Ergothioneine and related histidine derivatives in the gas phase: tautomer structures determined by IRMPD spectroscopy and theory

Abstract

l-Ergothioneine (ET) is a sulfur-containing derivative of the amino acid histidine that offers unique antioxidant properties. The enzyme independent redox-chemistry of ET relies on the availability of the thiol tautomer to allow oxidative formation of disulfide bridges, i.e., the tautomeric equilibrium. To study the intrinsic properties of ET the tautomeric equilibrium is studied in the gas-phase by infrared multiphoton dissociation (IRMPD) spectroscopy. The IR ion spectra of isolated molecular ions of ET and of the biosynthetic precursors of ET, i.e., hercynine and N-methyl-hercynine are acquired. The analyte structures are independently investigated by density functional theory (DFT) and computed linear IR-spectra of tautomer ion structures are compared with the gas-phase spectra for identification. For the molecular ion of ET the simulated IR spectra of thione and thiol structures match the recorded IRMPD spectrum and that prevents an individual structure assignment. On the other hand, theory suggests that ET adopts a thione tautomer in MeOH solution which could be carried over from the condensed phase to gas phase and could be kinetically trapped after effective electrospray phase transfer and desolvation. Such a non-thermal behavior is also found for the molecular ions of protonated hercynine and N-methyl-hercynine. Contrary to that, the sodium complex ions of ET, hercynine and N-methyl-hercynine adopt the respective ground structures predicted by theory, which are reliably identified spectroscopically. For ET the thione tautomer is by far the most stable isomer in the sodium complex molecular ion.

Breslow Intermediates (Amino Enols) and Their Keto Tautomers: First Gas‐Phase Characterization by IR Ion Spectroscopy

“…Similar cases of nonthermal behavior have previously been reported [24–26] . A prominent example is ergothionein, a 2‐mercaptohistidine trimethyl betaine, which preferably adopts a thione tautomeric ion structure in MeOH solution, which is also carried over to and identified in the gas phase [27] …”

Hydrogen tunneling avoided: enol-formation from a charge-tagged phenyl pyruvic acid derivative evidenced by tandem-MS, IR ion spectroscopy and theory

“…a thione ion structure in the gas phase. 29 To probe this aspect, a number of geometry optimizations were performed using a simulated MeOH solvent environment. In particular, we investigated isomers 4B, 4C, 4E, and 4F as the most probable isomers in the gas phase, based on the experimental IRMPD data.…”

“…Frequencies were scaled by 0.97 in the wavenumber range of 600-1900 cm Ð1 and in the wavenumber range of 3400-3800 cm Ð1 with a factor of 0.95 to account for anharmonicity and convoluted with a Gaussian line shape function with a FWHM of 12 cm Ð1 to facilitate comparison with experiment. 29,31,43 Energy differences quoted throughout the paper are based on Gibbs free energies (298 K, 1 bar). All transition states were checked to connect the correct energy minima through an intrinsic reaction coordinate calculation.…”

Selecting and identifying gas-phase protonation isomers of nicotineH+ using combined laser, ion mobility and mass spectrometry techniques

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14] This can be an analytical problem when protomers dissociate to different product ions under activation, a phenomenon that can confound assignment by comparison to reference spectra. Differences in the photodissociation of protomers have been used to assign protomer populations, [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] although it is difficult to predict how the electronic spectroscopy and photodissociation will be affected by differences in protonation site. Hence, analysing the photodissociation of selected protomers, can provide insights into the effects of protonation on excited quantum states of ions while progressing towards the use of photo-dissociation as a method to disambiguate and assign protomers.…”

“…Previous studies have taken advantage of the differences in photoactivity of protomers and made assignments by comparing theoretical transition simulations to experimental results obtained by UV photodissociation action spectroscopy, [13][14][15][16][17][24][25] or IRMPD. [10][11][18][19][20][21][22][23] Dessent and co-workers have demonstrated the potential for moderate-resolution UV action spectra, coupled with TD-DFT analysis, to detect and assign protomers of nicotinamide and paminobenzoicacid. 12,26 These studies reported different action spectrum profiles of Oprotonated or N-protonated isomers.…”