resumo
Solution behavior of lomefloxacin (lmx) complexes with copper(II) in the presence and absence of 1,10-phenanthroline (phen) was studied in aqueous solution, by potentiometry. The results obtained showed that under physiological conditions (micromolar concentration range and pH 7.4) only copper(II):lmx:phen ternary complexes are stable. Hence, a novel copper(II) ternary complex of lomefloxacin with the 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(lmx)(phen)(NO3)]center dot 5H(2)O, lmx acts as a bidentate ligand coordinating the metal cation, 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) center is occupied axially by an oxygen atom from the nitrate ion. Minimum inhibitory concentration (MIC) determinations of the complex and comparison with free lomefloxacin in various E. coli strains indicated that the Cu-complex is an antimicrobial which is as efficient as the free antibiotic but strongly suggest that the cell intake route of both species is different. Moreover, spectrophotometric stability studies suggest that the solution of the complex synthesized is considerably more photostable than the free fluoroquinolone supporting, therefore, the complex's suitability as a candidate for further biological testing in fluoroquinolone-resistant microorganisms with possible reduced side-effects. (C) 2013 Elsevier Inc. All rights reserved.
palavras-chave
INTRAMOLECULAR STACKING INTERACTIONS; RAY STRUCTURAL CHARACTERIZATION; OUTER-MEMBRANE PROTEINS; ESCHERICHIA-COLI K-12; IN-VITRO; FLUOROQUINOLONE ANTIBACTERIALS; CRYSTAL-STRUCTURE; METAL-IONS; QUINOLONE ANTIBIOTICS; AQUEOUS-SOLUTION
categoria
Biochemistry & Molecular Biology; Chemistry
autores
Fernandes, P; Sousa, I; Cunha-Silva, L; Ferreira, M; de Castro, B; Pereira, EF; Feio, MJ; Gameiro, P
nossos autores
Isabel Cristina de Sá Correia de Sousa
Investigador Júnioragradecimentos
This work was funded by FEDER funds through the Programa Operacional Factores de Competitividade - COMPETE, the Quadro de Referencia Estrategico Nacional - QREN and by national funds through Fundacao para a Ciencia e a Tecnologia (FCT, Portugal) through EU-MRTN-CT-2005-019335 (Translocation), PTDC/SAU-FAR/111414/2009, and PEst-C/EQB/LA0006/2011 projects. The authors are also grateful for specific funding toward the purchase of the single-crystal X-ray diffractometer. IS thanks FCT for the PhD scholarship SFRH/BD/47486/2008. MJF and LCS are in debt to Programa Ciencia 2008 (Programa Operacional Potencial Humano) for their financial support.