Effect of peracylation of beta-cyclodextrin on the molecular structure andon the formation of inclusion complexes: An X-ray study

The molecular structures of peracylated beta -cyclodextrins (CDs)-heptakis( 2,3,6-tri-O-acetyl)-beta -CD (TA), heptakis(2,3,6-tri-O-propanoyl)-beta -CD (TP), and heptakis(2,3,6-tri-O-butanoyl)-beta -CD (TB)-have been determine d by single crystal X-ray structure analysis. Due to the lack of O2(...)O3 ' hydrogen bonds between adjacent glucose units of the peracylated CDs, the macrocycles are elliptically distorted into nonplanar boat-shaped structur es. The glucose units are tilted with respect to the O4 plane to relieve st eric hindrance between adjacent acyl chains. In TB, all glucose units adopt the common C-4(1)-chair conformation and one butanoyl chain intramolecular ly penetrates the cavity, whereas, in TA and TP, one glucose unit each occu rs in S-O(2)-skew-boat conformation and one acyl chain closes the O6 side l ike a lid. In each of the three homologous molecules the intramolecular sel f-inclusion and lidlike orientation of acyl chains forces the associated O5 -C5-C6-O6 torsion angle into a trans-conformation never observed before for unsubstituted CD; the inclusion behavior of TA, TP, and TB in solution has been studied by circular dichroism spectroscopy with the drug molsidomine and several organic compounds. No inclusion complexes are formed, which is attributed to the intramolecular closure of the molecular cavity by one of the acyl chains.