Exploring the effect of supramolecular structures of micelles and cyclodextrins on fluorescence emission of local anesthetics

Abstract

Benzocaine (ethyl 4-aminobenzoate, 4) and its derivatives ethyl 2-aminobenzoate, 2, and ethyl 3-aminobenzoate, 3, were found to form association complexes with supramolecular structures of micelles and cyclodextrins (CDs). The fluorescence emission of 2, 3 or 4 dissolved in the pseudo-micellar phase or included into α-, β-, or γ-CD cavity increases dramatically with respect to that observed in only water. High percentages of organic solvents like dioxane, acetonitrile, DMSO in the aqueous solution lead to a similar effect. The stability constants of the complexes formed between these drugs and cyclodextrins have been determined. In neutral or acid medium, a 1:1 stoichiometry for drug:CD complexes have been found, whereas in alkaline medium 1:2 stoichiometry was also detected in some cases. Kinetic studies of both the nitrosation of the amine group and the alkaline hydrolysis of the ester function was employed to infer the conformation of the complexes as well as to evaluate their stability constants. Theoretical calculations to optimize the molecular structure of 2, 3 and 4 allow us to propose possible geometries of the complexes that are in agreement with the experimental data.