Ciprofloxacin metal complexes and linked dimers as potential antimicrobial agents

Antimicrobial resistance is one of the biggest threats to public health globally. Modifications to ciprofloxacin, a commercially available fluoroquinolone antibiotic, could overcome increasing antimicrobial resistance and increase its antimicrobial activity. Ciprofloxacin contains several potential donor atoms, which can be used to coordinate to a metal ion. Coordination of ciprofloxacin to bioavailable metal ions such as iron(III) could promote bacterial uptake of the metallo-ciprofloxacin complex, making it a more effective antimicrobial agent over ciprofloxacin. The coordination of ciprofloxacin to metal ions with antimicrobial properties such as bismuth(III) could also further enhance the antimicrobial properties. Presented are two novel iron(III)-ciprofloxacin complexes, a novel zinc(II)- ciprofloxacin complex and a bismuth(III)-ciprofloxacin complex. The metallo-ciprofloxacin complexes presented have been characterised using a variety of techniques, including X-ray crystallography, X-ray fluorescence (XRF), fourier-transform infrared spectroscopy (FTIR), elemental analysis, solid state nuclear magnetic resonance (ssNMR) and melting point. Another modification that can be made to the structure of ciprofloxacin is to design and synthesise a linked dimers. A dimeric compound could bridge across the binding sites of the intracellular target enzyme, DNA gyrase. Previously reported fluoroquinolone dimers have been found to possess enhanced antimicrobial properties as well as anti-tumour properties. Presented are two ciprofloxacin dimers, the first featuring an ethylenediaminetetraacetic acid (EDTA) linker and the second a diethylenetriamine pentaacetate (DTPA) linker. The EDTA and DTPA linkers have also been suggested to have antimicrobial properties due to their metal�chelating properties and therefore could further enhance the effectiveness of the ciprofloxacin dimers presented. The linked ciprofloxacin ligands presented have been characterised using nuclear magnetic resonance (NMR), High-performance liquid chromatography (HPLC), FTIR, elemental analysis and melting point.