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

• Published in: Journal of inorganic biochemistry Vol. 131; pp. 21 - 29
• Main Authors: Fernandes, Patrícia, Sousa, Isabel, Cunha-Silva, Luís, Ferreira, Mariana, de Castro, Baltazar, Pereira, Eulália F., Feio, Maria J., Gameiro, Paula
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2014
• Subjects: Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Bacterial resistance; Coordination Complexes - chemical synthesis; Coordination Complexes - chemistry; Coordination Complexes - pharmacokinetics; Copper - chemistry; Copper - pharmacology; Crystallography, X-Ray; Drug Stability; Escherichia coli; Escherichia coli - drug effects; Fluoroquinolones; Fluoroquinolones - chemical synthesis; Fluoroquinolones - chemistry; Fluoroquinolones - pharmacology; Hydrogen-Ion Concentration; Lomefloxacin; Metalloantibiotics; Microbial Sensitivity Tests; Potentiometry - methods; Solution equilibria; Solutions; Spectrophotometry, Infrared; Spectrophotometry, Ultraviolet; Fluoroquinolones; Bacterial resistance; Metalloantibiotics; Solution equilibria; Lomefloxacin
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2013.10.013

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 pH7.4) 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)]·5H2O, 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. Aqueous solution behavior of lomefloxacin copper(II)-complexes with and without 1, 10-phenanthroline was studied. Under physiological conditions only the ternary copper(II):lmx:phen complex was stable hence it was synthesized and characterized. Microbiological studies suggested a distinct entry route for the metalloantibiotic and free fluoroquinolone, a possible way to counteract microbial resistance. [Display omitted] •Solution behavior of Cu(II):lmx complexes with and without 1, 10-phenanthroline was studied.•Under physiological conditions (μM range, pH7.4) only Cu(II):lmx:phen complexes are stable.•[Cu(lmx)(phen)(NO3)]·5H2O was synthesized and characterized by UV–Vis and IR spectroscopy.•X-ray crystallography showed distorted square-pyramidal geometry for the complex.•MIC assays showed that Cu-complex is as efficient as free lmx but influx route varies.