Chemistry Research Laboratory, Department of Chemistry, University of Oxford , Mansfield Road, Oxford, OX1 3TA U.K.
J Am Chem Soc. 2017 Sep 6;139(35):12228-12239. doi: 10.1021/jacs.7b06144. Epub 2017 Aug 28.
The application of chiral interlocked host molecules for discrimination of guest enantiomers has been largely overlooked, which is surprising given their unique three-dimensional binding cavities capable of guest encapsulation. Herein, we combined the stringent linear geometric interaction constraints of halogen bonding (XB), the noncovalent interaction between an electrophilic halogen atom and a Lewis base, with highly preorganized and conformationally restricted chiral cavities of [2]rotaxanes to achieve enantioselective anion recognition. Representing the first detailed investigation of the use of chiral XB rotaxanes for this purpose, extensive H NMR binding studies and molecular dynamics (MD) simulation experiments revealed that the chiral rotaxane cavity significantly enhances enantiodiscrimination compared to the non-interlocked free axle and macrocycle components. Furthermore, by examining the enantioselectivities of a family of structurally similar XB [2]rotaxanes containing different combinations of chiral and achiral macrocycle and axle components, the dominant influence of the chiral macrocycle in our rotaxane design for determining the effectiveness of chiral discrimination is demonstrated. MD simulations reveal the crucial geometric roles played by the XB interactions in orientating the bound enantiomeric anion guests for chiral selectivity, as well as the critical importance of the anions' hydration shells in governing binding affinity and enantiodiscrimination.
手性主体分子在对映异构体的识别中具有潜在的应用价值，但这一领域却长期被忽视，这令人惊讶，因为这些主体分子具有独特的三维结合腔，能够包合客体分子。在此，我们结合卤键（XB）的严格线性几何相互作用限制和路易斯碱与亲电卤原子之间的非共价相互作用，以及[2]轮烷高度预组织和构象受限的手性空腔，实现了对阴离子的对映选择性识别。这代表了首次详细研究手性 XB 轮烷在这方面的应用，广泛的 1H NMR 结合研究和分子动力学（MD）模拟实验表明，与非键合的自由轴和大环组件相比，手性轮烷空腔显著增强了对映体的区分能力。此外，通过研究一系列结构相似的含有不同手性和非手性大环和轴组件的 XB [2]轮烷对映选择性，证明了我们在轮烷设计中手性大环在确定手性识别有效性方面的主导作用。MD 模拟揭示了 XB 相互作用在定向结合的对映体阴离子客体以实现手性选择性方面所起的关键几何作用，以及阴离子水合壳在控制结合亲和力和对映体选择性方面的重要性。
