Synthesis, structure, spectroscopic properties and cytotoxic effect of some thiosemicarbazone complexes of palladium

Abstract

Reaction of salicylaldehyde thiosemicarbazone (H₂L¹), 2-hydroxyacetophenone thiosemicarbazone (H₂L²) and 2-hydroxynaphthaldehyde thiosemicarbazone (H₂L³) (general abbreviation H₂L, where H₂ stands for the two dissociable protons, one phenolic proton and one hydrazinic proton) with Na₂[PdCl₄] affords a family of polymeric complexes of type [{Pd(L)}_n]. Reaction of the polymeric species with two monodentate ligands (D), viz. triphenylphosphine (PPh₃) and 4-picoline (pic), has yielded complexes of type [Pd(L)(D)]. These mixed-ligand complexes have also been obtained from reaction of the thiosemicarbazones with [Pd(PPh₃)₂Cl₂] and [Pd(pic)₂Cl₂]. Crystal structures of [Pd(L¹)(PPh₃)] and [Pd(L²)(pic)] have been determined. The [Pd(L)(D)] complexes show characteristic ¹H NMR spectra and intense absorptions in the visible and ultraviolet region. They also fluoresce in the visible region at ambient temperature. In vitro cytotoxicity screenings of the complexes along with four human clinical drugsviz.cisplatin, BCNU, 5-fluorouracil (5-FU) and hydroxyurea have been carried out in two human tumor cell lines, namely promyelocytic leukemia HL-60 and histiocytic lymphoma U-937. [Pd(L²)(PPh₃)] shows the lowest IC₅₀ value and is found to be much more cytotoxic than the reference anticancer drugs in both the cell lines. An apoptosis study in HL-60 with [Pd(L²)(PPh₃)] confirms that at 10 µM concentration it induces apoptosis to a greater extent than cisplatin and camptothecin.