A comparative study of alpha-N-pyridyl thiosemicarbazones: Spectroscopic properties, solution stability and copper(II) complexation

作者：Domotor Orsolya; May Nora V; Pelivan Karla; Kiss Tamas; Keppler Bernhard K; Kowol Christian R; Enyedy Eva A^*

来源：Inorganica Chimica Acta, 2018, 472: 264-275.

DOI：10.1016/j.ica.2017.07.001

• Thiosemicarbazones
• Cu(II) complexes
• Isomers
• Fluorometry
• Speciation

The effects of methyl substituents at different positions on the 2-formylpyridine thiosemicarbazone (FTSC) core structure on various physico-chemical properties were investigated. Proton dissociation processes, aqueous solution stability, isomer distribution in different solvents, fluorescence properties and lipophilic character of FTSC, pyridine-2-carboxaldehyde N-4,N-4-dimethylthiosemicarbazone (PTSC), 2-acetylpyridine thiosemicarbazone (AcFTSC) and 2-acetylpyridine N-4,N-4-dimethylthiosemicarbazone (AcPTSC) were studied and compared under the same conditions. There are more and more indications that Cu(II) ions play an important role in the biological activity of anticancer thiosemicarbazones. Therefore, the complex formation equilibria of FTSC with Cu(II) ions were studied by pH-potentiometry, UV-visible spectrophotometry and electron paramagnetic resonance (EPR) spectroscopy to determine stoichiometry, stability constants and solution structures of the complexes formed in aqueous solution (with 30% DMSO). Mono-ligand complexes in different protonation states were identified such as [CuLH](2+), [CuL](+) and [CuL(OH)] with (N-pyridyl,N,S)(H2O), (N-pyridyl,N,S-)(H2O) and (N-pyridyl,N,S-)(OH) coordination modes, respectively. At ligand excess two kinds of isomers of a bis complex [CuL2] were detected at pH > 7, in which binding of the ligands via (N-pyridyl,N,S-)(N) and (N-pyridyl,N,S-)(S-) donor sets is probable at the equatorial positions. Based on the stability data, [CuL](+) complexes of the alpha-N-pyridyl thiosemicarbazones are predominant at pH 7.4 at 1:1 metal-to-ligand ratio possessing such high solution stability that their decomposition is not likely even at biologically relevant micromolar concentrations. In addition, FTSC and all methylated derivatives investigated show similar Cu(II) binding abilities which is in contrast to the respective Fe(II)/(III) complexes where terminal dimethylation distinctly increases the solution stabilities.

• 出版日期2018-3-1