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. 
&#xa

Remoción de plaguicidas MCPA e Imazapic de solución acuosa con materiales carbonosos

El objetivo general de este trabajo se orienta a la búsqueda de alternativas simples y accesibles para la remediación de aguas contaminadas, teniendo en cuenta que la presencia de contaminantes emergentes en nuestros recursos hídricos, tales como fármacos y pesticidas, es motivo de preocupación para la salud y seguridad ambiental. Se realizaron estudios de adsorción de dos pesticidas: MCPA (ácido 4-cloro-2-metil fenoxiacético) e Imazapic (ácido 2-[4,5-dihidro-4-metil-4-(1-metiletil)-5-oxo-1H-imidazol-2-il]-5-metil-3-piridin carboxílico), en dos diferentes tipos de material carbonoso. Fueron utilizados dos tipos de carbón activado, cada uno con diferentes características físicas y químicas, CAT-Ox 4 sulfuro de hidrógeno, adquirido en pellets de 4mm y CARBOPAL MB 4S (Donau). Se realizaron diferentes experimentos en batch de los herbicidas MCPA e Imazapic sobre dos tipos de carbón activado, CAT y CARBOPAL, bajo diferentes condiciones. Ambos materiales parecen ser muy efectivos removiendo estos contaminantes, pero CAT parece tener una mayor capacidad. Ambos pesticidas siguen cinéticas de adsorción de pseudo segundo orden en ambos materiales, lo que indicaría una mayor contribución de quimisorción con formación de monocapa. La capacidad de adsorción (qe) de herbicidas es significativamente influenciada por el valor de pH. En el presente estudio, ambos pesticidas tienen una disminución en la capacidad de adsorción cuando se utilizan condiciones básicas debido a que la superficie de los carbones están cargadas negativamente y en estas condiciones los herbicidas se encuentran en forma aniónica. Además, diferentes modelos fueron analizados para predecir propiedades de cada proceso de adsorción. MCPA se adapta al modelo teórico de Langmuir en ambos materiales. Debido a esto, se predice un proceso de quimisorción con la formación de una monocapa. Por otro lado, Imazapic se adapta al modelo GAB sobre CAT y CARBOPAL, con la formación de multicapas. La capacidad de adsorción es muy alta, por lo que ambos materiales pueden ser usados como método efectivo y de bajo costo para remover MCPA e Imazapic de recursos acuosos.Trabajo presentado por el Centro de Estudio de Compuestos Orgánicos (CEDECOR

Mass spectrometric study of the photooxidation of the ophthalmic drugs timolol and pindolol

A mass spectrometric study of the photooxidation products of the ophthalmic drugs pindolol (1-[1H-indol-4-yloxyl]-3-[isopropylamino]-2-propanol) and timolol (S-[-]-1-[t-butylamino]-3-[(4-morpholino-1,2,5-thiadiazol-3-yl)oxyl]-2-propanol) in water has been performed by LC-MS. Based on these data and the assumption that photooxidation mainly occurs through singlet molecular oxygen attack, a possible reaction mechanism is proposed. The mechanistic pathways involve singlet oxygen attack to the pindolol indole ring and oxidation of the pindolol isopropyl or timolol terbutyl methyl groups.Instituto de Investigaciones Fisicoquímicas Teóricas y AplicadasLaboratorio de Estudio de Compuestos Orgánico

A large ongoing outbreak of hepatitis A predominantly affecting young males in Lazio, Italy; August 2016 - March 2017

The hepatitis A virus (HAV) is mainly transmitted through the faecal-oral route. In industrialized countries HAV infection generally occurs as either sporadic cases in travelers from endemic areas, local outbreak within closed/semi-closed population and as foodborne community outbreak. Recently, an increasing number of HAV infection clusters have been reported among young men-who-have-sex-with-men (MSM). The Lazio Regional Service for the epidemiology and control for infectious diseases (SeRESMI) has noticed an increase of acute hepatitis A (AHA) since September 2016. Temporal analysis carried out with a discrete Poisson model using surveillance data between January 2016 and March 2017 evidenced an ongoing outbreak of AHA that started at the end of August. Molecular investigation carried out on 130 out of 513 cases AHA reported until March 2017 suggests that this outbreak is mainly supported by an HAV variant which is currently spreading within MSM communities across Europe (VRD_521_2016). The report confirms that AHA is an emerging issue among MSM. In addition through the integration of standard (case based) surveillance with molecular investigation we could discriminate, temporally concomitant but epidemiologically unrelated, clusters due to different HAV variants. As suggested by the WHO, in countries with low HAV circulation, vaccination programmes should be tailored on the local epidemiological patterns to prevent outbreaks among high risk groups and eventual spillover of the infection in the general population

