Triphenylphosphane Pt(II) complexes containing biologically active natural polyphenols: Synthesis, crystal structure, molecular modeling and cytotoxic studies

Abstract

Platinum complexes bearing phosphane ligands in cis configuration with deprotonated flavonoids (3-hydroxyflavone, quercetin) and deprotonated ethyl gallate were synthesized starting from cis-[PtCl2(PPh3)2]. In all cases, O,O′ chelate structures were obtained. While quercetin and ethyl gallate complexes are quite stable in solution, the 3-hydroxyflavonate complex undergoes a slow aerobic photodegradation in solution with formation of salicylic and benzoic acids. The X-ray diffraction structures of quercetin and ethyl gallate complexes are reported. Cell cycle studies (in the dark) of the complexes in two human cell lines revealed that the cytotoxic activity of the complex bearing 3-hydroxyflavonate is higher than those exhibited by 3-hydroxyflavone or by cis-[PtCl2(PPh3)2] alone. Density functional theory studies on the hydrolysis pathway for the 3-hydroxyflavone and ethyl gallate complexes explained the different cytotoxic activity observed for the two compounds on the basis of the different intermediates formed during hydrolysis (relatively inert hydroxy Pt complexes for ethyl gallate and monoaqua complexes for 3-hydroxyflavone).