title: Molecular dynamics study of a heteroditopic-calix[4]diquinone-assisted transfer of KCl and dopamine through a water-chloroform liquid-liquid interface.
abstract: The ability of two heteroditopic calix[4]diquinone receptors to transport a KCl ion-pair and a dopamine zwitterion through a water-chloroform interface was investigated via molecular dynamics (MD) simulations. Gas-phase conformational analysis has been carried on KCl and dopamine receptor binding associations and the lowest energy structures found in both cases show that the recognition of KCl and dopamine zwitterion occurs through multiple and cooperative N-H...anion and O...cation bonding interactions, with the receptor adopting equivalent folded conformations stabilized by pi-stacking interactions. The unconstrained MD simulations performed on KCl and dopamine complexes inserted in either the chloroform or water phase revealed that receptors are preferentially located at the interface with the hydrophobic tert-butyl groups of the calix[4]diquinone moiety immersed in the chloroform bulk while the polar anion binding cavity is directed toward the water phase. When the KCl complex is placed in chloroform, the release of the ion-pair occurs only after the first contact with the water interface, being a nonsimultaneous event, with the chloride anion leaving the receptor before the potassium cation. The dopamine, via the -NH(3)(+) binding entity, remains bound to the receptor during the entire time of the MD simulation (10 ns). In contrast, when both complexes were inserted in the water bulk, the full release of KCl and dopamine are fast events. The potentials of mean force (PMFs), associated with the migration of the complexes from chloroform to water through the interface, were calculated from steered molecular dynamics (SMD) simulations. The PMFs for the free KCl and zwitterionic dopamine migrations were also obtained for comparison purposes. The transport of KCl from water to chloroform (the reverse path) mediated by the receptor has a free energy barrier estimated in 6.50 kcal mol(-1), which is 3.0 kcal mol(-1) smaller than that found for the free KCl. The transport of dopamine complex along the reverse path is characterized by downhill energy profile, with a small free energy barrier of 6.56 kcal mol(-1).
authors.affiliation: Departamento de Química-CICECO and Secção Autonóma de Ciências da Saúde, Universidade de Aveiro, 3810-193 Aveiro, Portugal.
authors.forename: Sérgio M
authors.initials: SM
authors.lastname: Santos
authors.forename: Paulo J
authors.initials: PJ
authors.lastname: Costa
authors.forename: Michael D
authors.initials: MD
authors.lastname: Lankshear
authors.forename: Paul D
authors.initials: PD
authors.lastname: Beer
authors.forename: Vítor
authors.initials: V
authors.lastname: Félix
mesh_terms: D047250:Calixarenes / Q000737:chemistry*; D002725:Chloroform / Q000737:chemistry*; D004298:Dopamine / Q000737:chemistry*; D006860:Hydrogen Bonding; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D011189:Potassium Chloride / Q000737:chemistry*; D011809:Quinones / Q000737:chemistry*; D013816:Thermodynamics; D014867:Water / Q000737:chemistry*
chemical_list: D011809:Quinones; C528544:calix(4)diquinone; D014867:Water; D047250:Calixarenes; D011189:Potassium Chloride; D002725:Chloroform; D004298:Dopamine