Role of pyridine hydrogen-bonding sites in recognition of basic amino acid side chains.

A series of three, new artificial receptors for guanidinium and ammonium guests has been synthesized. All three receptors have highly preorganized clefts bearing two carboxylate groups. They differ in the number of nitrogen atoms contained in their clefts, as follows: four N atoms in receptor 3, three N atoms in 4, and two nitrogens in 5. Crystallographic studies have produced the solid-state structures of the following guanidinium complexes of each receptor: 3.2CH(3)CH(2)NHC(NH(2))(2)(+), 4.2CH(3)NHC(NH(2))(2)(+), and 5.2C(NH(2))(3)(+). The conformations of the receptor molecules in all three complexes are very similar. N-Alkylguanidinium guests are bound in the clefts of 3 and 4 in similar manners, despite the loss of one hydrogen-bond acceptor nitrogen in 4 and the possible hindrance of the cavity by a CH group. In the guanidinium complex of 5, neither guest enters the cavity containing two CH groups. Complexation studies were conducted in methanol by (1)H NMR titration for several guanidinium and ammonium guests, including derivatives of the amino acids arginine and lysine. Receptor 5 binds all such guests weakly (K(s) < 4000), while 3 binds most guests very strongly (K(s) > 100 000). Receptor 3 is selective for arginine versus lysine, while 4 binds lysine better than does 3. The results generally underscore the importance of receptor preorganization and hydrogen-bonding complementarity in the design of receptors that can serve as probes for biomolecules.