Copper complexation by isatin β-thiosemicarbazones in aqueous solution

Abstract

The reactions in aqueous solution between cupric ion and water-soluble derivatives of the antiviral drug methisazone (1-methylisatin β-thiosemicarbazone, mibt) have been investigated. Alkalimetric titrations and n.m.r. experiments showed that 5-sulfonatoisatin β-thiosemicarbazone, sibt (3), its 1-methyl derivative, msibt (4), and also p-sulfonatobenzaldehyde thiosemicarbazone, sbat (5), reduce cupric ion and form copper(I) complexes. Stability constants were obtained from measurements of pH and pCu⁺ on solutions of copper(II) nitrate and excess ligand (I = 0.15 M KNO₃, at 37º). The pCu⁺ values were obtained with an ORION solid state copper electrode. At pH 6-7.5 and moderate excess of ligand, polymeric complexes with an approximate 1 : 1 copper(1)-to-ligand ratio are formed: Cu_nL_n or Cu_nL_n+,H with n > 6. Monomeric complexes CuL₂^3- predominate at higher pH and in the presence of a more than twentyfold excess of ligand. The stability constants log β₂ are 17.9 for sibt, 18.5 for msibt and 19.8 for sbat. At physiological pH (7.4), the order of stability is msibt > sibt & sbat, with conditional stability constants log β₂ = 16.2, 15.7 and 13.4, respectively. Comparison with penicillamine shows that some in vivo complexation of copper(I) by methisazone may be possible. On the other hand, a histidinato-copper(II) complex is formed in the presence of histidine.