Structure and UV solvatochromic shifts of sulfamethoxazole in alcoholic solvents and water

Abstract

The structural properties and UV solvatochromic shifts of sulfamethoxazole in alcoholic solvents and water have been investigated using UV spectroscopy and the AM1 method. The two most important conformers of the compound exhibit non-planar structures with different dipolar moments. In order to explain the experimental dipolar moment of sulfamethoxazole in ethanol (11.61D), it was proposed that these two conformers are in equilibrium. It was thus determined that the corresponding equilibrium constant is 6.36×10−2, which implies that, in equilibrium, there is 94.02% of Conf1 and 5.98% of Conf2. It was also proposed that the drug interacts with the solvents by means of intermolecular hydrogen bonds, forming solvent–solute association complexes of 4:1 stoichiometry. In this way, it could be determined that the dipolar moment of complex (EtOH)4–Conf1 (11.68D) of sulfamethoxazole is practically identical to the experimental value. On the other hand, it was observed that the main UV absorption band of sulfamethoxazole, which is associated to strong π→π∗ transitions, suffers hypsochromic shifts when the permittivity of the solvents increases. A very good correlation was obtained between the theoretical structural and UV spectroscopic magnitudes of the compound and the experimental properties of the solvating solvents. It was concluded that the solvatation of sulfamethoxazole is determined by the hydrogen-bond-donor and hydrogen-bond-acceptor capabilities, as well as by the polarity of the solvents. It was further concluded that the (Solvent)4–Conf1 complex is the species that determines the main dielectric and UV spectroscopic properties of sulfamethoxazole in the solvents analyzed.