Photo-activated Carbon dots (CDs) as Catalysts in the Knoevenagel Condensation: A Mechanistic Study by Dual-Mode Monitoring via ESI-MS.

Carbon dots (CDs) obtained from 5-(hydroxymethyl)furfural (5-HMF) were activated by a 365 nm-UV irradiation source and employed in the Knoevenagel condensation to investigate their photocatalytic mechanism. To this end, electrospray ionization mass spectrometry (ESI-MS) was used to monitor the time progress of the condensation and follow the formation of the final product in positive and negative ion modes at once. The intervention of the superoxide radical anion in the photocatalytic mechanism of CDs was highlighted.

Stereoselectivity in electrosprayed confined volumes: asymmetric synthesis of warfarin by diamine organocatalysts in microdroplets and thin films.

The asymmetric synthesis of warfarin in microdroplets and thin films generated by an electrospray ionization (ESI) source is reported. This is one of the first examples of an enantioselective organocatalyzed reaction in electrosprayed confined volumes. The optimal conditions in terms of system setting were established for this reaction.

Sulfuric Acid Catalyzed Esterification of Amino Acids in Thin Film.

The esterification reaction of different amino acids with methanol catalyzed by H2SO4 was first studied in the small volume of thin films generated by ESI microdroplet deposition. The reaction is promoted by the pneumatic spray of the ESI source and reaches its maximum efficiency at a thin film temperature of 70 °C. Selective esterification of the COOH moiety was demonstrated. Microdroplet size and thin film volume and lifetime are critical parameters that influenced the reaction outcome. As expected, l-tyrosine and l-phenylalanine having aromatic side chain substituents were the most reactive amino acids, reaching absolute yields of around 40-50%. The amino acid esterification catalyzed by H2SO4 in a thin film occurs under synthetic conditions in which the same reaction in the bulk is not observed.

Sulfur Dioxide Oxidation by Zinc and Zinc Oxide Nitrate/Nitrite Complexes in the Gas Phase: An Interplay between Redox-Active Ligands and Metal.

Different oxidative pathways of sulfur dioxide promoted by ZnO(NO3 )2 - , Zn(NO3 )2 - and Zn(NO2 )(NO3 )- are revealed by a joint investigation by mass spectrometry and theoretical calculations. The reactions are triggered by [Zn2+ -O- ⋅]+ or by the low-valence Zn+ through oxygen ion transfer or electron transfer to SO2 , respectively. The NOx - ligands intervene in the oxidation only when sulfur dioxide is converted to SO3 - or SO2 - , leading to the formation of zinc sulfate and zinc sulfite coordinated to nitrate or nitrite anions. Kinetic analyses show that the reactions are fast and efficient, and theory discloses the elementary steps, namely oxygen ion transfer, oxygen atom transfer and electron transfer, occurring through similar energy landscapes for the three reactive anions.

In-Depth Chemical Characterization of Punica granatum L. Seed Oil.

Fruit seeds belonging to the pomegranate cultivar "Granata" were subjected to extraction and oily component analysis, with the aim of obtaining information about their composition. The presence of conjugated isomers of linolenic acid (CLNA isomers) in the oily phase extracted from the seeds gives a high added value to this part of the fruit, which is too often considered and treated as waste. The separated seeds were subjected to a classic Soxhlet extraction with n-hexane or extraction with supercritical CO2, assisted by ethanol. The resulting oils were evaluated by 1H and 13C-NMR and AP-MALDI-MS techniques. Differences in the triacylglycerols composition, with particular regard to punicic acid and other CLNA content, were studied in depth. Results showed the prevalence of punicic acid in the triacylglycerol mixture up to the 75%, with clear preponderance in the extract by supercritical fluids. Consequently, other CLNA isomers are, altogether, two-fold less represented in the supercritical extract than in the Soxhlet one. The two oily residues were subjected to solid phase extraction (SPE) and to HPLC-DAD analysis for the polyphenolic isolation and characterization. In addition to HPLC analysis, which showed different content and composition, DPPH analysis to evaluate the antiradical potential showed that the extract obtained with supercritical CO2 was much more active.

