Characterization, phase-solubility, and molecular modeling of inclusion complex of 5-nitroindazole derivative with cyclodextrins.

The slightly water-soluble 5-nitroindazole derivative (5-NI) and its inclusion with either beta-cyclodextrin (betaCD) or Heptakis (2,6-di-O-methyl)-beta-cyclodextrin (DMbetaCD) were investigated. The stoichiometric ratios and stability constants describing the extent of formation of the complexes were determined by phase-solubility measurements obtaining type-A(L) diagrams in both cases. According to the continuous variation method (Job's plot) a 1:1 stoichiometry has been proposed for the complexes. Also electrochemical studies were carried out on both CDs complexes, where the observed change in the E(PC) value for DMbetaCD indicated a lower feasibility of the nitro group reduction. The detailed spatial configuration is proposed based on two-dimensional NMR methods. These results are further interpreted using molecular modeling studies. The latter results are in good agreement with the experimental data.