Fine-Tuning Ligand−Receptor Design for Selective Molecular Recognition of Dicarboxylic Acids

Abstract

The host-guest interaction between the hexaaza macrocyclic ligand 3,7,11,18,22,26-hexaazatricyclo[26.2.2.2]tetratriaconta-1(31),13(34),14,16(33),28(32),29-hexaene (P3) and three rigid dicarboxylic acids (isophthalic acid, H2is; phthtalic acid, H2ph; and terephthalic acid, H2te) has been investigated using potentiometric equilibrium methods and NMR spectroscopy including the measurement of intermolecular nuclear Overhauser effects (NOEs) and self-diffusion coefficients (D). Ternary complexes are formed in aqueous solution as a result of hydrogen bond formation and Coulombic interactions between the host and the guest. In the [(H6P3)(is)]4+ complex, those bonding interactions reach a maximum yielding a log K6R of 4.74. Competitive distribution diagrams and total species distribution diagrams are used to illustrate the main features of these systems. In particular, a selectivity of over 89% at p[H] = 5.0 is obtained for the complexation of the is versus the te substrates. The recognition capacity of P3 over dicarboxylic acids (da) is compared to the related hexaaza macrocycle Me2P3 (7,22-dimethyl-3,7,11,18,22,26-hexaazatricyclo[26.2.2.2]tetratriaconta-1(30),13,15,28,31,33-hexaene) that binds da with a lesser strength, and it is not selective. Theoretical calculations performed at molecular dynamics level have also been carried out and point out that the origin of selectivity is mainly due to the capacity of the P3 ligand receptor to adapt to the geometry of the dicarboxylic acid to form relatively strong hydrogen bonds.