AM1 calculations on inclusion complexes of cyclomaltoheptaose (β-cyclodextrin) with 1,7-dioxaspiro[5.5]undecane and nonanal, and comparison with experimental results

Semiempirical calculations on cyclomaltoheptaose (βCD), 1,7-dioxaspiro[5.5]undecane (1), nonanal (2), and the inclusion complexes of βCD with 1 and 2 were carried out using the AM1 method. The structure of βCD after complete geometry optimization was in very good agreement with crystallographic structures. Moreover, the calculated dipole moment of βCD was found to depend strongly upon the orientation of the primary hydroxyl groups. Different possible positions of the guest molecules in the βCD cavity were examined, a few of them resulting in a gain of energy. These corresponded to partial inclusion of 1 from the secondary side but total inclusion of 2. Conclusions regarding the geometries of the complexes were in satisfactory agreement with the dominant structures in aqueous solutions as derived from NMR experiments. Thermodynamic data (ΔH0, ΔS0) in aqueous solutions were obtained from vanʹt Hoff plots using 1H NMR, and were compared with the computed heats of formation. The forces responsible for host-guest association are discussed in the light of the above results.