Synthesis, structure and biological activity of copper(II) complexes with oxolinic acid

The neutral mononuclear copper complexes with the quinolone antibacterial drug oxolinic acid in the presence or not of a nitrogen donor heterocyclic ligand 1,10-phenanthroline, 2,2'-bipyridine or 2,2'-dipyridylamine have been synthesized and characterized with infrared, UV-visible and electron paramagnetic resonance spectroscopies. The experimental data suggest that oxolinic acid acts as a deprotonated bidentate ligand and is coordinated to the metal ion through the pyridone and one carboxylate oxygen atoms. The crystal structure of (chloro)(1,10-phenanthroline)(oxolinato) copper(II), 2, has been determined with X-ray crystallography. For all complexes a distorted square pyramidal environment around Cu(II) is suggested. The EPR (electron paramagnetic resonance) behavior of 2 in aqueous solutions indicates mixture of dimeric and monomeric species. The investigation of the interaction of the complexes with calf-thymus DNA has been performed with diverse spectroscopic techniques and showed that the complexes are bound to calf-thymus DNA. The antimicrobial activity of the complexes has been tested on three different microorganisms. The complexes show a decreased biological activity in comparison to the free oxolinic acid.     

Delving into the complex picture of Ti(IV)-citrate speciation in aqueous media: Synthetic, structural, and electrochemical considerations in mononuclear Ti(IV) complexes containing variably deprotonated citrate ligands

The aqueous reaction of TiCl₄ with citric acid at pH ∼ 4 (KOH), led to the surprising isolation of a species assembly K₃[Ti(C₆H₆O₇)₂(C₆H₅O₇)] · K₄[Ti(C₆H₅O₇)₂(C₆H₆O₇)] · 10H₂O (1). The same system at pH ∼ 3 (neocuproine), led to the crystalline material (C₁₄H₁₃N₂)₂[Ti(C₆H₆O₇)₃] · 5H₂O (2), while at pH 5.0 (NaOH), afforded Na₃[Ti(C₆H₆O₇)₂(C₆H₅O₇)] · 9H₂O (3). Analytical, spectroscopic and structural characterization of 1, 2 and 3 revealed their distinct nature exemplified by mononuclear complexes bearing variably deprotonated citrates bound to Ti(IV). Solid-state ¹³C MAS NMR spectroscopy in concert with solution ¹³C and ¹H NMR on 3 provided ample evidence for the existence of bound citrates of distinct coordination mode to the metal ion. Cyclic voltammetry defined the electrochemical signature of complex 2, thereby projecting the physicochemical profile of the species formulated by the aforementioned properties. Comparison of cyclic voltammetric data on available discrete Ti(IV)-citrate species depicts the electrochemical profile and an E_1/2 value trend of the species in that binary system’s aqueous speciation, further substantiating the redox behavior of mononuclear Ti(IV)-citrate species in a pH-sensitive fashion. Collectively, the well-defined discrete species in 1-3 reflect and corroborate a synthetically challenging yet complex pH-specific picture of the aqueous Ti(IV) chemistry with the physiological citric acid, and shed light on the pH-dependent speciation in the binary Ti(IV)-citrate system.     

Synthesis, isolation, spectroscopic and structural characterization of a new pH complex structural variant from the aqueous vanadium(V)-peroxo-citrate ternary system

In a pH-specific fashion, V₂O₅, citric acid and H₂O₂ reacted at pH 5.5-6.0 and afforded a red crystalline product at 4 °C. Elemental analysis pointed to the molecular formulation . Complex 1 was further characterized by UV/Vis, FT-IR, NMR, cyclic voltammetry, and X-ray crystallography. The X-ray structure of 1 reveals two dinuclear vanadium-peroxo-citrate subunits, A and B, linked through a hydrogen bond. In both A and B, the citrate ligands have different protonation states, ultimately affording a pentagonal bipyramidal geometry around each V(V) ion. The peroxide ligands bind V(V) in a side-on fashion. pH-Dependent, non-thermal and thermal transformations of 1 unravel its connection with key participants in the vanadium-peroxo-citrate ternary system and project its association with other non-peroxo binary complexes of variable vanadium oxidation state, geometry, citrate binding mode and state of protonation. Overall, the surprising twist in the aqueous synthetic chemistry of the investigated ternary system: (a) projects a new pH structural variant (species A) as a component of the speciation; (b) provides an in-depth look at that speciation under specific pH conditions; and (c) offers significant insight into the aqueous structural speciation of vanadium with peroxide and citrate, and its potential relevance to biological processes.     

