Chiral Imidazolium Receptors for Citrate and Malate: The Importance of the Preorganization

A family of simple receptors formed by two or three cationic imidazolium arms attached to a central aromatic linkage and displaying different conformational flexibility has been synthesized from the enantiopure (1S,2S)-2-(1-H-imidazol-1-yl)-cyclohexanol. The crystal structures of the corresponding bromides of two of the hosts showed remarkable differences. The tripodal receptor with a trimethylated central benzene ring (1a) showed a cone-type conformation defining an inner anion-binding site, while the bipodal molecule with the central meta-phenylene spacer (m-2a) displayed an extended conformation. The binding properties of the chiral imidazolium hosts toward citrate, isocitrate and the two enantiomers of malate have been studied by H-1 NMR titration experiments in 9:1 CD3CN:CD3OH at 298.15 K. Interestingly, 1a showed a stronger interaction with dianionic malate than with the trianionic citrate or isocitrate, suggesting that the smaller guest is better accommodated in the host cavity. Among this family, 1a proved to be the best receptor due to a combination of a larger number of electrostatic and H-bonding interactions and to a more efficient preorganization in the cone-type conformation. This preorganization effect is also present in solution as confirmed by H-1 NMR spectroscopy.