Dithiocarbazate complexes with the [M(PPh3)]2+ (M═Pd or Pt) moiety: Synthesis, characterization and anti-Tripanosoma cruzi activity

New neutral Pd(II) and Pt(II) complexes of the type [M(L)(PPh3)] (M═Pd or Pt) were prepared in crystalline form in high-yield synthesis with the S-benzyldithiocarbazates and S-4-nitrobenzyldithiocarbazates derivatives from 2-hydroxyacetophenone, H2L1a and H2L1b, and benzoylacetone, H2L2a and H2L2b. The new complexes [Pt(L1a)(PPh3)] (1), [Pd(L1a)(PPh3)] (2), [Pt(L1b)(PPh3)] (3), [Pd(L1b)(PPh3)] (4), [Pt(L2a)(PPh3)] (5), [Pd(L2a)(PPh3)] (6), [Pt(L2b)(PPh3)] (7) and [Pd(L2b)(PPh3)] (8) were characterized on the basis of elemental analysis, conductivity measurements, UV–visible, IR, electrospray ionization mass spectrometry (ESI-MS), NMR (1H and 31P) and by X-ray diffraction studies. The studies showed that differently from what was observed for the H2L1a and H2L1b ligands, H2L2a and H2L2b assume cyclic forms as 5-hydroxypyrazolinic. Upon coordination, H2L2a and H2L2b suffer ring-opening reaction, coordinating in the same manner as H2L1a and H2L1b, deprotonated and in O,N,S-tridentate mode to the (MPPh3)2+ moiety. All complexes show a quite similar planar fourfold environment around the M(II) center. Furthermore, these complexes exhibited biological activity on extra and intracellular forms of Trypanosoma cruzi in a time- and concentration-dependent manner with IC50 values ranging from 7.8 to 18.7 μM, while the ligand H2L2a presented a trypanocidal activity on trypomastigote form better than the standard drug benznidazole.

Graphical AbstractReactions of S-benzyldithiocarbazates derived from 2-hydroxyacetophenone (H2L1) and benzoylacetone (H2L2) with [MCl2(PPh3)2] (M═Pd or Pt) afford square-planar complexes of the type [M(L)(PPh3)], which exhibited high activity on extra and intracellular forms of Trypanosoma cruzi.Figure optionsDownload as PowerPoint slide