Synthesis, characterization and antibacterial studies of a copper(II) levofloxacin ternary complex

• Published in: Journal of inorganic biochemistry Vol. 110; pp. 64 - 71
• Main Authors: Sousa, Isabel, Claro, Vasco, Pereira, João Lino, Amaral, Ana Luísa, Cunha-Silva, Luís, de Castro, Baltazar, Feio, Maria J., Pereira, Eulália, Gameiro, Paula
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-05-2012
• Subjects: Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Bacterial resistance; Copper - chemistry; Copper - pharmacology; Escherichia coli; Escherichia coli - growth & development; Escherichia coli Infections - drug therapy; Fluoroquinolones; Levofloxacin; Metalloantibiotics; Ofloxacin - chemical synthesis; Ofloxacin - chemistry; Ofloxacin - pharmacology; Solution equilibria; Fluoroquinolones; Levofloxacin; Bacterial resistance; Metalloantibiotics; Solution equilibria
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2012.02.003

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)(H2O)](NO3).2H2O, 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.
Aqueous solution behaviour of levofloxacin copper(II)–complexes with and without 1, 10-phenanthroline was studied. Under physiological conditions only the ternary copper(II):lvx:phen complex was stable hence it was synthesised and characterized. Microbiological studies suggested a distinct entry route for the metallocomplex and free fluoroquinolone, a possible way to counteract microbial resistance. [Display omitted]
► Solution behavior of Cu(II):lvx complexes with and without 1, 10-phenanthroline was studied. ► Under physiological conditions (μM range, pH 7.4) only Cu(II):lvx:phen complexes are stable. ► [Cu(lvx)(phen)(H2O)](NO3).2H2O was synthesized and characterized by UV–Vis and IR spectroscopy. ► X-Ray crystallography showed distorted square-pyramidal geometry for the complex. ► MIC determinations indicated that the Cu-complex is as efficient as the free lvx.