title: Protomers of benzocaine: solvent and permittivity dependence.
abstract: The immediate environment of a molecule can have a profound influence on its properties. Benzocaine, the ethyl ester of para-aminobenzoic acid that finds an application as a local anesthetic, is found to adopt in its protonated form at least two populations of distinct structures in the gas phase, and their relative intensities strongly depend on the properties of the solvent used in the electrospray ionization process. Here, we combine IR-vibrational spectroscopy with ion mobility-mass spectrometry to yield gas-phase IR spectra of simultaneously m/z and drift-time-resolved species of benzocaine. The results allow for an unambiguous identification of two protomeric species: the N- and O-protonated forms. Density functional theory calculations link these structures to the most stable solution and gas-phase structures, respectively, with the electric properties of the surrounding medium being the main determinant for the preferred protonation site. The fact that the N-protonated form of benzocaine can be found in the gas phase is owed to kinetic trapping of the solution-phase structure during transfer into the experimental setup. These observations confirm earlier studies on similar molecules where N- and O-protonation have been suggested.
authors.affiliation: †Fritz-Haber-Institut der Max-Planck-Gesellschaft, Faradayweg 4-6, 14195 Berlin, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Warnke
authors.affiliation: †Fritz-Haber-Institut der Max-Planck-Gesellschaft, Faradayweg 4-6, 14195 Berlin, Germany.
authors.forename: Jongcheol
authors.initials: J
authors.lastname: Seo
authors.affiliation: ‡Biomolecular and Analytical Mass Spectrometry Group, Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp, Belgium.
authors.forename: Jasper
authors.initials: J
authors.lastname: Boschmans
authors.affiliation: ‡Biomolecular and Analytical Mass Spectrometry Group, Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp, Belgium.
authors.forename: Frank
authors.initials: F
authors.lastname: Sobott
authors.affiliation: §School of Life Sciences, University of Warwick, Coventry CV47AL, United Kingdom.
authors.forename: James H
authors.initials: JH
authors.lastname: Scrivens
authors.affiliation: ∥Department of Chemistry and Biochemistry, University of California Santa Barbara, Santa Barbara, California 93106, United States.
authors.forename: Christian
authors.initials: C
authors.lastname: Bleiholder
authors.affiliation: ∥Department of Chemistry and Biochemistry, University of California Santa Barbara, Santa Barbara, California 93106, United States.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Bowers
authors.affiliation: †Fritz-Haber-Institut der Max-Planck-Gesellschaft, Faradayweg 4-6, 14195 Berlin, Germany.
authors.forename: Sandy
authors.initials: S
authors.lastname: Gewinner
authors.affiliation: †Fritz-Haber-Institut der Max-Planck-Gesellschaft, Faradayweg 4-6, 14195 Berlin, Germany.
authors.forename: Wieland
authors.initials: W
authors.lastname: Schöllkopf
authors.affiliation: ⊥Freie Universität Berlin, Institute of Chemistry and Biochemistry - Organic Chemistry, Takustrasse 3, 14195 Berlin, Germany.
authors.forename: Kevin
authors.initials: K
authors.lastname: Pagel
authors.affiliation: †Fritz-Haber-Institut der Max-Planck-Gesellschaft, Faradayweg 4-6, 14195 Berlin, Germany.
authors.forename: Gert
authors.initials: G
authors.lastname: von Helden
mesh_terms: D000779:Anesthetics, Local / Q000737:chemistry*; D001566:Benzocaine / Q000737:chemistry*; D008958:Models, Molecular; D011522:Protons; D012997:Solvents; D021241:Spectrometry, Mass, Electrospray Ionization; D013055:Spectrophotometry, Infrared
chemical_list: D000779:Anesthetics, Local; D011522:Protons; D012997:Solvents; D001566:Benzocaine