Influence of the phosphine arrangement on the reactivity of palladium(II) and platinum(II) polyphosphine complexes with copper(I) chloride

The distorted square-planar complexes [Pd(PNHP)Cl]Cl (1) (PNHP = bis[2-(diphenylphosphino)ethyl]amine), [M(P₃)Cl]Cl [P₃ = bis[2-(diphenylphosphino)ethyl]phenylphosphine; M = Pd (2), Pt (3)] and [Pt(NP₃)Cl]Cl (5) (NP₃ = tris[2-(diphenylphosphino)ethyl]amine), coexisting in the later case with a square-pyramidal arrangement, react with one equivalent of CuCl to give the mononuclear heteroionic systems [M(L)Cl](CuCl₂) [L = PNHP, M = Pd (1a); L = P₃, M = Pd (2a), Pt (3a); L = NP₃, M = Pt (5a)]. The crystal structure of 3a confirms that Pt(II) retains the distorted square-planar geometry of 3 in the cation with P₃ acting as tridentate chelating ligand, the central P atom being trans to one chloride. The counter anion is a nearly linear dichlorocuprate(I) ion. However, the five-coordinate complexes [Pd(NP₃)Cl]Cl (4), [M(PP₃)Cl]Cl (M = Pd (6), Pt (7); PP₃ = tris[2-(diphenylphosphino)ethyl] phosphine) containing three fused five-membered chelate rings undergo a ring-opening by interaction with one (4, 6, 7) and two (6, 7) equivalents of CuCl with formation of neutral MCu(L)Cl₃ [L = NP₃, M = Pd (4a); L = PP₃, M = Pd (6a), Pt (7a)] and ionic [MCu(PP₃)Cl₂](CuCl₂) [M = Pd (6b), Pt (7b)] compounds, respectively. The heteronuclear systems were shown by ³¹P NMR to have structures where the phosphines are acting as tridentate chelating ligands to M(II) and monodentate bridging to Cu(I). Further additions of CuCl to the neutral species 6a and 7a in a 1:1 ratio resulted in the achievement of the ionic complexes 6b and 7b with ions as counter anions. It was demonstrated that the formation of heterobimetallic or just mononuclear mixed salt complexes was clearly influenced by the polyphosphine arrangement with the tripodal ligands giving the former compounds. However, complexes [M(NP₃)Cl]Cl constitute one exception and the type of reaction undergone versus CuCl is a function of the d⁸ metal centre.     

Synthesis, crystal structure, spectral properties and cytotoxic activity of platinum(II) complexes of 2-acetyl pyridine and pyridine-2-carbaldehyde N(4)-ethyl-thiosemicarbazones

The reactions of Na2PtCl4 with pyridine-2-carbaldehyde and 2-acetyl pyridine N(4)-ethyl-thiosemicarbazones, HFo4Et and HAc4Et respectively, afforded the complexes [Pt(Fo4Et)Cl], [Pt(HFo4Et)2]Cl2, [Pt(Fo4Et)2] and [Pt(Ac4Et)Cl], [Pt(HAc4Et)2]Cl2 x 2H2O, [Pt(Ac4Et)2]. The new complexes have been characterized by elemental analyses and spectroscopic studies. The crystal structure of the complex [Pt(Ac4Et)Cl] has been solved. The anion of Ac4E coordinates in a planar conformation to the central platinum(II) through the pyridyl N, azomethine N and thiolato S atoms. Intermolecular hydrogen, non-hydrogen bonds, pi-pi and weak Pt-pi contacts lead to aggregation and a supramolecular assembly. The cytotoxic activity for the platinum(II) complexes in comparison to that of cisplatin and thiosemicarbazones was evaluated in a pair of cisplatin-sensitive and -resistant ovarian cancer cell lines A2780 and A2780/Cp8. The platinum(II) complexes showed a cytotoxic potency in a very low micromolar range and were found able to overcome the cisplatin resistance of A2780/Cp8 cells.     

