Hydration Isomers of Protonated Phenylalanine and Derivatives: Relative Stabilities from Infrared Photodissociation

Abstract

The binding sites of water molecules to protonated Phe and its derivatives are investigated using infrared photodissociation (IRPD) spectroscopy and kinetics as well as by computational chemistry. Calculated relative energies for hydration of PheH(+) at various sites on the N- and C-termini depend on the type of theory and basis set used, and no one hydration site was consistently calculated to be most favorable. Infrared photodissociation (IRPD) spectra between approximately 2650 and 3850 cm(-1) are reported for PheH(+)(H(2)O)(1-4) at 133 K and compared to calculated absorption spectra of low-energy hydration isomers, which do not resemble the IRPD spectra closely enough to unambiguously assign spectral bands. The IRPD spectra of PheH(+)(H(2)O)(1-4) are instead compared to those of N,N-Me(2)PheH(+)(H(2)O)(1,2), N-MePheH(+)(H(2)O)(1-3), and PheOMeH(+)(H(2)O)(1-3) at 133 K, which makes possible systematic band assignments. A unique band associated with a binding site not previously reported for PheH(+)(H(2)O), in which the water molecule accepts a hydrogen bond from the N-terminus of PheH(+) and donates a weak hydrogen bond to the pi-system of the side chain, is identified in the IRPD spectra. IRPD kinetics at laser frequencies resonant with specific hydration isomers are found to be biexponential for N,N-Me(2)PheH(+)(H(2)O), N-MePheH(+)(H(2)O), and PheH(+)(H(2)O). Relative populations of ions with water molecules attached at various binding sites are determined from fitting these kinetic data, and relative energies for hydration of these competitive binding sites at 133 K are obtained from these experimental values.

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

“…In addition, conformer-selective experiments,s uch as double resonance spectroscopy,could be very helpful to disentangle the assignment of the n(NH o )r ange. Another alternative would be the stepwise methylation of the amino group of PEA, as it was used for protonated phenylalanine, [29] to discriminate the different n(NH o )s ignatures, according to the location of the methyl group. Additionally,i ft he temperature effect is confirmed, the "desolvation" of binding site (1) could be studied in detail by meanso fI Ro rU Vs pectroscopy in at emperature-controlled iont rap.…”

“…Hydration of protonated amino acids has frequently been characterized because of its biological relevance. In particular,t he competition between the possible water-binding sites (NH 3 + , COOH)h as thoroughly been exploredt hrough the examples of protonated phenylalanine, [29] valine, [30] glycine, [31] tryptophan, [32,33] and tyrosine. [33] Hydration can also influence the protonation site [34][35][36] and, similar to the neutrals pecies, also the conformation of protonated biomolecules.…”

“…[66] Moreover,a ni nsertion structure similar to H + PEA(G)-H 2 O(1) has been detected for indanol-H 2 O, in which H 2 Oa cceptst he Hb ond from the hydroxy group (OH···O) and donates an OH···p Hb ond to the aromatic ring of indane, therebyl ocking the indanolc onformation. [67] Furthere xamples of hydrated protonated aromatic molecules, in which H 2 Oi nserts between an aromatic core and ap ositively charged group, include multihydrated protonated phenylalanine [29] and tryptophan. [32] In IRPD spectra of these untagged hydrates, the n(OHp)b and occurs at 3580 cm À1 ,t hat is, close to the frequency of cold H + PEA-H 2 O-Rg at 3564 cm À1 (D).…”

“…The À15 cm À1 redshift may indicatet hat H 2 Oi ss lightly more strongly p bonded in the latter clustera nd/or the clusteri sc older.H + PEA-H 2 Oi s the first monohydrate detected experimentally,i nw hich H 2 Oi s insertedb etween aprotonated primarya mine and an aromatic ring. For other protonated primary amines, like in monohydrated protonated phenylalanine, [29] tryptophan and tryptamine, [32] the insertion isomer has not been detected experimentally,b ecause it is predicted to be only al ocal minimume ven at 0K.…”

Diagnostic NH and OH Vibrations for Oxazolone and Diketopiperazine Structures: b2 from Protonated Triglycine

“…Only in the past decade, further developments of OPOs allowed IRMPD spectroscopy experiments on trapped ions in mass spectrometers [27]. Most of these photodissociation experiments have been carried out on relatively weakly-bound complexes, such as metal-and/or water-tagged complexes [28][29][30][31][32][33][34][35][36].…”