A simple,direct synthesis of 3-vinylindoles from the carbocation-catalysed dehydrative cross-coupling of ketones and indoles. A combined experimental and computational study

A straightforward synthesis of a library of largely new 3-vinylindoles via a clean dehydrative coupling reaction between ketones and indoles has been developed. Highly stable, non-nucleophilic aryl(2-methylindol-3-yl)methylium salts have been used as efficient Lewis acid catalysts. The advantages of the reaction are the use of equimolar amounts of inexpensive and easily available reagents, the low catalyst amount, high atom efficiency, the production of only one molecule of water as a by-product and the mild reaction conditions. Computational studies of two specific reaction mechanism instances show that both steric and electronic effects heavily influence the nature of the final products, whether a methyl group in position 2 of the indole is present or absent.     

A Jocic-type approach for a practical and scalable synthesis of pyrrolonaphthoxazepine (PNOX)-based potent proapoptotic agents

We developed a Jocic-type protocol for the construction of the pyrrolonaphthoxazepine (PNOX) core. After an initial investigation based on the isolation of a trichloromethyl carbinol derivative, we shifted our attention towards a multicomponent single-step protocol. Screening of a variety of bases and solvents led to the identification of the optimum conditions for the preparation of the key α-aryloxy carboxylic acids to undergo intramolecular cyclization. The novel chemical route significantly improved overall yields for the preparation of PNOX-based compounds and was successfully extended to the preparation of 1,4-benzoxazinone-based templates.     

Das Verhalten von Ringstickstoff bei der Mikromethode nach Kjeldahl

Zusammenfassung Bei gleichzeitiger Anwesenheit von Ringstickstoff und Seitenkettenstickstoff läßt sich letzterer nach Reduktion der Substanz mit Jodwasserstoffsäure und rotem Phosphor durch Aufschluß mit konz. Schwefelsäure, Quecksilberacetat und Kaliumsulfat nachKjeldahl bestimmen. Aus der Differenz gegen den nachDumas-Zimmermann ermittelten Gesamtstickstoffgehalt wird der Anteil der Substanz an Ringstickstoff bestimmt. Die bisher untersuchten Substanzen lassen erkennen, daß bei der beschriebenen Modifikation desKjeldahl-Verfahrens der stickstoffhaltige Ring nur unter bestimmten strukturellen Voraussetzungen angegriffen wird. Die daraus ableitbaren Regeln werden diskutiert und bieten neue Möglichkeiten zur Erforschung struktureller und analytischer Probleme.

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Summary TheKheldahl method can be applied when both ring nitrogen and side chain nitrogen are present, if the latter is reduced with hydriodic acid and red phosphorus, followed by digestion with conc. sulfuric acid, mercuric acetate and potassium sulfate. The content of the substance in ring nitrogen is found from the difference between the total nitrogen obtained by theDumas-Zimmermann procedure. The materials studied up now show that in the modification of theKheldahl method just described, the nitrogenbearing ring is attacked only under certain structural conditions. The rules derived from these findings are discussed. They offer new possibilities for the study of structural and analytical problems.

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Résumé Dans le cas de la présence simultanée de l'azote dans le noyau et les chaînes latérales, on peut doser ce dernier par réduction de la substance à l'aide d'acide iodhydrique et de phosphore rouge, suivie d'une attaque à l'aide d'acide sulfurique concentré, d'acétate de mercure et de sulfate de potassium suivantKjeldahl. On détermine l'azote cyclique de la substance par différence avec l'azote total trouvé par la méthode deDumas-Zimmermann. Les substances étudiées jusqu'ici montrent que le cycle azoté n'est attaqué que suivant des positions structurales définies en suivant le procédé modifié deKjeldahl que l'on vient de décrire. Les lois qui en dérivent sont discutées et offrent de nouvelles possibilités pour la recherche des problèmes structuraux et analytiques.

     

Specific anions effects of on the stability of azurin in ice

This investigation represents a first attempt to gain a quantitative estimate of the effects of the anions sulfate, citrate, acetate, chloride and thiocyanate on the thermodynamic stability (DeltaG degrees) of a model globular protein in ice at -15 degrees C. The method, based on guanidinium chloride denaturation of the azurin mutant C112S from Pseudomonas aeruginosa, distinguishes between the effects of cooling to subfreezing temperatures from those induced specifically by the formation of a solid ice phase. The results confirm that, both in liquid and frozen states, kosmotropes (sulfate, citrate and acetate) increase significantly protein stability, relative to chloride, whereas the chaotrope thiocyanate decreases it. Throughout, their stabilizing efficacy was found to rank according to the Hofmeister series, sulfate>citrate>acetate>chloride>thiocyanate, although the magnitude of Delta(DeltaG degrees) exhibited a distinct sensitivity among the anions to low temperature and to ice formation. In the liquid state, lowering the temperature from +20 to -15 degreesC weakens considerably the stabilizing efficacy of the organic anions citrate and acetate. Among the anions sulfate stands out as the only strong stabilizer at subfreezing temperatures while SCN- becomes an even stronger denaturant. Freezing of the solution in the presence the "neutral" salt NaCl destabilizes the protein, DeltaG degrees progressively decreasing up to 3-4 kcal/mol as the fraction of liquid water in equilibrium with ice (VL) is reduced to less than 1%. Kosmotropes do attenuate the decrease in protein stability in ice although in the case of citrate and acetate, their efficacy diminishes sharply as the liquid fraction shrinks to below 2.7%. On the contrary, sulfate is remarkable for it maintains constantly high the stability of azurin in liquid and frozen solutions, down to the smallest VL (0.5%) examined. Throughout, the reduction in DeltaG degrees caused by the solidification of water correlates with the decrease in the denaturant m value, an indirect indication that protein-ice interactions generally lead to partial unfolding of the native state. It is proposed that binding of the kosmotropes to the ice interface may inhibit protein adsorption to the solid phase and thereby counter the ice perturbation.     

