Inclusion Complex Formation of β-Cyclodextrin with the Nonsteroidal Anti-Inflammatory Drug Flufenamic Acid: Computational Study

Structural study and thermodynamics of complexation between beta-cyclodextrin (beta-CD) and flufenamic acid (FFA) are explored by means of several quantum chemical methods. The different orientation modes of FFA in the cavity of beta-CD are studied. PM3MM, ONIOM2 and DFT methods show that the complex FFA/beta-CD in A orientation is found to be the most favorable energetically. The statistical thermodynamic calculations at 1 atm and 298.15 K reveal that the complexation process is exothermic and enthalpically driven. Finally, the calculated chemical shifts of free FFA and its complex at B3LYP/6-31G(d) level by employing the Gauge-Including Atomic Orbital (GIAO) method are in good agreement with NMR experimental data.