Macrotricyclic quaternary tetraammonium receptors: Halide anion recognition and interfacial activity at an aqueous interface. A molecular dynamics investigation

We report a molecular dynamics study of the halide inclusion complexes X− ⊂ L4+ of a macrotricyclic tetrahedral receptor L4+ built from four quaternary ammonium sites connected by six (CH2)n chains. The hydrophilic/hydrophobic character of the complexes is investigated at a water/chloroform interface, represented explicitly and, despite their +3 charge and “spherical” shape, they are found to display amphiphilic behavior and to concentrate at the interface. The more lipophilic N‐substituted CH2ϕ derivative, as well as less charged models are more surface active than the N‐Me substituted host. In relation with the Hofmeister series, I− exo neutralizing counterions are compared with Cl− anions and are found to sit closer to the interface, which becomes more neutral. The “macrocyclic interfacial effect” is investigated by a comparison of L4+ complexes with their acyclic counterparts. Finally, we address the question of anion binding selectivity by L4+ and its L  14+ and L  24+ topological isomers. F− is too small for these three hosts, while I− is too big. According to free energy perturbation calculations, Cl− is preferred to Br−, but somewhat more by L  14+ than by L4+. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 1532–1543, 2002