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Protomers of benzocaine: solvent and permittivity dependence.

Journal of the American Chemical Society (2015-03-12)
Stephan Warnke, Jongcheol Seo, Jasper Boschmans, Frank Sobott, James H Scrivens, Christian Bleiholder, Michael T Bowers, Sandy Gewinner, Wieland Schöllkopf, Kevin Pagel, Gert von Helden
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Benzocaine, ≥99% (HPLC)
Supelco
Benzocaine, Pharmaceutical Secondary Standard; Certified Reference Material
Benzocaine, European Pharmacopoeia (EP) Reference Standard
USP
Benzocaine, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Ethyl 4-aminobenzoate, 98%