动圆二色性（VCD）对CD对映体的绝对构型进行了研究和区分。结果表明，在1150 cm处最强的VCD谱带出现在环绕CD环的糖苷键的C-O伸缩振动处。由此可见，手性光辐射可以选择性地激发d-CD或l-CD。镜像CDs的酶敏感性差异很大，这表明它们可能具有不同的生化和药用用途。例如，氨基酸等小手性分子的电泳迁移可以通过d-CD和l-CD轻松且可预测地逆转。
