Franc Perdih

Different types of copper complexes with the quinolone antimicrobial drugs ofloxacin and norfloxacin: structure, DNA- and albumin-binding.

Three novel copper(II) complexes with the second-generation quinolone antibacterial agents norfloxacin (nfH) and ofloxacin (ofloH) have been synthesized resulting in the complexes [Cu(nfH)(phen)Cl]Cl·5H(2)O (1·5H(2)O), [Cu(nfH)(2)]Cl(2)·6H(2)O (2·6H(2)O) and [Cu(II)(ofloH)(2)][(Cu(I)Cl(2))(2)] (3), respectively. The crystal structures of the complexes have been determined by X-ray crystallography revealing that the quinolones act as bidentate ligands coordinated to Cu(II) atom through the pyridone oxygen and a carboxylato oxygen. UV study of the interaction of the quinolones and the complexes with calf-thymus DNA (CT DNA) has shown that they can bind to CT DNA with [Cu(II)(ofloxacin)(2)][(Cu(I)Cl(2))(2)] exhibiting the highest binding constant to CT DNA. The cyclic voltammograms of the complexes in the presence of CT DNA solution have shown that the interaction of the complexes with CT DNA is mainly through electrostatic binding. DNA solution viscosity measurements have shown that the interaction of the compounds with CT DNA by classical intercalation may be ruled out. Competitive studies with ethidium bromide (EB) indicate that the complexes can partially displace the DNA-bound EB suggesting low to moderate competition with EB. Norfloxacin, ofloxacin and their copper complexes exhibit good binding propensity to human or bovine serum albumin protein having relatively high binding constant values.

Synthesis and Characterization of VIVO Complexes of Picolinate and Pyrazine Derivatives. Behavior in the Solid State and Aqueous Solution and Biotransformation in the Presence of Blood Plasma Proteins

Oxidovanadium(IV) complexes with 5-cyanopyridine-2-carboxylic acid (HpicCN), 3,5-difluoropyridine-2-carboxylic acid (HpicFF), 3-hydroxypyridine-2-carboxylic acid (H2hypic), and pyrazine-2-carboxylic acid (Hprz) have been synthesized and characterized in the solid state and aqueous solution through elemental analysis, IR and EPR spectroscopy, potentiometric titrations, and DFT simulations. The crystal structures of the complexes (OC-6-23)-[VO(picCN)2(H2O)]·2H2O (1·2H2O), (OC-6-24)-[VO(picCN)2(H2O)]·4H2O (2·4H2O), (OC-6-24)-Na[VO(Hhypic)3]·H2O (4), and two enantiomers of (OC-6-24)-[VO(prz)2(H2O)] (Λ-5 and Δ-5) have been determined also by X-ray crystallography. 1 presents the first crystallographic evidence for the formation of a OC-6-23 isomer for bis(picolinato) V(IV)O complexes, whereas 2, 4, and 5 possess the more common OC-6-24 arrangement. The strength order of the ligands is H2hypic ≫ HpicCN > Hprz > HpicFF, and this results in a different behavior at pH 7.40. In organic and aqueous solution the three isomers OC-6-23, OC-6-24, and OC-6-42 are formed, and this is confirmed by DFT simulations. In all the systems with apo-transferrin (VO)2(apo-hTf) is the main species in solution, with the hydrolytic V(IV)O species becoming more important with lowering the strength of the ligand. In the systems with albumin, (VO)(x)HSA (x = 5, 6) coexists with VOL2(HSA) and VOL(HSA)(H2O) when L = picCN, prz, with [VO(Hhypic)(hypic)](-), [VO(hypic)2](2-), and [(VO)4(μ-hypic)4(H2O)4] when H2hypic is studied, and with the hydrolytic V(IV)O species when HpicFF is examined. Finally, the consequence of the hydrolysis on the binding of V(IV)O(2+) to the blood proteins, the possible uptake of V species by the cells, and the possible relationship with the insulin-enhancing activity are discussed.

