Kinetic and mechanistic significance of the chemical activation of ciprofloxacin for conjugation chemistry

Abstract

AbstractCiprofloxacin is an important category of fluroquinolones that has versatile applications in imaging when conjugated with different ligands. For conjugation chemistry, chemical activation of the carboxylic group at the third position is an important step. Here, we study the kinetics for the activation of the acidic group of ciprofloxacin by N‐hydroxysuccinimide (NHS) and dicyclohexylcarbodiimide (DCC). The extent of the reaction was followed by registering a decrease in absorbance at 332, 412, and 423 nm by monitoring the consumption of ciprofloxacin as a function of [NHS], [DCC], pH, ionic strength, and temperature by varying only one parameter at a time while keeping all other parameters constant. The reaction between ciprofloxacin and NHS, in the presence of DCC, exhibits a 1:1:1 stoichiometry. The reaction is found to show first‐order dependence on the concentration of ciprofloxacin to the order of 103 s−1(kobs) and zero order with respect to the concentrations of NHS and DCC, respectively. The activation parameters and thermodynamic quantities vis‐à‐vis Ea, ΔH≠, and ΔS≠ have been computed with respect to the forward reaction as 12.024, 131.43, and 27.31 J K−1 mol−1, respectively, which provided additional support to the proposed kinetic pathway. © 2009 Wiley Periodicals, Inc. Int J Chem Kinet 41: 349–356, 2009