Design of transition metal chelates with biological activity. Potentiometric study of complex formation equilibria between 2-amino-N-hydroxy-3-(p-hydroxyphenyl) propanamide and nickel(II), copper(II), and hydrogen ions in aqueous solution

Abstract

The species distribution and relevant stability of species present in aqueous solutions of nickel(II) and copper(II) with L-tyrosinehydroxamic acid [2-amino-N-hydroxy-3-(p-hydroxyphenyl)propan-amide, ahhpp] were obtained by potentiometric titrations in 0.5 mol dm^–3 KCl solution at 25 °C. The protonation constants of the ligand and the formation constants of several metal complexes have been calculated from potentiometric data with the aid of the SUPERQUAD program. The ligand forms with metals the complexes [Cu(HL)]⁺, [Cu(HL)₂], [CuL₂]^2–; and [Ni(HL)₂], [Ni-(HL)L]^–, [NiL₂]^2–, [Ni(OH)L₂]^3–, where the ligand L^2–=^–OC₆H₄CH₂(H₂N)CHC(O)NHO^–. The following cumulative formation constants β_pqr=[M_pH_qL_r]/[M]^p[H]^q[L]^r were obtained: ahhpp, log β₀₁₁= 9.931(2), log β₀₂₁, = 18.850(2), log β₀₃₁, = 25.806(4); Cu^II-ahhpp, log β₁₁₁= 20.162(22), log β₁₂₂= 33.123(59), log β₁₀₂= 14.064(50); Ni^II–ahhpp, log β₁₂₂ 33.668(14), log β₁₁₂= 25.700(46), log β₁₀₂= 16.186(58), log β_1–12= 6.646(48). The H⁺ of the ‘protonated’ complexes, which appear at intermediate pH values (5.5–9.0), is probably bound to the p-oxygen of the phenyl group, not involved in the chelate ring. The probable structures of the chelated compounds formed in aqueous solution are deduced by structural analysis of the solid state, and their stability constants are compared with those of analogous chelated compounds.