title: Bidentate urea-based chiral selectors for enantioselective high performance liquid chromatography: synthesis and evaluation of "Crab-like" stationary phases.
abstract: A rational approach for the design and preparation of two new "Crab-like" totally synthetic, brush-type chiral stationary phases is presented. Enantiopure diamines, namely 1,2-diaminocyclohexane and 1,2-diphenyl-1,2-ethylene-diamine were treated with 3-(triethoxysilyl)propyl isocyanate, to yield reactive ureido selectors that were eventually attached to unmodified silica particles through a stable, bidentate tether, through a facile two-step one-pot procedure. A full chemical characterization of the new materials has been obtained through solid-state NMR (both (29)Si and (13)C CPMAS) spectroscopy. Columns packed with the two Crab-like chiral stationary phases allow for different mechanisms of separation: normal phase liquid chromatography, reversed phase liquid chromatography and polar organic mode and show a high stability at basic pH values. In particular, the Crab-like column containing the 1,2-diphenyl-1,2-ethylene-diamine selector proved a promising candidate for the resolution of a wide range of racemates (including benzodiazepines, N-derivatized amino acids, and free carboxylic acids) both in normal phase and polar organic mode. An Hmin of 9.57 at a μsf of 0.80mm/s (corresponding to 0.8mL/min) was obtained through van Deemter analysis, based on toluene, for the Crab-like column with the 1,2-diphenyl-1,2-ethylene-diamine selector (250mm×4.6mm I.D.), with a calculated reduced height equivalent to a theoretical plate (h) of only 1.91. Finally, comparative studies were performed with a polymeric commercially available P-CAP-DP column in order to evaluate enantioselectivity and resolution of the Crab-like columns.
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Università di Roma, P.le Aldo Moro 5, 00185 Roma, Italy.
authors.forename: Dorina
authors.initials: D
authors.lastname: Kotoni
authors.forename: Claudio
authors.initials: C
authors.lastname: Villani
authors.forename: David S
authors.initials: DS
authors.lastname: Bell
authors.forename: Donatella
authors.initials: D
authors.lastname: Capitani
authors.forename: Pietro
authors.initials: P
authors.lastname: Campiglia
authors.forename: Francesco
authors.initials: F
authors.lastname: Gasparrini
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation*; D003514:Cyclohexylamines / Q000737:chemistry; D003959:Diamines / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008958:Models, Molecular; D009281:Naphthalenes / Q000737:chemistry; D012997:Solvents / Q000737:chemistry; D013237:Stereoisomerism; D014050:Toluene / Q000737:chemistry; D014508:Urea / Q000737:chemistry*
chemical_list: D000596:Amino Acids; D003514:Cyclohexylamines; D003959:Diamines; D009281:Naphthalenes; D012997:Solvents; C031721:naphthalene; D014050:Toluene; D014508:Urea; C030435:1,2-cyclohexanediamine