title: Release of high-energy water as an essential driving force for the high-affinity binding of cucurbit[n]urils.
abstract: Molecular dynamics simulations and isothermal titration calorimetry (ITC) experiments with neutral guests illustrate that the release of high-energy water from the cavity of cucurbit[n]uril (CBn) macrocycles is a major determinant for guest binding in aqueous solutions. The energy of the individual encapsulated water molecules decreases with increasing cavity size, because larger cavities allow for the formation of more stable H-bonded networks. Conversely, the total energy of internal water increases with the cavity size because the absolute number of water molecules increases. For CB7, which has emerged as an ultrahigh affinity binder, these counteracting effects result in a maximum energy gain through a complete removal of water molecules from the cavity. A new design criterion for aqueous synthetic receptors has therefore emerged, which is the optimization of the size of cavities and binding pockets with respect to the energy and number of residing water molecules.
authors.affiliation: Melville Laboratory for Polymer Synthesis and Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.
authors.forename: Frank
authors.initials: F
authors.lastname: Biedermann
authors.forename: Vanya D
authors.initials: VD
authors.lastname: Uzunova
authors.forename: Oren A
authors.initials: OA
authors.lastname: Scherman
authors.forename: Werner M
authors.initials: WM
authors.lastname: Nau
authors.forename: Alfonso
authors.initials: A
authors.lastname: De Simone
mesh_terms: D001952:Bridged-Ring Compounds / Q000737:chemistry*; D006860:Hydrogen Bonding; D014867:Water
chemical_list: D001952:Bridged-Ring Compounds; D014867:Water