Synthesis,characterization, DNA interaction,and cytotoxicity of novel Pd(II) and Pt(II) complexes

Four complexes [Pd(L)(bipy)Cl]·4H₂O (1), [Pd(L)(phen)Cl]·4H₂O (2), [Pt(L)(bipy)Cl]·4H₂O (3), and [Pt(L)(phen)Cl]·4H₂O (4), where L = quinolinic acid, bipy = 2,2’-bipyridyl, and phen = 1,10-phenanthroline, have been synthesized and characterized using IR, ¹H NMR, elemental analysis, and single-crystal X-ray diffractometry. The binding of the complexes to FS-DNA was investigated by electronic absorption titration and fluorescence spectroscopy. The results indicate that the complexes bind to FS-DNA in an intercalative mode and the intrinsic binding constants K of the title complexes with FS-DNA are about 3.5?×?10⁴ M^?1, 3.9?×?10⁴ M^?1, 6.1?×?10⁴ M^?1, and 1.4?×?10⁵ M^?1, respectively. Also, the four complexes bind to DNA with different binding affinities, in descending order: complex 4, complex 3, complex 2, complex 1. Gel electrophoresis assay demonstrated the ability of the Pt(II) complexes to cleave pBR322 plasmid DNA.     

Platinum(II) oxalato complexes with adenine-based carrier ligands showing significant in vitro antitumor activity

[Pt(L)₂(ox)] (1), [Pt(2-OMeL)₂(ox)] (2), [Pt(3-OMeL)₂(ox)] (3), [Pt(2,3-diOMeL)₂(ox)] (4), [Pt(2,4-diOMeL)₂(ox)] (5), [Pt(3,4-diOMeL)₂(ox)] (6) and [Pt(3,5-diOMeL)₂(ox)]·4H₂O (7) platinum(II) oxalato (ox) complexes were synthesized using the reaction of potassium bis(oxalato)platinate(II) dihydrate with 2-chloro-N6-(benzyl)-9-isopropyladenine or its benzyl-substituted analogues (nL). The complexes 1-7, which represent the first platinum(II) oxalato complexes involving adenine-based ligands, were fully characterized by various physical methods including multinuclear and two dimensional NMR spectroscopy. A single-crystal X-ray analysis of [Pt(2,4-diOMeL)₂(ox)]·2DMF (5·2DMF; DMF = N,N′-dimethylformamide), proved the slightly distorted square-planar geometry in the vicinity of the Pt(II) ion with one bidentate-coordinated oxalate dianion and two adenine derivatives (nL) coordinated to the Pt(II) centre through the N7 atom of an adenine moiety, thereby giving a PtN₂O₂ donor set. In vitro cytotoxicity of the prepared complexes was tested by an MTT assay against osteosarcoma (HOS) and breast adenocarcinoma (MCF7) human cancer cell lines. The best results were achieved for the complexes 2 and 5 in the case of both cell lines, whose IC₅₀ values equalled 3.6 ± 1.0, and 4.3 ± 2.1 μM (for 2), and 5.4 ± 3.8, and 3.6 ± 2.1 μM (for 5), respectively. The IC₅₀ equals 9.2 ± 1.5 μM against MCF7 cells in the case of 1. The in vitro cytotoxicity of the mentioned complexes significantly exceeded commercially used platinum-based anticancer drugs cisplatin (34.2 ± 6.4 μM and 19.6 ± 4.3 μM) and oxaliplatin (> 50.0 μM for both cancer cell lines).     

Crystal structures of Pt(II) and Pd(II) complexes with the free radical 4-aminoTEMPO

Pt(II) and Pd(II) compounds containing the free radical 4-aminoTEMPO (4amTEMPO) were synthesized and characterised by X-ray diffraction methods. The disubstituted complexes cis- and trans-Pt(4amTEMPO)₂I₂ were studied. The trans isomer was prepared from the isomerisation of the cis analogue. The two Pd(II) compounds trans-Pd(4amTEMPO)₂X₂ (X = Cl and I) were also characterised by crystallographic methods. A mixed-ligand complex cis-Pt(DMSO)(4amTEMPO)Cl₂ was synthesized from the isomerisation of the trans isomer in hot water. Its crystal structure was also determined. In all the complexes, the 4amTEMPO ligand is bonded to the metal through the -NH₂ group, since the nitroxide O atom is not a good donor atom for the soft Pt(II) and Pd(II) metals. The conformation of the 4-aminoTEMPO ligand was compared to those of the few reported structures in the literature.     

