Introducing N-Heteroaromatic Bases into Copper(II) Thiosemicarbazon Complexes: A Way to Change their Biological Activity.

Three new copper(II) complexes, [Cu(1,10-Phen)(L)] (1), [Cu(2,2'-Bpy)(L)] (2) and [Cu(3,4-Lut)(L)] (3), where H2 L=2-[(2,4-dihydroxyphenyl)methylidene]-N-(prop-2-en-1-yl)hydrazine-1-carbothioamide, 1,10-Phen=1,10-phenanthroline, 2,2'-Bpy=2,2'-bipyridine, 3,4-Lut=3,4-lutidine, have been synthesized and characterized by elemental analysis, FTIR spectroscopy and single crystal X-ray crystallography (1, 2). All compounds are mononuclear. The introduction of a monodentate N-heteroaromatic base (3,4-dimethylpyridine) has led to a significant increase of antimicrobial activity against Gram-negative Escherichia coli and antifungal activity against Candida albicans compared to the pro-ligand and the precursor complex [Cu(L)H2 O]. The introduction of bidentate N-heteroaromatic bases did not lead to such increase of antimicrobial and antifungal activities. Moreover, complex 3 surpasses the inhibitory activity of tetracycline toward Enterobacter cloacae and the inhibitory activity of fluconazole toward Candida parapsilosis and Cryptococcus neoformans. The study of antioxidant activity against cation radicals ABTS⋅+ showed that complexes 1-3 are more active than Trolox, but only introduction of the monodentate N-heteroaromatic base (3,4-dimethylpyridine) led to the increase of antioxidant properties compared to the precursor complex.

Synthesis, Structure, and Biologic Activity of Some Copper, Nickel, Cobalt, and Zinc Complexes with 2-Formylpyridine N 4-Allylthiosemicarbazone.

A series of zinc(II) ([Zn(H2O)(L)Cl] (1)), copper (II) ([Cu(L)Cl] (2), [Cu(L)Br] (3), [Cu2(L)2(CH3COO)2]·4H2O (4)), nickel(II) ([Ni(HL)2]Cl2·H2O (5)), and cobalt(III) ([Co(L)2]Cl (6)) complexes were obtained with 2-formylpyridine N 4-allylthiosemicarbazone (HL). In addition another two thiosemicarbazones (3-formylpyridine N 4-allylthiosemicarbazone (HL a) and 4-formylpyridine N 4-allylthiosemicarbazone (HL b)) have been obtained. The synthesized thiosemicarbazones have been studied using 1H and 13C NMR spectroscopy, IR spectroscopy, and X-ray diffraction analysis. The composition and structure of complexes were studied using elemental analysis, IR and UV-Vis spectroscopies, molar conductivity, and magnetic susceptibility measurements. Single crystal X-ray diffraction analysis elucidated the structure of thiosemicarbazones HL, HL a, and HL b, as well as complexes 4 and 5. The antiproliferative properties of these compounds toward a series of cancer cell lines (HL-60, HeLa, BxPC-3, RD) and a normal cell line (MDCK) have been investigated. The nickel complex shows high selectivity (SI > 1000) toward HL-60 cell line and is the least toxic. The zinc complex shows the highest selectivity toward RD cell line (SI = 640). The copper complexes (2-4) are the most active molecular inhibitors of proliferation of cancer cells, but exhibit not such a high selectivity and are significantly more toxic. Zinc and copper complexes manifest high antibacterial activity. It was found that calculated at B3LYP level of theory different reactivity descriptors of studied compounds strongly correlate with their biological activity.

Crystal Engineering of Schiff Base Zn(II) and Cd(II) Homo- and Zn(II)M(II) (M = Mn or Cd) Heterometallic Coordination Polymers and Their Ability to Accommodate Solvent Guest Molecules.

