Solution speciation of potential anticancer metal complexes of salicylaldehyde semicarbazone and its bromo derivative

The stoichiometry and thermodynamic stability of copper(II), vanadium(IV/V), iron(II)/(III) and gallium(III) complexes of salicylaldehyde semicarbazone (SSC, HL) and its 5-bromo derivative (Br-SSC, HL) have been determined by pH-potentiometry, UV–Vis spectrophotometry, EPR, 1H and 51V NMR spectroscopy in 30% (w/w) dimethyl sulfoxide/water solvent mixture. Proton dissociation processes and lipophilicity of the ligands were also studied in detail. Formation of mono-ligand complexes such as [ML], [MLH−1], [MLH−2] was found with copper(II), vanadium(IV/V), while bis-ligand species of iron(II)/(III) and gallium(III) such as [ML2], [ML2H−1] and [ML2H−2] were also detected, in which the ligands coordinate via monoanionic (O−,N1,O) or dianionic (O−,N1,O−) modes. The bromine substituent on the phenol ring has no significant impact on the stability and binding modes but provides a remarkably enhanced lipophilic character, which is advantageous for the bioactivity. The Ga(III)–salicylaldehyde semicarbazone species show unambiguously higher stability; whereas Cu(II) species have somewhat lower stability relative to the corresponding thiosemicarbazone analogues, however no decomposition of the Cu(II) complex was observed even at micromolar concentrations at physiological pH.

Stability of salicylaldehyde semicarbazone complexes formed with Ga(III) is higher, while with Cu(II) is lower compared to the analogue thiosemicarbazone. Bromine substituent on the phenol ring has no significant impact on the stability but the bioactivity.Figure optionsDownload as PowerPoint slide