Mn2+, Co2+, Cu2+ and Zn2+ complexes with two macrocyclic ligands bearing L-lactate-like functions: potentiometric studies and evaluation of superoxide-scavenging properties of the Mn2+ complex

Some aerobic organisms devoid of SOD use Mn2+ chelates to scavenge the O-2( -) radical. Since the Mn2+-bis(lactato)diaquo complex is known as having a high SOD-like activity, we prepared manganese(II) complexes with triazamacr ocyclic ligands bearing L-lactate-like functions in order to obtain model c ompounds able to disproportionate the superoxide radical. Thus, two macrocy clic ligands, N,N'N "-tris[2(S)-hydroxybutyric acid]-1,4,7-triazacyclononan e, L-1, and N,N'N "-tris[2(S)-hydroxybutyric acid]-1,5,9-triazacyclododecan e, L-2, were prepared and their capacity to retain the Mn2+ ion in aqueous solution was determined from potentiometric experiments. The chelating prop erties in aqueous solution of each ligand towards Co2+ Cu2+ and Zn2+ ions w ere also determined. L-1 forms complexes with Mn2+, Co2+, Cu2+ and Zn2+ ion s with stability constants of 8.33(5), 15.78(5), 17.65(3) and 14.32(1), res pectively. L-2 forms complexes with Cu2+ and Zn2+ ions with stability const ants of 10.67(1) and 6.98(3), respectively. But the constants related to th e Mn2+ and Co2+ complexes were too low to be determined by the method used. The stability constants values calculated for L-2 complexes are significan tly lower than those for the corresponding complexes of L-1. Additional spe ctroscopic measurements were carried out on the Mn2+-L-1 system. The electr onic spectrum of this system showed a pH-dependence that may be consistent with the formation of hydroxo-species as the ESR spectra recorded at 120 K did not show oxidation of the Mn+ ion in the pH range studied. The superoxi de-scavenging activity of the manganese(II)-L-1 complex was investigated us ing the cytochrome c assay. The Mn2+-L-1 system showed an IC50 value of 1.7 mu M which indicates that it appears as a potent SOD mimic. (C) 2000 Elsev ier Science S.A. All rights reserved.