Andrej Pevec

Click-Triazole N2 Coordination to Transition-Metal Ions Is Assisted by a Pendant Pyridine Substituent

We report that 1-(2-picolyl)-1,2,3-triazole (click triazole) forms stable complexes with transition-metal ions in which the coordination involves the triazole N2 nitrogen atom and the pendant 2-picolyl group. This is exemplified by model compound 1-(2-picolyl)-4-phenyl-1H-1,2,3-triazole (L(x)) and its complexes with transition-metal ions of Pt(II), Pd(II), Cu(II), Ru(II), and Ag(I). The coordination was investigated experimentally and theoretically. Ligand L(x) easily reacted at room temperature with cis-[PtCl(2)(DMSO)(2)], [Pd(CH(3)CN)(4)](BF(4))(2), CuCl(2), [RuCl(mu-Cl)(eta(6)-p-cymene)](2), and AgNO(3) to give stable chelates [PtCl(2)L(x)] (1), [Pd(L(x))(2)](BF(4))(2) (2), [CuCl(2)(L(x))(2)] (3), [RuCl(eta(6)-p-cymene)L(x)]OTf (4), and [Ag(2)(L(x))(2)(NO(3))(2)] (5), respectively, in 60-98% yield. The structures of 1-5 were unambiguously confirmed by NMR spectroscopy and single-crystal X-ray diffraction analysis. Density functional theory calculations were carried out in order to theoretically investigate the stabilization factors in 1-5. A comparison of the chelating properties of ligand L(x) was made with structurally similar and isomeric 1-(2-aminoethyl)-substituted 1,2,3-triazole (L(y)) and 4-(2-aminoethyl)-substituted 1,2,3-triazole (L(z)). The complexation affinity of L(x) was attributed to pi-back-donation from the metal to the pendant pyridine side arm, whereas the stability of the complexes involving L(y) and L(z) mainly originates from efficient pi-back-donation to the triazole ring.

Synthesis and the crystal structures of a monoanionic tetrafluorodentate ligand and its complex with lanthanum ion

Abstract New organotitanium fluorides [Hdmpy]+[(C5Me4R)2Ti2F7]− (R=Me 4, Et 5, dmpy=2,6-dimethylpyridine, lutidine) have been prepared from (C5Me4R)TiF3 and 2,6-dimethylpyridine·(HF)2. The compounds 4 and 5 react with La(CF3SO3)3 to give [La{(C5Me4R)2Ti2F7}3] (R=Me 6, Et 7) containing the [(C5Me4R)2Ti2F7]− anion as a tetrafluorodentate ligand in the crystal structures of 4 and 7. The cation–anion pair is connected by a hydrogen bond in 4 and the all-fluorine environment of 12 fluorine atoms coordinated to a lanthanum ion is found in 7.

Coordination number 12 in praseodymium and 11 in neodymium complexes with organofluorotitanate ligands

Abstract The complexes of [Pr{(C5Me5)2Ti2F7}3] 2 and [Nd{(C5Me5)2Ti2F7}3] 3 were obtained by the reaction of [Hdmpy]+[(C5Me5)2Ti2F7]− 1 (dmpy=2,6–dimethylpyridine, C5H3NMe2), with praseodymium(III) and neodymium(III) trifluoromethanesulfonate. The X–ray crystal structures of 2 and 3 exhibit a fluorine environment of 12 at the praseodymium and of 11 at the neodymium with [(C5Me5)2Ti2F7]− acting as well as a tetra- and as a three-fluorodentate ligand. Both complexes retained their structures in solution. Complex 2 is the first molecular compound containing PrF bonds.

Synthesis, characterization, DFT calculation and biological activity of square-planar Ni(II) complexes with tridentate PNO ligands and monodentate pseudohalides. Part II.

Three square-planar complexes of Ni(II) with condensation derivative of 2-(diphenylphosphino)benzaldehyde and 4-phenylsemicarbazide and monodentate pseudohalides have been synthesized and characterized on the basis of the results of X-ray, NMR and IR spectroscopy and elemental analysis. Investigated complexes exhibited moderate antibacterial and cytotoxic activity. The most pronounced cytotoxic activity (in the range of cisplatin) to HeLa cell line was observed for ligand and all the complexes. Azido complex and ligand induced concentration dependent cell cycle arrest in the S phase, as well as decrease of percentage of cells in G1 phase, without significant increase of apoptotic fraction of cells. The interaction of the azido complex and ligand with CT-DNA results in changes in UV-Vis spectra typical for non-covalent bonding. The observed intrinsic binding constant of azido complex-CT-DNA and ligand-CT-DNA were 3.22 × 10(5) M(-1) and 2.79 × 10(5) M(-1). The results of DNA cleavage experiments showed that azido complex nicked supercoiled plasmid DNA.

Synthesis, crystal structures and antimicrobial activity of azido and isocyanato Zn(II) complexes with the condensation product of 2-quinolinecarboxaldehyde and Girard’s T reagent

Abstract Two Zn(II) complexes with the condensation product of 2-quinolinecarboxaldehyde and trimethylammonium acetohydrazide chloride (Girard’s T reagent) (HLCl) and monodentate pseudohalides (azide and cyanate) have been synthesized and characterized by elemental analysis, IR and NMR spectroscopy, and single-crystal X-ray diffraction. In both complexes, the coordination surroundings of the Zn(II) ions consist of a deprotonated hydrazone ligand coordinated through an NNO set of donor atoms and two monodentate pseudohalides (N3– or NCO–) at the remaining coordination sites. The Zn(II) complexes showed low to moderate activity against laboratory control strains of pathogenic bacteria and fungi.

