Kinetic studies on the oxidation of oxyhemoglobin by biologically active iron thiosemicarbazone complexes: relevance to iron-chelator-induced methemoglobinemia

Basha, Maram T., Rodríguez, Carlos, Richardson, Des R., Martínez, Manuel and Bernhardt, Paul V. (2013) Kinetic studies on the oxidation of oxyhemoglobin by biologically active iron thiosemicarbazone complexes: relevance to iron-chelator-induced methemoglobinemia. Journal of Biological Inorganic Chemistry, 19 3: 349-357. doi:10.1007/s00775-013-1070-9


Author Basha, Maram T.
Rodríguez, Carlos
Richardson, Des R.
Martínez, Manuel
Bernhardt, Paul V.
Title Kinetic studies on the oxidation of oxyhemoglobin by biologically active iron thiosemicarbazone complexes: relevance to iron-chelator-induced methemoglobinemia
Journal name Journal of Biological Inorganic Chemistry   Check publisher's open access policy
ISSN 0949-8257
1432-1327
Publication date 2013-12-08
Year available 2013
Sub-type Article (original research)
DOI 10.1007/s00775-013-1070-9
Open Access Status Not Open Access
Volume 19
Issue 3
Start page 349
End page 357
Total pages 9
Place of publication Heidelberg, Germany
Publisher Springer
Language eng
Formatted abstract
The oxidation of oxyhemoglobin to methemoglobin has been found to be facilitated by low molecular weight iron(III) thiosemicarbazone complexes. This deleterious reaction, which produces hemoglobin protein units unable to bind dioxygen and occurs during the administration of iron chelators such as the well-known 3-aminopyridine-2-pyridinecarbaldehyde thiosemicarbazone (3-AP; Triapine), has been observed in the reaction with FeIII complexes of some members of the 3-AP structurally-related thiosemicarbazone ligands derived from di-2-pyridyl ketone (HDpxxT series). We have studied the kinetics of this oxidation reaction in vitro using human hemoglobin and found that the reaction proceeds with two distinct time-resolved steps. These have been associated with sequential oxidation of the two different oxyheme cofactors in the α and β protein chains. Unexpected steric and hydrogen-bonding effects on the FeIII complexes appear to be the responsible for the observed differences in the reaction rate across the series of HDpxxT ligand complexes used in this study.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online ahead of print 8 December 2013.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Chemistry and Molecular Biosciences
 
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Created: Fri, 10 Jan 2014, 20:47:19 EST by Miss Abigail Downie on behalf of School of Chemistry & Molecular Biosciences