Skip to main content
Journal cover image

The kinetics of dimethylhydroxypyridinone interactions with iron(iii) and the catalysis of iron(iii) ligand exchange reactions: implications for bacterial iron transport and combination chelation therapies.

Publication ,  Journal Article
Harrington, JM; Mysore, MM; Crumbliss, AL
Published in: Dalton transactions (Cambridge, England : 2003)
May 2018

Many microbes acquire environmental Fe by secreting organic chelators, siderophores, which possess the characteristics of a high and specific binding affinity for iron(iii) that results in the formation of thermodynamically stable, and kinetically inert iron(iii) complexes. Mechanisms to overcome the kinetic inertness include the labilization of iron(iii) by means of ternary complex formation with small chelators. This study describes a kinetic investigation of the labilization of iron(iii) between two stable binding sites, the prototypical siderophore ferrioxamine B and EDTA, by the bidentate siderophore mimic, 1,2-dimethyl-3-hydroxy-4-pyridinone (L1, H(DMHP)). The proposed mechanism is substantiated by investigating the iron(iii) exchange reaction between ferrioxamine B and H(DMHP) to form Fe(DMHP)3, as well as the iron(iii) exchange from Fe(DMHP)3 to EDTA. It is also shown that H(DMHP) is a more effective catalyst for the iron(iii) exchange reaction than bidentate hydroxamate chelators reported previously, supporting the hypothesis that chelator structure and iron(iii) affinity influence low denticity ligand facilitated catalysis of iron(iii) exchange reactions. The results are also discussed in the context of the design and use of combination chelator therapies in the treatment of Fe overload in humans.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Dalton transactions (Cambridge, England : 2003)

DOI

EISSN

1477-9234

ISSN

1477-9226

Publication Date

May 2018

Volume

47

Issue

20

Start / End Page

6954 / 6964

Related Subject Headings

  • Pyridones
  • Ligands
  • Kinetics
  • Iron Overload
  • Iron Chelating Agents
  • Iron
  • Ion Transport
  • Inorganic & Nuclear Chemistry
  • Hydroxamic Acids
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Harrington, J. M., Mysore, M. M., & Crumbliss, A. L. (2018). The kinetics of dimethylhydroxypyridinone interactions with iron(iii) and the catalysis of iron(iii) ligand exchange reactions: implications for bacterial iron transport and combination chelation therapies. Dalton Transactions (Cambridge, England : 2003), 47(20), 6954–6964. https://doi.org/10.1039/c8dt01329b
Harrington, James M., Manu M. Mysore, and Alvin L. Crumbliss. “The kinetics of dimethylhydroxypyridinone interactions with iron(iii) and the catalysis of iron(iii) ligand exchange reactions: implications for bacterial iron transport and combination chelation therapies.Dalton Transactions (Cambridge, England : 2003) 47, no. 20 (May 2018): 6954–64. https://doi.org/10.1039/c8dt01329b.
Harrington, James M., et al. “The kinetics of dimethylhydroxypyridinone interactions with iron(iii) and the catalysis of iron(iii) ligand exchange reactions: implications for bacterial iron transport and combination chelation therapies.Dalton Transactions (Cambridge, England : 2003), vol. 47, no. 20, May 2018, pp. 6954–64. Epmc, doi:10.1039/c8dt01329b.
Journal cover image

Published In

Dalton transactions (Cambridge, England : 2003)

DOI

EISSN

1477-9234

ISSN

1477-9226

Publication Date

May 2018

Volume

47

Issue

20

Start / End Page

6954 / 6964

Related Subject Headings

  • Pyridones
  • Ligands
  • Kinetics
  • Iron Overload
  • Iron Chelating Agents
  • Iron
  • Ion Transport
  • Inorganic & Nuclear Chemistry
  • Hydroxamic Acids
  • Humans