Palladium(II) and platinum(II) complexes of 2-hydroxy acetophenone N(4)-ethylthiosemicarbazone - crystal structure and description of bonding properties

Reaction of H₂PtCl₄ and K₂PdCl₄ with 2-hydroxyacetophenone N(4)-ethylthiosemicarbazone, H₂Ap4Et, afforded [Pt(Ap4Et)(H₂Ap4Et)] and [Pd(Ap4Et)(H₂Ap4Et)]. Their crystal and molecular structures are reported and represent the first 1:2 thiosemicarbazone complexes with ligands having both different formal charge and denticity. The dianion, Ap4Et²⁻, coordinates in a planar conformation to palladium(II) or platinum(II) via the phenolato O, imine N and thiolato S atoms, while the neutral molecule exhibits monodentate coordination by the thione S atom. Intra-, intermolecular hydrogen bonds and C-H?π contacts lead to aggregation and a supramolecular assembly. Electronic, IR, and NMR spectral data, as well as electrochemical measurements, are included. The pK_a values of the poorly water soluble H₂Ap4Et were obtained spectrophotometrically in aqueous solutions of constant ionic strength.     

Hydrolysis of the amide bond in histidine- and methionine-containing dipeptides promoted by pyrazine and pyridazine palladium(II)-aqua dimers: Comparative study with platinum(II) analogues

Two dinuclear palladium(II) complexes, [{Pd(en)Cl}₂(μ-pz)](NO₃)₂ and [{Pd(en)Cl}₂(μ-pydz)](NO₃)₂, have been synthesized and characterized by elemental microanalysis and spectroscopic (¹H and ¹³C NMR, IR and UV–vis) techniques (en is ethylenediamine; pz is pyrazine and pydz is pyridazine). The square planar geometry of palladium(II) metal centers in these complexes has been predicted by DFT calculations. The chlorido complexes were converted into the corresponding aqua complexes, [{Pd(en)(H₂O)}₂(μ-pz)]⁴⁺ and [{Pd(en)(H₂O)}₂(μ-pydz)]⁴⁺, and their reactions with N-acetylated l-histidylglycine (Ac–l–His–Gly) and l-methionylglycine (Ac–l–Met–Gly) were studied by ¹H NMR spectroscopy. The palladium(II)-aqua complexes and dipeptides were reacted in 1:1 M ratio, and all reactions performed in the pH range 2.0 < pH < 2.5 in D₂O solvent and at 37 °C. In the reactions of these complexes with Ac–l–His–Gly and Ac–l–Met–Gly dipeptides, the hydrolysis of the amide bonds involving the carboxylic group of both histidine and methionine amino acids occurs. The catalytic activities of the palladium(II)-aqua complexes were compared with those previously reported in the literature for the analogues platinum(II)-aqua complexes, [{Pt(en)(H₂O)}₂(μ-pz)]⁴⁺ and [{Pt(en)(H₂O)}₂(μ-pydz)]⁴⁺.     

