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.