Tautomeric Equilibria Studies by Mass Spectrometry

Tautomerism in organic chemistry has been extensively studied in condensed phase by spectrometric methods, mainly by IR and NMR techniques. Mass spectrometry studies start 40 years ago but just recently it has been recognized the importance of the mass spectral data for the study of tautomerism in the gas phase.
Mass spectrometry can provide valuable information in regard to tautomeric equilibria when studying mass spectra among the members of different families of organic compounds.
The relevance of the mass spectral data resides on several facts but there are two that are of key importance:
1-	Mass spectral fragmentation assignments should be tautomer specific since the corresponding abundances ratios are supposed to be correlated to the keto/enol contents.
2-	Ionization in the ion source is supposed to have no effect on the position of the equilibrium so that the results reflect the tautomers content in the gas phase previous to ionization.
Some of the carbonylic compounds do not exhibit noticeable tautomerism so the fragment abundances assigned to the enol form is very low or not measurable. Since enolization is more noticeable in the case of thio-derivatives (which correlates adequately with the oxygenated analogues), the study of their mass spectra is an interesting choice to reach some degree of generalization. 
In addition, experimental findings are supported by semiempirical theoretical calculations, which probed to be adequate not only for supporting tendency correlations among the members of a compound family but also to calculate heats of tautomerization in gas phase.
Reports using mass spectrometry for tautomerism are becoming less common. One of the reasons is that now it would appear that the interpretation of MS results is not as straightforward as it was once believed, even though in a recent review it was written that: “Mass spectrometry is the most informative and practical method for studying and identifying tautomers in the gas phase” [1]. 
In fact, mass spectrometry seems to be very informative for studying and identifying tautomers, because in this case external factors like solvents, intermolecular interactions, etc., can be excluded by transferring the tautomeric system into gas phase, where the process becomes truly unimolecular [1].
This review covers the study of Tautomerism by Mass Spectrometry in the last four decades. 
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Evidence for a Double Well in the First Triplet Excited State of 2-Thiouracil

The computationally predicted presence of two structurally distinct minima in the first triplet excited (T₁) state of 2-thiouracil (2TU) is substantiated by sub-picosecond transient vibrational absorption spectroscopy (TVAS) in deuterated acetonitrile solution. Following 300 nm ultraviolet excitation to the second singlet excited state of 2TU, a transient infrared absorption band centered at 1643 cm^–1 is observed within our minimum time resolution of 0.3 ps. It is assigned either to 2TU molecules in the S₁ state or to vibrationally hot T₁-state molecules, with the latter assignment more consistent with recent computational and experimental studies. The 1643 cm^–1 band decays with a time constant of 7.2 ± 0.8 ps, and there is corresponding growth of several further bands centered at 1234, 1410, 1424, 1443, 1511, 1626, and 1660 cm^–1 which show no decline in intensity over the 1 ns time limit of our measurements. These spectral features are assigned to two different conformations of 2TU, corresponding to separate energy minima on the T₁-state potential energy surface, on the basis of their extended lifetimes, computed infrared frequencies, and the observed quenching of the bands by addition of styrene. Corresponding measurements for the 4-thiouracil (4TU) isomer show sub-picosecond population of the T₁ state, which vibrationally cools with a time constant of 5.2 ± 0.6 ps. However, TVAS measurements in the carbonyl stretching region do not distinguish the two computed T₁-state conformers of 4TU because of the similarity of their vibrational frequencies

Photofragment Translational Spectroscopy Studies of H Atom Loss Following Ultraviolet Photoexcitation of Methimazole in the Gas Phase

The ultraviolet (UV) photodissociation of gas-phase methimazole has been investigated by H Rydberg atom photofragment translational spectroscopy methods at many wavelengths in the range of 222.5–275 nm and by complementary electronic structure calculations. Methimazole is shown to exist predominantly as the thione tautomer, 1-methyl-2­(3H)-imidazolinethione, rather than the commonly given thiol form, 2-mercapto-1-methylimidazole. The UV absorption spectrum of methimazole is dominated by the S4 ← S0 transition of the thione tautomer, which involves electron promotion from an a′ (py) orbital localized on the sulfur atom to a σ* orbital localized around the N–H bond. Two H atom formation pathways are identified following UV photoexcitation. One, involving prompt, excited-state N–H bond fission, yields vibrationally cold but rotationally excited methimazolyl (Myl) radicals in their first excited (Ã) electronic state. The second yields H atoms with an isotropic recoil velocity distribution peaking at low kinetic energies but extending to the energetic limit allowed by energy conservation given a ground-state dissociation energy D0(Myl–H) ∼24 000 cm–1. These latter H atoms are attributed to the unimolecular decay of highly vibrationally excited S0 parent molecules. The companion electronic structure calculations provide rationales for both fragmentation pathways and the accompanying product energy disposals and highlight similarities and differences between the UV photochemistry of methimazole and that of other azoles (e.g., imidazole) and with molecules like thiourea and thiouracil that contain similar N–CS motifs

