Synthesis, characterization and anti-tumor activity of Pd(II) complexes with 4,5-benzo-3H-1,2-dithiole-3-thione

Reaction of Na 2 [PdCl 4 ] with two equivalents of 4,5-benzo-3H-1,2-dithiole-3-thione (btt) affords cis -[PdCl 2 (κ 1 -btt) 2 ] ( 1 ), which provides a convenient entry into mixed-ligand btt complexes. Addition of one equivalent of a range of diamines or diphosphines gives the salts [Pd(κ 1 -btt) 2 (κ 2 -diamine)]Cl 2 ( 2a – d ) (diamine = en, dap, bipy, phen) and [Pd(btt) 2 (κ 2 -diphosphine)]Cl 2 ( 3a – c ) (diphosphine = dppe, dppp, dppf) in good yields. In contrast, two equivalents of dppm result in [Pd(κ 1 -btt) 2 (κ 1 -dppm) 2 ]Cl 2 ( 4 ), where the diphosphine binds in a monodentate fashion. Two equivalents of PPh 3 result in a mixture of cis - and trans -isomers of [Pd(κ 1 -btt) 2 (PPh 3 ) 2 ]Cl 2 ( 5a – b ) (ca. 1:5 ratio); the pure trans -isomer 5b was isolated by ion-exchange chromatography. The cis -isomer 5a could be synthesized independently from the reaction of cis -[PdCl 2 (PPh 3 ) 2 ] with two equivalents of btt. In all of these complexes, the btt ligand binds in a monodentate manner through the exocyclic thione sulfur. The anti-tumor activities of representative examples, cis -[PdCl 2 (κ 1 -btt) 2 ] ( 1 ), cis -[Pd(κ 1 -btt) 2 (κ 1 -dppm) 2 ]Cl 2 ( 4 ) and cis -[Pd(κ 1 -btt) 2 (PPh 3 ) 2 ] ( 5a ), were evaluated by cell proliferation assays and phase-contrast microscopy against prostate cancer cell lines PC3, DU145 and LNCaP, with complexes 1 and 4 showing potent anti-proliferative effects (TGI values of 19.2 and 21.1 µg/mL, respectively) against LnCaP cells. Graphical abstract