Synthesis, Structural Characterization and Biological Activity Evaluation of Novel Cu(II) Complexes with 3-(trifluoromethyl)phenylthiourea Derivatives.

Copper complexes with 1,3-disubstituted thiourea derivatives, all containing 3-(trifluoromethyl)phenyl tail and 1-alkyl/halogen-phenyl substituent, were synthesized. The experimental spectroscopic studies and theoretical calculation revealed that two ligands coordinate to Cu(II) in a bidentate fashion via thiocarbonyl S and deprotonated N atoms of thiourea moiety. Such monomers are characteristic of alkylphenylthiourea complexes, whereas the formation of a sandwich-type dimer is observed for halogeno derivatives. For the first time, the structural identifications of CuN2S2-based complexes using experimental and theoretical X-ray absorption near edge structure are demonstrated. The dimeric halogeno derivatives showed higher antimicrobial activity in comparison with alkylphenylthiourea complexes. The Cu(II) complex of 1-(4-chloro-3-nitrophenyl)-3-[3-(trifluoromethyl)phenyl]thiourea was active against 19 strains of methicillin-resistant Staphylococci (MIC = 2 µg/mL). This derivative acted as a dual inhibitor of DNA gyrase and topoisomerase IV isolated from Staphylococcus aureus. Additionally, complexes of halogenphenylthiourea strongly inhibited the growth of mycobacteria isolated from tuberculosis patients, even fourfold stronger than the reference isoniazid. The complexes exerted weak to moderate antitumor activity (towards SW480, SW620, and PC3) being non-toxic towards normal HaCaT cells.

Zeolites at the Molecular Level: What Can Be Learned from Molecular Modeling.

This review puts the development of molecular modeling methods in the context of their applications to zeolitic active sites. We attempt to highlight the utmost necessity of close cooperation between theory and experiment, resulting both in advances in computational methods and in progress in experimental techniques.

Computational refinement of the puzzling red tetrasulfur chromophore in ultramarine pigments.

We investigated the cryptic red chromophore, accompanying the blue S3˙- radical in ultramarine pigments, which usually was tentatively assigned to an unspecified isomer of either neutral S4 or ionic S4˙- species. To reveal its identity, we performed the first systematic density functional studies on periodic and large cluster models of red ultramarines, considering several S4/S4˙- isomers embedded in aluminosilicate cages. For both neutral and charged tetrasulfides the most stable confined isomer is the planar C2v one. The only plausible candidate for the red chromophore among the tetrasulfur species is the planar C2v isomer of the neutral S4 molecule, which, apart from being thermodynamically preferable, strongly absorbs green light and its vibrational modes match very well with the available Raman data. The C2v-S4˙- radical, if present at all in red ultramarines, could be identified by strong absorption in the near infrared region and possibly by the slightly larger isotropic value of the g tensor than that of the S3˙- radical.

Structure and anticancer activity of Cu(II) complexes with (bromophenyl)thiourea moiety attached to the polycyclic imide.

A series of nine copper complexes were synthesized by reacting 1,3-disubstituted thioureas with copper(II) chloride. The new compounds were characterized by elemental analysis, infrared, ultraviolet-visible and X-ray absorption spectroscopies as well as molecular modelling. The molecular structure of complexes in the solid state consists of two thiourea ligands chelated to the Cu(II) ion through the S and deprotonated N atoms (CuN2S2). The coordination polyhedron of metal cation in powdered samples exhibits two different geometries. Pseudo-tetrahedral structure is observed for noncentrosymmetric complexes with cis-N2S2 arrangement around Cu(II). A distorted square planar geometry is characteristic for centrosymmetric compounds with trans arrangements of chelating atoms around the central ion. All complexes after dissolving in dimethyl sulfoxide adopt a centrosymmetric coordination, while after diluting this solution with water, the reorganization of atoms around the metal cation is observed, leading to the formation of a tetrahedral compounds. Initial ligands and Cu(II) complexes were evaluated for their cytotoxicity. Two complexes with 4- and 3-bromophenyl attached to the (1,7,8,9,10-pentamethyl-3,5-dioxo-4-azatricyclo[5.2.1.02,6]dec-8-en-4-yl)thiourea moiety (Cu1, Cu3) are cytotoxic against SW480 and PC3 cells (IC50 4-19 µm), and non-cytotoxic against HaCaT cells (IC50 ≥ 84 µm), being more selective than doxorubicin and cisplatin used as references. The compounds induced apoptosis in cancer cells, however, Cu3 was estimated to be highly active inducer of late apoptosis in SW480 and PC3 cells at lower toxicity against normal cells. The likely mechanism of action of complexes is correlated with decreasing release of IL-6 in cancer cell lines.

Local atomic order of the amorphous TaO x thin films in relation to their chemical resistivity.

