Molecular receptors. Structural effects and substrate recognition in binding of organic and biogenic ammonium ions by chiral polyfunctional macrocyclic polyethers bearing amino-acid and other side-chains

The stability constants of the complexes formed by the polyfunctional macro-cyclic receptor molecules of type 1 with cationic substrates have been determined and analyzed in terms of structural factors. The binding strength is dominated by electrostatic interactions; the tetracarboxylate 1 (O⁻) forms by far the most stable complexes of all known macrocyclic polyethers. Lipophilic groups also significantly enhance stabilities, stressing the role of such residues in biological receptor sites. The complexation selectivity of organic ammonium cations is determined by two main factors: (a) central discrimination, resulting from the macrocyclic cavity, strongly favors binding of primary ammonium cations with respect to more highly substituted ones and also distinguishes among (R-NH₃⁺)-substrates differently substituted on the C(α)-atom; (b) lateral discrimination arises from interactions between the substrate and the side chains borne by the macrocycle; again electrostatic and lipophilic group effects play the major role; diammonium cations are especially strongly bound. Complexation of biogenic amines follows the same trends; for instance noradrenaline and norephedrine are selectively bound with respect to adrenaline and ephedrine, pointing towards potential applications in selective binding and transport of biologically active substances. © 1982 Verlag GmbH & Co. KGaA, Weinheim