Synthesis and characterization of Pt(II) and Pt(II)/Ru(II) complexes with the bidentate bridging ligand dipyrido(2,3-a:3′,2′-h)phenazine (dpop)

Three new complexes [Pt(dpop)(Cl)₂], [(Cl)₂Pt(dpop)Pt(Cl)₂] and [(bpy)₂Ru(dpop)Pt(Cl)₂](PF₆)₂ (dpop = dipyrido(2,3-a:3′,2′-h)phenazine) were prepared and studied. The electronic absorption spectra of the complexes display Pt dπ → dpop π* and Ru dπ → dpop π* MLCT transitions at longer wavelengths than for previously reported similar complexes. Results of cyclic voltammograms show reversible dpop centered reductions while for the mixed metal [(bpy)₂Ru(dpop)Pt(Cl)₂]²⁺ an irreversible Pt(II) oxidative wave precedes the Ru(II) oxidation/reduction couple. Spectroelectrochemical results show that all oxidative and reductive processes are completely reversible. The [(Cl)₂Pt(dpop)Pt(Cl)₂] complex cleaves in solution with pseudo-first order kinetics resulting in loss of the Pt dπ → dpop π* MLCT transition at 545 nm.     

Synthesis and characterisation of palladium(II) and platinum(II) compounds containing pyrazole-derived ligands: crystal structure of [PdCl2(HL)] (HL = 3-phenyl-5-(2-pyridyl)pyrazole)

Reaction of the ligands 3-phenyl-5-(2-pyridyl)pyrazole (HL¹), 3,5-bis(2-pyridyl)pyrazole (HL²), 3-methyl-5-(2-pyridyl)pyrazole (HL³) and 3-methyl-5-phenylpyrazole (HL⁴) with [MCl₂(CH₃CN)₂] (M = Pd(II), Pt(II)) or [PdCl₂(cod)] gives complexes with stoichiometry [PdCl₂(HL)₂] (HL = HL¹, HL², HL³), [Pt(L)₂] (L = L¹, L², L³) and [MCl₂(HL⁴)₂] (M = Pd(II), Pt(II)). The new complexes were characterised by elemental analyses, conductivity measurements, infrared and ¹H NMR spectroscopies. The crystal and molecular structure of [PdCl₂(HL¹)] was resolved by X-ray diffraction, and consists of monomeric cis-[PdCl₂(HL¹)] molecules. The palladium centre has a typical square planar geometry, with a slight tetrahedral distortion. The tetra-coordinated metal atom is bonded to one pyridine nitrogen, one pyrazolic nitrogen and two chloro ligands in a cis disposition. The ligand HL¹ is not completely planar.     

Palladium(II) oxalato complexes involving N6-(benzyl)-9-isopropyladenine-based N-donor carrier ligands: Synthesis, general properties, H, C and N{H} NMR characterization and in vitro cytotoxicity

Reactions of potassium bis(oxalato)palladate dihydrate, K₂[Pd(ox)₂]·2H₂O, with two molar equivalents of N6-(benzyl)-9-isopropyladenine-based organic molecules (L_1-7), i.e. 2-chloro-N6-(2-methoxybenzyl)-9-isopropyladenine (L₁), 2-chloro-N6-(3-methoxybenzyl)-9-isopropyladenine (L₂), 2-chloro-N6-(3,5-dimethoxybenzyl)-9-isopropyladenine (L₃), 2-(1-ethyl-2-hydroxyethylamino)-N6-(benzyl)-9-isopropyladenine (L₄), 2-(1-ethyl-2-hydroxyethylamino)-N6-(2-methoxybenzyl)-9-isopropyladenine (L₅), 2-(1-ethyl-2-hydroxyethylamino)-N6-(3-methoxybenzyl)-9-isopropyladenine (L₆) and 2-(1-ethyl-2-hydroxyethylamino)-N6-(4-methoxybenzyl)-9-isopropyladenine (L₇), provided a series of seven palladium(II) oxalato (ox) complexes of the general formula [Pd(ox)(L_1-7)₂]·nH₂O (1-7; n = 0 for 4, 5 and 7, ¾ for 1 and 2, 1 for 6, and 3 for 3). The compounds were characterized by elemental analysis, IR, Raman, ¹H, ¹³C and ¹⁵N{¹H} NMR spectroscopy, ESI+ mass spectrometry, molar conductivity and TG/DTA thermal analysis. The geometry of [Pd(ox)(L₂)₂] (2) was optimized on the B3LYP/6-311G∗/LANL2DZ level of theory. The complexes 4-7 represent the first palladium(II) oxalato complexes with a PdN₂O₂ donor set, which involve highly potent purine-based cyclin-dependent kinase (CDK) inhibitors (L_4-7) as carrier N-donor ligands. The selected complexes 1, 3-5 and 7 were tested by an MTT assay for their in vitro cytotoxic activity against human osteosarcoma (HOS) cancer cell line. The highest activity was found for the complexes 5 (IC₅₀ = 34.9 μM) and 7 (IC₅₀ = 39.2 μM).     

