Mavroudis A. Demertzis

Platinum(II) complexes with 2-acetyl pyridine thiosemicarbazone: Synthesis, crystal structure, spectral properties, antimicrobial and antitumour activity

An interesting series of new platinum complexes has been synthesized by the reaction of Na(2)PtCl(4) with 2-acetyl pyridine thiosemicarbazone, HAcTsc. The new complexes, [Pt(AcTsc)Cl], [Pt(HAcTsc)(2)]Cl(2) and [Pt(AcTsc)(2)], have been characterized by elemental analyses and spectroscopic studies. The crystal structure of the complex [Pt(AcTsc)Cl] has been solved by single-crystal X-ray diffraction. The anion of HAcTsc coordinates in a planar conformation to the central platinum(II) through the pyridyl N, azomethine N and thiolato S atoms. Double intermolecular hydrogen bonds (NH-Cl), pi-pi and weak Pt-Pt and Pt-pi contacts lead to aggregation and to a two-dimensional supramolecular assembly. The antibacterial and antifungal effect of the novel platinum(II) complexes and the related palladium(II) complexes, [Pd(AcTsc)Cl], [Pd(HAcTsc)(2)]Cl(2) and [Pd(AcTsc)(2)], were studied in vitro. The complexes were found to have a completely lethal effect on Gram+ bacteria, while the same complexes showed no bactericidal effect on Gram- bacteria. Additionally, the complexes [Pt(AcTsc)(2)] and [Pd(AcTsc)(2)] showed effective antifungal activity towards yeast. Among these compounds [33], the most effective in inducing antitumour and cytogenetic effects are the complexes [Pt(AcTsc)(2)] and [Pd(AcTsc)(2)] while the rest, display marginal cytogenetic and antitumour effects.

PALLADIUM(II) COMPLEXES OF 2-ACETYLPYRIDINE N(4) -METHYL, N(4)-ETHYL AND N(4)-PHENYL-THIOSEMICARBAZONES. CRYSTAL STRUCTURE OF CHLORO(2-ACETYLPYRIDINE N(4)-METHYLTHIOSEMICARBAZONATO) PALLADIUM(II). SYNTHESIS, SPECTRAL STUDIES, IN VITRO AND IN VIVO ANTITUMOUR ACTIVITY

The reactions of 2-acetylpyridine N(4)-methyl, (HAc4Me) N(4)-ethyl (HAc4Et) and N(4)-Phenyl (HAc4Ph) thiosemicarbazone with palladium(II) were studied. The ligands and the palladium(II) complexes have been characterized by spectroscopic techniques. The structure of [Pd(Ac4Me)Cl] has been determined by single-crystal x-ray diffraction. The protonation constants of HAc4Me and HAc4Et, Ka1 and Ka2, were determined by spectrophotometry. The effect of palladium compounds on DNA synthesis of P388 and L1210 cell cultures is also reported. Some of these compounds increased the life span of mice bearing tumors.

Palladium(II) and platinum(II) complexes of pyridine-2-carbaldehyde thiosemicarbazone with potential biological activity. Synthesis, structure and spectral properties. Extended network via hydrogen bond linkages of [Pd(PyTsc)Cl]

Abstract The reactions of Li2PdCl4 and Na2PtCl4 with pyridine-2-carbaldehyde thiosemicarbazone, HPyTsc, afforded the complexes [Pd(PyTsc)Cl], [Pd(PyTsc)2] and [Pt(PyTsc)Cl], [Pt(PyTsc)2]. The new complexes have been characterized by elemental analyses and spectroscopic studies. A crystal structure of [Pd(PyTsc)Cl] shows that the anion of PyTsc coordinates in a planar conformation to the central palladium(II) through the pyridyl N, azomethine N and thiolato S atoms. The planar molecules are linked into polymeric chains by N–H··N and N–H··S hydrogen bonding. The protonation constants of the ligand, Ka1 and Ka2, were determined by spectrophotometry and the logarithms of their values were found to be equal to 11.58±0.05 and 3.94±0.02 respectively. Correlation of the antitumor activity of these complexes to the structure and to reduction potential is reported. The compounds [Pt(PyTsc)2] and [Pd(PyTsc)2] were found to exhibit the higher in vivo antitumor activity and the lower cytotoxicity.

Coordinating properties of 2-acetylpyridine thiosemicarbazone. Palladium(II) complexes with neutral and deprotonated ligand. X-ray structure of bromo(2-acetylpyridine thiosemicarbazonato) palladium(II)

Abstract The preparation of the complexes PdLX, [Pd(HL) 2 ]X 2 and PdL 2 (X = Cl, Br; HL and L the neutral and deprotonated ligand) is described. The new complexes have been characterized by elemental analyses, conductivity measurements and spectroscopic (IR and UV-vis) studies and the crystal and molecular structure of PdLBr has been determined by single-crystal X-ray diffraction. The palladium atom has a square planar geometry with three donor atoms (NNS) coming from L to form a planar tricyclic ligating system, and one bromide atom. All data are discussed in terms of assigned structural type and the nature of the bonding. The protonation constants of the ligand, K a1 and K a2 , were determined by spectrophotometry and the logarithms of their values were found to be equal to 11.43 ± 0.02 and 3.98 ± 0.02.

