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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Effect of recombinant human nerve growth factor eye drops in patients with dry eye: a phase IIa, open label, multiple-dose study

Background: Dry eye disease (DED) affects more than 14% of the elderly population causing decrease of quality of life, high costs and vision impairment. Current treatments for DED aim at lubricating and controlling inflammation of the ocular surface. Development of novel therapies targeting different pathogenic mechanisms is sought-after. The aim of this study is to evaluate safety and efficacy of recombinant human nerve growth factor (rhNGF) eye drops in patients with DED. Methods: Forty consecutive patients with moderate to severe DED were included in a phase IIa, prospective, open label, multiple-dose, clinical trial to receive rhNGF eye drops at 20 μg/mL (Group 1: G1) or at 4 μg/mL (Group 2: G2) concentrations, two times a day in both eyes for 28 days (NCT02101281). The primary outcomes measures were treatment-emerged adverse events (AE), Symptoms Assessment in Dry Eye (SANDE) scale, ocular surface staining and Schirmer test. Results: Of 40 included patients, 39 completed the trial. Both tested rhNGF eye drop concentrations were safe and well tolerated. Twenty-nine patients experienced at least one AE (14 in G1 and 15 in G2), of which 11 had at least 1 related AE (8 in G1 and 3 in G2). Both frequency and severity of DED symptoms and ocular surface damage showed significant improvement in both groups, while tear function improved only in G1. Conclusions: The data of this study indicate that rhNGF eye drops in both doses is safe and effective in improving symptoms and signs of DED. Randomised clinical trials are ongoing to confirm the therapeutic benefit of rhNGF in DED. Trial registration number: NCT02101281

A structural study of a C3H3 species coadsorbed with CO on Pd(1 1 1)

The combination of chemical-state-specific C 1s scanned-energy mode photoelectron diffraction (PhD) and O K-edge near-edge X-ray absorption fine structure (NEXAFS) has been used to determine the local adsorption geometry of the coadsorbed C3H3 and CO species formed on Pd(1 1 1) by dissociation of molecular furan. CO is found to adopt the same geometry as in the Pd(1 1 1)c(4 × 2)-CO phase, occupying the two inequivalent three-fold coordinated hollow sites with the C–O axis perpendicular to the surface. C3H3 is found to lie with its molecular plane almost parallel to the surface, most probably with the two ‘outer’ C atoms in equivalent off-atop sites, although the PhD analysis formally fails to distinguish between two distinct local adsorption sites

The adsorption structure of furan on Pd(1 1 1)

The structure of molecular furan, C4H4O, on Pd(1 1 1) has been investigated by O K-edge near-edge X-ray absorption fine structure (NEXAFS) and C 1s scanned-energy mode photoelectron diffraction (PhD). NEXAFS shows the molecule to be adsorbed with the molecular plane close to parallel to the surface, a conclusion confirmed by the PhD analysis. Chemical-state specific C 1s PhD data were obtained for the two inequivalent C atoms in the furan, the α-C atoms adjacent to the O atom, and the β-C atoms bonded only to C atoms, but only the PhD modulations for the α-C emitters were of sufficiently large amplitude for detailed evaluation using multiple scattering calculations. This analysis shows the α-C atoms to be located approximately 0.6 Å off-atop surface Pd atoms with an associated C–Pd bondlength of 2.13 ± 0.03 Å. Two alternative local geometries consistent with the data place the O atom in off-atop or near-hollow locations, and for each of these local structures there are two equally-possible registries relative to the fcc and hcp hollow sites. The results are in good agreement with earlier density functional theory calculations which indicate that the fcc and hcp registries are equally probable, but the PhD results fail to distinguish the two distinct local bonding geometries

Participatory design, beyond the local

This workshop aims at stimulating and opening a debate around the capacity of Participatory Design (PD) and other co-design approaches to deliver outcomes and methodologies that can have an impact and value for reuse well beyond the local context in which they were originally developed. This will be achieved by stimulating the submission of position papers by researchers from the PD community and beyond.These papers will be discussed during the workshop in order to identify challenges, obstacles but also potentials for scaling up PD processes and results from the local to the global.</p

Photoelectron diffraction: from phenomenological demonstration to practical tool

The potential of photoelectron diffraction—exploiting the coherent interference of directly-emitted and elastically scattered components of the photoelectron wavefield emitted from a core level of a surface atom to obtain structural information—was first appreciated in the 1970s. The first demonstrations of the effect were published towards the end of that decade, but the method has now entered the mainstream armoury of surface structure determination. This short review has two objectives: First, to outline the way that the idea emerged and the way this evolved in my own collaboration with Neville Smith and his colleagues at Bell Labs in the early years: Second, to provide some insight into the current state-of-the art in application of (scanned-energy mode) photoelectron diffraction to address two key issue in quantitative surface structure determination, namely, complexity and precision. In this regard a particularly powerful aspect of photoelectron diffraction is its elemental and chemical-state specificity

Validation of the inverted adsorption structure for free-base tetraphenyl porphyrin on Cu(111)

Utilising normal incidence X-ray standing waves we rigourously scrutinise the “inverted model” as the adsorption structure of free-base tetraphenyl porphyrin on Cu(111). We demonstrate that the iminic N atoms are anchored at near-bridge adsorption sites on the surface displaced laterally by 1.1 ± 0.2 Å in excellent agreement with previously published calculations

Photoelectron diffraction investigation of the structure of the clean TiO2(110)(1×1) surface

The surface relaxations of the rutile TiO2(110)(1×1) clean surface have been determined by O 1 s and Ti 2p3∕2 scanned-energy mode photoelectron diffraction. The results are in excellent agreement with recent low-energy electron diffraction (LEED) and medium energy ion scattering (MEIS) results, but in conflict with the results of some earlier investigations including one by surface x-ray diffraction. In particular, the bridging O atoms at the surface are found to relax outward, rather than inward, relative to the underlying bulk. Combined with the recent LEED and MEIS results, a consistent picture of the structure of this surface is provided. While the results of the most recent theoretical total-energy calculations are qualitatively consistent with this experimental consensus, significant quantitative differences remain

Food habits, Life style, Genetic background in tumour initiation and progression of Reproductive system

The relationship between diet and health is really engaging, it has been showed that modifications in dietary intake and the benefits of the Mediterranean diet, can importantly increase life expectancy, reducing the risk of chronic disease and improve quality of life. In this way, several studies assigned a highest reduction in tumor incidence to monosaturated and saturated lipids present in vegetables, such olive oil. On these basis, this study will be focused on the comprehension and understanding of initiation and progression phases linked to environmental stressors and food habits in the tumours of the reproductive system (breast and ovarian cancer). Recently it has been described the potential effect of the olive tree (Olea europaea) leaves, oil and fruits to inhibit proliferation and to induce apoptosis in different cancer cell lines. The phenolic fraction of Olive extract becomes specially interesting, including a polyphenol called Oleuropein (OL) present at higher levels in olives and leaves- as well as its hydrolysis metabolite, Hydroxytyrosol (HT). Taking this background into account, we have focused our research in the analysis of Olive leaf extracts with a high content in OL (48%) as a potential cell viability reducing agent on a malignant triple negative breast cancer cell line, MDA-MB- 231, which is highly aggressive. On this model, cell viability was measured with a MTS assay 24 and 48 h after the treatment with the Olive extract. The preliminary results seem to indicate that this extract at high concentrations (200-400µg/mL) determines a reduction in the MDA- MB-231 cell viability