Optically Active Hexaazamacrocycles: Protonation Behavior and Chiral-Anion Recognition

Abstract

The protonation features of two optically active 22-membered hexaazamacrocycles possessing one (L1) or two (L2) (R,R)-cyclohexane-1,2-diamine moieties have been studied by means of potentiometric 1H- and 13C-NMR techniques. This study allows the determination of the basicity constants and the stepwise protonation sites. The presence of the cyclohexane decreases the protonation ability, and this effect can be explained in terms of conformational and electrostatic factors. Binding of different chiral dicarboxylates has been studied by potentiometry. Macrocycle L2 presents higher anion-complexation equilibrium constants than L1. The stability of the diastereoisomeric complexes depends on the pH, and the structures of the macrocycles and anions. Receptor L1⋅6 H+ shows moderate D-selectivity towards tartrate anion, whereas L2⋅6 H+ exhibits a good preference for N-Ac-D-aspartate. Both protonated L1 and L2 form strong complexes with N-Ac-glutamate, and the stoichiometry of the complex depends on the degree of protonation and the absolute configuration of the anion. For this last anion, both azamacrocycles exhibit a clear D-preference.