New Palladium(II), Platinum(II) and Silver(I) complexes of 2-amino-4,6-dithio-1,3,5-triazine; synthesis, characterization and DNA binding properties

Abstract

Inorganic medicinal chemistry has been focused for many years on the study of the anticancer activity of transition metal complexes, especially those based on the Pt(II) ion. Since the 1,3,5-triazine molecule has significant biological activity, we thought that the development of new metallo-chemotherapeutic agents involving the triazine moiety might be of interest. With this in mind, we have now synthesized several mixed-ligand transition metal complexes with the 2-amino-4,6-dithio-1,3,5-triazine (Hat) ligand that also contain 2,2'bipyridine (bpy), 1,10-phenanthroline (phen) or triphenylphosphine (PPh3) as a secondary ligand. On the basis of various spectral [IR, NMR (1H, 13C, 31P), UV–vis and EI-mass] measurements and other physical analyses (molar conductivity, elemental analysis and TGA), two modes of coordination are proposed for the Hat ligand. The first is a neutral bidentate mode through either the amino-N(2) and cyclic-N(3) atoms or the thione-S(4) and cyclic-N(3) atoms. The second mode is a mononegative bidentate one via the deprotonated cyclic-N(1) atom and either the amino-N(2) or the thione-S(6) atom. The dissociation constant of Hat, as well as the stoichiometries and the formation constants of Co(II), Ni(II), Cu(II), Zn(II), Pd(II), Pt(II), [M(L)Cl2] (L = bpy, 2PPh3) and Ag(I) complexes in saline solution (pH 7.4), have been determined using both Job's and the molar ratio methods. The calf thymus (CT-DNA)-binding properties of several of the complexes have been determined using UV–vis spectroscopy. The binding constants (Kb) of the CT-DNA complexes indicate their high to moderate binding abilities, which may be the result of steric hindrance around the metal ions owing to the presence of the bulky bpy or PPh3 ligands.