Study of the interaction between progesterone and β-cyclodextrin by electrochemical techniques and steered molecular dynamics

The interaction of progesterone with β-cyclodextrin (β-CD) was studied by differential pulse polarography. The aim of the present work was to study the effect of β-CD on the electrochemical behavior of progesterone in aqueous solution and also to analyze the molecular interactions involved in formation of the inclusion complex. The complex with stoichiometry of 1:1 was thermodynamically characterized. In addition, steered molecular dynamics (SMD) was used to investigate the energetic properties of formation of the inclusion complex along four different pathways (reaction coordinates), considering two possible orientations. From multiple trajectories along these pathways, the potentials of mean force for formation of the β-CD progesterone inclusion complex were calculated. The energy analysis was in good agreement with the experimental results. In the β-CD progesterone inclusion complex, a large portion of the steroid skeleton is included in the β-CD cavity. The lowest energy was found when the D-ring of the guest molecule is located near the secondary hydroxyls of the β3-CD cavity. In the most probable orientation, one intermolecular hydrogen bond is formed between the O of the C-20 keto group of the progesterone and a secondary hydroxyl of the β-CD.