The mono(catecholamine) derivatives as iron chelators: synthesis, solution thermodynamic stability and antioxidant properties research

Abstract

There is a growing interest in the development of new iron chelators as novel promising therapeutic strategies for neurodegenerative disorders. In this article, a series of mono(catecholamine) derivatives, 2,3-bis(hydroxy)-<i>N</i>-(hydroxyacyl)benzamide, containing a pendant hydroxy, have been synthesized and fully characterized by nuclear magnetic resonance, Fourier transform infrared spectroscopy and mass spectrum. The thermodynamic stability of the chelators with Fe^III, Mg^II and Zn^II ions was then investigated. The chelators enable formation of (3 : 1) Fe^III complexes with high thermodynamic stability and exhibited improved selectivity to Fe^III ion. Meanwhile, the results of 1,1-diphenyl-2-picryl-hydrazyl assays of mono(catecholamine) derivatives indicated that they all possess excellent antioxidant properties. These results support the hypothesis that the mono(catecholamine) derivatives be used as high-affinity chelator for iron overload situations without depleting essential metal ions, such as Mg^II and Zn^II ions.