Structure, antimicrobial activity, albumin- and DNA-binding of manganese(II)–sparfloxacinato complexes

Manganese(II) complexes with the quinolone antimicrobial agent sparfloxacin (Hsf) in the absence or presence of the nitrogen-donor heterocyclic ligands 1,10-phenanthroline (phen), 2,2′-bipyridine (bipy), 2,2′-bipyridylamine (bipyam) or pyridine (py) were synthesized and characterized with diverse physicochemical and spectroscopic techniques. The crystal structure of complex [Mn(sf)2(phen)]·4MeOH was determined by X-ray crystallography. In the resultant complexes, the deprotonated sparfloxacinato ligands are bidentately bound to manganese(II) through the pyridone oxygen and a carboxylato oxygen. The antimicrobial activity of the complexes was tested against four different microorganisms (Escherichia coli, Xanthomonas campestris, Staphylococcus aureus and Bacillus subtilis) and was found to be similar to or higher than free Hsf. The binding of the complexes to calf-thymus DNA (CT DNA) was monitored by UV spectroscopy and DNA viscosity measurements, which indicated intercalation as the most possible mode, and the DNA-binding constants of the complexes were calculated. The ability of the complexes to displace ethidium bromide (EB) from the EB–DNA complex was also investigated. Fluorescence emission spectroscopy was used to evaluate the interaction of the complexes with human or bovine serum albumin proteins revealing their binding with relatively high binding constant values.

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.

Effect of ring size on the exo/endo selectivity of a thermal double cycloaddition of fused pyran-2-ones.

A study of an unusual effect of the size of the ring fused to 2H-pyran-2-ones on the exo/endo selectivity of a thermal double cycloaddition of N-substituted maleimides or maleic anhydride yielding bicyclo[2.2.2]octene derivatives is presented. With subtle variations of starting compounds and reaction conditions exclusively exo,exo or exo,endo products can be prepared.

Influence of noncovalent interactions on the structures of metal-organic hybrids based on a (VO2(2,6-pydc)) tecton with cations of imidazole, pyridine and its derivatives†

Seven different dioxido(pyridine-2,6-dicarboxylato)vanadate(V) compounds with pyridinium (Hpy+) (1·2H2O and 1), 2-hydroxypyridinium (H2pyon+) (2·H2O), 4-aminopyridinium (H4apy+) (3·H2O and 3), 4-(dimethylamino)pyridinium (Hdmap+) (4·H2O) and imidazolium (Himd+) (5) cations have been prepared via different pathways starting either from pyridine-2,6-dicarboxylic acid or its esters, and were structurally characterized by single-crystal X-ray diffraction. The vanadium metal center in dioxido(pyridine-2,6-dicarboxylato)vanadate(V) anion is pentacoordinated in all of the compounds: having two oxido oxygen atoms in a mutual cis position and a tridentate pyridine-2,6-dicarboxylic ligand. Study of hydrogen bonds and weak interactions in the compounds revealed the relationship between the type of cation and the hydrogen bonding network in the compounds. While in 1·2H2O, 2·H2O and 4·H2O a one-dimensional (band, pillar or chain) hydrogen bonding network via N/O–H⋯O bonds is preferred, anhydrous 3 and 3·H2O favor a two-dimensional hydrogen-bonded framework, and the Himd+ cation facilitates a three-dimensional hydrogen bonding in 5. The unique vanadium coordination environment with two easily accessible oxido oxygen atoms of the VO2+ unit is suitable for the construction of non-covalent metal–organic hybrids. In 2·H2O, 3·H2O, 4·H2O and 5 both oxido oxygen atoms of the VO2+ unit participate as acceptors, however, in 1·2H2O and 3 only one oxido oxygen atom is involved in classical hydrogen bonding. Besides N/O–H⋯O hydrogen bonding, also other weak non-covalent interactions, such as C–H⋯O, π⋯π and C–H⋯π interactions, play an important role in stabilizing the crystal lattices.

Different coordination modes and supramolecular aggregations in copper(II) pentane-2,4-dionato compounds with 2-pyridone and 3-hydroxypyridine

Copper(II) bis(pentane-2,4-dionato-κ2O,O′) compounds with 2-pyridone (1) and 3-hydroxypyridine (2) were prepared by the reaction of bis(pentane-2,4-dionato-κ2O,O′)copper(II) with selected ligands. The coordination of Cu(II) in both compounds is square pyramidal with the fifth coordination site occupied by the carbonyl oxygen atom of the 2-pyridone ligand in 1 and by the nitrogen atom of 3-hydroxypyridine in 2. The X-ray crystallographic studies revealed different crystal aggregation influenced by the ability of the 2-pyridone ligand to act as a hydrogen bond donor and acceptor, and 3-hydroxypyridine acting only as a hydrogen bond donor. Intermolecular N–H···O hydrogen bonding forms dimers in 1 and infinite chains in 2. Three-dimensional aggregation is achieved by π–π interactions and C–H···π (arene) hydrogen bonding.Graphical abstract