Intrarectal Administration of Adelmidrol plus Hyaluronic Acid Gel Ameliorates Experimental Colitis in Mice and Inhibits Pro-Inflammatory Response in Ex Vivo Cultured Biopsies Derived from Ulcerative Colitis-Affected Patients.

Improving clinical outcomes and delaying disease recrudescence in Ulcerative Colitis (UC) patients is crucial for clinicians. In addition to traditional and new pharmacological therapies that utilize biological drugs, the development of medical devices that can ameliorate UC and facilitate the remission phase should not be overlooked. Drug-based therapy requires time to be personalized and to evaluate the benefit/risk ratio. However, the increasing number of diagnosed UC cases worldwide necessitates the exploration of new strategies to enhance clinical outcomes. By incorporating medical devices alongside pharmacological treatments, clinicians can provide additional support to UC patients, potentially improving their condition and slowing down the recurrence of symptoms. Chemically identified as an azelaic acid derivative and palmitoylethanolamide (PEA) analog, adelmidrol is a potent anti-inflammatory and antioxidant compound. In this study, we aimed to evaluate the effect of an intrarectal administration of 2% adelmidrol (Ade) and 0.1% hyaluronic acid (HA) gel formulation in both the acute and resolution phase of a mouse model of colitis induced via DNBS enema. We also investigated its activity in cultured human colon biopsies isolated from UC patients in the remission phase at follow-up when exposed in vitro to a cytomix challenge. Simultaneously, with its capacity to effectively alleviate chronic painful inflammatory cystitis when administered intravesically to urological patients such as Vessilen, the intrarectal administration of Ade/HA gel has shown remarkable potential in improving the course of colitis. This treatment approach has demonstrated a reduction in the histological damage score and an increase in the expression of ZO-1 and occludin tight junctions in both in vivo studies and human specimens. By acting independently on endogenous PEA levels and without any noticeable systemic absorption, the effectiveness of Ade/HA gel is reliant on a local antioxidant mechanism that functions as a "barrier effect" in the inflamed gut. Building on the findings of this preliminary study, we are confident that the Ade/HA gel medical device holds promise as a valuable adjunct in supporting traditional anti-UC therapies.

Kinetic Study of the Maillard Reaction in Thin Film Generated by Microdroplets Deposition.

The Maillard reaction kinetics in the confined volume of the thin film produced by ESI microdroplet deposition was studied by mass spectrometry. The almost exclusive formation of the Amadori product from the reaction of D-xylose and D-glucose toward L-glycine and L-lysine was demonstrated. The thin film Maillard reaction occurred at a mild synthetic condition under which the same process in solution was not observed. The comparison of the thin film kinetics with that of the reaction performed in solution showed strong thin film rate acceleration factors.

Free N-heterocyclic carbenes from Brønsted acidic ionic liquids: Direct detection by electrospray ionization mass spectrometry.

RATIONALE: The occurrence of N-heterocyclic carbenes in imidazolium-based ionic liquids has long been discussed, but no spectroscopic evidence has been reported yet due to their transient nature. The insertion of an ionizable acid group into the cation scaffold of an ionic liquid which acts as a charge tag allows for the direct detection of free carbenes by mass spectrometry. METHODS: Three different Brønsted acidic ionic liquids were synthesized: 1-methyl-3-carboxymethylimidazolium chloride (MAICl), 1-methyl-3-carboxymethylimidazolium acetate (MAIAc) and the corresponding 2-(3-methyl-1H-imidazol-3-ium-1-yl)acetate zwitterion (MAI - H). The speciation of these compounds was then analysed by electrospray ionization ion-trap mass spectrometry in the negative ion mode. RESULTS: The C2-H deprotonation of the imidazolium cation leading to the formation of the corresponding carbene is highly affected by the basic properties of the counter-anion. In the case of MAICl and MAI - H ionic liquids, no charged species corresponding to the free N-heterocyclic carbene was detected. On the contrary, in the presence of a sufficiently basic anion, such as acetate of MAIAc ionic liquid, an intense signal related to the free carbenic species was observed without the addition of an external base. CONCLUSIONS: In situ formation of free N-heterocyclic carbenes from Brønsted acidic ionic liquids was demonstrated, highlighting the crucial role of anion basicity in promoting the C2-H proton abstraction from imidazolium cations with a carboxylic side chain.

