NMR studies of host-guest complexes of anionic cyclophanes with dopamine and its analogues in aqueous media

NMR studies were carried out on the complexation of dopamine, tyramine and phenethylamine with cyclophanes that incorporate two phenylene groups in the macrocyclic framework and four pendant carboxylate arms: the cyclophanes studied were 2,9,18,25-tetraoxo-4,7,20,23-tetrakis(carboxymethyl)-1,4,7,10,17,20,23,26- octaaza[10.10]paracyclophane(1), its 2,5-dimethyl-p-phenylene derivative (2) and tetramethyl-p-phenylene derivative (3). The formation constants of the 1:1 host-guest complexes, K = [HG]/[H][G], were determined as: 17-23 for the complexes of 1 with the aromatic amines; 20 for 2-dopamine complex, 12-14 for 2-tyramine and 3-8 for 2-phenethylamine; 16 for 3-dopamine, 6 for 3-tyramine and 4 for 3-phenethylamine. The formation constants of the complexes of the methyl-substituted cyclophanes, 2 and 3, show a clear increase in the order phenethylamine < tyramine < dopamine, whereas the stabilities of the complexes of 1 are less dependent on the nature of the guest molecules. The introduction of methyl groups increases the selectivity towards dopamine, although the stabilities of the complexes are decreased by the steric effect of the methyl groups. The benzene rings of the host and guest molecules are stacked face-to-face in a slipped manner. Transannular interaction in this stack and an electrostatic interaction between the NH₃⁺ group of the guest and the -CO₂^- group of the host are the major binding forces for complexation.