resumo
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).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. (C) 2012 Elsevier Inc. All rights reserved.
palavras-chave
INTRAMOLECULAR STACKING INTERACTIONS; OUTER-MEMBRANE PERMEABILITY; ESCHERICHIA-COLI; METAL-IONS; AQUEOUS-SOLUTION; 1,10-PHENANTHROLINE; CIPROFLOXACIN; QUINOLONES; RESISTANCE; CRYSTAL
categoria
Biochemistry & Molecular Biology; Chemistry
autores
Sousa, I; Claro, V; Pereira, JL; Amaral, AL; Cunha-Silva, L; de Castro, B; Feio, MJ; Pereira, E; Gameiro, P
nossos autores
Isabel Cristina de Sá Correia de Sousa
Investigadoragradecimentos
The authors are grateful to Fundacao para a Ciencia e a Tecnologia (FCT, Portugal) for funding through EU-MRTN-CT-2005-019335 (Translocation) and PTDC/SAU-FAR/111414/2009 projects and also for specific funding toward the purchase of the single-crystal X-ray diffractometer. IS thanks FCT for the PhD scholarship SFRH/BD/47486/2008.