Reaction of [MCl2(CH3CN)2] (M = Pd(II), Pt(II)) compounds with N1-alkylpyridylpyrazole-derived ligands

Palladium(II) and platinum(II) complexes with N-alkylpyridylpyrazole-derived ligands, 2-(1-ethyl-5-phenyl-1H-pyrazol-3-yl)pyridine (L¹) and 2-(1-octyl-5-phenyl-1H-pyrazol-3-yl)pyridine (L²), cis-[MCl₂(L)] (M = Pd(II), Pt(II)), have been synthesised. Treatment of [PdCl₂(L)] (L = L¹, L²) with excess of ligand (L¹, L²), pyridine (py) or triphenylphosphine (PPh₃) in the presence of AgBF₄ and NaBPh₄ produced the following complexes: [Pd(L)₂](BPh₄)₂, [Pd(L)(py)₂](BPh₄)₂ and [Pd(L)(PPh₃)₂](BPh₄)₂. All complexes have been characterised by elemental analyses, conductivity, IR and NMR spectroscopies. The crystal structures of cis-[PdCl₂(L²)] (2) and cis-[PtCl₂(L¹)] (3) were determined by a single crystal X-ray diffraction method. In both complexes, the metal atom is coordinated by one pyrazole nitrogen, one pyridine nitrogen and two chlorine atoms in a distorted square-planar geometry. In complex 3, π-π stacking between pairs of molecules is observed.     

Synthesis, X-ray crystal structure and NMR characterisation of mononuclear Pd(II) and Pt(II) complexes of didentate ligands with NN′-donor set

Two new 3,5-dimethylpyrazolic derived ligands that are N1-substituted by diamine chains, 1-[2-(diethylamino)ethyl]-3,5-dimethylpyrazole (L1) and 1-[2-(dioctylamino)ethyl]-3,5-dimethylpyrazole (L2) were synthesised. Reaction of the ligands, L1 and L2, with [MCl₂(CH₃CN)₂] yielded [MCl₂(L)] (M = Pd(II), Pt(II)) complexes. These complexes were characterised by elemental analyses, conductivity measurements, IR, ¹H, ¹³C{¹H} and ¹⁹⁵Pt{¹H} NMR spectroscopies. The crystal structure of [PdCl₂(L1)] was determined by single-crystal X-ray diffraction methods. The structure consists of mononuclear units. The Pd(II) atom is coordinated by a pyrazolic nitrogen, an amine nitrogen and two chlorine atoms in a cis disposition. In this structure, C-H?Cl, C-H?H-C and C-H?C-H intermolecular interactions have been identified.     

Imidazolate-bridged dicopper(II) and copper(II)–zinc(II) complexes of macrocyclic ligand with methylimidazol pendants: Model study of copper(II)–zinc(II) superoxide dismutase

