Patricia E. Allegretti

Tautomeric equilibrium of amides and related compounds: theoretical and spectral evidences

Abstract The tautomeric equilibrium of several amides and related compounds is studied experimentally via mass spectrometry techniques. Experimental findings are complemented with theoretical calculations in order to rationalise mass spectra results of some amides, thioamides, ureas and thioureas. Some further possible studies are pointed out in order to complement present findings. Both mass spectra and theoretical results indicate that tautomerism involves neutral species rather than the ionic analogues. Besides, thio-derivatives have a relatively higher tendency to occur as imidols.

Separation of keto–enol tautomers in β-ketoesters: a gas chromatography–mass spectrometric study

Abstract The gas chromatographic behaviour for some β-ketoesters was studied. Additionally, the feasibility of the gas chromatographic separation of the corresponding tautomer forms was examined. In this work mass spectrometric detection allowed identification of both keto and enol forms and an estimation of their relative amounts for methylacetoacetate, α-chloromethylacetoacetate, ethylacetoacetate and α-chloroethylacetoacetate. This finding demonstrates slow tautomerisation kinetics permitting the chemical identity maintenance of the tautomers.

Oxidation of di- and tripeptides of tyrosine and valine mediated by singlet molecular oxygen, phosphate radicals and sulfate radicals

Kinetics and mechanism of the oxidation of tyrosine (Tyr) and valine (Val) di- and tripeptides (Tyr-Val, Val-Tyr and Val-Tyr-Val) mediated by singlet molecular oxygen [O(2)((1)Delta(g))], phosphate (HPO(4)(*-) and PO(4)(*2-)) and sulfate (SO(4)(*-)) radicals was studied, employing time-resolved O(2)((1)Delta(g)) phosphorescence detection, polarographic determination of dissolved oxygen and flash photolysis. All the substrates were highly photooxidizable through a O(2)((1)Delta(g))-mediated mechanism. Calculated quotients between the overall and reactive rate constants for the quenching of O(2)((1)Delta(g)) by Tyr-derivatives (k(t)/k(r) values, accounting for the efficiency of the effective photooxidation) were 1.3 for Tyr, 1 for Tyr-Val, 2.8 for Val-Tyr and 1.5 for Val-Tyr-Val. The effect of pH on the kinetics of the photooxidative process confirms that the presence of the dissociated phenolate group of Tyr clearly dominates the O(2)((1)Delta(g)) quenching process. Products analysis by LC-MS indicates that the photooxidation of Tyr di- and tripeptides proceeds with the breakage of peptide bonds. The information obtained from the evolution of primary amino groups upon photosensitized irradiation is in concordance with these results. Absolute rate constants for the reactions of phosphate radicals (HPO(4)(*-) and PO(4)(*2-), generated by photolysis of the P(2)O(8)(4-) at different pH) and sulfate radicals (SO(4)(*-), produced by photolysis of the S(2)O(8)(2-)) with Tyr peptides indicate that for all the substrates, the observed tendency in the rate constants is: SO(4)(*-) > or = HPO(4)(*-) > or = PO(4)(*2-). Formation of the phenoxyl radical of tyrosine was detected as an intermediate involved in the oxidation of tyrosine by HPO(4)(*-).

Determination of thermodynamic parameters of tautomerization in gas phase by mass spectrometry and DFT calculations: Keto-enol versus nitrile-ketenimine equilibria.

The study of tautomerics equilibria is really important because the reactivity of each compound with tautomeric capacity can be determined from the proportion of each tautomer. In the present work the tautomeric equilibria in some γ,δ-unsaturated β-hydroxynitriles and γ,δ-unsaturated β-ketonitriles were studied. The first family of compounds presents two possible theoretical tautomers, nitrile and ketenimine, while the second one presents four possible theoretical tautomers, keto-nitrile, enol (E and Z)-nitrile and keto-ketenimine. The equilibrium in gas phase was studied by gas chromatography-mass spectrometry (GC-MS). Tautomerization enthalpies were calculated by this methodology, and results were compared with those obtained by density functional theory (DFT) calculations, observing a good agreement between them. Nitrile tautomers were favored within the first family of compounds, while keto-nitrile tautomers were favored in the second family.

