Peter Herich

Copper(II) complexes with new fluoroquinolones: Synthesis, structure, spectroscopic and theoretical study, DNA damage, cytotoxicity and antiviral activity.

Copper(II) complexes with fluoroquinolones in the presence of the nitrogen donor heterocyclic ligands 1,10-phenanthroline have been considered in detail. The phenanthroline moiety was introduced into the ligand environment with the aim to determine whether the nuclease activity is feasible. All suitable X-ray structures of the complexes under study reveal a distorted square pyramidal coordination geometry for Cu(II) atom. The conformational and spectroscopic (FT-IR and UV-visible) behavior has been analyzed and has been interpreted with respect to B3LYP/6-311G* calculations including molecular dynamics. The ability of the complexes to cleave DNA was studied by agarose gel electrophoresis with plasmid DNA pBSK+. The results have confirmed that the complexes under study behave as the chemical nucleases. Nuclease like activity in the absence of hydrogen peroxide allows us to deduce an interaction of the complexes with the DNA resulting in the conversion of supercoiled circular DNA to the nicked form. The DNA cleavage activity enhanced by the presence of hydrogen peroxide demonstrates the participation of reactive oxygen species, such as superoxide radical anions and hydroxyl radicals which presence was confirmed independently using the standard radical scavenging agents. It has been suggested that the radical formation through the Fenton/Haber-Weiss reaction is mediated by the redox cycling mechanisms with the participation of cupric/cuprous ions. Cytotoxic activity was evaluated as the 50% cytotoxic concentration (CC50). The potential effects of tested compounds on replication of murine gammaherpesvirus 68 (MHV-68) under in vitro conditions were also evaluated. However, no antiviral activity against MHV-68 was observed.

Preparation and Spectroscopic, Magnetic, and Electrochemical Studies of Mono-/Biradical TEMPO Derivatives

A comparison set of mono-/biradical TEMPO derivatives was prepared, novel compounds were fully characterized, and their physicochemical properties were determined. Cyclic voltammetry revealed reversible redox behavior for all studied nitroxides. Moreover, the electron-withdrawing substituents increased the oxidation potential of the respective nitroxides in comparison to electron-donating groups. While EPR spectra of monoradicals in dichloromethane at 295 K reveal the expected three-line signal, spectra of biradicals show more complex features. DFT and MP2 calculations indicate that the EPR splitting pattern of dinitroxide 7 could be explained by its interactions with solvent molecules. In the solid state, mononitroxides 4 and 5 behave as a Heisenberg antiferromagnetic chain, whereas dinitroxides 6-8 are almost isolated paramagnetic diradicals coupled in an antiferromagnetic manner.

Antimicrobial Activity and Urease Inhibition of Schiff Bases Derived from Isoniazid and Fluorinated Benzaldehydes and of Their Copper(II) Complexes

In order to evaluate the influence of substitution on biological properties of Schiff bases and their metal complexes, a series of differently substituted fluorine-containing Schiff bases starting from the drug isoniazid (isonicotinylhydrazide) were prepared and their structures were established by single-crystal X-ray diffraction. Also, four copper(II) complexes of these Schiff bases were synthesized. The prepared compounds were evaluated for their antimicrobial activity and urease inhibition. Two of the Schiff bases exerted activity against C. albicans. All copper(II) complexes showed excellent inhibitory properties against jack bean urease, considerably better than that of the standard inhibitor acetohydroxamic acid.

Conformational, spectroscopic, and molecular dynamics DFT study of precursors for new potential antibacterial fluoroquinolone drugs.

Biological activity, functionality, and synthesis of (fluoro)quinolones is closely related to their precursors (for instance 3-fluoroanilinoethylene derivatives) (i.e., their functional groups, conformational behavior, and/or electronic structure). Herein, the theoretical study of 3-fluoroanilinoethylene derivatives is presented. Impact of substituents (acetyl, methyl ester, and ethyl ester) on the conformational analysis and the spectral behavior is investigated. The B3LYP/6-311++G** computational protocol is utilized. It is found that the intramolecular hydrogen bond N-H···O is responsible for the energetic preference of anti (a) conformer (anti position of 3-fluoroanilino group with respect to the C═C double bond). The Boltzmann ratios of the conformers are related to the differences of the particular dipole moments and/or their dependence on the solvent polarity. The studied acetyl, ethyl ester, and methyl ester substituted fluoroquinolone precursors prefer in the solvent either EZa, ZZa, or both conformers equally, respectively. In order to understand the degree of freedom of rotation of the trans ethyl ester group, B3LYP/6-311G** molecular dynamic simulations were carried out. Vibrational frequencies, electron transitions, as well as NMR spectra are analyzed with respect to conformational analysis, including the effect of the substituent. X-ray structures of the precursors are presented and compared with the results of the conformational analysis.

N-(2-Chlorophenyl)-4-methylbenzamide

The asymmetric unit of the title compound, C14H12ClNO, contains two independent molecules in which the dihedral angles between the two aromatic rings are 51.76 (6) and 51.48 (7)°. The crystal structure is stabilized by intermolecular N—H⋯O hydrogen bonds, which link the molecules into chains running along the c axis.

N-(2,3-Dimethyl-phen-yl)-4-methylbenzamide.