A large ongoing outbreak of hepatitis A predominantly affecting young males in Lazio, Italy; August 2016 - March 2017

The hepatitis A virus (HAV) is mainly transmitted through the faecal-oral route. In industrialized countries HAV infection generally occurs as either sporadic cases in travelers from endemic areas, local outbreak within closed/semi-closed population and as foodborne community outbreak. Recently, an increasing number of HAV infection clusters have been reported among young men-who-have-sex-with-men (MSM). The Lazio Regional Service for the epidemiology and control for infectious diseases (SeRESMI) has noticed an increase of acute hepatitis A (AHA) since September 2016. Temporal analysis carried out with a discrete Poisson model using surveillance data between January 2016 and March 2017 evidenced an ongoing outbreak of AHA that started at the end of August. Molecular investigation carried out on 130 out of 513 cases AHA reported until March 2017 suggests that this outbreak is mainly supported by an HAV variant which is currently spreading within MSM communities across Europe (VRD_521_2016). The report confirms that AHA is an emerging issue among MSM. In addition through the integration of standard (case based) surveillance with molecular investigation we could discriminate, temporally concomitant but epidemiologically unrelated, clusters due to different HAV variants. As suggested by the WHO, in countries with low HAV circulation, vaccination programmes should be tailored on the local epidemiological patterns to prevent outbreaks among high risk groups and eventual spillover of the infection in the general population

Tautomeric acetoacetate monomers as building units of functional copolymers

Although synthetic polymers from tautomeric functional monomers have emerged as a new kind of materials due to potential applications their interest needs still to be revealed. In this work we have synthesized two series of tautomeric acetoacetate copolymers, with different composition, microstructure and properties. We have selected allyl acetoacetate (AAA) and 2-(acetoacetoxy)ethyl methacrylate (AEMA) monomers to copolymerize with styrene (St). The bulk copolymerization initiated with azobisisobutyronitrile was carried out at 60 °C for different monomer feed compositions and times. The products were characterized by 1H NMR, HSQC NMR and size exclusion chromatography. The calculated monomer reactivity ratio obtained for poly(St-co-AAA) and for poly(St-co-AEMA), show noteworthy differences in the copolymerization behavior; r1r2 take values near 1 and zero for poly(St-co-AAA) and poly(St-co-AEMA), respectively. The glass transition temperature (Tg) values for copolymers were determined by differential scanning calorimetry. Two Tg temperatures were found for poly(St-co-AAA) which were close to the Tg values of corresponding homopolymers. On the other hand, only one Tg values characterized the St-co-AEMA copolymers system. Thermal stability has been studied by thermo gravimetric analysis (TGA). The copolymers St-co-AAA and St-co-AEMA exhibited higher thermal stability than homopolymer AAA and AEMA, respectively. Due to the functional group present in both monomers, they exhibit tautomeric equilibrium; an interesting NMR study in solution allowed us to demonstrate that the displacement of equilibrium depends on composition, microstructure and solvents. In view of future applications as nanomatrices for tissue engineering, these tautomeric copolymers (St-co-AAA), were nanostructured in AAO nanocavities and its morphological and surface characteristics analyzed by SEM.Peer Reviewe

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

Enol and Enethiol Occurrence for Some Ketones and Thioketones. Mass Spectrometry and Theoretical Calculations

Abstract: The mass spectra of ketones can provide valuable information with regards to keto-enol equilibria occurring in the gas phase. Mass spectra of selected ketones and thioketones have been analysed and specific fragmentation assignments have been done to characterised and weigh co-existing keto and enol tautomers. Thioketones are of particular interest due to their tendency to shift the tautomeric equilibrium towards the enethiol form. The predictive value of this methodology is not only supported by the influence of these compound’s nature and size of the substituent on these equilibria but also by the good correlation found between the selected fragments abundances ratio and semi-empirical calculation (AM1) of the corresponding heats of tautomerization

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.Fil: Ruiz, Danila Luján. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Química. Laboratorio de Estudio de Compuestos Orgánicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Schiavoni, Maria de Las Mercedes. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Química. Laboratorio de Estudio de Compuestos Orgánicos; ArgentinaFil: Laurella, Sergio Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Química. Laboratorio de Estudio de Compuestos Orgánicos; ArgentinaFil: Giussi, Juan Martín. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Química. Laboratorio de Estudio de Compuestos Orgánicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Furlong, Jorge J.P.. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Química. Laboratorio de Estudio de Compuestos Orgánicos; ArgentinaFil: Allegretti, Patricia E.. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Química. Laboratorio de Estudio de Compuestos Orgánicos; Argentin