title: Selective, direct detection of acetylcholine in PBS solution, with self-assembled fluorescent nano-particles: experiment and modelling.
abstract: We report synthesis, characterisation and molecular modelling of a new fluorescent cyclotriveratrylene probe for acetylcholine in aqueous media, with emission around 430 nm thanks to extended conjugation. The probe discriminates acetylcholine from choline, with respective binding constants 540 and 240 M(-1) in PBS buffered saline solution, an order of magnitude improvement over the previous best performance. Dynamic light scattering and transmission electron microscopy show the new probe self-assembles in ca. 5 nm diameter particles in PBS medium. Molecular modelling suggests that the high fluorescence quantum yield of the probe, 20% in aqueous media, is due to features of the molecular arrangement in the nano-particles, contributing both to exposure of the complexation site and to shielding of the fluorescent π system from quenching by water. Titration data for other quaternary ammoniums and modelling indicate that recognition of acetylcholine vs. choline depends on specific electrostatic interactions, and to a lesser extent on exclusion of water by hydrophobic-hydrophilic segregation. Probe-substrate interactions enhance the fluorescence of the probe by shielding against water and by flattening the π system.
authors.affiliation: Institut des Sciences Moléculaires, UMR 5255 du C.N.R.S., Institut Polytechnique de Bordeaux et Université de Bordeaux, 351, Cours de la Libération, 33405 Talence Cedex, France. gosse@enscbp.fr.
authors.forename: Lisa
authors.initials: L
authors.lastname: Erieau-Peyrard
authors.forename: Claire
authors.initials: C
authors.lastname: Coiffier
authors.forename: Patrice
authors.initials: P
authors.lastname: Bordat
authors.forename: Didier
authors.initials: D
authors.lastname: Bégué
authors.forename: Sabine
authors.initials: S
authors.lastname: Chierici
authors.forename: Sandra
authors.initials: S
authors.lastname: Pinet
authors.forename: Isabelle
authors.initials: I
authors.lastname: Gosse
authors.forename: Isabelle
authors.initials: I
authors.lastname: Baraille
authors.forename: Ross
authors.initials: R
authors.lastname: Brown
mesh_terms: D000109:Acetylcholine / Q000032:analysis*; D002021:Buffers; D047250:Calixarenes / Q000737:chemistry*; D002794:Choline / Q000032:analysis; D005456:Fluorescent Dyes / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D053758:Nanoparticles; D010710:Phosphates; D012965:Sodium Chloride; D012996:Solutions
chemical_list: C000603922:4-(2-7,12-bis(2-(4-carboxyphenyl)ethynyl)-3,8,13-trimethoxy-10,15-dihydro-5H-tribenzo(a,d,g)cyclononen-2-ylethynyl)benzoic acid; D002021:Buffers; D005456:Fluorescent Dyes; D010710:Phosphates; D012996:Solutions; D047250:Calixarenes; D012965:Sodium Chloride; D002794:Choline; D000109:Acetylcholine