New Pd(II) and Pt(II) complexes with N,S-chelated pyrazolonate ligands: molecular and supramolecular structure and preliminary study of their in vitro antitumoral activity.

New Pd(II) and Pt(II) complexes [ML2] (HL=a substituted 2,5-dihydro-5-oxo-1H-pyrazolone-1-carbothioamide) have been synthesized by reacting K2MCl4 (M=Pd, Pt) or Pd(OAc)2 with beta-ketoester thiosemicarbazones. The structures of seven of these complexes were determined by X-ray diffraction. Although all exhibit a distorted square-planar coordination with trans- or (in one case) cis-[MN2S2] kernels, their supramolecular arrangements vary widely from isolated molecules to 3D-networks. The in vitro antitumoral assays performed with two HL ligands and their metal complexes showed significant cytostatic activity for the latter, with the most active [ML2] derivative (a palladium complex) being about sixteen times more active than cis-DDP against the cisplatinum-resistant cell line A2780cisR.

Electrospray ionization mass spectrometry in the structural characterization of some diphenyllead(IV) thiosemicarbazonates.

The behavior in electrospray ionization mass spectrometry (ESI-MS) conditions of some complexes formed by Pb(C6H5)2(OAc)2 with salicylaldehyde, 2-ketobutyric acid, pyridine-2-carbaldehyde, 2-acetylpyridine, and 2-benzoylpyridine thiosemicarbazones, was studied in detail with the aid of collisional experiments performed by ion trap. The homoleptic complexes of tridentate thiosemicarbazonate dianions (TSC2-) lose the phenyl groups first, destabilizing the high oxidation state of the metal and leading to Pb(II) complexes in which the TSC2- ligand or a part of it remains coordinated to the metal. The main difference among the complexes derives from the presence of a carboxylate group on the 2-ketobutyric acid thiosemicarbazonato ligand, which probably interacts with a Na+ cation leading to ESI-generated [M+Na]+ species. In the absence of the carboxylate group, the production of abundant protonated molecules is observed. These different behaviors have been rationalized from the structural point of view. The heteroleptic mononuclear complexes, including thiosemicarbazonate and AcO- monoanions in the coordination sphere, do not yield intact ionized molecular species, and the most abundant ESI-generated ion is due to AcO- loss. The spectrum of the binuclear heteroleptic complex formed by the salicylaldehyde thiosemicarbazonate monoanion is conditioned by the weak bonding interaction displayed by the acetate bridge. MSn experiments yield important information on the relative ligand-Pb bond strengths. This work forms part of the search for chelating agents that can be used for effective chemotherapy of organolead poisoning.

Reactions of thiosemicarbazones derived from beta-keto amides and beta-keto esters with Zn(II) and Cd(II) acetates: influence of metal, substitution, reagent ratio and temperature on metal-induced cyclization.

Zinc(II) and cadmium(II) acetates were reacted in methanol under various experimental conditions with thiosemicarbazones derived from beta-keto amides or beta-keto esters (HTSC). Some of these reactions afforded thiosemicarbazonate complexes [M(TSC)2] with IR and NMR spectra compatible with N,S-coordination, but most gave complexes [ML2], where HL is a substituted 2,5-dihydro-5-oxo-1H-pyrazole-1-carbothioamide resulting from cyclization of the HTSC. Some of these pyrazolonates and two of the HL ligands were studied by X-ray diffractometry, and their structures are discussed. Surprisingly, the reactions of zinc(II) acetate with HTSC in 1:1 mol ratio usually gave a third, previously unreported type of complex with a dideprotonated ligand, [Zn(L-H)], which was also formed when [ZnL2] and Zn(OAc)2 interacted at room temperature in 1:1 mol ratio. These L-H complexes are highly insoluble in all common solvents, which hinders their characterization but suggests that they are polymeric in nature.

Compositional and structural variety of diphenyllead(IV) complexes obtained by reaction of diphenyllead dichloride with thiosemicarbazones.

The reactions of PbPh(2)Cl(2) in methanol with acetophenone, salicylaldehyde, pyridine-2-carbaldehyde, 2-acetylpyridine, and 2-benzoylpyridine thiosemicarbazones (HATSC, HSTSC, HPyTSC, HAcPyTSC, and HBPyTSC, respectively) were explored. Despite the similarities among these ligands, the reactions afforded solids with very diverse compositions and structural characteristics, which were in most cases analyzed by X-ray diffractometry (as was the structure of the free ligand HBPyTSC). In the complexes [PbPh(2)Cl(2)(HATSC)](2), [PbPh(2)Cl(2)(HSTSC)(2)], [(PbPh(2)Cl(HPyTSC)(2))][PbPh(2)Cl(3)(MeOH)](2), and [PbPh(2)Cl(PyTSC)] the metal atoms are surrounded by more or less distorted octahedral coordination polyhedra; if both strong and weak interactions are considered, the lead atom in [PbPh(2)Cl(AcPyTSC)] has coordination number 7 and distorted pentagonal bipyramidal coordination geometry, while [(PbPh(2)(BPyTSC))(2)(PbPh(2)Cl(4))].2MeOH contains two different types of lead atom, one with octahedral and the other with pentagonal bipyramidal coordination. The complexes (H(2)AcPyTSC)[PbPh(2)Cl(3)] and [PbPh(2)Cl(HAcPyTSC)][PbPh(2)Cl(3)], which were also isolated, could not be crystallized. All these complexes are soluble in DMSO, and the compositions of these solutions were investigated using conductivity measurements and (1)H and (207)Pb NMR spectroscopy.

Metal-induced cyclization of thiosemicarbazones derived from beta-keto amides and beta-keto esters: open-chain and cyclized ligands in zinc(II) complexes.

The reactions of Zn(OAc)(2) with acetoacetanilide, methyl acetoacetate, o-acetoacetanisidide, and ethyl 2-methylacetoacetate thiosemicarbazones (HTSC(1), HTSC(2), HTSC(3), and HTSC(4), respectively) were explored in methanol. With HTSC(1), HTSC(2), and HTSC(3), following isolation of the corresponding zinc(II) thiosemicarbazonates [Zn(TSC(x))(2)] (x = 1, 2, 3), the mother liquors afforded pyrazolonate complexes [ZnL(1)(2)(H(2)O)] (HL(1) = 2,5-dihydro-3-methyl-5-oxo-1H-pyrazole-1-carbothioamide) that had been formed by cyclization of the corresponding TSC(-). The reaction of HTSC(4) with zinc(II) acetate gave only the pyrazolonate complex [ZnL(2)(2)(H(2)O)] (HL(2) = 2,5-dihydro-3,4-dimethyl-5-oxo-1H-pyrazole-1-carbothioamide). All compounds were studied by IR and NMR spectroscopy, and HTSC(3), [Zn(TSC(3))(2)] x DMSO, [ZnL(1)(2)(H(2)O)] x 2DMSO, and [ZnL(2)(2)(H(2)O)] x 2DMSO were also studied by X-ray diffractometry, giving a thorough picture of the cyclization process. In preliminary tests of the effects of HL(1) and [ZnL(1)(2)(H(2)O)] on rat paw inflammatory edema induced by carrageenan, HL(1) showed antiinflammatory activity.