In the molecule of the title compound, C16H17NO, the two aromatic rings are almost perpendicular to each other [dihedral angle 85.90 (5)°]. The crystal structure is stabilized by intermolecular N—H⋯O hydrogen bonds which link the molecules, forming C(4) chains running along the c axis.

Charge density study of bis(clonixato)bis(ethanol) bis(imidazole)copper(II) complex

Abstract An experimental electronic structure of bis(clonixato)bis(ethanol) bis(imidazole)copper(II) complex, [Cu(cln)2(im)2(EtOH)2] (cln=clonixato, im=imidazole) (1) has been obtained from single-crystal X-ray diffraction data collected at 100 K using an Incoatec IμS Ag microfocus source. Metal-ligand (ML) bonds and hydrogen bonds (HBs) have been analysed using topological analysis of the experimental electron density with the atoms in molecules (AIM) approach. The central copper atom is octahedrally coordinated by two oxygen atoms from two clonixato anions and two nitrogen atoms from two imidazole ligands in equatorial plane. In axial positions are two oxygen atoms from two ethanol molecules. AIM analysis establishes that the central copper atom is bonded more strongly to the clonixato anion that to the imidazole or ethanol molecules. AIM analysis of two intramolecular and one intermolecular hydrogen bonds permits to estimate their strength. We show that the hydrogen bonds are strong enough to protect the molecule from decomposition in solvent media and to disable the more reactive imidazole-Cu-clonixato complex from interacting with e.g. a macromolecule. The electrostatic potential of the complex shows a highly positive value on the central atom, so the complex is highly reactive in an interaction with negative ligands.

Charge-density study of bis(clonixato)bis(ethanol)bis(imidazole)copper(II) complex

Clonixin or chlonixic acid is a novel member of fenamate family drugs that show non-steroidal anti-inflammatory, antipyretic, analgesic and platelet-inhibitory actions when administered intravenously or intramuscularly. It is used primarily in the treatment of chronic arthritic conditions and certain soft tissue disorders associated with pain and inflammation. The complex was prepared by standard procedure. The solution of Cu(CO2CH3)2 · H2O (1.0 mmol) in EtOH (50 cm3) was added to imidazole (2.0 mmol) resulting in the blue-coloured solution. Clonixin (2.0 mmol) was added to the mixture afterwards, changing the colour of the solution to green. The final solution was stirred at room temperature for 24 hours. The crystals, suitable for X-ray diffraction, were formed by slow evaporation of the solution. Experiments were performed by means of Stoe STADIVARI diffractometer with a Dectris Pilatus 300K detector and with an Incoatec IμS Ag microfocus source (Ag-Ka, ? = 0.56083 Å) at 100 K using a nitrogen gas open-flow cooler Cobra Oxford Cryosystems. Data reduction was processed using X-Area (Stoe, 2016), where the value of average redundancy was 13.1 and Rint of 4.71%. Direction cosines were applied for anisotropic secondary extinction correction. The results of multipole refinement and the topological analysis were performed via XD2006.

Charge Density Study of two Ni(III) and Ni(II) complexes

Experimental charge density of two nickel complexes with oxidation state +3 and +2 of composition (CH3(Ph)3P)+[Ni(bdtCl2)2]-, C31H22Cl4S4P1Ni1 [I] and (CH3(Ph)3P)+[Ni(bdtCl2)2]dimethylsulfoxide solvate, C25H20Cl2S2P1Ni0.5; C2H6SO [II], (bdtCl2 = 3,6dichloro-1,2-benzenedithiole ), has been studied. The coordination of Ni central atom by bdtCl2 as a non-innocent ligand gives rise to interesting electronic properties. Compounds I and II crystalize in a monoclinic space groups P 21/c and II in P 21/n, respectively. Their coordination is square-planar with the chromophore [NiS4]. Obvious differences for interatomic distances in metallocycles were found. For I in Ni1-S1-C1-C6-S2-Ni1 there are bond lengths of 2.1534(1), 1.7375(5), 1.4144(8), 1.7327(5), 2.1432(1) Å; and in Ni2-S3C7-C12-S4-Ni2 there are bond lengths of 2.1453(1), 1.7390(5), 1.4133(7), 1.7387(5), 2.1523(1) Å. For II in Ni1-S1-C1-C6-S2-Ni1 there are bond lengths of 2.1776(2), 1.7437(8), 1.4169(11), 1.7431(8), 2.1663(2) Å. Significantly longer distances for II are in good agreement with the lower oxidation state of central atom. Very accurate data for I an II complexes were obtained with Oxford Diffraction CCD GEMINI R diffractometer at 100K. Multipolar refinement and consecutive topological analysis was performed using XD package. Differences in distribution of electron density in both complexes will be disscussed and compared with quantum-chemical calculations at BP86/VTZP level of theory [1]. This work has been supported by Slovak Grant Agency APVV and VEGA (APVV-0202-10 and 1/0679/11).

Comparative study of the electron distribution in 3dorbitals

C446 measurements on a non-deuterated hydroquinone clathrate sample have shown high quality positional and thermal parameters. The obtained atomic displacement parameters are investigated and compared with data from the same compound at the High Flux Isotope Reactor and an X-ray source. The obtained positional and thermal parameters from the neutron experiment are used in combination with high quality X-ray data for a state-of-the-art charge density refinement. The investigation of these hydroquinone host-guest systems revealed significant charge redistribution of the host structure with the so-called weakly interacting guest solvent molecule.