Two new homo- and hetero-dinuclear complexes, [Cu₂L(im)](ClO₄)₃4H₂O (1) and [CuZnL(im)](ClO₄)₃4H₂O (2) (where Im=1H-1midazole and L = 3, 6, 9, 16, 19, 22-hexaaza-6, 19-bis(1H-imidazol-4-ylmethyl)tricycle[22, 2, 2, 2^11,14]triaconta-1, 11, 13, 24, 27, 29-hexaene) were synthesized and characterized as model compounds for the active site of copper(II)–zinc(II) superoxide dismutase (Cu₂Zn₂–SOD). X-ray crystal structure analysis revealed that the metal centers in both complexes exhibit distorted trigonal-bipyramid coordination geometry and the CuCu and CuZn distances are both 6.02 Å. Magnetic and ESR spectral measurements of 1 showed antiferromagnetic exchange interactions between the imidazolate-bridged Cu(II) ions. The ESR spectrum of 2 displays typical signals of mononuclear Cu(II) complex, demonstrating the formation of heterodinuclear complex 2 rather than a mixture of homodinuclear Cu(II)/Zn(II) complexes. pH-dependent ESR and UV–visible spectral measurements manifest that the imidazolate exists as a bridging ligand from pH 6 to 11 for both complexes. The IC₅₀ values of 1.96 and 1.57 μM [per Cu(II) ion] for 1 and 2 suggest that they are good models for the Cu₂Zn₂–SOD.     

Anti-oxidant,in vitro,in vivo anti-inflammatory activity and antiproliferative activity of mefenamic acid and its metal complexes with manganese(II), cobalt(II), nickel(II), copper(II) and zinc(II)

Some new complexes of mefenamic acid with potentially interesting biological activity are described. The complexes of mefenamic acid [Mn(mef)₂(H₂O)₂], 1, [Co(mef)₂(H₂O)₂], 2, [Ni(mef)₂(H₂O)₂], 3, [Cu(mef)₂(H₂O)]₂, 4 and [Zn(mef)₂], 5, were prepared by the reaction of mefenamic acid, a potent anti-inflammatory drug with metal salts. Optical and infrared spectral data of these new complexes are reported. Monomeric six-coordinated species were isolated in the solid state for Mn(II), Ni(II) and Co(II), dimeric five-coordinated for Cu(II) and monomeric four-coordinated for Zn(II). In DMF or CHCl₃ solution the coordination number is retained and the coordinated molecules of water are replaced by solvent molecules. The anti-oxidant properties of the complexes were evaluated using the 1,1-diphenyl-2-picrylhydrazyl, DPPH, free radical scavenging assay. The scavenging activities of the complexes were measured and compared with those of the free drug and vitamin C. We have explored their ability to inhibit soybean lipoxygenase, β-glucuronidase and trypsin- induced proteolysis. The complex [Mn(mef)₂(H₂O)₂] exhibits the highest antioxidant activity and the highest inhibitory effect against the soybean lipogygenase (LOX), properties that are not demonstrated by mefenamic acid. Their inhibitory effects on rat paw edema induced by Carrageenan was studied and compared with those of mefenamic acid. The complex [Zn(mef)₂] exhibited a strong inhibitory effect at 0.1 mmol/Kg B.W. (81.5 ± 1.3% inhibition), superior to the inhibition induced by mefenamic acid at the same dose (61.5 ± 2.3% inhibition). Mefenamic acid and its metal complexes have been evaluated for antiproliferative activity in vitro against the cells of three human cancer cell lines: MCF-7 (human breast cancer cell line), T24 (bladder cancer cell line), A-549 (non-small cell lung carcinoma) and a mouse fibroblast L-929 cell line. The copper(II) complex displays against T24, MCF-7 and L-929 cancer cell lines, IC₅₀ values in a μM range similar to that of the antitumor drug cis-platin and they are considered for further stages of screening in vitro and/or in vivo as agents with potential antitumor activity.     

Squarato-metal(II) complexes. 1: Structural and magnetic characterization of squarato-bridged dinuclear nickel(II) and copper(II) complexes

