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 1H 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 1H NMR spectroscopy.