Based on solvothermal synthesis, self-assembly of the heptadentate 2,6-diacetylpyridine bis(nicotinoylhydrazone) Schiff base ligand (H2L) and Zn(II) and/or Cd(II) salts has led to the formation of three homometallic [CdL]n (1), {[CdL]∙0.5dmf∙H2O}n (2) and {[ZnL]∙0.5dmf∙1.5H2O}n (3), as well as two heterometallic {[Zn0.75Cd1.25L2]∙dmf∙0.5H2O}n (4) and {[MnZnL2]∙dmf∙3H2O}n coordination polymers. Compound 1 represents a 1D chain, whereas 2-5 are isostructural and isomorphous two-dimensional structures. The entire series was characterized by IR spectroscopy, thermogravimetric analysis, single-crystal X-ray diffraction and emission measurements. 2D coordination polymers accommodate water and dmf molecules in their cage-shaped interlayer spaces, which are released when the samples are heated. Thus, three solvated crystals were degassed at two temperatures and their photoluminescent and adsorption-desorption properties were recorded in order to validate this assumption. Solvent-free samples reveal an increase in volume pore, adsorption specific surface area and photoluminescence with regard to synthesized crystals.

Effect of the Substitution Pattern (Peripheral vs Non-Peripheral) on the Spectroscopic, Electrochemical, and Magnetic Properties of Octahexylsulfanyl Copper Phthalocyanines.

In order to investigate the substitution position effect on the spectroscopic, electrochemical, and magnetic properties of copper phthalocyanines, a detailed structure-property analysis has been performed by examining two copper phthalocyanines that are octasubstituted by hexylsulfanyl chains respectively in the peripheral (Cu-P) and non-peripheral (Cu-NP) positions. Cu-NP showed a marked near-IR maximum absorption compared to Cu-P and, accordingly, a smaller HOMO-LUMO energy gap, calculated via the electrochemical results and simulations in the gas phase, as well as for Cu-NP from its crystallographic data. An electron-spin resonance (ESR) technique is used to extract the g values from the powder spectra that are taken at room temperature. The g values were determined to be g∥ = 2.160 and g⊥ = 2.045 for Cu-P and g∥ = 2.150 and g⊥ = 2.050 for Cu-NP. These values indicate that the paramagnetic copper center in both phthalocyanines has axial symmetry with a planar anisotropy ( g∥ > g⊥). The ESR spectra in solution could be obtained only for Cu-P. Curie law is used to fit the experimental data of the magnetic susceptibility versus temperature graphs, and the Curie constant ( C) and diamagnetic/temperature-independent paramagnetic (α) contributions are deduced as 0.37598 (0.39576) cm3·K/mol and -23 × 10-5 (25 × 10-5) cm3/mol respectively for Cu-P and Cu-NP. The room temperature magnetic moment value (1.70 µB) is close to the spin-only value (1.73 µB) for the peripheral complex, showing that there is no orbital contribution to µeff. In contrast, at room temperature, the value of the magnetic moment (1.77 µB) is above the spin-only value, showing an orbital contribution to the magnetic moment. Cu-NP's room temperature magnetic moment value is larger than the value for Cu-P, demonstrating that the orbital contribution to the magnetic moment depends upon the substituent position. The magnitudes of the effective magnetic moment values also support that both Cu-P and Cu-NP complexes have square-planar coordination. This result is consistent with the determined g values. The spin densities were determined experimentally, and the results suggest that the positions of the substituents affect these values (0.469 for Cu-P and 0.490 for Cu-NP).

Synthesis, structure and toxicity evaluation of ethanolamine nitro/chloronitrobenzoates: a combined experimental and theoretical study.

