Synthesis, characterization and cytotoxicity studies of palladium(II)–proflavine complexes

An investigation of the reaction of Pd(II) complexes with proflavine (3,6-diaminoacridine) resulted in the isolation of the compounds [Pd(terpy)(proflavine)](NO3)(HSO4)3H2O, 1, (terpy = 2,2′:6′,2″-terpyridine), [Pd(en)(proflavineH))](NO3)(SO4), 2, (en = ethylenediamine), and [Pd(proflavineH)Cl2](SO4)0.5H2O, 3. They have been isolated and characterized by NMR, IR, and electro-spray ionization mass spectrometry techniques and by elemental analyses. The proflavine was bonded to the Pd(II) through the endocyclic nitrogen in 1, but through the proflavine NH2 in 2. Compound 3 appeared to be polymeric in the solid state with a 1:1 mole ratio of Pd(II):proflavine. Upon solution of 3 in DMSO, two unique species were formed. In one species the Pd(II) was bonded to two proflavines through the endocyclic nitrogen (1:2 mole ratio) and in the other species, a Pd(II) was bonded to each NH2 group of a single proflavine (2:1 mole ratio). Molecular modeling of the equilibrium geometry by Spartan 8 produced structures which were consistent with the experimental data on the solutions of the three compounds. In vitro cytotoxicity testing against two breast cancer cell lines and one ovarian cancer cell line showed that compounds 1 and 3 had significant activity.

Graphical AbstractPd(II) complexes were reacted with proflavine to form new compounds with Pd(II) bonded to proflavine either through the endocyclic N or the amino N, depending on the ligand on the Pd(II). Shown are the proposed structures of the complexes formed when the polymeric compound, [Pd(proflavineH)Cl2](SO4)0.5H2O was dissolved in DMSO.Figure optionsDownload as PowerPoint slide