Accelerated d-Fructose Acid-Catalyzed Reactions in Thin Films Formed by Charged Microdroplets Deposition.

Thin films derived by the deposition of charged microdroplets generated in the ESI source of a mass spectrometer act as highly concentrated reaction vessels in which the final products of an ion-molecule reaction can be isolated by their precipitation onto a solid surface under ambient conditions. In this study, the ESI Z-spray source supplied to a Q-TOF Ultima mass spectrometer was used to investigate the d-fructose acid-catalyzed reactions by microdroplets deposition onto a stainless-steel target surface. High conversion ratios of d-fructose into 5-hydroxymethylfuraldehyde (5-HMF), 5-methoxymethylfuraldehyde (5-MMF), and difructrose anhydrides (DFAs) were obtained with HCl and KHSO4 as metal-free catalysts by using synthetic conditions under which the same products in bulk are not formed. Furthermore, the reaction outcome was found to be highly sensitive to the catalyst and the solvent employed as well as to the ESI source parameters influencing the thin film formation from microdroplets deposition onto the solid surface.

The Peroxymonocarbonate Anion HCO4- as an Effective Oxidant in the Gas Phase: A Mass Spectrometric and Theoretical Study on the Reaction with SO2.

The peroxymonocarbonate anion, HCO4-, the covalent adduct between the carbon dioxide and hydrogen peroxide anion, effectively reacts with SO2 in the gas phase following three oxidative routes. Mass spectrometric and electronic structure calculations show that sulphur dioxide is oxidised through a common intermediate to the hydrogen sulphate anion, sulphur trioxide, and sulphur trioxide anion as primary products through formal HO2-, oxygen atom, and oxygen ion transfers. The hydrogen sulphite anion is also formed as a secondary product from the oxygen atom transfer path. The uncommon nucleophilic behaviour of HCO4- is disclosed by the Lewis acidic properties of SO2, an amphiphilic molecule that forms intermediates with characteristic and diagnostic geometries with peroxymonocarbonate.

Intracluster Sulphur Dioxide Oxidation by Sodium Chlorite Anions: A Mass Spectrometric Study.

The reactivity of [NaL·ClO2]- cluster anions (L = ClOx-; x = 0-3) with sulphur dioxide has been investigated in the gas phase by ion-molecule reaction experiments (IMR) performed in an in-house modified Ion Trap mass spectrometer (IT-MS). The kinetic analysis revealed that SO2 is efficiently oxidised by oxygen-atom (OAT), oxygen-ion (OIT) and double oxygen transfer (DOT) reactions. The main difference from the previously investigated free reactive ClO2- is the occurrence of intracluster OIT and DOT processes, which are mediated by the different ligands of the chlorite anion. This gas-phase study highlights the importance of studying the intrinsic properties of simple reacting species, with the aim of elucidating the elementary steps of complex processes occurring in solution, such as the oxidation of sulphur dioxide.

Charge-Tagged N-Heterocyclic Carbenes (NHCs): Revealing the Hidden Side of NHC-Catalysed Reactions through Electrospray Ionization Mass Spectrometry.

N-heterocyclic carbenes (NHCs) are key intermediates in a variety of chemical reactions. Owing to their transient nature, the interception and characterization of these reactive species have always been challenging. Similarly, the study of reaction mechanisms in which carbenes act as catalysts is still an active research field. This Minireview describes the contribution of electrospray ionization mass spectrometry (ESI-MS) to the detection of charge-tagged NHCs resulting from the insertion of an ionic group into the molecular scaffold. The use of different mass spectrometric techniques, combined with the charge-tagging strategy, allowed clarification of the involvement of NHCs in archetypal reactions and the study of their intrinsic chemistry.

