Solution studies on binary and ternary complexes of copper(II) with some fluoroquinolones and 1,10-phenanthroline: Antimicrobial activity of ternary metalloantibiotics.
ABSTRACT Interaction of norfloxacin and ofloxacin with copper(II) and copper(II)/phenanthroline has been studied in aqueous solution and the stability constants of the binary complexes Cu(II)/fluoroquinolone and of the ternary complexes Cu(II)/phenanthroline/fluoroquinolone have been determined by potentiometry and UV-vis spectrophotometry. The stability constants for the binary and ternary complexes of norfloxacin were always higher than those found for ofloxacin and comparing the values obtained for the binary and ternary species (DeltalogK) it is possible to conclude that the ternary complexes are more stable than the binary ones, suggesting that an interaction occurs between the ligands in the ternary complexes. From the distribution diagrams it is possible to state that at physiological pH 7.4, the copper ternary complexes, are the main species in solution not only at the concentration used to determined the stability constants but also at the minimum inhibitory concentration. The antibacterial activity of these complexes, in different bacterial strains, was determined, at physiological pH, and the results obtain show that these ternary complexes may be good candidates as metalloantibiotics.
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ABSTRACT: The speciation of Cu2+, Ni2+ and Zn2+ ions in the presence of the fluoroquinolones (FQs) moxifloxacin, ofloxacin, levofloxacin and ciprofloxacin, in human blood plasma was studied under physiological conditions by computer simulation. The speciation was calculated using an updated model of human blood plasma including over 6,000 species with the aid of the program Hyss2009. The identity and stability of metal-FQ complexes were determined by potentiometric (310 K, 0.15 mol/L NaCl), spectrophotometric, spectrofluorimetric, ESI-MS and 1H-NMR measurements. In the case of Cu2+ ion the concentration of main low molecular weight (LMW) plasma complex (Cu(Cis)His) is very slightly influenced by all examined FQs. FQs show much higher influence on main plasma Ni2+ and Zn2+ complexes: (Ni(His)2 and Zn(Cys)Cit, respectively. Levofloxacin exhibits the highest influence on the fraction of the main nickel complex, Ni(His)2, even at a concentration level of 3 × 10-5 mol/L. The same effect is seen on the main zinc complex, Zn(Cys)Cit. Calculated plasma mobilizing indexes indicate that ciprofloxacin possesses the highest mobilizing power from plasma proteins, toward copper ion, while levofloxacin is the most influential on nickel and zinc ions. The results obtained indicate that the drugs studied are safe in relation to mobilization of essential metal ions under physiological conditions. The observed effects were explained in terms of competitive equilibrium reactions between the FQs and the main LMW complexes of the metal ions.Molecules (Basel, Switzerland). 01/2014; 19(8):12194-223.
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ABSTRACT: By means of microcalorimetry, the effect of four copper(II) complexes on Tetrahymena growth was investigated. The extent and duration of the inhibitory effect on the metabolism, judged by the rate constant, k, and the half inhibition concentration, IC(50), varied with the different complexes. The results showed that the half inhibition concentrations IC(50) of CuCl(2), (C(9)H(6)NO)(2)Cu and [Cu(phen)(2)]Cl(2)[Symbol: see text]6H(2)O were 9.9 x 10(-4), 2.0 x 10(-4), and 2.6 x 10(-4) mol/L, respectively. The sequence of antibiotic activity of these three complexes was: (C(9)H(6)NO)(2)Cu > [Cu(phen)(2)]Cl(2)[Symbol: see text]6H(2)O > CuCl(2). The growth rate constants of [Cu(phen)(3)]Cl(2)[Symbol: see text]6H(2)O did not change obviously with the increase of concentrations, but [Cu(phen)(3)]Cl(2)[Symbol: see text]6H(2)O also can prolong the time of Tetrahymena growth.Biological trace element research 11/2009; 137(1):117-24. · 1.92 Impact Factor
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ABSTRACT: Solution behavior of levofloxacin (lvx) complexes with copper(II) in the presence and absence of phen was studied in aqueous solution, by potentiometry. The results obtained show that under physiological conditions (micromolar concentration range and pH 7.4) only copper(II):lvx:phen ternary complexes are stable. Hence, a novel copper(II) ternary complex of fluoroquinolone levofloxacin with nitrogen donor heterocyclic ligand phen was synthesized and characterized by means of UV-Visible and IR spectroscopy, elemental analysis and X-Ray crystallography. In the synthesized complex (1), [Cu(lvx)(phen)(H(2)O)](NO(3)).2H(2)O, levofloxacin acts as a bidentate ligand coordinating to the metal, in its anionic form, through the carbonyl and carboxyl oxygens and phen coordinates through two N-atoms forming the equatorial plane of a distorted square-pyramidal geometry. The fifth ligand of the penta-coordinated Cu(II) centre is occupied axially by an oxygen atom from a water molecule. Minimum inhibitory concentration (MIC) determinations of the complex and comparison with free levofloxacin in various E. coli strains indicated that the Cu-complex is as efficient an antimicrobial as the free antibiotic (both in the case of the dissolved synthesized complex and the complex formed following stoichiometric mixture of the individual components in solution). Moreover, results strongly suggest that the cell intake route of both species is different supporting, therefore, the complex's suitability as a candidate for further biological testing in fluoroquinolone-resistant microorganisms.Journal of inorganic biochemistry 02/2012; 110:64-71. · 3.25 Impact Factor