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 (1<i>S</i>,2<i>S</i>)-2-(1-<i>H</i>-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 (<b>1a</b>) showed a cone-type conformation defining an inner anion-binding site, while the bipodal molecule with the central <i>meta</i>-phenylene spacer (<i>m</i>-<b>2a</b>) 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 ¹H NMR titration experiments in 9:1 CD₃CN:CD₃OH at 298.15 K. Interestingly, <b>1a</b> 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, <b>1a</b> 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 ¹H NMR spectroscopy