Host-guest interactions between sildenafil and cyclodextrins: Spectrofluorometric study and molecular dynamic modeling

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 (-6.01kcal/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.