A new series of dinuclear squarato-bridged nickel(II) and copper(II) complexes [Ni₂(2,3,2-tet)₂(μ_1,3-C₄O₄)(H₂O)₂](ClO₄)₂ (1), [Ni₂(aepn)₂(μ_1,3-C₄O₄)(H₂O)₂](ClO₄)₂ (2), [Cu₂(pmedien)₂(μ_1,3-C₄O₄)(H₂O)₂](ClO₄)₂.4H₂O (3) and [Cu₂(DPA)₂(μ_1,2-C₄O₄)(H₂O)₂](ClO₄)₂ (4) where is the dianion of 3,4-dihydroxycyclobut-3-en-1,2-dione (squaric acid), 2,3,2-tet = 1,4,8,11-tetraazaundecane, aepn = N-(2-aminoethyl)-1,3-propanediamine, pmedien = N,N,N′,N″,N″-pentamethyldiethylenetriamine and DPA = di(2-pyridylmethyl)amine were synthesized and structurally characterized by X-ray crystallography. The spectral and structural characterization as well as the magnetic behaviour of these complexes is reported. In this series, structures consist of the groups as counter ions and the bridging the two M(II) centers in a μ-1,3- (1-3) and in a μ-1,2-bis(monodentate) (4) bonding fashions. The coordination geometry around the Ni(II) ions in 1 and 2 is six-coordinate with distorted octahedral environment achieved by N atoms of the amines and by one or two oxygen atoms from coordinated water molecules, respectively. In the Cu(II) complexes 3 and 4, a distorted square pyramidal geometry is achieved by the three N-atoms of the aepn or DPA and by an oxygen atom from a coordinated water molecule. The electronic spectra of the complexes in aqueous solutions are in complete agreement with the assigned X-ray geometry around the M(II) centers. The complexes show weak antiferromagnetic coupling with ∣J∣ = 1.8-4.2 cm⁻¹ in the μ-1,3- bridged squarato compounds 1-3, and J = −16.1 cm⁻¹ in the corresponding μ-1,2- bridged squarato complex 4. The magnetic properties are discussed in relation to the structural data.     

New cationic palladium(II) compounds with several bidentate nitrogen-donor ligands: Synthesis, spectroscopic analyses and X-ray crystal structure

A series of PdN₄core complexes has been synthesised. Reaction of [PdCl₂(CH₃CN)₂] with N-alkylaminopyrazole (NN′) ligands, 1-[2-(ethylamino)ethyl]-3,5-dimethylpyrazole (deae), 1-[2-(ⁱpropylamino)ethyl]-3,5-dimethylpyrazole (deai), and 1-[2-(^tbutylamino)ethyl]-3,5-dimethylpyrazole (deat) in the presence of AgBF₄ led to [Pd(NN′)₂](BF₄)₂. These palladium(II) compounds were characterised by elemental analyses, conductivity measurements, IR, ¹H and ¹³C{¹H} NMR spectroscopies. The NMR studies of the complexes prove the rigid conformation of the ligands when they are complexed. The X-ray analyses of one representative complex, [Pd(deat)₂](BF₄)₂, is reported. The crystal structure consists of discrete centrosymmetric cations involving a coordinated Pd(N_pz)₂(N_amino)₂core with planar geometry and anions.     

Dithiocarbazate complexes with the [M(PPh3)] (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, H₂L^1a and H₂L^1b, and benzoylacetone, H₂L^2a and H₂L^2b. The new complexes [Pt(L^1a)(PPh₃)] (1), [Pd(L^1a)(PPh₃)] (2), [Pt(L^1b)(PPh₃)] (3), [Pd(L^1b)(PPh₃)] (4), [Pt(L^2a)(PPh₃)] (5), [Pd(L^2a)(PPh₃)] (6), [Pt(L^2b)(PPh₃)] (7) and [Pd(L^2b)(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 H₂L^1a and H₂L^1b ligands, H₂L^2a and H₂L^2b assume cyclic forms as 5-hydroxypyrazolinic. Upon coordination, H₂L^2a and H₂L^2b suffer ring-opening reaction, coordinating in the same manner as H₂L^1a and H₂L^1b, 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 H₂L^2a presented a trypanocidal activity on trypomastigote form better than the standard drug benznidazole.     