Synthesis, characterization, DFT calculations and antimicrobial activity of pentagonal-bipyramidal Zn(II) and Cd(II) complexes with 2,6-diacetylpyridine-bis(trimethylammoniumacetohydrazone)

Abstract Isothiocyanate complexes of Zn(II) and Cd(II) with the condensation product of 2,6-diacetylpyridine and trimethylammoniumacetohydrazide (Girard’s T reagent) were synthesized, characterized, and their antimicrobial activities were evaluated. The structures of the complexes were determined by elemental analysis, IR, and NMR spectroscopy. The crystal structure of the Zn(II) complex was also determined. Quantum-chemical calculations of the geometry and total energy of isomers of 2,6-diacetylpyridine-bis(trimethylammoniumacetohydrazone) were performed in vacuum and methanol solution, with the aim to explain conformational behavior and E/Z isomerism of this compound. DFT calculations of the molecular structures and the relative stabilities of linkage isomers of the Cd(II) complex showed that the isomer with N–Cd–N coordination of SCN− is the most stable. Complexes of Zn(II) and Cd(II) exhibited low to moderate activity against the tested microbial strains.

Investigation of antitumor potential of Ni(II) complexes with tridentate PNO acylhydrazones of 2-(diphenylphosphino)benzaldehyde and monodentate pseudohalides

Square-planar azido Ni(II) complex with condensation product of 2-(diphenylphosphino)benzaldehyde and Girard’s T reagent was synthesized and its crystal structure was determined. Cytotoxic activity of the azido complex and previously synthesized isothiocyanato, cyanato and chlorido Ni(II) complexes with this ligand was examined on six tumor cell lines (HeLa, A549, K562, MDA-MB-453, MDA-MB-361 and LS-174) and two normal cell line (MRC-5 and BEAS-2B). All the investigated nickel(II) complexes were cytotoxic against all tumor cell lines. The newly synthesized azido complex showed selectivity to HeLa and A549 tumor cell lines compared to the normal cells (for A549 IC50 was similar to that of cisplatin). Azido complex interferes with cell cycle phase distribution of A549 and HeLa cells and possesses nuclease activity towards supercoiled DNA. The observed selectivity of the azido complex for some tumor cell lines can be connected with its strong DNA damaging activity.

Synthesis, crystal structures and antimicrobial activity of square-planar chloride and isocyanate Ni(II) complexes with the condensation product of 2-(diphenylphosphino)benzaldehyde and Girard's T reagent

Square-planar isocyanate and chloride Ni(II) complexes with tridentate PNO condensation product of 2-(diphenylphosphino)benzaldehyde and Girard’s T reagent have been synthesized and their crystal structures were determined. These Ni(II) complexes with different monodentate ligands, chloride, cyanate, and thiocyanate were tested for their antimicrobial activities against pathogenic microorganisms. The ligand and Ni(II) complexes were active not only against laboratory control strains of bacteria and yeast, but also on clinical isolates of Escherichia coli and Pseudomonas aeruginosa strains resistant to most of the clinically used antibiotics. Graphical abstract

Synthesis, characterization and antimicrobial activity of pentagonal-bipyramidal isothiocyanato Co(II) and Ni(II) complexes with 2,6-diacetylpyridine bis(trimethylammoniumacetohydrazone)

Abstract Pentagonal-bipyramidal isothiocyanato Co(II) and Ni(II) complexes with condensation product of 2,6-diacetylpyridine and trimethylammoniumacetohydrazide (Girard’s T reagent) were synthesized and characterized by elemental analyses, IR and UV–vis spectra, molar conductivity, and magnetic susceptibility. Crystal structures of the Co(II) and Ni(II) complexes were also determined. Antimicrobial activities of the ligand and metal complexes were examined.

The 1,3-diaryltriazenido(p-cymene)ruthenium(II) complexes with a high in vitro anticancer activity.

1,3-Diaryltriazenes (1) were let to react with [RuCl2(p-cymene)]2 in the presence of trimethylamine to give neutral 1,3-diaryltriazenido(p-cymene)ruthenium(II) complexes, [RuCl(p-cymene)(ArNNNAr)] (2). The molecular composition of the products 2 was confirmed by NMR spectroscopy and mass spectrometry. The structures of the selected complexes were confirmed by a single crystal X-ray analysis. All triazenido-ruthenium complexes were highly cytotoxic against human cervical carcinoma HeLa cells with IC50 below 6μM, as determined by a spectrophotometric MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) method. The most active was [RuCl(p-cymene)(ArNNNAr)] (Ar=4-Cl-3-(CF3)-C6H3) (2g) with IC50 of 0.103±0.006μM. In comparison with the data for the non-coordinated triazenes 1, the triazenido-ruthenium complexes 2 exhibited up to 560-times higher activity. Three selected complexes were highly cytotoxic also against several tumor cell lines: laryngeal carcinoma HEp-2 cells and their drug-resistant HEp-2 subline (7T), colorectal carcinoma HCT-116 cells, lung adenocarcinoma H460 cells, and mammary carcinoma MDA-MB-435 cells. The compounds 2g and [RuCl(p-cymene)(ArNNNAr)] (Ar=4-I-C6H4) (2j) were similarly cytotoxic against parental and drug-resistant cells. Time and dose dependent accumulation of the cells in the S phase of the cell cycle was induced by the compound 2g, triggering apoptosis. Our preliminary results indicate triazenido-ruthenium complexes as promising anticancer drug candidates.