Synthesis and characterisation of two new catechol-based iron(III) ion-sequestering agents

Abstract

The new compounds 1,4,10,13-tetrakis(2,3-dihydroxybenzoyl)-7,16-dimethyl-1,4,7,10,13,16-hexaazacyclooctadecane (H8L1) and 1,4,7,10,13,16-hexakis(2,3-dihydroxybenzoyl)-1,4,7,10,13,16-hexaazacyclooctadecane (H12L2), having macrocyclic skeletons bearing four and six catechol hanging groups, respectively, have been synthesized and characterised. The crystal structure of H8L1·2dmso·2H2O (dmso = dimethyl sulfoxide), has been solved by single-crystal X-ray analysis. The equilibrium constants for protonation of the macrocycles and complexation of Fe3+ have been studied by potentiometric procedures in water–dmso (50∶50 v/v), 0.1 mol dm–3 NMe4Cl, at 298.1 ± 0.1 K. Both compounds are able to form mono- and di-nuclear iron(III) complexes of very high stability. These results indicate that the two compounds are thermodynamically able to scavenge Fe3+ from iron(III) transferrin. Their effectiveness as scavengers has been demonstrated by spectrophotometric measurements on the transmetallation reactions occurring in the presence of diiron(III) transferrin in aqueous solution. For comparison, the drug desferrioxamine B (DFB) has been also considered under the same experimental conditions. In 0.1 mol dm–3 phosphate buffer, at pH 7.4, both H8L1 and H12L2 remove iron from diiron(III) transferrin, the transmetallation reactions being much faster for H12L2 than for DFB which is slightly more effective than H8L1.