NMR study and computational assays of meclofenamic Na salt and β-cyclodextrin inclusion complex

Complexation in solution between meclofenamate sodium (MCF) and beta-cyclodextrin was studied using one- and two-dimensional H-1 NMR spectroscopy and molecular docking coupled with ab initio calculations. The large variation of chemical shifts from protons located inside the hydrophobic cavity of beta-cyclodextrin, provided clear evidence of inclusion complexation. The stoichiometry of the inclusion complex was determined to be 1:1, using the method of continuous variation. To ascertain the solution geometry of the host-guest complex a ROESY experiment was carried out. The results suggested a preferential binding of the dichlorophenyl moiety of the guest molecule within the beta-cyclodextrin cavity, conformation which also sustained by the theoretical computational investigations. The association constant of the inclusion complex was determined using H-1 NMR titration method in solution followed by a non-linear least-square regression implemented in CONSTEQ, a software developed in our group. After a preliminary molecular docking investigation, the most probable conformation was subjected to ab initio calculations using SIESTA software package, to characterize more precisely the stabilization energy of the 1:1 inclusion complex.