Variation in essential oil content and composition of Ridolfia segetum Moris based on 30-hour prolonged fractionated extraction procedure.

A comprehensive study on essential oil samples extracted from Ridolfia segetum Moris (Apiaceae) collected in Tarquinia (Italy) is reported. In this study, a 30-hour, fractionated, steam distillation procedure for essential oil preparation was applied. The gas chromatographic-mass spectrometry analysis showed monoterpene o-cymene and phenylpropanoid dill-apiol as the major essential oil's constituents revealing a new chemotype dependent on extraction duration. Great impact of the duration of the distillation process on chemical profile of essential oil was observed; prolonged distillation gives chemically more diverse essential oil samples. Preliminary microbiological evaluations of the essential oils samples revealed some activity, although not high, against Candida albicans.

Base-Assisted Conversion of Protonated d-Fructose to 5-HMF: Searching for Gas-Phase Green Models.

A gas-phase investigation of the d-fructose dehydration reaction in the presence of base has been performed by the joint application of mass spectrometric techniques and theoretical calculations. Protonated addition products of d-fructose and base were generated in the gas phase by electrospray ionization using several bases of different proton affinity. The intermediates, products and decomposition channels were investigated by ion trap mass spectrometry. Electronic structure calculations allowed the identification of the ionic intermediates and products of a selected system containing NH3, helping to rationalize the observed reaction pathways. The obtained results show that the final product, the protonated 5-hydroxymethyl-2-furaldheyde [5-HMF]H+, is better formed using selected bases and only if these remain clustered until the end of the dehydration process.

Application of microemulsions for the removal of synthetic resins from paintings on canvas.

Traditional cleaning methods with organic solvents often are not suitable for removal of aged resin so researchers have to find new formulations. In this work, a case study is reported in which new microemulsions were applied on the surface of a painting covered by some aged resin layers used during a previous restoration. Based on the quality of the intervention and the analysis of a sample of the varnish carried out with both MALDI-TOF and ATR-IR spectrometers, it was conjectured that this undesired material could be an acrylic polymer. So it was chosen to use xylene, ethyl acetate and propylene carbonate (XYL and EAPC) microemulsions (O/W oil in water). The first is able to solubilise only acrylic polymers, the second may solve both acrylic and vinyl resins. The first has had the greatest effect allowing complete varnish removal and original artwork restoration.

Novel Symmetrical Benzazolyl Derivatives Endowed with Potent Anti-Heparanase Activity.

Heparanase is the only mammalian endo-ß-d-glucuronidase involved in a variety of major diseases. The up-regulation of heparanase expression increases tumor size, angiogenesis, and metastasis, representing a validated target in the anti-cancer field. To date, only a few small-molecule inhibitors have been described, but none have gotten through pre-clinical development. Previously, we explored 2-(4-(4-(bromo-methoxybenzamido)benzylamino)phenyl) benzazole derivatives as anti-heparanase agents, proposing this scaffold for development of broadly effective heparanase inhibitors. Herein, we report an extended investigation of new symmetrical 2-aminophenyl-benzazolyl-5-acetate derivatives, proving that symmetrical compounds are more effective than asymmetrical analogues, with the most-potent compound, 7g, being active at nanomolar concentration against heparanase. Molecular docking studies were performed on the best-acting compounds 5c and 7g to rationalize their interaction with the enzyme. Moreover, invasion assay confirmed the anti-metastatic potential of compounds 5c, 7a, and 7g, proving the inhibition of the expression of proangiogenic factors in tumor cells.

From ascorbic acid to furan derivatives: the gas phase acid catalyzed degradation of vitamin C.

