Kinetic aspects of iron(III)-chelation therapy with deferasirox (DFX) revealed by the solvolytic dissociation rate of the Fe(III)–DFX complex estimated with capillary electrophoretic reactor

Ryota Suzuki, Nobuhiko Iki

Research output: Contribution to journalArticlepeer-review

Abstract

Capillary electrophoresis was used to estimate the solvolytic dissociation rate (kd) of metal complexes of deferasirox (DFX, H3L), a drug used to treat iron overload. Inert CoIIIL23− did not dissociate. The estimated kd value for FeIIIL23− was (2.7 ± 0.3) × 10−4 s−1 (298 K, pH 7.4). The kd values of other complexes (AlIIIL23−, NiIIL24−, and MnIIL) were in the range 10−3–10−4 s−1. In contrast, ZnIIL and CuIIL were too labile to allow kd estimation. The fact that the half-life of FeIIIL23− (43.3 min) is shorter than the blood half-life of DFX (8–16 h) implies that the blood concentration of DFX should be high enough to prevent dissociation of FeIIIL23−. The possibility of a safer iron-chelation therapy that avoids excretion of other essential metal ions such as ZnII is discussed, highlighting the importance of selectivity in terms of kinetic stability.

Original languageEnglish
Article number112131
JournalJournal of Inorganic Biochemistry
Volume241
DOIs
Publication statusPublished - 2023 Apr

Keywords

  • Chelation therapy
  • Dissociation kinetics
  • Iron
  • Ligand design
  • Metal complex
  • Pharmacokinetics

Fingerprint

Dive into the research topics of 'Kinetic aspects of iron(III)-chelation therapy with deferasirox (DFX) revealed by the solvolytic dissociation rate of the Fe(III)–DFX complex estimated with capillary electrophoretic reactor'. Together they form a unique fingerprint.

Cite this