Recognition of dicarboxylate anions by a ditopic hexaazamacrocycle containing bis-p-xylyl spacers

Abstract

The hexaprotonated form of the hexaazamacrocycle, 7,22-dimethyl-3,7,11,18,22,26-hexaazatricyclo[26.2.2.2.13.16]tetratriaconta-1(30),13,15,28,31,33-hexaene, (H6Me2[30]pbz2N6)6+, was used as a receptor for the molecular recognition of aliphatic and aromatic carboxylate substrates. The receptor–substrate binding behaviour of (H6Me2[30]pbz2N6)6+ with aliphatic [−O2C(CH2)nCO2−, n = 0 to 4] and aromatic (benzoate, phthalate, isophthalate, and terephthalate) substrates was evaluated by potentiometry and 1H NMR spectroscopy. The association constants of the entities formed were determined in H2O at 298.0 K and 0.1 M KNO3 (by potentiometry) and in D2O (by 1H NMR). The constants for the aliphatic substrates are much lower than for the aromatic ones. NMR spectroscopy allowed the conclusion that the recognition process might involve H-bonding, electrostatic and π–π stacking interactions, the strength and the type of them depending on the substrate. The cooperative conjugation of the three types of interactions only occurs when terephthalate is the substrate. Molecular dynamics simulations (MD) in a periodic box of water solvent molecules were also used to investigate the nature of the binding association between the receptor and the three aromatic dicarboxylate anions (phthalate, isophthalate, and terephthalate). These studies confirmed that the (H6Me2[30]pbz2N6)6+ receptor encapsulates the terephthalate anion with the formation of an inclusion supermolecule stabilized by multiple N–H⋯O hydrogen bonding and π–π interactions. The molecular recognition between the receptor and the other two aromatic anions, phthalate and isophthalate, also occurs via N–H⋯O hydrogen bonds, but outside of the macrocyclic cavity. The results are discussed in terms of energetic and entropic contributions and showed that the binding association between the receptor and these anions is favourable.