Heteroditopic receptor based on crown ether and cyclen units for the recognition of zwitterionic amino acids

The molecular recognition of five targeted amino acids differing in the nature of the side (R)- group and in the size of the aliphatic chain, glycine (Hgly), phenylalanine (Hphe), glutamic acid (Hglu−), 4-aminobutyric acid (Hgaba), and 6-aminohexanoic acid (Heahx), has been studied with a new heteroditopic receptor based in two distinct macrocycles, a cyclen and a crown ether moiety. The bismacrocycle L was synthesized via the bis-aminal route allowing to obtain the designed compound in gram scale and in good yield. Protonation constants of L and its binding constants with amino acids were determined by potentiometry in H2O/MeOH (1:1 v/v) solutions at 298.2 K and I=0.10 mol dm−3 in NMe4NO3. Stronger binding ability of the HnLn+ receptor for α-amino acids, Hgly and Hphen, than for the other studied substrates were found. Structural data derived from NMR studies showed that the binding of α-amino acids result from the cooperative participation of hydrogen bonds between the carboxylate group of amino acids and the polyammonium sites of cyclen, and the ion-dipole interactions between the ammonium group of the amino acids and the oxygen atoms of the crown ether.