Co-conformational variability of cyclodextrin complexes studied by induced circular dichroism of azoalkanes.

The solution structures of the beta-cyclodextrin complexes between 2,3-diazabicyclo[2.2.2]oct-2-ene (1) and its 1-isopropyl-4-methyl derivative 2 have been investigated by means of induced circular dichroism (ICD) and MM3-92 force-field calculations, which considered the effect of solvation within a continuum approximation. Of primary interest was the so-called co-conformation of the host-guest complex, i.e., the relative orientation of the guest within the host. A pool of low-energy complex structures, which were located by means of a Monte Carlo simulated annealing routine, was generated to evaluate the dynamic co-conformational variability of the complexes. The ICD effects were calculated for the computed low-energy structures by applying a semiempirical method. The experimental and theoretical ICD as well as the calculated low-energy complex geometries suggest solution co-conformations in which the parent compound 1 adapts a lateral arrangement with the ethano bridge of the guest penetrating deepest into the cavity and the azo group aligning parallel to the plane of the upper rim. In contrast, the alkyl derivative 2 prefers a frontal co-conformation with the isopropyl group penetrating deepest into the cavity and the azo group aligning perpendicular to the plane of the upper rim. The validity of the predictions of the Harata rule regarding the sign and the intensity of the ICD signals for the n(-)pi, n(+)pi, and pipi transition of the azo chromophore in dependence on the complex co-conformation are discussed. With respect to the co-conformational variability of the complexes of the two azoalkanes, it was observed that the nearly spherical guest 1 forms a geometrically better defined complex than the sterically biased, alkyl-substituted derivative 2. This dichotomy is attributed to the largely different modes of binding for azoalkanes 1 and 2. It is concluded that the goodness-of-fit in a host-guest complex cannot be directly related to the "tightness-of-fit".