Abstract

Sildenafil (SF) was included in cyclodextrins (CD) to enhance its solubility. Spectrofluorometry was used to confirm the complexation constant (stability constant). The orientations of SF inside the β-CDs and γ-CDs were fully illustrated. Molecular dynamics simulations were performed on two inclusion complexes (β-CD/SF and γ-CD/SF) in the aqueous system. The polar methylpiperazine group was found to locate inside the β-CD cavity, both in the wide and narrow side and was positioned 2°A from the center. In contrast, the methylpiperazine group did not fit well within the γ-CD cavity. Moreover, these results also confirmed hydrogen bonding that the highest number of bonding formed between the polar methylpiperazine sulfonyl structure and the hydroxyl group of β-CD. The simulated binding free energy of the methylpiperazine-β-CD inclusion complex (−6.01 kcal/mol), featured a large contribution from electrostatic and van der Waals forces, which was the most stable complex. The association constant of β-CD/SF (12.3) was higher than γ-CD/SF (3.3) and confirmed with in silico measurements of binding free energy. In summary, SF forms a stable complex with β-CD.