Inherently chiral compounds, such as calixarenes, are chiral due to a nonplanar three-dimensional (3D) structure. Determining their conformation is essential to understand their properties, with nuclear magnetic resonance (NMR) spectroscopy being one applicable method. Using alignment media to measure residual dipolar couplings (RDCs) to obtain structural information is advantageous when classical NMR parameters like the nuclear Overhauser effect (NOE) or J-couplings fail. Besides providing more accurate structural information, the alignment media can induce different orientations of enantiomers. In this study, we examined the ability of polyglutamates with different side-chain moieties─poly-γ-benzyl-l-glutamate (PBLG) and poly-γ-p-biphenylmethyl-l-glutamate (PBPMLG) ─to enantiodifferentiate the inherently chiral phenoxathiin-based thiacalix[4]arenes. Both media, in combination with two solvents, allowed for enantiodiscrimination, which was, to the best of our knowledge, proved for the first time on inherently chiral compounds. Moreover, using the experimental RDCs, we investigated the calix[4]arenes conformational preferences in solution, quantitatively analyzed the differences in the alignment of the enantiomers, and discussed the pitfalls of the use of the RDC analysis.

Department of Chemistry Technical University of Darmstadt Alarich Weiss Straße 16 64287Darmstadt Germany

Department of Organic Chemistry University of Chemistry and Technology Prague Technická 5 166 28Prague 6 Czech Republic

Department of Physical and Macromolecular Chemistry Charles University Hlavova 8 128 00Prague 2 Czech Republic

Department of Solid State Chemistry University of Chemistry and Technology Prague Technická 5 166 28Prague 6 Czech Republic

Faculty of Mathematics and Physics Charles University Ke Karlovu 3 121 16Prague 2 Czech Republic

Institute of Organic Chemistry and Biochemistry Czech Academy of Sciences Flemingovo náměstí 542 160 00Prague 6 Czech Republic

Laboratory of NMR Spectroscopy University of Chemistry and Technology Prague Technická 5 166 28Prague 6 Czech Republic

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