Determination of dimethylarginine levels in rats using HILIC-MS/MS: an in vivo microdialysis study

Nitric oxide (NO) is one of the most important mediators and neurotransmitters and its levels change under pathological conditions. NO production may be regulated by endogenous nitric oxide synthase (NOS) inhibitors, in particular asymmetric dimethylarginine (ADMA). Most of the interest is focused on ADMA, since this compound is present in plasma and urine and accumulation of ADMA has been described in many disease states but little is known about cerebrospinal fluid (CSF) concentrations of this compound and of its structural isomer symmetric dimethylarginine (SDMA). To determine the levels of methylarginines, we here present a new hydrophilic interaction chromatography (HILIC)-MS/MS method for the precise determination of these substances in CSF from microdialysis samples of rat prefrontal cortex (PFC). The method requires only minimal sample preparation and features isotope-labelled internal standards.     

Molecular Machines Working on Surfaces and at Interfaces

In the past ten years a great variety of artificial molecular machines have been constructed, and very interesting concepts for controlling molecular‐level movements by external inputs have been developed. Most of the studies, however, have been performed in solution, where the investigated systems contain a huge number of molecules which behave independently from one another because they cannot be addressed individually. Before such systems can find applications in many fields of technology, they must be interfaced with the macroscopic world by ordering them in some way so that they can behave coherently and can be addressed in space. The problem of obtaining ordered arrays of molecular machines can be addressed by a variety of techniques, which include deposition on surfaces, incorporation into polymers, organization at interfaces, and immobilization in membranes or porous materials. In the last few years, the development of scanning‐probe techniques has also enabled direct observation and manipulation of single molecular‐machine molecules on surfaces. Techniques of this kind have opened novel routes to the study of molecular machines, and have also contributed to better understanding the differences between movement at the macroscopic and molecular levels. This paper reviews some recent achievements in the field of molecular machines working on surfaces and at interfaces, as single molecules or ordered arrays. Hybrid natural–artificial machines are also discussed, and the working mechanism of some natural machines is illustrated for the purpose of comparison.     

Polyviologen dendrimers as hosts and charge-storing devices

Two dendrimers were designed and synthesized that contain a 1,3,5-trisubstituted benzenoid core and incorporate 9 and 21 viologen (4,4'-bipyridinium) units in their branches in addition to hydrophilic (aryloxy) terminal groups. For comparison purposes, model compounds containing one and two viologen units were also studied. These polycationic dendrimers form strong host-guest complexes with the dianionic form of the red dye eosin in dilute CH(2)Cl(2) solutions. Titration experiments, based on fluorescence measurements, showed that each viologen unit in the dendritic structures becomes associated with an eosin dianion. Electrochemical (in MeCN) and photosensitization (in CH(2)Cl(2)) experiments revealed that only a fraction of the viologen units present in the dendritic structures can be reduced. This fraction corresponds to the number of viologen units present in the outer shells of the dendrimers. The reasons for incomplete charge pooling are discussed. Comparison with the behavior of polyviologen dendrimers that are terminated with bulky tetraarylmethane groups and were studied previously enabled the role played by the terminal groups in the redox and hosting properties to be elucidated.     

Synthesis and Characterization of Star‐Shaped Diblock Poly(ε‐caprolactone)/Poly(ethylene oxide) Copolymers

Summary: Star‐shaped hydroxy‐terminated poly(ε‐caprolactone)s (ssPCL), with arms of different lengths, were obtained by ring‐opening polymerization (ROP) of ε‐caprolactone initiated by pentaerythritol, and were condensed with α‐methyl‐ω‐(3‐carboxypropionyloxy)‐poly(ethylene oxide)s ( = 550–5 000) to afford four‐armed PCL‐PEO star diblock copolymers (ssPCL‐PEO). The polymers were characterized by ¹H and ¹³C NMR spectroscopy and size‐exclusion chromatography (SEC). The melting behavior of ssPCLs was studied by differential scanning calorimetry (DSC). X‐ray diffraction and DSC techniques were used to investigate the crystalline phases of ssPCL‐PEOs.

The part of the synthesis of four‐armed star‐shaped diblock poly(ε‐caprolactone)‐poly(ethylene oxide) copolymers as described.     

Fruit Wastes as a Valuable Source of Value-Added Compounds: A Collaborative Perspective

The by-products/wastes from agro-food and in particular the fruit industry represents from one side an issue since they cannot be disposed as such for their impact on the environment but they need to be treated as a waste. However, on the other side, they are a source of bioactive healthy useful compounds which can be recovered and be the starting material for other products in the view of sustainability and a circular economy addressing the global goal of “zero waste” in the environment. An updated view of the state of art of the research on fruit wastes is here given under this perspective. The topic is defined as follows: (i) literature quantitative analysis of fruit waste/by-products, with particular regards to linkage with health; (ii) an updated view of conventional and innovative extraction procedures; (iii) high-value added compounds obtained from fruit waste and associated biological properties; (iv) fruit wastes presence and relevance in updated databases. Nowadays, the investigation of the main components and related bioactivities of fruit wastes is being continuously explored throughout integrated and multidisciplinary approaches towards the exploitation of emerging fields of application which may allow to create economic, environmental, and social value in the design of an eco-friendly approach of the fruit wastes.