K. Kano et al., MECHANISM FOR BINDING TO THE FLEXIBLE CAVITY OF PERMETHYLATED ALPHA-CYCLODEXTRIN, Journal of inclusion phenomena and molecular recognition in chemistry, 22(4), 1995, pp. 285-298
The cavity of alpha-cyclodextrin (alpha-CDx) is too small to include o
-toluic acid (o-TA) while it is filled by p-toluic acid (p-TA) to form
a relatively stable inclusion complex. Such strict selectivity is asc
ribed to a rigid structure of the alpha-CDx cavity which is stabilized
by intramolecular hydrogen bonds between the O(2) hydroxyl groups and
the O(3) hydroxyl groups of adjacent glucopyranose units. Meanwhile,
the substrate selectivity of hexakis(2,3,6-tri-O-methyl)-alpha-CDx (TM
e-alpha-CDx) remains somewhat obscure because of the flexible nature o
f its cavity. The absence of the intramolecular hydrogen bonds seems t
o cause the flexible nature of the TMe-alpha-CDx cavity leading to an
induced-fit type inclusion. The structures of the inclusion complexes
have been presented on the basis of the H-1 NMR data. The thermodynami
c parameters indicate that the complexation of TMe-alpha-CDx with o-TA
or p-TA is the entropically favorable process. The entropically favor
able complexation of TA with TMe-alpha-CDx seems to occur through dehy
dration from the CO2H group of TA which is situated at the hydrophobic
CDx cavity. The dipole-dipole interaction has been regarded as the fo
rce which dominates the orientation of the polar guest molecule in the
CDx cavity.