Recently, the inclusion compound formed by doxycycline and modified CD was investigated. In the inclusion compound, the unstable site of doxycycline was protected by the hydrophobic CD cavity. However, the guest arrangement inside CD cavity has not identified. In some situations, the correlation between protons of the guest and host in a 2D-ROESY experiment can be compatible with head and tail spatial arrangements. In the present work, the most stable guest spatial arrangement for the inclusion of doxycycline into beta-CD was evaluated at B97-D/6-311++(2d,p) level of theory. For sake of comparison, tetracycline inclusion compound was also studied. (C) 2017 Published by Elsevier B.V.