Steric influence on platinum(II) ascorbate complexes

From the reaction between dihydroxoplatinum(II) and l-ascorbic acid, two types of platinum(II) ascorbate complexes were obtained and structurally characterized with ethylenediamine (en), N,N-dimethylethylenediamine (dmen) and N,N,N′-trimethylethylenediamine (trimen) as stabilizing ligands. In [Pt(en)(asc-C,O)] (1), [Pt(dmen)(asc-C,O)] (2) and [Pt(trimen)(asc-C,O)] (4), the ascorbate dianion forms a five-membered chelate ring, coordinating to the Pt(II) ion at the 2-carbon and the 5-oxygen atoms (C,O-chelate). From the same mother solution, crystals of [Pt(trimen)(asc-O,O′)] (3) were obtained during the precipitation of 4; in 3 the ascorbate is bound to the Pt at the 2- and 3-oxygen atoms (O,O′-chelate). Compounds 3 and 4 are the first well-characterized linkage isomers among the transition-metal ascorbate complexes. The O,O′-chelated 3 slowly changes to the C,O-chelated 4 in an aqueous solution. Bulkiness of the stabilizing ligand, i.e. en, dmen and trimen has an influence on the formation of the C,O-chelated species, 1, 2 and 4.     

Synthesis and characterisation of new N1-alkyl-3,5-dipyridylpyrazole derived ligands. Study of their reactivity with Pd(II) and Pt(II)

Two new pyrazole-derived ligands, 1-ethyl-3,5-bis(2-pyridyl)pyrazole (L¹) and 1-octyl-3,5-bis(2-pyridyl)pyrazole (L²), both containing alkyl groups at position 1 were prepared by reaction between 3,5-bis(2-pyridyl) pyrazole and the appropriate bromoalkane in toluene using sodium ethoxide as base.The reaction between L¹, L² and [MCl₂(CH₃CN)₂] (M = Pd(II), Pt(II)) resulted in the formation complexes of formula [MCl₂(L)] (M = Pd(II), L = L¹ (1); M = Pd(II), L = L² (2); M = Pt(II), L = L¹ (3); M = Pt(II), L = L² (4)). These complexes were characterised by elemental analyses, conductivity measurements, infrared, ¹H, ¹³C{¹H} NMR and HMQC spectroscopies. The X-ray structure of the complex [PtCl₂(L²)] (4) was determined. In this complex, Npyridine and Npyrazole donor atoms coordinate the ligand to the metal, which complete its coordination with two chloro ligands in a cis disposition.     

Evaluation of in vitro cytotoxicity and hepatotoxicity of platinum(II) and palladium(II) oxalato complexes with adenine derivatives as carrier ligands

In vitro antitumour activity of the [Pt(ox)(L_n)₂] (1-7) and [Pd(ox)(L_n)₂] (8-14) oxalato (ox) complexes involving N6-benzyl-9-isopropyladenine-based N-donor carrier ligands (L_n) against ovarian carcinoma (A2780), cisplatin resistant ovarian carcinoma (A2780cis), malignant melanoma (G-361), lung carcinoma (A549), cervix epitheloid carcinoma (HeLa), breast adenocarcinoma (MCF7) and osteosarcoma (HOS) human cancer cell lines was studied. Some of the tested complexes were even several times more cytotoxic as compared with cisplatin employed as a positive control. The improved cytotoxic effect was demonstrated for the platinum(II) complexes 3 (IC₅₀ = 3.2 ± 1.0 μM and 3.2 ± 0.6 μM) and 5 (IC₅₀ = 4.0 ± 1.0 μM and 4.1 ± 1.4 μM) against A2780 and A2780cis, as compared with 11.5 ± 1.6 μM, and 30.3 ± 6.1 μM determined for cisplatin, respectively. The significant in vitro cytotoxicity against MCF7 (IC₅₀ = 8.2 ± 3.8 μM for 12) and A2780 (IC₅₀ = 5.4 ± 1.2 μM for 14) was evaluated for the palladium(II) oxalato complexes, which again exceeded cisplatin, whose IC₅₀ equalled 19.6 ± 4.3 μM against the MCF7 cells. Selected complexes were also screened for their in vitro cytotoxic effect in primary cultures of human hepatocytes and they were found to be non-hepatotoxic.