Furan derivatives, potentially carcinogenic to humans, can be formed, in addition to carbohydrates and other sources, from the degradation of ascorbic acid (AA). At present, the mechanisms involved in the ascorbic acid degradation are not yet fully understood. In this study, we reported a gas-phase investigation, performed using Triple Quadrupole (TQ/MS) and Ion Trap Mass Spectrometry (QIT/MS) together with quantum mechanical calculations at the B3LYP/6-31+G(d,p) level of theory, on the non-oxidative degradation mechanism of l-ascorbic acid (AA) to furan derivatives. Gaseous protonated ascorbic acid ions, the AAH+ ionic reagents, were generated by Electrospray Ionization (ESI) of an aqueous AA solution added with a mild protonation reagent. The Collisionally Induced Dissociation (CID) mass spectra of the AAH+ ions displayed gaseous fragment ions corresponding to the degradation intermediates and reaction products, which were structurally characterized and identified. Precise mechanistic insights were achieved by using l-[1-13C]-AA. On the basis of experimental and computational results, the gas phase non-oxidative acid catalyzed degradation mechanism of ascorbic acid is proposed, a benchmark point for the comprehension of the mechanism in the condensed phase.

Antimicrobial and Antibiofilm Activity and Machine Learning Classification Analysis of Essential Oils from Different Mediterranean Plants against Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a ubiquitous organism and opportunistic pathogen that can cause persistent infections due to its peculiar antibiotic resistance mechanisms and to its ability to adhere and form biofilm. The interest in the development of new approaches for the prevention and treatment of biofilm formation has recently increased. The aim of this study was to seek new non-biocidal agents able to inhibit biofilm formation, in order to counteract virulence rather than bacterial growth and avoid the selection of escape mutants. Herein, different essential oils extracted from Mediterranean plants were analyzed for their activity against P. aeruginosa. Results show that they were able to destabilize biofilm at very low concentration without impairing bacterial viability. Since the action is not related to a bacteriostatic/bactericidal activity on P. aeruginosa, the biofilm change of growth in presence of the essential oils was possibly due to a modulation of the phenotype. To this aim, application of machine learning algorithms led to the development of quantitative activity-composition relationships classification models that allowed to direct point out those essential oil chemical components more involved in the inhibition of biofilm production. The action of selected essential oils on sessile phenotype make them particularly interesting for possible applications such as prevention of bacterial contamination in the community and in healthcare environments in order to prevent human infections. We assayed 89 samples of different essential oils as P. aeruginosa anti-biofilm. Many samples inhibited P. aeruginosa biofilm at concentrations as low as 48.8 µg/mL. Classification of the models was developed through machine learning algorithms.

Sideritis romana L. subsp. purpurea (Tal. ex Benth.) Heywood, a new chemotype from Montenegro.

A study on essential oil fractions of the Western Balkan endemic Sideritis romana L. subsp. purpurea (Tal. ex Benth.) Heywood collected in Montenegro is reported. The 24-h systematic steam distillation extraction procedure was performed. The gas chromatographic/mass spectrometric (GC/MS) analysis of the fractions showed γ-elemene and spathulenol as two main constituents, revealing a new chemotype of this plant species. Although varying in the content of these two main compounds, which makes the fractions quite different between each other, evaluation of the anti-Candida activity showed the lack of any significant efficacy.

Essential oil extraction, chemical analysis and anti-Candida activity of Foeniculum vulgare Miller - new approaches.

A comprehensive study on essential oil samples of Foeniculum vulgare Miller from Tarquinia (Italy) is reported. A 24-h systematic steam distillation was performed on different harvested samples applying different extraction times. The GC-MS analysis of the residue outcome showed o-cymene, α-phellandrene, α-pinene and estragole as the major constituents. The predominance and continued presence of o-cymene makes this fennel oil a rather unique chemotype. An evident correlation between the antifungal activity and phenological stage is demonstrated. The most active fractions were particularly rich in estragole, as well as a significant amount of fenchone that possibly exerts some additive effect in the expression of overall antifungal potency. Pre-fruiting material produced oil particularly rich in o-cymene. With reference to the duration of the extraction, the maximum amount of oil was released within the first 3 h, whereas the reproductive phase material needed at least 6 h for the extraction.