Vanadium polypyridyl compounds as potential antiparasitic and antitumoral agents: new achievements

In the search for new therapeutic tools against diseases produced by kinetoplastid parasites five vanadyl complexes, [V^IVO(L-2H)(phen)], including 1,10-phenanthroline (phen) and tridentate salicylaldehyde semicarbazone derivatives as ligands have been synthesized and characterized in the solid state and in solution by using different techniques. EPR suggested a distorted octahedral geometry with the tridentate semicarbazone occupying three equatorial positions and phen coordinated in an equatorial/axial mode. The compounds were evaluated in vitro on epimastigotes of Trypanosoma cruzi, causative agent of Chagas disease, Leishmania panamensis and Leishmania chagasi and on tumor cells. The complexes showed higher in vitro anti-trypanosomal activities than the reference drug Nifurtimox (IC₅₀ values in the range 1.6-3.8 μM) and increased activities in respect to the free semicarbazone ligands. In vitro activity on promastigote and amastigote forms of Leishmania showed interesting results. The compounds [VO(L1-2H)(phen)] and [VO(L3-2H)(phen)], where L1 = 2-hydroxybenzaldehyde semicarbazone and L3 = 2-hydroxy-3-methoxybenzaldehyde semicarbazone, resulted active (IC₅₀ 2.74 and 2.75 μM, respectively, on promastigotes of L. panamensis; IC₅₀ 19.52 and 20.75 μM, respectively, on intracellular amastigotes of L. panamensis) and showed low toxicity on THP-1 mammalian cells (IC₅₀ 188.55 and 88.13 μM, respectively). In addition, the complexes showed cytotoxicity on human promyelocytic leukemia HL-60 cells with IC₅₀ values of the same order of magnitude as cisplatin. The interaction of the complexes with DNA was demonstrated by different techniques, suggesting that this biomolecule could be a potential target either in the parasites or in tumor cells.     

Synthesis and structural analysis of palladium biscarbene complexes derived from bisimidazolium ligand precursors

The palladation of potentially chelating bisimidazolium ligand precursors with palladium acetate gives bridging bimetallic, chelating monometallic, and homoleptic tetracarbene complexes. The coordination mode of the biscarbene ligand has been identified by spectroscopic analysis and crystallographic characterization of representative complexes, including the first example of a biscarbene A-frame structure. Substantial concentrations of free acetate favor the formation of tetracarbene over biscarbene palladium complexes, while in the absence of a base, the concentration of reactants influences the selectivity for bridging bimetallic versus chelating monometallic species. Preliminary kinetic and mechanistic studies indicate that chelating biscarbene palladium acetate complexes are intermediates in the formation of the homoleptic tetracarbene complexes. Probably due to the high trans effect of the biscarbene ligand, such complexes are more efficient palladating agents for bisimidazolium salts than palladium acetate.     

Preparation and structural organisation of heteroleptic tetraphenylantimony(V) complexes comprising unidentately and bidentately coordinated O,O′-dialkyldithiophosphate groups: Multinuclear (C, P) CP/MAS NMR and single-crystal X-ray diffraction studies

O,O′-dipropyldithiophosphate and O,O′-di-iso-butyldithiophosphate (Dtph) tetraphenylantimony(V) complexes of the general formula [Sb(C₆H₅)₄{S₂P(OR)₂}] (R = C₃H₇, i-C₄H₉) were prepared and studied by means of ¹³C, ³¹P CP/MAS NMR spectroscopy and single-crystal X-ray diffraction. Distorted octahedral and trigonal bipyramidal molecular structures have been established for prepared complexes. These unexpected structural distinctions between chemically related compounds are defined by the principally different coordination modes of O,O′-dipropyldithiophosphate and O,O′-di-iso-butyldithiophosphate ligands in their molecular structures (i.e., S,S′-bidentate chelating and S-unidentately coordinated, respectively). To characterise quantitatively phosphorus sites in both species of dithiophosphate ligands, ³¹P chemical shift anisotropy parameters (δ_aniso and η) were calculated from spinning sideband manifolds in MAS NMR spectra. The ³¹P chemical shift tensors for the bidentate chelating and unidentately coordinated dithiophosphate ligands display a profoundly rhombic and nearly axially symmetric characters, respectively.