Speciation studies of antibacterial drugs

Speciation studies are important for understanding the behavior of a given component (metal or organic/inorganic ligand) in a multi-component solution, allowing the determination of the distribution of the different physical and chemical forms in which the component is present in a system. By means of the speciation studies, the thermodynamic parameters of reaction can be determined, allowing in turn to obtain information about its bioavailability, toxicity and environmental impact [1-2]. In this context, the behavior in terms of acid-base properties, solubility and interactions with calcium of two biologically relevant drugs, namely Ofloxacin and Ornidazole, was studied at different experimental conditions, in aqueous solution of sodium chloride [3]. These ligands are synthetic antibacterial drugs commonly used for the treatment of urinary tract and intestinal protozoan infections, respectively. Ofloxacin is a fluoroquinolone and belongs to the class of quinolones, while Ornidazole is a derivative of 5-nitroimidazole and has a significant efficacy on patients, due to its long half-life time. The investigation were carried out by means of potentiometric and UV-Vis spectrophotometric measurements at 0.15 < I/mol dm-3 < 1.00 and 288.15 < T/K < 318.15. The elaboration of experimental data allowed to obtain two protonation constants for Ofloxacin, and one for Ornidazole, attributable for the first ligand to the nitrogen atom in position 4 on the piperazine ring and to the -COOH group, and to the –OH group for Ornidazole. Solubility measurements performed on small aliquots of ligands, led to the determination of the solubuility and neutral species concentration at different experimental conditions and to the calculation of dissolution enthalpies at I = 0.15 mol L-1. The knowledge of the protonation constants at different temperatures, allowed by means of a Van’t Hoff equation, the calculation of the enthalpy change value of reactions. A Debye Hückel type equation was used to model the dependence of the stability constants on the ionic strength. As regards the interaction of Ofloxacin and Ornidazole with calcium, quite simple speciation models were obtained, characterized by species with low stability. By using the empirical pL0.5 parameter, the sequestering ability of the two ligands towards Ca2+ was quantified at different ionic strengths, temperatures and pHs.