LAUSR

Molecular dynamics (MD) simulations were carried out to study the host–guest complexation in aqueous solution between cucurbit[7]uril (CB7) and the neutral and protonated forms of benzimidazole derivatives. Complexation occurs via encapsulation of the hydrophobic part (benzene ring) of the guest within the CB7 hydrophobic cavity, and the interactions of the amine group(s) of the imidazole ring of the guest with the CB7 carbonyl portals. The molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) method is used to estimate the host–guest Gibbs energy of binding. The results indicate that CB7 binds the protonated form more strongly than the neutral one, and that the dominant contribution to the Gibbs energy of complexation for the neutral and protonated guests is associated, respectively, with the host–guest van der Waals and electrostatic interactions. Quantum chemical calculations using dispersion-corrected density functional theory (DFT) are used to calculate the binding affinities and to predict the pKa values of the free and complexed guests. The calculated pKa values for the free guests reveal excellent agreement with the experimental values, while for the complexed guests, general trends are obtained.