IR spectrum of the protonated neurotransmitter 2-phenylethylamine: dispersion and anharmonicity of the NH₃⁺–π interaction

Abstract

The structure and dynamics of the highly flexible side chain of (protonated) phenylethylamino neurotransmitters are essential for their function. The geometric, vibrational, and energetic properties of the protonated neutrotransmitter 2-phenylethylamine (H(+)PEA) are characterized in the N-H stretch range by infrared photodissociation (IRPD) spectroscopy of cold ions using rare gas tagging (Rg = Ne and Ar) and anharmonic calculations at the B3LYP-D3/(aug-)cc-pVTZ level including dispersion corrections. A single folded gauche conformer (G) protonated at the basic amino group and stabilized by an intramolecular NH(+)-π interaction is observed. The dispersion-corrected density functional theory calculations reveal the important effects of dispersion on the cation-π interaction and the large vibrational anharmonicity of the NH3(+) group involved in the NH(+)-π hydrogen bond. They allow for assigning overtone and combination bands and explain anomalous intensities observed in previous IR multiple-photon dissociation spectra. Comparison with neutral PEA reveals the large effects of protonation on the geometric and electronic structure.

Competing Insertion and External Binding Motifs in Hydrated Neurotransmitters: Infrared Spectra of Protonated Phenylethylamine Monohydrate

“…Especially, one NH group in H + PEA(G) is already involved in the intramolecular NH + ···p Hb ond with the aromatic ring, whereas the other two are free (Figure1). [9] In H + PEA(A), none of the three NH groups is involved in an intramolecular interaction, therefore the three NH-bound isomers of H + PEA(A)-H 2 Oa re expected to be similarand close in energy.Owing to the C s symmetry of H + PEA(A), two of them are degenerate ( + PEA(G) to around3 .01 and 3.00 . This noncooperative effect arises mainly from nonadditive three-body inductioni nteractions typical for sequential interior solvation of the positive charge, [41] in this case mostlyl ocalized on the ammonium group.…”

“…[8,9] The less stable extended anti conformer,H + PEA(A), in which the side chain is oriented away from the aromatic core, is not observed in the gas phase, neither at room temperature [8] nor in ac old supersonic expansion. [9] This contrasts with the results obtained for neutralP EA, which experimentally adopts four different anti and gauche conformations in the gas phase. [12][13][14][15][16][17] Protonationo fP EA substantially increases the strengtho ft he intramolecular NH (+ +) ···p Hb ond and strongly stabilizes H + PEA(G) with respect to H + PEA(A),w hich thusl ocks the H + PEA monomer in as ingle conformation.…”

“…For example, ephedrine experiences ap rotonation-induced folding of its side chain, stabilized by both NH + ···O and NH + ···p interactions, although it undergoes ac ompetitive methyl-methyl repulsion, which slightly destabilizes the folded conformer. [3] In protonated PEA (H + PEA;F igure 1), which has been thoroughly describedp reviously, [8][9][10] the folding of the ethylammonium side chain in the gauche conformer H + PEA(G) is forced by as ingle intramolecular NH + ···p Hb ond between the terminal ammonium group and the aromatic p electron system of the phenyl ring. [8,9] The less stable extended anti conformer,H + PEA(A), in which the side chain is oriented away from the aromatic core, is not observed in the gas phase, neither at room temperature [8] nor in ac old supersonic expansion.…”

“…[3] In protonated PEA (H + PEA;F igure 1), which has been thoroughly describedp reviously, [8][9][10] the folding of the ethylammonium side chain in the gauche conformer H + PEA(G) is forced by as ingle intramolecular NH + ···p Hb ond between the terminal ammonium group and the aromatic p electron system of the phenyl ring. [8,9] The less stable extended anti conformer,H + PEA(A), in which the side chain is oriented away from the aromatic core, is not observed in the gas phase, neither at room temperature [8] nor in ac old supersonic expansion. [9] This contrasts with the results obtained for neutralP EA, which experimentally adopts four different anti and gauche conformations in the gas phase.…”

“…Comparison of the experimental IRPD spectra of the untagged,Ar-, and Ne-tagged H + PEA-H 2 Oc lusters with the linear IR absorption spectra calculated for the three most stable H + PEA-H 2 Oi somers (B3LYP-D3/aug-cc-pVTZ).T he experimental IRPD spectrum of H + PEA-Ne 2 and the corresponding spectrum calculated for H + PEA(G) are also plotted. [9] ChemPhysChem 2016, 17,232 -243…”