Crystallographic evaluation of the conformation of quetiapine included in β-cyclodextrin

Single-crystal X-ray diffraction and theoretical calculations were conducted for insights into the β-cyclodextrin (β-CD)-quetiapine inclusion complex structure. β-CD and quetiapine form a host-guest inclusion complex at a ratio of 2:1 in which the β-CD molecules form head-to-head dimers with their secondary hydroxyl groups linked by multiple hydrogen bonds. Quetiapine is totally contained within the β-CD cavity and exhibits two kinds of disorder (parts 1 and 2) in opposite directions in the β-CD complex. To clarify the mobility of the guest molecule in the β-CD cavity, theoretical molecular conformational calculations, crystal optimization and crystal energy calculations were conducted using CONFLEX software. The results of theoretical molecular conformation calculations showed that the mobility of quetiapine is restricted because its tricyclic structure is covered by β-CD. The results of crystal energy calculations indicated that the conformation of disorder part 1, which has high occupancy, was more stable.