Issue 38, 2023

Impact of human serum albumin on CuII and ZnII complexation by ATSM (diacetyl-bis(N4-methylthiosemicarbazone)) and a water soluble analogue

Abstract

The chelator diacetyl-bis(N4-methylthiosemicarbazone) (ATSM) and its complexes with CuII and ZnII are becoming increasingly investigated for medical applications such as PET imaging for anti-tumour therapy and the treatment of amyotrophic lateral sclerosis. However, the solubility in water of both the ligand and the complexes presents certain limitations for in vitro studies. Moreover, the stability of the CuII and ZnII complexes and their metal exchange reaction against the potential biological competitor human serum albumin (HSA) has not been studied in depth. In this work it was observed that the ATSM with an added carboxylic group into the structure increases its solubility in aqueous solutions without altering the coordination mode and the conjugated system of the ligand. The poorly water-soluble CuII– and ZnII–ATSM complexes were prevented from precipitating due to the binding to HSA. Both HSA and ATSM show a similar thermodynamic affinity for ZnII. Finally, the CuII-competition experiments with EDTA and the water-soluble ATSM ligands yielded an apparent log Kd at pH 7.4 of about −19. When ATSM was added to CuII- and ZnII-loaded HSA, withdrawing of ZnII was kinetically favoured, but this metal is slowly substituted by the CuII afterwards taken from HSA so that this protein could be considered as a source of CuII for ATSM.

Graphical abstract: Impact of human serum albumin on CuII and ZnII complexation by ATSM (diacetyl-bis(N4-methylthiosemicarbazone)) and a water soluble analogue

Supplementary files

Article information

Article type
Paper
Submitted
25 Jul 2023
Accepted
07 Sep 2023
First published
11 Sep 2023
This article is Open Access
Creative Commons BY license

Dalton Trans., 2023,52, 13758-13768

Impact of human serum albumin on CuII and ZnII complexation by ATSM (diacetyl-bis(N4-methylthiosemicarbazone)) and a water soluble analogue

Á. Martínez-Camarena, A. Sour and P. Faller, Dalton Trans., 2023, 52, 13758 DOI: 10.1039/D3DT02380J

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