Infrared spectroscopy of protonated neurotransmitters: dopamine, histamine, serotonin

Infrared spectra of the protonated neurotransmitter histamine: competition between imidazolium and ammonium isomers in the gas phase.

Anita Lagutschenkov, Judith Langer, Giel Berden, Jos Oomens and Otto Dopfer

The infrared (IR) spectrum of protonated histamine (histamineH+) was recorded in the 575–1900 cm-1 fingerprint range by means of IR multiple photon dissociation (IRMPD) spectroscopy. The IRMPD spectrum of mass-selected histamineH+ ions was obtained in a Fourier transform ion cyclotron resonance mass spectrometer coupled to an electrospray ionization source and an IR free electron laser. A variety of isomers were identified and characterized by quantum chemical calculations at the B3LYP and MP2 levels of theory using the cc-pVDZ basis set. The low-energy isomers are derived from various favourable protonation sites—all of which are N atoms—and different orientations of the ethylamine side chain with respect to the heterocyclic imidazole ring. The measured IRMPD spectrum was monitored in the NH3 loss channel and exhibits 14 bands in the investigated spectral range, which were assigned to vibrational transitions of the most stable isomer, denoted A. This imidazolium-type isomer A with protonation at the imidazole ring and gauche conformation of the ethylamine side chain is significantly stabilized by an intramolecular ionic Np–H+Na hydrogen bond to the ethylamino group. The slightly less stable ammonium-type isomer B with protonation at the ethylamino group is only a few kJ mol-1 higher in energy and may also provide a minor contribution to the observed IRMPD spectrum. Isomer B is derived from A by simple proton transfer from imidazole to the ethylamino group along the intramolecular Np–H+Na hydrogen bond via a low barrier, which is calculated to be of the order of 5–15 kJ mol-1. Significantly, the most stable structure of isolated histamineH+ differs from that in the condensed phase by both the protonation site and the conformation of the side chain, emphasizing the important effects of solvation on the structure and function of this neurotransmitter. The effects of protonation on the geometric and electronic structure of histamine are evaluated by comparing the calculated properties of isomer A with those of the most stable structure of neutral histamine A(n). © 2011 the Owner Societies.
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Reference: Physical Chemistry Chemical Physics 13 (2011) 15644-15656.

Infrared Spectra of Protonated Neurotransmitters: dopamine

Anita Lagutschenkov, Judith Langer, Giel Berden, Jos Oomens, and Otto Dopfer

Abstract: The infrared (IR) spectrum of the isolated protonated neurotransmitter dopamine was recorded in the fingerprint range (570–1880 cm-1) by means of IR multiple photon dissociation (IRMPD) spectroscopy. The spectrum was obtained in a Fourier transform ion cyclotron resonance mass spectrometer equipped with an electrospray ionization source, which was coupled to a free electron laser (FEL). The spectroscopic studies are complemented by quantum chemical calculations at the B3LYP and MP2 levels of theory using the cc-pVDZ basis set. Several low-energy isomers with protonation occurring at the amino group are predicted in the energy range 0–50 kJ mol-1. Good agreement between the measured IRMPD spectrum and the calculated linear absorption spectra is observed for the two gauche conformers lowest in energy and free energy at both levels of theory, denoted g-1 and g+1. Minor contributions of higher lying gauche isomers cannot be ruled out spectroscopically but their calculated energies suggest only minor population in the sampled ion cloud. In all these gauche structures, one of the three protons of the ammonium group is pointing toward the catechol subunit, thereby maximizing the intramolecular NH–p interaction of the positive charge with the aromatic ring. In total, 16 distinct vibrational bands are observed in the IRMPD spectrum and assigned to individual normal modes of the energetically most stable g-1 conformer, with deviations of less than 24 cm-1 (average 11 cm-1) between measured and calculated frequencies. Comparison with neutral dopamine reveals the effects of protonation on the geometric and electronic structure. © 2011 the Owner Societies.
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Reference: Physical Chemistry Chemical Physics 13 (2011) 2815-2823.

Infrared Spectra of Protonated Neurotransmitters: Serotonin

Anita Lagutschenkov, Judith Langer, Giel Berden, Jos Oomens, and Otto Dopfer

Abstract: The gas-phase IR spectrum of the protonated neurotransmitter serotonin (5-hydroxytryptamine) was measured in the fingerprint range by means of IR multiple photon dissociation (IRMPD) spectroscopy. The IRMPD spectrum was recorded in a Fourier transform ion cyclotron resonance mass spectrometer coupled to an electrospray ionization source and an IR free electron laser. Quantum chemical calculations at the B3LYP and MP2 levels of theory using the cc-pVDZ basis set yield six low-energy isomers in the energy range up to 40 kJ/mol, all of which are protonated at the amino group. Protonation at the indole N atom or the hydroxyl group is substantially less favorable. The IRMPD spectrum is rich in structure and exhibits 22 distinguishable features in the spectral range investigated (530-1885 cm-1). The best agreement between the measured IRMPD spectrum and the calculated linear IR absorption spectra is observed for the conformer lowest in energy at both levels of theory, denoted g-1. In this structure, one of the three protons of the ammonium group points toward the indole subunit, thereby maximizing the intramolecular NH+-p interaction between the positive charge of the ammonium ion and the aromatic indole ring. This mainly electrostatic cation-p interaction is further stabilized by significant dispersion forces, as suggested by the substantial differences between the DFT and MP2 energies. The IRMPD bands are assigned to individual normal modes of the g-1 conformer, with frequency deviations of less than 29 cm-1 (average less than 13 cm-1). The effects of protonation on the geometric and electronic structure are revealed by comparison with the corresponding structural, energetic, electronic, and spectroscopic properties of neutral serotonin. © 2010 American Chemical Society.
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Reference: Journal of Physical Chemistry A 114 (2010) 13268-13276.

Principal investigator: Otto Dopfer