Ab initio molecular dynamics simulations and experimental speciation study of levofloxacin under different pH conditions

Levofloxacin is an extensively employed broad-spectrum antibiotic belonging to the fluoroquinolone class. Despite the extremely wide usage of levofloxacin for a plethora of diseases, the molecular characterization of this antibiotic appears quite poor in the literature. Moreover, the acid-base properties of levofloxacin-crucial for the design of efficient removal techniques from wastewaters-have never extensively been investigated so far. Here we report on a study on the behavior of levofloxacin under standard and diverse pH conditions in liquid water by synergistically employing static quantum-mechanical calculations along with experimental speciation studies. Furthermore, with the aim of characterizing the dynamics of the water solvation shells as well as the protonation and deprotonation mechanisms, here we present the unprecedented quantum-based simulation of levofloxacin in aqueous environments by means of state-of-the-art density-functional-theory-based molecular dynamics. This way, we prove the cooperative role played by the aqueous hydration shells in assisting the proton transfer events and, more importantly, the key place held by the nitrogen atom binding the methyl group of levofloxacin in accepting excess protons eventually present in water. Finally, we also quantify the energetic contribution associated with the presence of a H-bond internal to levofloxacin which, on the one hand, stabilizes the ground-state molecular structure of this antibiotic and, on the other, hinders the first deprotonation step of this fluoroquinolone. Among other things, the synergistic employment of quantum-based calculations and speciation experiments reported here paves the way toward the development of targeted removal approaches of drugs from wastewaters.