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.