Markus Schütz, Aude Bouchet, Barbara Chiavarino, Maria Elisa Crestoni, Simonetta Fornarini, Otto Dopfer
Chem. Eur. J 22 8124-8136 (2016). DOI

Travail réalisé sur le site de l’Université Paris Sud.

Abstract

Fluorination of pharmaceutical compounds is a common tool to modulate their physiochemical properties. We determine the effects of site-specific aromatic fluorine substitution on the geometric, energetic, vibrational, and electronic properties of the protonated neurotransmitter 2-phenylethylamine (xF-H+PEA, x=ortho, meta, para) by infrared multiphoton photodissociation (IRMPD) in the fingerprint range (600–1750 cm−1) and quantum chemical calculations at the B3LYP-D3/aug-cc-pVTZ level. The IRMPD spectra of all ions are assigned to their folded gauche conformers stabilized by intramolecular NH+⋅⋅⋅π hydrogen bonds (H-bonds) between the protonated amino group and the aromatic ring. H→F substitution reduces the symmetry and allows for additional NH+⋅⋅⋅F interactions in oF-H+PEA, leading to three distinct gauche conformers. In comparison to oF-H+PEA, the fluorination effects on the energy landscape (energy ordering and isomerization barriers) in pF-H+PEA and mF-H+PEA with one and two gauche conformers are less pronounced. The strengths of the intramolecular NH+⋅⋅⋅F and NH+⋅⋅⋅π bonds are analyzed by the noncovalent interaction (NCI) method.