1H NMR and protonation constants of new metal-chelating macrocycles, oxocyclopolyamines with pendant carboxymethyl groups, and the stabilities of their Mg 2+ and Ca 2+ complexes

Abstract

Potentiometry and 1H NMR have been used to study the protonation of a new series of 12−, 13−, 15−, 16− and 17-membered metal-chelating macrocycles with two or three pendant carboxymethyl groups. In the 12− and 13-membered macrocycles, ethylenediaminetetraacetate and ethylenediamine or propanediamine units are linked by two amide groups; in the 15−, 16−, and 17-membered macrocycles, diethylenetriaminepentaacetate and diamine units are linked by two amide groups. The protonation constants K n ( n = 1, 2, 3) of these new macrocyclic ligands are significantly smaller than the corresponding values for tetraaza and triaza macrocycles such as 1,4,7,10-tetraazacyclododecane- N, N′, N″, N″′-tetraacetic acid (DOTA) and 1,4,7-triazacyclononane- N, N′, N″-triacetic acid (NOTA). The protonation sites have been identified by measuring the 1H NMR chemical shifts at different pD values. Protonation corresponding to K 1 occurs on the amine nitrogen atoms. In the successive protonations, protons are distributed on the amine nitrogen atoms and the carboxylate oxygen atoms so as to minimize electrostatic repulsion. The low basicities of the amine nitrogen atoms in these new macrocycles are attributable to the introduction of amide groups into the ring system. As a consequence of the low basicities of the macrocycles, the formation constants of their Mg 2+ and Ca 2+ chelates are much lower than the corresponding values of EDTA. The ratio of the two formation constants, K f ( Ca) K f ( Mg) , varies in an unpredictable manner with the size of the macrolytic ligand.