Fluoroquinolones and their complexes with metal ions, studied with density functional theory

Fluoroquinolone antibiotics might lead to severe side effects, collectively known as fluoroquinolone-associated disability (FQAD). The origin of this phenomenon is unknown, but has been suggested to involve chelation of biologically important ions such as Fe³⁺. In this study, DFT calculations were used to estimate the Gibbs energies of binding of biologically-relevant ions (Mg²⁺, Ca²⁺, Mn²⁺, Fe³⁺ and Zn²⁺) to ciprofloxacin, a prototype of fluoroquinolone antibiotics. The results show preferable binding of Fe³⁺ to ciprofloxacin, with binding affinity that is over 50 kcal mol⁻¹. The binding of the ions to ciptofloxacin is compared to their binding to tetracycline, a metal binding antibiotic that is not a fluoroquinolone. The affinity of Fe³⁺ and most other ions to tetracycline was found to be even higher, which leads to the conclusion that ion binding is not the cause for FQAD. Overall, this study demonstrates the usability of a computational-chemistry based approach to a problem within biomedicine. Methodological and structural aspects of the binding are also discussed.