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Effects of Aromatic Fluorine Substitution on Protonated Neurotransmitters: The Case of 2‐Phenylethylamine
Author(s) -
Schütz Markus,
Bouchet Aude,
Chiavarino Barbara,
Crestoni Maria Elisa,
Fornarini Simonetta,
Dopfer Otto
Publication year - 2016
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201600798
Subject(s) - conformational isomerism , protonation , infrared multiphoton dissociation , intramolecular force , chemistry , hydrogen bond , photodissociation , aromaticity , infrared spectroscopy , aromatic amino acids , stereochemistry , non covalent interactions , crystallography , isomerization , computational chemistry , photochemistry , ion , molecule , amino acid , organic chemistry , biochemistry , catalysis
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 ( x F‐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 o F‐H + PEA, leading to three distinct gauche conformers. In comparison to o F‐H + PEA, the fluorination effects on the energy landscape (energy ordering and isomerization barriers) in p F‐H + PEA and m F‐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.