BACKGROUND: Nitroaromatic and chloronitroaromatic compounds have been a subject of great interest in industry and recently in medical-pharmaceutic field. 2-Chloro-4-nitro/2-chloro-5-nitrobenzoic acids and 4-nitrobenzoic acid are promising new agents for the treatment of main infectious killing diseases in the world: immunodeficiency diseases and tuberculosis. RESULTS: New ethanolamine nitro/chloronitrobenzoates were synthesized and characterized by X-ray crystallography, UV-vis, FT-IR and elementary analysis techniques. The toxicity of the compounds prepared and correspondent components was evaluated using Hydractinia echinata as test system. A significant lower toxicity was observed for nitro-derivative compared with chloronitro-derivatives and individual components. Crystallographic studies, together with the chemical reactivity and stability profiles resulted from density functional theory and ab initio molecular orbital calculations, explain the particular behavior of ethanolamine 4-nitrobenzoate in biological test. CONCLUSIONS: The experimental and theoretical data reveal the potential of these compounds to contribute to the design of new active pharmaceutical ingredients with lower toxicity.

Synthesis, crystal structure and biological activity of 2-hydroxyethylammonium salt of p-aminobenzoic acid.

p-Aminobenzoic acid (pABA) plays important roles in a wide variety of metabolic processes. Herein we report the synthesis, theoretical calculations, crystallographic investigation, and in vitro determination of the biological activity and phytotoxicity of the pABA salt, 2-hydroxyethylammonium p-aminobenzoate (HEA-pABA). The ability of neutral and anionic forms of pABA to interact with TIR1 pocket was investigated by calculation of molecular electrostatic potential maps on the accessible surface area, docking experiments, Molecular Dynamics and Quantum Mechanics/Molecular Mechanics calculations. The docking study of the folate precursor pABA, its anionic form and natural auxin (indole-3-acetic acid, IAA) with the auxin receptor TIR1 revealed a similar binding mode in the active site. The phytotoxic evaluation of HEA-pABA, pABA and 2-hydroxyethylamine (HEA) was performed on the model plant Arabidopsis thaliana ecotype Col 0 at five different concentrations. HEA-pABA and pABA acted as potential auxin-like regulators of root development in Arabidopsis thaliana (0.1 and 0.2 mM) and displayed an agravitropic root response at high concentration (2 mM). This study suggests that HEA-pABA and pABA might be considered as potential new regulators of plant growth.

Experimental determination of spin-dependent electron density by joint refinement of X-ray and polarized neutron diffraction data.

New crystallographic tools were developed to access a more precise description of the spin-dependent electron density of magnetic crystals. The method combines experimental information coming from high-resolution X-ray diffraction (XRD) and polarized neutron diffraction (PND) in a unified model. A new algorithm that allows for a simultaneous refinement of the charge- and spin-density parameters against XRD and PND data is described. The resulting software MOLLYNX is based on the well known Hansen-Coppens multipolar model, and makes it possible to differentiate the electron spins. This algorithm is validated and demonstrated with a molecular crystal formed by a bimetallic chain, MnCu(pba)(H(2)O)(3)·2H(2)O, for which XRD and PND data are available. The joint refinement provides a more detailed description of the spin density than the refinement from PND data alone.

Interaction of thioether groups at the open coordination sites of palladium(II) and platinum(II) complexes probed by luminescence spectroscopy at variable pressure.

The crystal structures of [PtCl(2)(ttcn)], [PdCl(2)(ttcn)], [Pt(ethylenediamine)(ttcn)](PF(6))(2), and [Pd(ethylenediamine)(ttcn)](PF(6))(2) (ttcn = 1,4,7-trithiacyclononane) show short apical metal---S(ttcn) distances, qualitatively indicating an interaction. Luminescence spectroscopy was used to study these crystalline complexes at room temperature and variable hydrostatic pressure. The luminescence band maximum of [PdCl(2)(ttcn)] shows a pressure-induced blue shift of +6 cm(-1)/kbar, while the platinum(II) compounds show a red shift of approximately -20 cm(-1)/kbar. This difference is rationalized in terms of a competition between blue shifts due to pressure-induced metal-ligand bond shortening in the equatorial plane and increasing out-of-plane distance of the metal center, and a red shift due to the approach of the apical sulfur donor to the metal center. Density functional theory (DFT) calculations indicate d-d luminescence transitions and a different nature of the highest occupied molecular orbital (HOMO) for [PdCl(2)(ttcn)] than for [PtCl(2)(ttcn)], while the lowest unoccupied molecular orbitals (LUMOs) are identical in character. This electronic structure difference is used to rationalize the different pressure effects.

