Iztok Turel

The interactions of metal ions with quinolone antibacterial agents

Abstract The quinolones are a group of synthetic antibacterial agents structurally related to nalidixic acid. The absorption of quinolone drugs is lowered when they are consumed simultaneously with magnesium or aluminium antacids. Many other ions found in pharmaceuticals cause similar effect. The proposed reason for such behaviour is the chelate bonding of the quinolone to the metal. In the review article, selected crystal structures of quinolone–metal compounds are presented and discussed. The results of different physico-chemical methods (thermal analysis, potentiometric measurements, IR, UV–vis, NMR spectroscopy) as well as some results of bioactivity tests are also included.

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.

Interaction of Zn(II) with quinolone drugs: Structure and biological evaluation

Zinc complexes with the third-generation quinolone antibacterial drugs levofloxacin and sparfloxacin have been synthesized and characterized. The deprotonated quinolones act as bidentate ligands coordinated to zinc ion through the pyridone and a carboxylato oxygen atom. The crystal structures of [bis(aqua)bis(levofloxacinato)zinc(II)], 1, and [bis(sparfloxacinato)(1,10-phenanthroline)zinc(II)], 3, have been determined by X-ray crystallography. The biological activity of the complexes has been evaluated by examining their ability to bind to calf-thymus DNA (CT DNA) by UV spectroscopy and viscosity measurements. UV studies of the interaction of the complexes with DNA have revealed that they can bind to CT DNA probably by the intercalative binding mode which has also been verified by DNA solution viscosity measurements. The DNA binding constants have been also calculated. A competitive study with ethidium bromide (EB) showed that the complexes exhibit the ability to displace the DNA-bound EB indicating that they bind to DNA in strong competition with EB for the intercalative binding site. The interaction of the complexes with human and bovine serum albumin proteins has been studied by fluorescence spectroscopy showing that the complexes exhibit good binding propensity to these proteins having relatively high binding constant values. The biological properties of the complexes have been evaluated in comparison to the previously reported Zn(II) complexes with the first- and second-generation quinolones oxolinic acid and enrofloxacin.

Crystal structure and characterization of the bismuth(III) compound with quinolone family member (ciprofloxacin). Antibacterial study

Two bismuth(III) compounds of ciprofloxacin (cf) were synthesized. The crystal structure of one--(cfH2) (cfH) [BiCl6].2H2O (cfH2 = doubly protonated molecule of cf, cfH = protonated molecule of cf)--is presented and discussed. The compound crystallizes in the monoclinic space group P 21/c with a = 17.758(4), b = 7.600(10), c = 31.908(6) A, beta = 101.03(2)0, Z = 4. The charge of the isolated hexachlorobismuthate(III) anions is compensated with protonated of molecules (ionic interactions). One of the cf molecules is protonated at carbonyl oxygen O(1) and nitrogen N(24) of the piperazine residue, and the other at N(24) only. Two water molecules participate in the hydrogen bond network. Antimicrobial activity of this compound was tested against different microorganisms. The results of TG and FT-IR measurements are also included.

Interactions of oxovanadium(IV) and the quinolone family member--ciprofloxacin.

The interactions of quinolone ciprofloxacin (cfH) and oxovanadium(IV) were studied by various methods. Green crystals of a complex [V(IV)O(cf)(2)(H(2)O)] were isolated and the molecular connectivities established, although the crystal structure was not perfectly refined due to the instability of the crystals. Based on a plausible interpretation of the data sets, two cf anions bidentately coordinate to a vanadyl cation through carboxylate and carbonyl oxygen atoms; in addition, there is a water molecule in the coordination sphere. Solution techniques (cyclic voltammetry, electronic and electron paramagnetic resonance spectroscopy, potentiometric measurements) confirmed the presence of various species in the solution, the composition of which strongly depends on the conditions in the system. The antibacterial activity of the complex against various microorganisms was tested and it was established that its activity is similar to that of free ciprofloxacin.

Synthesis, crystal structure, and characterization of three novel compounds of the quinolone family member (norfloxacin)

The synthesis of three novel compounds of norfloxacin (nf) is reported. Their crystal structures are presented and discussed. The first compound, (nfH2)Cl2. H2O (nfH2 = doubly protonated molecule of nf), crystallizes in the monoclinic space group P 21/c with a = 8.438(2), b = 14.281(3), c = 15.012(3) A, β = 93.87(3)°, Z = 4. The carbonyl oxygen O(1) is protonated, and this proton is bonded via intramolecular hydrogen bond to the oxygen O(11) of the carboxylic group (O(11) … O(1) = 2.605(4) A). The terminal nitrogen atom N(24) the piperazine group is also protonated. The positive charge of the nf molecule is neutralized by two chloride anions. The crystal structure is stabilized by numerous hydrogen bonds of the type OH … O, OH … Cl, NH … Cl. The compounds (nfH2)(nfH)[CuCl4]Cl.H2O and (nfH2)(nfH)[ZnCl4]Cl.H2O (nfH = monoprotonated molecule of nf) are isostructural and both crystallize in P 21/c. Both structures are ionic consisting of a tetrachlorometalate (II) anion and two nonequivalent, protonated nf molecules. It seems that in strongly acidic media, the proton is bonded between O(1) and carboxylic oxygen, which prevents the coordination of the metal ions to this position. The results of other measurements (TG, FT-IR, Raman spectroscopy) are also included.