Synthesis and characterization of tetrakis-μ-2-[(2,6dichlorophenyl) amino] benzeneacetodiaquodicopper(II) dihydrate and tetrakis-μ-2-[(2,6dichlorophenyl)amino]benzeneaceto dimethylformamidodicopper(II)

Abstract Complexes of diclofenac (L), [CuL2(H2O)]22H2O, and [CuL2(DMF)]2 were prepared by the reaction of the sodium salt of this potent antiinflammatory drug with CuCl2. The new symmetric binuclear copper(II) complex [CuL2(DMF)]2 crystallizes in the monoclinic space group P21/n with cell constants a = 10.807(1), b = 15.429(2), c = 19.360(2), β = 92.508(3), V = 3225(1) A 3 , and Z = 2 . The structure was determined from 5456 out of a total of 5768 unique reflections. The final values for R1, wR2, and GOF for all data are 0.0602, 0.1066, and 1.030, respectively. The crystal structure consists of a binuclear quadruply bridged neutral molecule. The four carboxylato groups from four ligands are in the familar bidentate syn,syn η1:η1:μ2 bridging mode. The metal coordination geometry is described as a perfect square bipyramid with a water or dimethyloformamide oxygen occupying both apical positions. Optical, infrared, electron paramagnetic resonance, magnetic, and electrochemical properties of these complexes are also reported.

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.

Palladium(II) complexes of 2-acetylpyridine N(4)-propyl, N(4)-dipropyl- and 3-hexamethyleneiminylthiosemicarbazones with potentially interesting biological activity. Synthesis, spectral properties, antifungal and in vitro antitumor activity

Abstract Some new palladium(II) complexes of 2-acetylpyridine N(4)-propyl- and N(4)dipropyl- and 3-hexamethyleneiminylthiosemicarbazones with potentially interesting biological activity were described. The thiosemicarbazones and their palladium(II) complexes have been characterized by spectroscopic, and electrochemical techniques. The protonation constants of HAc4P Ka1 and Ka2, were determined by spectrophotometry and the pK1a and pKa2 values are equal to 12.23 ±0.02 and 4.11 ±0.02. The antifungal properties and the effect selected compounds on DNA synthesis of P388 and L1210 cell cultures is reported.

Structures and spectral properties of palladium(II) complexes of 2-acetylpyridine N(4)-dimethylthiosemicarbazone

Anions [loss of N(3) hydrogen of 2-acetylpyridine N(4)-dimethylthiosemicarbazone (HAc4DM)] coordinate in a planar conformation to a central palladium(II) through the pyridyl nitrogen, azomethine nitrogen and thiolato sulfur atoms. The fourth coordination site is occupied by either a bromo, chloro or a second Ac4DM ligand bonding via its thiolato sulfur atom. A crystal structure of [Pd(Ac4DM)Br] shows it to be planar, while the structure of [Pd(Ac4DM)2] has the unusual coordination of the two anions bonding differently to the palladium centre. Spectral and structural similarities and differences between these and related nickel(II) and copper(II) complexes are considered.

Palladium(II) complexes of 4-formylantipyrine N(3)-substituted thiosemicarbazones: first example of X-ray crystal structure and description of bonding properties

Abstract Reaction of 4-formylantipyrine with thiosemicarbazide, N(3)-methylthiosemicarbazide and N(3)-ethylthiosemicarbazide produced the expected thiosemicarbazones, 1, 2 and 3. The three thiosemicarbazones were then reacted with K2PdCl4 to produce [Pd(NS)2] complexes, 4, 5, and 6, respectively, with coordination by the imine nitrogen and thiolate sulfur of the anionic thiosemicarbazone moiety. The thiosemicarbazones and their palladium complexes have been characterized by spectral IR, UV–Vis and 1H, 13C NMR and electrochemical techniques. The crystal structure of 6 has been obtained and found to be highly symmetrical with a trans arrangement of the two bidentate ligands.

In vitro and in vivo antitumor activity of platinum(II) complexes with thiosemicarbazones derived from 2-formyl and 2-acetyl pyridine and containing ring incorporated at N(4)-position: Synthesis, spectroscopic study and crystal structure of platinum(II) complexes with thiosemicarbazones, potential anticancer agents

Reactions of thiosemicarbazones of 2-formyl and 2-acetyl pyridine and containing an azepane ring (hexamethyleneiminyl ring) incorporated at N(4)-position, HL(1) (1) and HL(2) (2) with platinum(II) afforded the complexes, [Pt(L(1))Cl] (3) and [Pt(L(2))Cl] (4). Characterization of the compounds was accomplished by means of elemental analysis and spectroscopic techniques NMR, UV-vis and IR spectroscopy. The single-crystal X-ray structure of complex [Pt(L(2))Cl] (4) shows that the ligand monoanion coordinates in a planar conformation to the metal via the pyridyl N atom, the imine-N atom, and thiolato S-atom. Compounds 1-4 have been evaluated for antiproliferative activity in vitro against 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 L-929 (a fibroblast-like cell line cloned from strain L). Ligand 2 exhibited high activity as anticancer agent against all four cancer cell lines, while ligand 1 exhibited selectivity against MCF-7, L-929 cell lines and complex 4 against A-549, T-24 cancer cell lines. Also, the acute toxicity and antitumor activity were evaluated on leukemia P388-bearing mice. Complex 3 afforded five to six cures against leukemia P388. The in vivo results of the antitumor activity show the two platinum complexes as very effective chemotherapeutic antileukemic agents.