Mass Spectrometry as a Tool for the Determination of Heats of Tautomerization of Thioamides in the Gas Phase

Tautomerism of several thioamides was studied by mass spectrometry. The analysis of the corresponding mass spectra allowed some fragmentations to be assigned to specific tautomers and heats of tautomerization to be determined through temperature effects and electron energy studies. Experimental determinations were strongly supported by theoretical calculations. AM1 semi-empirical results indicate that the thioamide–thioimidol equilibrium can be studied by mass spectrometry. Also, additional evidence was obtained regarding tautomerism occurrence between neutral species.

Spectrometric and theoretical evidences for the occurrence of tautomeric structures of selected ketones

Abstract The enolisation degree of ketones is generally favoured by the increase of the steric effect exerted by the substitution α to the carbonyl group. The analysis of the corresponding mass spectra has allowed us to assign unambiguously some fragmentations to specific tautomers and to establish an acceptable correlation between the corresponding ion abundance ratios and the AM1 MO theoretical calculation of the approximate enolisation equilibrium constants.

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.

3-Hydroxy-4-methyl-4-pentenonitrile and 4-methyl-3-oxo-4-pentenonitrile: Study of the tautomerics equilibria in gas phase and in solution.

In the present work the tautomerics equilibria in 3-hydroxy-4-methyl-4-pentenonitrile and 4-methyl-3-oxo-4-pentenonitrile have been studied. The first compound presents two possible theoretical tautomers, nitrile and ketenimine. The second compound presents four possible theoretical tautomers ketonitrile, nitrile-enol (E and Z) and keto-ketenimine. The study of the equilibrium in gas phase was performed by gas chromatography-mass spectrometry (GC-MS), and in solution by proton nuclear magnetic resonance spectrometry ((1)H NMR). In gas phase, the ketonitrile tautomer was favoured, a result which was supported by theoretical calculations by the use of AM1 semi-empiric calculation. The experimental tautomerization heat values were in good agreement with the theoretical ones. The (1)H NMR spectra gave the additional evidence for the coexistence of the tautomers ketonitrile and enolnitrile for 4-methyl-3-oxo-4-pentenonitrile. The nitrile-ketenimine equilibrium for both compounds could not be observed by (1)H NMR spectra because of the low sensibility of this method. The ketonitrile-enolnitrile tautomerization heat of 4-methyl-3-oxo-4-pentenonitrile has been calculated and compared with the corresponding one in gas phase to evaluate the solvent effect.

Mass Spectral Study of the Occurrence of Tautomeric Forms of Thiohydantoins

Mass spectrometry is used to evaluate the occurrence of thio-enol structures among the several possible tautomers of thiohydantoins and dithiohydantoins. Mass spectra of differently-substituted thiohydantoins are examined looking for common mass spectral behaviors to be predicted. Ion fragmentations from specific tautomers allow the most stable thio-enol structure for both type of compounds. The mass spectrum of the alkylation product of 5,5-dimethyldithiohydantoin and the nuclear magnetic resonance spectra of the alkylation products of both 2-thiohydantoin and dithiohydantoin support the fact that the most likely thio-enol structure is determined by the presence of one or two thio-carbonyl groups in the hydantoin molecule.

The evidence for the occurrence of tautomeric structures for selected aldehydes and thioaldehydes

Mass spectra of selected aldehydes and thioaldehydes have been analyzed and specific fragmentation assignments have been done to keto and enol tautomers, although many peaks can be assigned to both forms (i.e. mass spectra are superimposed on one another). The enolization rate for aldehydes is generally favored by the increase in the steric effect caused by α substitution to the carbonyl group. The analysis of the corresponding mass spectra has allowed to establishing an acceptable correlation between selected ion abundances ratios and approximate enolization equilibrium constants (carried out by means of DFT calculations). The influence of temperature on the enol/keto selected fragments abundance ratios (for different aldehydes and thioaldehydes and for different pair of ions of the same compound whenever possible) is studied in order to estimate the enthalpy difference for the tautomeric equilibria. The results indicate that the thioketo-thioenol equilibrium can be studied by mass spectrometry and the ionization in the ion source have negligible effect on the position of that equilibrium.