Inclusion of nonopiate analgesic drugs in cyclodextrins.: II.: X-ray structure of a 1:1 β-cyclodextrin -: Acetaminophen complex

Single crystals of a 1 : 1 complex between beta-cyclodextrin (beta-CD) and the analgesic acetaminophen (paracetamol) have been prepared and the mode of inclusion of the drug has been determined from X-ray data collected at 293 K. Complex characterization by UV and thermogravimetric analyses yielded the composition beta-(CD . acetaminophen . 13.3H(2)O. The complex crystallizes in the space group C2 with a = 19.207(7), b = 24.48(1), c = 15.700(4)Angstrom, beta = 109.52(2)degrees and Z = 4 complex units in the crystal unit cell. The host molecules form dimeric motifs with C-2 crystallographic symmetry which pack in the channel mode. Guest molecules residing in the host dimer are disordered, each acetaminophen molecule being statistically distributed over two sites with equal occupancy. In each case, the guest hydroxyl group is located at the host primary face while the acetamide residue lies at the dimer interface. Two C-2-related water molecules are trapped inside the host cavity, being hydrogen bonded to the C-2-related carbonyl groups of one of the disordered guest conformers. Structural features of the complex are discussed with reference to recent spectroscopic and other studies aimed at elucidating the nature of the interaction between acetaminophen and beta-CD.