Structural and theoretical-experimental physicochemical study of trimethoprim/randomly methylated-β-cyclodextrin binary system.

Abstract Here we report the structural characterization, physicochemical study and molecular modeling of the inclusion complex of trimethoprim in randomly methylated beta-cyclodextrin. The phase-solubility diagram obtained at pH 7.0 exhibited a linear behavior for the RAMEB concentrations studied suggesting a 1:1 stoichiometry and absence of aggregation in solution. From stoichiometric determination by the continuous variation method we confirmed a 1:1 stoichiometry. To make a detailed characterization of the inclusion mode, spectroscopic measurements by infrared and 1D and 2D 1 H NMR spectroscopy provided evidence that the inclusion mode is characterized by inclusion of the trimethoxyphenyl ring in the cavity; interactions with methyl groups located in the border of the cavity were also detected. The structure proposed was also confirmed by semiempirical molecular modeling.