Structure, magnetic properties, polarized neutron diffraction, and theoretical study of a copper(II) cubane.

The paper reports the synthesis, X-ray and neutron diffraction crystal structures, magnetic properties, high field-high frequency EPR (HF-EPR), spin density and theoretical description of the tetranuclear CuII complex [Cu4L4] with cubane-like structure (LH2=1,1,1-trifluoro-7-hydroxy-4-methyl-5-aza-hept-3-en-2-one). The simulation of the magnetic behavior gives a predominant ferromagnetic interaction J1 (+30.5 cm(-1)) and a weak antiferromagnetic interaction J2 (-5.5 cm(-1)), which correspond to short and long Cu-Cu distances, respectively, as evidence from the crystal structure [see formulate in text]. It is in agreement with DFT calculations and with the saturation magnetization value of an S=2 ground spin state. HF-EPR measurements at low temperatures (5 to 30 K) provide evidence for a negative axial zero-field splitting parameter D (-0.25+/-0.01 cm(-1)) plus a small rhombic term E (0.025+/-0.001 cm(-1), E/D = 0.1). The experimental spin distribution from polarized neutron diffraction is mainly located in the basal plane of the CuII ion with a distortion of yz-type for one CuII ion. Delocalization on the ligand (L) is observed but to a smaller extent than expected from DFT calculations.

Channel architecture via self assembly of oxamide oximes complexes.

The nickel(II) and palladium(II) complexes of oxamide oximes substituted with alkyl chains of different length (C4-C8) were synthesized from the reaction of dichloroglyoxime with the corresponding amine derivatives. All compounds have been characterized by X-ray diffraction on single crystals and were found to be centrosymmetric at the metal center which is bound by the four oximic nitrogen atoms of two ligands in a square planar environment. Crystal structure analyses of Ni(II) and Pd(II) complexes showed that all of the Pd(II) complexes but only the hexyl-substituted oxamide oxime Ni(II) complex form infinite tubular channels. Their conformational analyses were carried out in order to understand the role of the chain length and of the metal center in the formation of the tubular channels and it was found that the formation of infinite tubular channels in crystals of Ni(II) and Pd(II) alkyl-substituted oxamide oxime complexes is related to the orientation of the alkyl chains relative to the central core.

N-acetyl-4-[(2-hydroxybenzylidene)amino]benzenesulfonamide monohydrate and N-acetyl-4-[(5-bromo-2-hydroxybenzylidene)amino]benzenesulfonamide monohydrate.

Molecules of the title compounds, C15H14N2O4S.H2O and C15H13BrN2O4S.H2O, adopt an E configuration about the azomethine C=N double bond. In both molecules, the two benzene rings and the azomethine group are practically coplanar, as a result of intramolecular hydrogen bonds involving the hydroxy O atom and azomethine N atom. The angular disposition of the bonds about the S atom deviates significantly from that of a regular tetrahedron. In the crystal structures, both compounds form two-dimensional layers parallel to the (100) plane.

The monoclinic polymorph of rac-5,7,7,12,12,14-hexamethyl-1,4,8,11-tetraazoniacyclotetradecane bis(hexafluorogermanate) tetrahydrate.

X-ray data were obtained for the monoclinic polymorph of rac-5,7,7,12,12,14-hexamethyl-1,4,8,11-tetraazoniacyclotetradecane bis(hexafluorogermanate) tetrahydrate, (C(16)H(40)N(4))[GeF(6)](2).4H(2)O. The tetraaza-macrocyclic cations lie across inversion centers in space group P2(1)/c. Water molecules and [GeF(6)](2-) anions form zigzag chains, which alternate in a three-dimensional network with the macrocyclic cations. The structure is sustained by multiple hydrogen bonds.