Synthetic receptors as models for alkali metal cation-pi binding sites in proteins

The alkali metal cations Na+ and K+ have several important physiological ro les, including modulating enzyme activity. Recent work has suggested that a lkali metal cations may be coordinated by pi systems, such as the aromatic amino acid side chains, The ability of K+ to interact with an aromatic ring has been assessed by preparing a family of synthetic receptors that incorp orate the aromatic side chains of phenylalanine, tyrosine. and tryptophan, These receptors are constructed around a diaza-18-crown-6 scaffold, which s erves as the primary binding site for an alkali metal cation. The ability o f the aromatic rings to coordinate a cation was determined by crystallizing each of the receptors in the presence of K+ and by solving the solid state structures. In all cases, complexation of K+ by the a system was observed. When possible, the structures of the unbound receptors also were determine d for comparison. Further proof that the aromatic ring makes an energetical ly favorable interaction with the cation was obtained by preparing a recept or in which the arene was perfluorinated. Fluorination of the arene reverse s the electrostatics, but the aromaticity is maintained. The fluorinated ar ene rings do not coordinate the cation in the solid state structure of the K+ complex. Thus, the results of the predicted electrostatic reversal were confirmed. Finally, the biological implications of the alkali metal cation- a interaction are addressed.