The experimental and theoretical studies of the local atomic order and chemical binding in tantalum oxide amorphous films are presented. The experimental studies were performed on thin films deposited at the temperature of 100 °C by atomic layer deposition on silicon (100) and glass substrates. Thin films of amorphous tantalum oxide are known to exhibit an extremely large extent of oxygen nonstoichiometry. Performed X-ray absorption and photoelectron studies indicated the oxygen over-stoichiometric composition in the considered films. Surplus oxygen atoms have 1s electron level with binding energy about 1 eV higher than these in reference Ta2O5 oxide. The density functional theory was applied to find the possible location of additional oxygen atoms. Performed calculation indicated that additional atoms may form the dumbbell defects, which accumulate the dangling oxygen bonds in orthorhombic structure and lead to increase of oxygen 1s level binding energy. The presence of this kind of oxygen-oxygen bonding may be responsible for increase of amorphous film chemical resistivity which is very important in many applications.

Synthesis, structural and antimicrobial studies of type II topoisomerase-targeted copper(II) complexes of 1,3-disubstituted thiourea ligands.

A series of Cu(II) complexes of 3-(trifluoromethyl)phenylthiourea derivatives was synthesized. Their structural properties were investigated by spectroscopic techniques (infrared and electron paramagnetic resonance), as well as molecular modeling. All studied coordination compounds are mononuclear complexes containing two chelating ligands bonded to the metal cation via S and deprotonated N atoms. The new chelates were evaluated for their antimicrobial potency. The complex of 1-(3,4-dichlorophenyl)-3-[3-(trifluoromethyl)phenyl]thiourea (3) presented the highest activity against Gram-positive pathogens, even stronger than the activity of its non-complexed counterpart and the reference drug. The compound also prevented the biofilm formation of methicillin-resistant and standard strains of staphylococcal cocci. The title derivatives were found to be effective inhibitors of DNA gyrase and topoisomerase IV isolated from Staphylococcus aureus. The binding modes of the ligand L3 with DNA gyrase and topoisomerase IV were presented.

Synthesis, structural studies and biological activity of novel Cu(II) complexes with thiourea derivatives of 4-azatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione.

The new Cu(II) complexes of 1/2/3-(bromophenyl)-3-(1,7,8,9-tetramethyl-3,5-dioxo-4-azatricyclo[5.2.1.02,6]dec-8-en-4-yl)thiourea derivatives have been synthesized. The spectroscopic studies together with density functional theory calculations of Cu(II) complexes revealed that two parent ligands coordinate to the copper cation in bidentate fashion via thiocarbonyl S and deprotonated N atoms forming rarely observed four-membered chelate ring, with nearly planar [CuN2S2] moiety. In solid state, the mononuclear complex is formed for thiourea derivative with 3-bromophenyl, whereas for Cu(II) connection with 2- and 4-bromophenyl-thioureas the formation of dinuclear complexes is observed, the latter formed by the stacking of mononuclear complexes. The microbiological activity of novel compounds has been evaluated. The Cu(II) complex with 4-bromophenyl ring connected to the thiourea moiety showed significant inhibition against standard strains of S. aureus and S. epidermidis. The range of minimal inhibitory concentration values is 2-4µg/mL. That compound exhibited antibiofilm potency and effectively inhibited the formation of biofilm of methicillin-susceptive strain of S. epidermidis ATCC 12228. Moreover, the cytotoxicity against the MT-4 cells of all obtained complexes has been evaluated. The complexes turned out to be non-cytotoxic for exponentially growing MT-4.

How can [Mo(IV)(CN)6](2-), an apparently octahedral (d)(2) complex, be diamagnetic? Insights from quantum chemical calculations and magnetic susceptibility measurements.

Quantum chemical calculations are employed to elucidate the origin of a puzzling diamagnetism for a hexacyanomolybdate(IV) anion, [Mo(CN)6](2-), which was previously reported by Szklarzewicz et al. [Inorg. Chem., 2007, 46, 9531-9533]. The diamagnetism is surprising because for the octahedral (d)(2) complex one would rather expect a (paramagnetic) triplet ground state, clearly favored over a (diamagnetic) singlet state by an exchange interaction between two d electrons in the t2g orbitals. Nevertheless, the present calculations reveal that the minimum energy structure of isolated [Mo(CN)6](2-) is not an octahedron, but a trigonal prism; the latter geometry allows maximization of a σ-donation from the cyanides to the electron-deficient Mo(iv) center. Unlike for the octahedron, for the trigonal prism structure the singlet and triplet spin states are close in energy to within a few kcal mol(-1). Although the actual relative energy of the two spin states turns out to be method-dependent, the complete active space calculations (CASPT2; with the appropriate choice of the IPEA shift parameter) can reproduce the singlet ground state, in agreement with the experimentally observed diamagnetism. Moreover, magnetic measurements reveal a slight increase of the magnetic susceptibility with the increase of temperature from 100 to 300 K, suggesting an admixture of a thermally induced paramagnetism (possibly due to Boltzmann population of the low-energy triplet state) on top of the dominant diamagnetism. Our prediction that the geometry of [Mo(CN)6](2-) should significantly deviate from the ideal octahedron, not only in the gas phase, but also in a periodic DFT model of the crystalline phase, as well as the experimentally confirmed diamagnetic properties, does not agree with the previously reported ideal octahedral structure. We suggest that this crystal structure might have been determined incorrectly (e.g., due to overlooked merohedral twinning or superstructure properties) and it should be re-investigated.

