Solution and biological behaviour of enrofloxacin metalloantibiotics: a route to counteract bacterial resistance?

Solution behaviour of enrofloxacin complexes with copper(II), nickel(II), cobalt(II) and zinc(II) in the presence and absence of 1, 10-phenanthroline 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) forms stable complexes. Binary copper(II)/enrofloxacin and ternary copper(II)/enrofloxacin/phenanthroline complexes were synthesised and characterized by elemental analysis, UV-visible spectroscopy and FTIR. The antimicrobial activity of these complexes and of copper(II)/enrofloxacin and copper(II)/enrofloxacin/phenanthroline solutions, prepared by mixing of the individual components in the same stoichiometric proportion and concentration range used for the synthesised complexes, was tested against two different Escherichia coli strains. Although, at a glance, the results point to a possible use of both complexes as metalloantibiotics, a detailed analysis shows that, at biological concentrations, the copper(II) binary complex does not exist and the antimicrobial activity observed is a consequence of its dissociation into free enrofloxacin. Consequently, only the ternary complex seems worth pursuing as a possible antimicrobial agent candidate. Moreover, as the biological studies showed, both the synthesised complexes and the solutions prepared by mixing the components exhibited the same behaviour. Hence, a new, faster and accurate methodology to screen metalloantibiotics prior to synthesis of the complexes is proposed.