Semi-empirical Pm3 Study on Complexation of Β-cyclodextrin with 5-flucytosine

The synthesis of the β-cyclodextrin-5-flucytosine inclusion complex in aqueous media has been recently reported, the characterization of the complex proving the complete inclusion of the 5-flucytosine molecule into the β-cyclodextrin cavity. Still, the type of interactions that stabilize the supramolecule and the structure of the complex have been poorly described. The present paper focuses on the use of quantum semi-empirical PM3 calculations to establish the equilibrium molecular geometry of a stable inclusion complex formed of 5flucytosine and β-cyclodextrin. Two types of stable complexes were obtained, with a small difference (~1 kJ) between the stabilization energies. In both cases, the major driving forces are the hydrogen bonds. The most stable of them, in vacuum, is a complex with a 5-flucytosine molecule located outside the βcyclodextrin cavity. The second one, containing a 5-flucytosine molecule included into the cyclodextrin cavity, was identified as a real complex, by previously reported H-NMR data. Despite the stabilization energies, the formation of the second inclusion complex with 5-flucytosine inside the cyclodextrin cavity is attributed to the solvent effect.