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

• DOI: 10.1007/s11243-019-00314-6
• Publication Date: 2019-09-03T21:02:56Z
• Authors: Subhi A. Al-Jibori; Mustafa A. Ulghafoor; Ahmet Karadağ; Ali Aydın; Hüseyin Akbaş; Santiago G. Ruiz
• Keywords: Materials Chemistry; 02 engineering and technology; 0210 nano-technology

Reaction of Na2[PdCl4] with two equivalents of 4,5-benzo-3H-1,2-dithiole-3-thione (btt) affords cis-[PdCl2(κ1-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(κ1-btt)2(κ2-diamine)]Cl2 (2a–d) (diamine = en, dap, bipy, phen) and [Pd(btt)2(κ2-diphosphine)]Cl2 (3a–c) (diphosphine = dppe, dppp, dppf) in good yields. In contrast, two equivalents of dppm result in [Pd(κ1-btt)2(κ1-dppm)2]Cl2 (4), where the diphosphine binds in a monodentate fashion. Two equivalents of PPh3 result in a mixture of cis- and trans-isomers of [Pd(κ1-btt)2(PPh3)2]Cl2 (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-[PdCl2(PPh3)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-[PdCl2(κ1-btt)2] (1), cis-[Pd(κ1-btt)2(κ1-dppm)2]Cl2 (4) and cis-[Pd(κ1-btt)2(PPh3)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.