Inclusion of parabens in β-cyclodextrin: A solution NMR and X-ray structural investigation

A parallel study was conducted of the inclusion of alkyl parabens (guests) in the host beta-cyclodextrin (beta-CD). H-1 NMR data indicated an insertion of the guest phenyl ring into the beta-CD cavity. The stoichiometry of each complex was 1:1, as determined by a continuous variation method that utilises the chemical shifts of the host protons. These chemical shifts were additionally used to determine the association constant yielding K values of 1631, 938, 460 and 2022 M-1 at 298 K for the methyl-, ethyl-, propyl- and butyl paraben solution state complexes, respectively. NOE experiments conducted on the methyl paraben solution complex indicated that the phenolic group of the guest was located at the secondary rim of the cyclodextrin cavity. Solid state structure analyses of the methyl and propyl paraben beta-CD complexes were performed. Both complexes crystallised at ambient temperature in the space group C2, Z=4 with a host to guest ratio of 1:1. Additionally, a second crystal structure between methyl paraben and beta-CD is reported. This complex crystallised at 7 degrees C in the space group P1, Z=2 with a 1:1 host-guest stoichiometry.