Computational studies of the encapsulation of ibuprofen and paracetamol into cucurbit[7]uril

Herein, theoretical methods were used to study the cucurbit[7]uril (CB[7]) as a possible carrier agent for the poor water soluble drugs ibuprofen (IBF) and paracetamol (PCT). These drugs form a stable inclusion complex with the CB[7] during 50 ns of molecular dynamics simulation preserving its solvation shell. Likewise CB[7], both complexes are soluble in water with calculated solvation enthalpy of –131 and –133 kcal/mol for isolated CB[7]. The binding free energy, obtained from the potential of mean force calculations, reveals that the IBF@CB[7] complex is more stable (–16.7 kcal/mol) than the PCT@CB[7] complex (–11.7 kcal/mol). Correspondingly, the binding energies obtained in DFT-D3/B3LY/6-31G(d,p) calculation are –30.07 and –24.51 kcal/mol for IBF@CB[7] and PCT@CB[7], respectively. The high energy gap of complexes implies their chemical stability. Our results indicate that the CB[7] can be a new carrier agent for IBF and PCT, improving their solubility and chemoprotection in aqueous media.