Synthesis of theophylline-based iridium(I) N-heterocyclic carbene complexes including fluorinated-thiophenolate ligands: preliminary evaluation of their in vitro anticancer activity

Abstract

A series of theophylline-based Ir(I) N-heterocyclic carbene complexes including fluorinated-thiolate ligands have been prepared and fully characterized. The molecular structures of the complexes [(NHC)Ir(SC6F5)(COD)] (3a) and [(NHC)Ir(SC6F4H-4)(COD)] (3b) were unambiguously determined by single crystal X-ray diffraction analysis. Both compounds were isostructural, having the theophylline-imidazolylidene ligand coordinated to the metal center and completing the coordination sphere with a 1,5-COD and thiophenolate ligands. Interestingly, both complexes exhibit both inter- and intra-molecular pi-stacking interactions between the fluorinated ring of the thiolate and the theophylline-based NHC ligand. Furthermore, for the series of Ir(I) NHC complexes preliminary in vitro anticancer activity experiments were performed on six human cancer cell-lines, i.e. glia cells of nervous central system (U-251), prostate (PC-3), leukemia (K-562), colon (HCT-15), breast (MCF-7) and lung (SKLU-1). Being complex (3) the one showing the best performance (compared to cisplatin) against PC-3 and SKLU-1 with IC50 values of 7.8 +/- 0.4 mu M and 10.7 +/- 0.7 mu M, respectively. Author Keywords: N-heterocyclic carbene; Iridium complexes; Theophylline complex; Cancer; Cytotoxic activity; Thiolate complexes; Xanthines.