Kinetico-mechanistic studies on methemoglobin generation by biologically active thiosemicarbazone iron(III) complexes

Basha, Maram T., Bordini, Jeane, Richardson, Des R., Martinez, Manuel and Bernhardt, Paul V. (2016) Kinetico-mechanistic studies on methemoglobin generation by biologically active thiosemicarbazone iron(III) complexes. Journal of Inorganic Biochemistry, 162 326-333. doi:10.1016/j.jinorgbio.2015.12.004


Author Basha, Maram T.
Bordini, Jeane
Richardson, Des R.
Martinez, Manuel
Bernhardt, Paul V.
Title Kinetico-mechanistic studies on methemoglobin generation by biologically active thiosemicarbazone iron(III) complexes
Journal name Journal of Inorganic Biochemistry   Check publisher's open access policy
ISSN 1873-3344
0162-0134
Publication date 2016
Year available 2015
Sub-type Article (original research)
DOI 10.1016/j.jinorgbio.2015.12.004
Open Access Status Not Open Access
Volume 162
Start page 326
End page 333
Total pages 8
Place of publication Philadelphia, PA, United States
Publisher Elsevier
Collection year 2017
Language eng
Formatted abstract
The oxidation of human oxyhemoglobin (HbO2) to methemoglobin (metHb) is an undesirable side effect identified in some promising thiosemicarbazone anti-cancer drugs. This is attributable to oxidation reactions driven by FeIII complexes of these drugs formed in vivo. In this work the FeIII complexes of selected 2-benzoylpyridine thiosemicarbazones (HBpT), 2-acetylpyridine thiosemicarbazones (HApT), and the clinically trialled thiosemicarbazone, Triapine® (3-amino-2-pyridinecarboxaldehyde thiosemicarbazone, H3-AP), have been studied. This was achieved by time-resolved UV-Visible absorption spectroscopy and the sequential oxidation of the α- and β-chains of HbO2 at distinctly different rates has been identified. A key structural element, namely a terminal -NH2 group on the thiosemicarbazone moiety, was found to be an important common feature of the most active HbO2 oxidising complexes that were investigated. Therefore, these studies indicate that an unsubstituted -NH2 moiety at the terminus of the thiosemicarbazone group should be avoided in the design of future compounds from this class.
Keyword Haemoglobin
Iron
Methemoglobin
Thiosemicarbazone
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Chemistry and Molecular Biosciences
 
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