Deferoxamine-Modified Hybrid Materials for Direct Chelation of Fe(III) Ions from Aqueous Solutions and Indication of the Competitiveness of In Vitro Complexing toward a Biological System.

Mateusz Pawlaczyk,Grzegorz Schroeder

doi:10.1021/acsomega.1c01411

Abstract

Deferoxamine (DFO) is one of the most potent iron ion complexing agent belonging to a class of trihydroxamic acids. The extremely high stability constant of the DFO–Fe complex (log β = 30.6) prompts the use of deferoxamine as a targeted receptor for scavenging Fe(III) ions. The following study aimed at deferoxamine immobilization on three different supports: poly(methyl vinyl ether-alt-maleic anhydride), silica particles, and magnetite nanoparticles, leading to a class of hybrid materials exhibiting effectiveness in ferric ion adsorption. The formed deferoxamine-loaded hybrid materials were characterized with several analytical techniques. Their adsorptive properties toward Fe(III) ions in aqueous samples, including pH-dependence, isothermal, kinetic, and thermodynamic experiments, were investigated. The materials were described with high values of maximal adsorption capacity qm, which varied between 87.41 and 140.65 mg g–1, indicating the high adsorptive potential of the DFO-functionalized materials. The adsorption processes were also described as intense, endothermic, and spontaneous. Moreover, an exemplary magnetically active deferoxamine-modified material has been proven for competitive in vitro binding of ferric ions from the biological complex protoporphyrin IX–Fe(III), which may lead to a further examination of the materials’ biological or medical applicability.

Highlights

Iron ions as microelements play a significant role in the stimulations of various functions in human organisms
The designed deferoxamine-functionalized hybrid materials were synthesized, characterized with several analytical techniques, and subsequently subjected to adsorption of Fe(III) ions from aqueous solutions to establish an influence of the support used on the adsorptive properties of the materials
The designed adsorbents consisted of three different supports, which were biocompatible polymeric chains of poly(methyl vinyl ether-alt-maleic anhydride) (PMVEAMA), commercially available amorphous silica microparticles functionalized with surface isocyanate and maleimide groups, and synthesized Fe3O4 nanoparticles encapsulated within the silica matrix, which underwent functionalization with deferoxamine via isocyanate− and maleimide−silyl linkers

Summary

Introduction

Iron ions as microelements play a significant role in the stimulations of various functions in human organisms. Among many classes of domains responsible for effective chelation of metal ions, siderophores are the ones that bind iron selectively or exhibit extremely high binding constants. Deferoxamine as a hexadentate molecule coordinates iron ions in a ratio of 1:1 with an extremely high stability constant β at a level of 4.0 × 1030. Its complexes with other metal ions are formed with much lower stability constants. This property has prompted deferoxaminemediated ion overload treatment for many years of clinical therapy.[4−7] free deferoxamine exhibits beneficial therapeutic effects, such as antifibrotic effects, protection against acetaminophen-induced liver injuries, or inhibition of neurodegenerative Alzheimer’s and Huntington’s diseases.[8−11]

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Results

Conclusion