Solution studies on binary and ternary complexes of copper(II) with some fluoroquinolones and 1,10-phenanthroline: Antimicrobial activity of ternary metalloantibiotics

Requimte, Departamento de Química, Faculdade de Ciências, 4169-007 Porto, Portugal.
International Journal of Pharmaceutics (Impact Factor: 3.79). 05/2007; 334(1-2):129-36. DOI: 10.1016/j.ijpharm.2006.10.035
Source: PubMed

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.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Microbial resistance to antibiotics is one of the biggest public health threats of the modern world. Antibiotic resistance is an area of much clinical relevance and therefore research that has the potential to identify agents that may circumvent it or treat resistant infections is paramount. Solution behavior of various fluoroquinolone (FQ) complexes with copper(II) in the presence and absence of 1,10-phenanthroline (phen) was studied in aqueous solution, by potentiometry and/or spectrophotometry, and are herein described. The results obtained showed that under physiological conditions (micromolar concentration range and pH 7.4) only copper(II):FQ:phen ternary complexes are stable. Hence, these complexes were synthesized and characterized by means of UV-visible and IR spectroscopy, elemental analysis and single-crystal X-Ray diffraction. In these complexes, the FQ acts as a bidentate ligand that coordinates the metal cation through the carbonyl and carboxyl oxygen atoms and phen coordinates through two N-atoms forming the equatorial plane of a distorted square-pyramidal geometry. The fifth position of the penta-coordinated Cu(II) centre is generally occupied axially by an oxygen atom from a water molecule or from a nitrate ion. Minimum inhibitory concentration (MIC) determinations of the complexes and comparison with free FQ in various E. coli strains indicate that the Cu-complexes are as efficient antimicrobials as the free antibiotic. Moreover, results strongly suggest that the cell intake route of both species is different supporting, therefore, the complexes’ suitability as candidates for further biological testing in FQ-resistant microorganisms.
    Journal of Inorganic Biochemistry 05/2014; In press. DOI:10.1016/j.jinorgbio.2014.05.007 · 3.27 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    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 08/2014; 19(8):12194-223. DOI:10.3390/molecules190812194 · 2.10 Impact Factor
  • Australian Journal of Chemistry 01/2012; 65(7):860-873. DOI:10.1071/CH12058 · 1.64 Impact Factor