Synthesis, structural studies and biological activity of new Cu(II) complexes with acetyl derivatives of 7-hydroxy-4-methylcoumarin.

The new Cu(II) complexes with 6-acetyl-7-hydroxy-4-methylcoumarin (HL1) and 8-acetyl-7-hydroxy-4-methylcoumarin (HL2) have been obtained by the electrochemical method. The density functional theory calculations and X-ray absorption spectroscopy techniques have been used to geometrically describe a series of new compounds. The studies have been focused on the coordination mode of the hydroxy ligands to the metallic centre. The complexes, Cu(HL1)2 and Cu(HL2)2⋅0.5H2O, have flat square geometry with oxygen atoms in the first coordination sphere. Two bidentate anionic coumarins are bonded to the metal cation via the acetyl and deprotonated hydroxyl O atoms. Biological activity, including microbiological and cytotoxic, has been evaluated and found to be enhanced in comparison with the parent ligands. Moreover, the Cu(II) complex with 8-acetyl-7-hydroxy-4-methylcoumarin shows similar antifungal activity as commercially used fluconazole.

Electronic view on ethene adsorption in Cu(I) exchanged zeolites.

Ethene adsorption on isolated Cu(i) sites in two types of zeolites (faujasite and MFI) is investigated by means of the embedded cluster method. Structures, energetic stabilities and C[double bond, length as m-dash]C stretching vibrations in adsorption complexes are discussed. Furthermore, for interpretative purposes, the interaction energies are decomposed, using novel approaches based on so called natural orbitals for chemical valence. Ethene is always symmetrically bound to Cu(i) ion by both C atoms. In some cases two local minima of similar stability on the potential energy surface, differing by Cu(i) site relaxation can be found that may be simultaneously populated in equilibrium. Binding energies usually decrease with the degree of reconstruction of Cu(i) site after adsorption, however, in particular cases, a more distorted structure can be slightly more stable if favorable pi* back donation overwhelms the distortion effects. Calculated values of binding energies for Cu(i)-Y zeolite (about 80 kJ mol(-1)) agree well with microcalorimetric data. We predict that ethene binding in MFI is over two times stronger (to the best of our knowledge no experimental data are available). The C[double bond, length as m-dash]C stretching frequency is not site specific, but depends only on the type of copper connectivity to oxygen nodes. The appearance of two C[double bond, length as m-dash]C bands in IR spectra of Cu(i)-faujasite can be explained as the effect of coexistence of two types of adsorption complexes, with Cu(i) coordinated to one or two framework tetrahedrons, respectively. In Cu(i)-MFI, only one type of adsorption complex with Cu(i) ion coordinated to a single tetrahedron exists, as only a single C[double bond, length as m-dash]C band is present in IR spectra.

Theoretical studies of Cu(I) sites in faujasite and their interaction with carbon monoxide.

Sitting, coordination, and properties of Cu(I) cations in zeolite faujasite are investigated using a combined quantum mechanics-interatomic potential function method. The coordination of Cu(I) ions depends on their location within the zeolite lattice. Cu(I) located inside the hexagonal prisms (site I') and in the plane of six-membered aluminosilicate rings on the walls of sodalite units (site II) is threefold coordinated, whereas Cu(I) located in the supercages (site III) is twofold coordinated. In agreement with available experimental data Cu(I) appears to be more strongly bound in sites I' and II than in site III. The binding energy of site II Cu(I) ions increases with the number of Al atoms, but only closest Al atoms have a substantial influence. The CO molecule binds more strongly onto sites with weaker bound cations and lower coordination. We assign the two CO stretching IR bands observed for Cu(I)-Y zeolites to sites II with one Al (2157-2161 cm(-1)) and two Al atoms (2140-2148 cm(-1)) in the six-membered aluminosilicate ring. For Cu(I)-X we tentatively assign the high frequency band to site III (2156-2168 cm(-1)) and the low-frequency band to site II with three Al atoms in the six-membered ring (2136-2138 cm(-1)).