An ab initio and AIM investigation into the hydration of 2-thioxanthine

<p>Abstract</p> <p>Background</p> <p>Hydration is a universal phenomenon in nature. The interactions between biomolecules and water of hydration play a pivotal role in molecular biology. 2-Thioxanthine (2TX), a thio-modified nucleic acid base, is of significant interest as a DNA inhibitor yet its interactions with hydration water have not been investigated either computationally or experimentally. Here in, we reported an <it>ab initio </it>study of the hydration of 2TX, revealing water can form seven hydrated complexes.</p> <p>Results</p> <p>Hydrogen-bond (H-bond) interactions in 1:1 complexes of 2TX with water are studied at the MP2/6-311G(d, p) and B3LYP/6-311G(d, p) levels. Seven 2TX^...H₂O hydrogen bonded complexes have been theoretically identified and reported for the first time. The proton affinities (PAs) of the O, S, and N atoms and deprotonantion enthalpies (DPEs) of different N-H bonds in 2TX are calculated, factors surrounding why the seven complexes have different hydrogen bond energies are discussed. The theoretical infrared and NMR spectra of hydrated 2TX complexes are reported to probe the characteristics of the proposed H-bonds. An improper blue-shifting H-bond with a shortened C-H bond was found in one case. NBO and AIM analysis were carried out to explain the formation of improper blue-shifting H-bonds, and the H-bonding characteristics are discussed.</p> <p>Conclusion</p> <p>2TX can interact with water by five different H-bonding regimes, N-H^...O, O-H^...N, O-H^...O, O-H^...S and C-H^...O, all of which are medium strength hydrogen bonds. The most stable H-bond complex has a closed structure with two hydrogen bonds (N(7)-H^...O and O-H^...O), whereas the least stable one has an open structure with one H-bond. The interaction energies of the studied complexes are correlated to the PA and DPE involved in H-bond formation. After formation of H-bonds, the calculated IR and NMR spectra of the 2TX-water complexes change greatly, which serves to identify the hydration of 2TX.</p

Raman and Computational Study on the Adsorption of Xanthine on Silver Nanocolloids

Xanthine is a nucleobase, deriving from adenine and guanine by deamination and oxidation processes, which may deposit in the human body causing diseases, similar to uric acid. Here, we have investigated the adsorption of xanthine on silver colloidal nanoparticles by means of surface-enhanced Raman scattering (SERS) with an exciting radiation in the near-infrared spectral region, where interference due to fluorescence does not occur, along with density functional theory calculations of molecule/metal model systems. By adopting a combined experimental and computational approach, we have identified the "marker" SERS bands of xanthine and the tautomer that preferentially binds the silver particles, as well as the molecular group involved in the interaction with metal. This investigation allows using the FT-SERS spectroscopy for biosensory and diagnostic purposes in body fluids, detecting abnormal levels of xanthine, and preventing metabolic diseases

Estudio de enlaces y reactividad unimolecular de dicationes organicos en fase gas

Tesis doctoral inédita. Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Quimica. Fecha de lectura: 12-12-200

Mass spectrometry as a tool for studying tautomerism

The review contains new data on tautomerism of organic compounds belonging to different classes, which were obtained by mass spectrometry and confirmed by quantum-chemical calculations.Laboratorio de Estudio de Compuestos OrgánicosInstituto de Investigaciones Fisicoquímicas Teóricas y Aplicada

Synergy effects in heavy metal Ion chelation with aryl- and aroyl-substituted thiourea derivatives

Detection and removal of metal ion contaminants have attracted great interest due to the health risks that they represent for humans and wildlife. Among the proposed compounds developed for these purposes, thiourea derivatives have been shown as quite efficient chelating agents of metal cations and have been proposed for heavy metal ion removal and for components of high-selectivity sensors. Understanding the nature of metal-ionophore activity for these compounds is thus of high relevance. We present a theoretical study on the interaction between substituted thioureas and metal cations, namely, Cd2+, Hg2+, and Pb2+. Two substituent groups have been chosen: 2-furoyl and m-trifluoromethylphenyl. Combining density functional theory simulations with wave function analysis techniques, we study the nature of the metal-thiourea interaction and characterize the bonding properties. Here, it is shown how the N,N′-disubstituted derivative has a strong affinity for Hg2+, through cation-hydrogen interactions, due to its greater oxidizing capacityR.B. acknowledges Fundación Carolina, Spain, for a Ph.D. fellowship. This work was partially supported by the MICINN, Spanish Ministry of Science and Innovation, project PID2019-110091GB-I00 and the “María de Maeztu” Program for Centers of Excellence in R&D (CEX2018-000805-M

Spectrometric Study of the Nitrile-Ketenimine Tautomerism

Mass spectrometry is used to evaluate the occurrence of the nitrile-ketenimine tautomerism. Mass spectra of two differently substituted nitriles, ethyl-4,4-dicyano-3-methyl-3-butenoate and diethyl-2-cyano-3-methyl-2-pentenodiate are examined looking for common mass spectral behaviors. Ion fragmentation assignments for specific tautomers allow to predict the presence of the corresponding structures. Additionally, the mass spectrum and nuclear magnetic resonance spectra of ethyl-4,4-dicyano-2,2-diethyl-3-methyl-3-butenoate and that of the corresponding amination product support the occurrence of the ketenimine tautomer in the equilibrium.Laboratorio de Estudio de Compuestos Orgánico