Vanadium and zinc complexes of 5-cyanopicolinate and pyrazine derivatives: synthesis, structural elucidation and in vitro insulino-mimetic activity study

Vanadium(V) compounds with 5-cyanopicolinato acid (HpicCN), pyrazine-2-carboxylic acid (Hprz) and 3-aminopyrazine-2-carboxylic acid (HprzNH2) and zinc compounds with HpicCN in the presence of 4-aminopyridine (4apy), pyridine (py) and 1,10-phenanthroline (phen) have been synthesized and characterized. The crystal structures of NH4[VO2(picCN)2] (3), NH4[VO2(prz)2] (4), NH4[VO2(przNH2)2]·H2O (5·H2O), [Zn(picCN)2(H2O)2] (6), [Zn(picCN)2(4apy)2]·C7H8 (7·C7H8), [Zn(picCN)2(4apy)] (8), [Zn(picCN)2(py)2] (9) and [Zn(picCN)2(phen)]·C7H8·2MeOH (10·C7H8·2MeOH) were determined by X-ray crystallography. The spatial arrangements of all the vanadium(V) complexes are similar, having carboxylate oxygen atoms in a mutual trans orientation. In the zinc bis(5-cyanopicolinato) complexes three different arrangements were found with trans (6) and a cis (7, 9 and 10) octahedral and square-pyramidal (8) geometries. The insulino-mimetic activity of selected VO(IV), VO2(V) and Zn(II) complexes was studied by in vitro inhibition of the free fatty acid (FFA) release from isolated rat adipocytes treated with epinephrine. All metal complexes showed insulino-mimetic activity and among them the VO(IV)–prz complex 2 was found to have higher insulino-mimetic activity than the positive control. The other vanadium compounds have activities similar to VOSO4. The Zn complexes also exhibited some insulino-mimetic activity. Introduction of the N-donor 4apy to the zinc picCN complex 8 significantly increased inhibition of FFA release compared to 6.

Structure and biological activities of metal complexes of flumequine

The reaction of CoCl2·6H2O with the quinolone antimicrobial agent flumequine (Hflmq) in the absence or presence of the α-diimines 2,2′-bipyridine (bipy), 1,10-phenanthroline (phen) or 2,2′-bipyridylamine (bipyam) resulted in the formation of four mononuclear complexes which were characterized with physicochemical and spectroscopic techniques. The crystal structures of [Co(flmq)2(bipy)]·2H2O, [Co(flmq)2(phen)]·1.6MeOH·0.4H2O and [Co(flmq)2(bipyam)]·H2O were determined by X-ray crystallography. The interaction of the complexes with calf-thymus DNA (CT DNA) was investigated by UV spectroscopy, viscosity measurements, cyclic voltammetry and competitive studies with ethidium bromide in order to evaluate the possible DNA-binding mode and to calculate the corresponding DNA-binding constants. The binding of the complexes to human or bovine serum albumin was studied by fluorescence emission spectroscopy and the corresponding binding constants were determined. The antimicrobial activity of the Co(II)–flumequine and the recently reported Cu(II)–flumequine complexes was tested against four different microorganisms (Escherichia coli, Xanthomonas campestris, Staphylococcus aureus and Bacillus subtilis) and was found to be similar to that of free Hflmq. The antiproliferative activity of previously reported complexes [Cu(flmq)(phen)Cl], [Zn(flmq)(phen)Cl] and [Ni(flmq)2(phen)] against human ovarian (A2780) and lung (A549) cancer cell lines is also reported in comparison to the cobalt analogue, [Co(flmq)(phen)Cl], 3, highlighting important differences among the various complexes which may be due to different uptake and modes of action.

Novel triazole-based ligands and their zinc(II) and nickel(II) complexes with a nitrogen donor environment as potential structural models for mononuclear active sites

Three new 1,2,3-triazole-based ligands with an N,N,N coordination core were prepared using a convergent synthetic protocol starting from racemic 2-amino-1-phenylethanol. They were tested as chelators for biorelevant ZnII or NiII ions. An N,N,N ligand with a terminal amino functionality coordinated the ZnII in a bidentate fashion, not including the triazole nitrogen. The ligand with two pendant 2-pyridyl groups acted as a tridentate ligand without an N2-triazole coordination to ZnII, while the ligand containing one 2-pyridyl group acted as an inverse-click chelator for NiII ions.