Synthesis and characterization of new transition metal complexes containing DNA intercalators of the acridine family

Abstract

The coordinating ability of two DNA intercalates of the acridine family, 4-hydroxyacridine (4-OH-Acrid) and acridine orange (AO), with the transition metal ions Ni(II), Pd(II) and Pt(II), are investigated. Octahedral complexes, [Ni(4-O-Acrid)₂(en)] (1), and [Ni(4-O-Acrid)₂(H₂O)₂] (2), are obtained when the 4-OH-Acrid ligand reacts with [Ni(Cl)₂(en)₂] and NiCl₂·6H₂O, respectively. Single crystal X-ray analysis of complex 1 has shown that two acridine molecules are bonded to nickel through their nitrogen and oxygen atoms in a chelate fashion. Moreover, when AO reacts with different Pd(II) and Pt(II) precursors, new triamine complexes of the general formula cis-[M(A)_n(Cl)(AO)]⁺X⁻ (M = Pd(II), Pt(II); A = en, NH₃; n = 1, 2; X⁻ = BF₄⁻, NO₃⁻, PF₆⁻) (3–6) are synthesized. Full characterization by IR, ¹H NMR and electrospray ionization mass spectrometry in solution has demonstrated the coordination of the AO ligand to the metal ion through the endocyclic nitrogen atom. The biological activity of these new acridine orange derivatives is conducted on complex cis-[Pt(NH₃)₂Cl(AO)][NO₃] (5). The cytotoxic activity of complex 5 is compared with that of cisplatin (cis-DDP) in DU145, A2780 and A2780-cp8 cancer cell lines and the results show that its activity is twice as effective as that of cisplatin in the two cis-DDP resistant cell lines DU145 and A2780-cp8, respectively.