Silver(I) Complexes Based on Oxadiazole-Functionalized α-Aminophosphonate: Synthesis, Structural Study, and Biological Activities

Abstract

Two silver(I) complexes, bis{diethyl[(5-phenyl-1,3,4-oxadiazol-2-yl-kappa N-3:kappa N-4-amino) (4-trifluoromethylphenyl)methyl]phosphonate-(tetrafluoroborato-kappa F)}-di-silver(I) and tetrakis-{diethyl[(5-phenyl-1,3,4-oxadiazol-2-yl-kappa N-3-amino)(4-trifluoromethylphenyl)methyl]phosphonate} silver(I) tetrafluoroborate, were prepared starting from the diethyl[(5-phenyl-1,3,4-oxadiazol-2-yl-amino)(4-trifluoromethylphenyl)methyl]phosphonate (1) ligand and AgBF4 salt in Ag/ligand ratios of 1/1 and 1/4, respectively. The structure, stoichiometry, and geometry of the silver complexes were fully characterized by elemental analyses, infrared, single-crystal X-ray diffraction studies, multinuclear NMR, and mass spectroscopies. The binuclear complex ([Ag-2(1)(2)(BF4)(2)]; 2) crystallizes in the monoclinic asymmetric space group P2(1)/c and contains two silver atoms adopting a {AgN2F} planar trigonal geometry, which are simultaneously bridged by two oxadiazole rings of two ligands, while the mononuclear complex ([Ag(1)(4)]BF4; 3) crystallizes in the non-usual cubic space group Fd-3c in which the silver atom binds to four distinct electronically enriched nitrogen atoms of the oxadiazole ring, in a slightly distorted {AgN4} tetrahedral geometry. The alpha-aminophosphonate and the monomeric silver complex were evaluated in vitro against MCF-7 and PANC-1 cell lines. The silver complex is promising as a drug candidate for breast cancer and the pancreatic duct with half-maximal inhibitory concentration (IC50) values of 8.3 +/- 1.0 and 14.4 +/- 0.6 mu M, respectively. Additionally, the interactions of the ligand and the mononuclear complex with Vascular Endothelial Growth Factor Receptor-2 and DNA were evaluated by molecular docking methods.