Crystal structure of ciprofloxacin hexahydrate and its characterization

Ciprofloxacin hexahydrate has been prepared and its crystal structure has been determined by X-ray crystallography. The molecule is in the zwitterionic form in solid state, the carboxylic proton being present at terminal piperazine nitrogen atom (N(74)) which is in contrast to the previously reported structures of quinolones. Water molecules are involved in a very complicated hydrogen bonding network. Different other techniques (IR, Raman spectroscopy, thermal and elemental analysis) were used to characterize the title compound and to compare its properties with similar compounds.

Physicochemical Studies and Anticancer Potency of Ruthenium η6-p-Cymene Complexes Containing Antibacterial Quinolones

With the aim of exploring the anticancer properties of organometallic compounds with bioactive ligands, Ru(arene) compounds of the antibacterial quinolones nalidixic acid (2) and cinoxacin (3) were synthesized, and their physicochemical properties were compared to those of chlorido(η6-p-cymene)(ofloxacinato-κ2O,O)ruthenium(II) (1). All compounds undergo a rapid ligand exchange reaction from chlorido to aqua species. 2 and 3 are significantly more stable than 1 and undergo minor conversion to an unreactive [(cym)Ru(μ-OH)3Ru(cym)]+ species (cym = η6-p-cymene). In the presence of human serum albumin 1−3 form adducts with this transport protein within 20 min of incubation. With guanosine 5′-monophosphate (5′-GMP; as a simple model for reactions with DNA) very rapid reactions yielding adducts via its N7 atom were observed, illustrating that DNA is a possible target for this compound class. A moderate capacity of inhibiting tumor cell proliferation in vitro was observed for 1 in CH1 ovarian cancer cells, whereas 2 and 3 turned out to be inactive.

Synthesis, characterization, and crystal structure of a copper(II) complex with quinolone family member (ciprofloxacin): bis(1)-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-piperazin-1ylquinoline-3-carboxylate) copper(II) chloride hexahydrate

The synthesis of the coordination compound [Cu(CF)2]Cl2.6H2O is reported. Its crystal structure is presented and discussed. The title compound crystallizes in the triclinic space group P1 with a = 9.369(2), b = 9.573(2), c = 11.206(2) A, α = 87.37(2), β = 80.58(2), γ = 86.25(2)°, Z = 988.8 A3 Z = 1, and Dc = 1.520 gcm−3. A structure determination, using three-dimensional MoKα x-ray data, resulted in conventional R and Rw values of 0.0399 and 0.0988, respectively, for 3495 unique reflexions for which I > 2σ(I). Refinement was based on F2. The copper atom at the center of inversion is surrounded in a plane by four oxygens (two of the carboxylate groups, two of the carbonyl groups), the corresponding CuO distances are 1.928(2) and 1.931(2) A, respectively. The two chlorine atoms are axially coordinated to Cu at larger distances than 2.688(2) A. The Cl atoms appeared to be disordered over three positions. The nearly planar moieties of Cu(CF)2 are packed parallel in the unit cell interconnected via hydrogen bonds of the type NH⋯O, OH⋯Cl and OH⋯O. The results of other physical measurements (TG, FT-IR, and various analyses) are also included.

COMPLEXES OF COPPER(II) ACETATE WITH NICOTINAMIDE : PREPARATION, CHARACTERIZATION AND FUNGICIDAL ACTIVITY; CRYSTAL STRUCTURES OF CU2(O2CCH3)4(NIA) AND CU2(O2CCH3)4(NIA)2

Abstract Three new copper (II) acetate complexes with nicotinamide (nia) were synthesized analyzed and characterized by standard chemical and physical methods and tested for fungicidal activity The crystal and molecular structures of the compounds [Cu2 (O2CCH3)4 (nia)] (1B) and [Cu2 (O2CCH3)4 (nia)2] (2) were determined by X-ray diffraction Both consist of binuclear units of bridging tetracarboxylate type however they differ in the bonding mode of nicotinamide molecules They are bonded at the apical positions of the dimers and connect them in an infinite chain in 1B On the other hand the dimers remain isolated in the structure of the compound 2 It seems that compound 1B is the first example where a nicotinamide molecule acts as a bidentate bridging ligand The results of EPR spectra agree with the dimeric nature of the complexes Dissolved in water or DMSO the compounds completely stop mycelial growth at a concentration of 50×10−3 mol l−1 Less concentrated solutions (up to 10×10−3 mol l−1) show weaker fungicidal activity.