Synthesis,spectroscopic, and structural characterization of the first aqueous cobalt(II)-citrate complex: toward a potentially bioavailable form of cobalt in biologically relevant fluids

Citric acid represents a class of carboxylic acids present in biological fluids and playing key roles in biochemical processes in bacteria and humans. Its ability to promote diverse coordination chemistries in aqueous media, in the presence of metal ions known to act as trace elements in human metabolism, earmarks its involvement in a number of physiological functions. Cobalt is known to be a central element of metabolically important biomolecules, such as B12, and therefore its biospeciation in biological fluids constitutes a theme worthy of chemical and biological perusal. In an effort to unravel the aqueous chemistry of cobalt in the presence of a physiologically relevant ligand, citrate, the first aqueous, soluble, mononuclear complex has been synthesized and isolated from reaction mixtures containing Co(II) and citrate in a 1:2 molar ratio at pH approximately 8. The crystalline compound (NH4)4[Co(C6H5O7)2] (1) has been characterized spectroscopically (UV/vis, EPR) and crystallographically. Its X-ray structure consists of a distorted octahedral anion with two citrate ligands fulfilling the coordination requirements of the Co(II) ion. The magnetic susceptibility measurements of 1 in the range from 6 to 295 K are consistent with a high-spin complex containing Co(II) with a ground state S=3/2. Corroborating this result is the EPR spectrum of 1, which shows a signal consistent with the presence of a Co(II) system. The spectroscopic and structural properties of the complex signify its potential biological relevance and participation in speciation patterns arising under conditions consistent with those employed for its synthesis and isolation.     

High resolution ultrasound-guided microinjection for interventional studies of early embryonic and placental development in vivo in mice

Background  

In utero microinjection has proven valuable for exploring the developmental consequences of altering gene expression, and for studying cell lineage or migration during the latter half of embryonic mouse development (from embryonic day 9.5 of gestation (E9.5)). In the current study, we use ultrasound guidance to accurately target microinjections in the conceptus at E6.5–E7.5, which is prior to cardiovascular or placental dependence. This method may be useful for determining the developmental effects of targeted genetic or cellular interventions at critical stages of placentation, gastrulation, axis formation, and neural tube closure.     

Synthetic analogue approach to metallobleomycins: syntheses, structure and properties of mononuclear and tetranuclear gallium(III) complexes of a ligand that resembles the metal-binding site of bleomycin

As part of our interest into the bioinorganic chemistry of gallium, gallium(III) complexes of the peptide ligand N-(2-(4-imidazolyl)ethyl)pyridine-2-carboxamide (pypepH2) resembling a fragment of the metal-binding domain of bleomycins (BLMs), have been isolated. Reaction of pypepH2 with (Et4N)[GaCl4] and Ga(acac)3 [acac- is the acetylacetonate(-1) ion] affords the mononuclear complex [Ga(pypepH)2]Cl.2H2O (1) and the tetranuclear complex [Ga4(acac)4(pypep)4].4.4H2O (2), respectively. Both complexes were characterized by single-crystal X-ray crystallography, IR spectroscopy and thermal decomposition data. The pypepH- ion in 1 behaves as a N(pyridyl), N(deprotonated amide), N(pyridine-type imidazole) chelating ligand. The doubly deprotonated pypep2- ion in 2 behaves as a N(pyridyl), N(deprotonated amide), N(imidazolate), N'(imidazolate) mu2 ligand and binds to one Ga(III) atom at its pyridyl, amide and one of the imidazolate nitrogens, and to a second metal ion at the other imidazolate nitrogen; a chelating acac- ligand completes six coordination at each Ga(III) centre. The IR data are discussed in terms of the nature of bonding and known structures. The 1H NMR spectrum of 1 suggests that the cation of the complex maintains its integrity in dimethylsulfoxide (DMSO) solution. Complexes 1 and 2 are the first synthetic analogues of metallobleomycins with gallium(III).     

Neutral and cationic mononuclear copper(II) complexes with enrofloxacin: structure and biological activity

The mononuclear copper complexes with the quinolone antibacterial drug enrofloxacin (=Herx) in the presence or not of a nitrogen donor heterocyclic ligand 1,10-phenanthroline (=phen) and 2,2'-bipyridine (=bipy) have been prepared and characterized. Interaction of copper(II) with deprotonated enrofloxacin leads to the formation of the neutral complex Cu(erx)2(H2O), 1, while the presence of phen or bipy leads to the formation of a neutral or a cationic mononuclear complex, respectively. The crystal structures of (chloro)(1,10-phenanthroline)(enrofloxacinato)copper(II), 2, and (aqua)(2,2'-bipyridine)(enrofloxacinato)copper(II) chloride, 3, have been determined with X-ray crystallography. The complexes have been studied with X-band electron paramagnetic resonance in aqueous solutions at liquid helium temperature. The study of the interaction of the complexes with calf-thymus DNA has been performed with diverse spectroscopic techniques and has showed that all complexes are bound to DNA by the intercalative mode. The antimicrobial efficiency of the complexes has been tested on three different microorganisms and the available evidence supports that the best inhibition is provided by Cu(erx)2(H2O) (minimum inhibitory concentration=0.125 microg mL(-1)) against Escherichia coli and Pseudomonas aeruginosa.