Alkaline earth and uranyl cation complexes of a calix[4]arene-tetraamide: MD and FEP simulations in aqueous and acetonitrile solutions and X-ray structure of its Sr(Picrate)(2) complex

We report the X-ray structure of the L . Sr(Picrate)(2) (L = tert-butyl-calix[4] arene-tetrakis(diethylamide)dagger and MD simulations on the L . M(2+) complexes in vacuo, in water and in acetonitrile solutions (M(2+) = Mg2+, Ca2+, Sr2+, Ba2+), with a comparison of 'converging' L(C) and 'diverging' L(D) conformers. Ln the simulated and solid-state structures of the L . Sr2+ complex, the cation is completely encapsulated within the polar pseudo-cavity of L, without coordination to its counterion in the crystal, or to solvent molecules in solution. Computations show that the L . M(2+) complexes are of converging type in water and in acetonitrile, This contrasts with the L . M(+) alkali cation complexes, which display conformational flexibility in solution. Subtle structural changes from Mg2+ to Ba2+ are compared in the gas phase and in solution. In the L . UO22+ hypothetical complex, simulated for comparison, the UO22+ cation is calculated to be less bound by L than the alkaline earth cations, The solvent content of the cone is shown to depend on the size of the complexed cation and modulated by the top-bottom mechanical coupling in the calixarene. Based on free energy perturbation calculations, we calculate a binding sequence of alkaline earth cations (Ca2+ > Sr2+ > Ba2+ > Mg2+) in agreement with experiment.