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•Contact K+/X− pairs in a charged monotopic receptor can be formed in the gas phase.•Their structure, classical or zwitterionic, depends on the basicity of X−.•Their reactivity ...towards 2,4-pentanediones has been investigated.•A mechanistic switchover is observed depending on the acidity of the dione.
An integrated FT-ICR and computational approach has been employed to investigate the gas phase structure and reactivity of ESI-formed complexes between organic and inorganic acids (HX) and a K+-containing hexaazamacrocycle (M). Two limiting structures are available to those complexes, either the classical MK+·XH or the zwitterionic MH+·K+·X− one, with the latter prevailing over the first by increasing the gas-phase acidity of the HX ligand. Both structures undergo the HX displacement when reacting with 2,4-pentanedione (P0) and its 1,1,1-trifluoro (P3) and 1,1,1,5,5,5-hexafluoro (P6) derivatives. The HX displacement efficiency is found to depend not only on the specific structure of the complex, but also on the acid/base properties of the diones. Among them, P3 displays the lowest reactivity towards the MK+·XH complexes. These findings are consistent with the co-existence of a direct HA-to-HX and a base-catalyzed A−-to-HX substitution channels. The P0<P3<P6 reactivity order, observed towards the zwitterionic MH+·K+·X− complexes, points to a HX displacement mechanism whose rate-determining step involves the prototropic transfer from HA to the X− moiety in the encounter complex. The present study provides an extremely rare piece of information on reactive events taking place on contact ion pairs (K+X−) inside a monotopic receptor (MH+).
Autophagy occurs at a basal level in all eukaryotic cells and may support cell survival or activate death pathways. Due to its pathophysiologic significance, the autophagic machinery is a promising ...target for the development of multiple approaches for anti-neoplastic agents. We have recently described the cytotoxic and pro-apoptotic mechanisms, targeting the tumour suppressor p53, of climacostol, a natural product of the ciliated protozoan Climacostomum virens. We report here on how climacostol regulates autophagy and the involvement of p53-dependent mechanisms. Using both in vitro and in vivo techniques, we show that climacostol potently and selectively impairs autophagy in multiple tumour cells that are committed to die by apoptosis. In particular, in B16-F10 mouse melanomas climacostol exerts a marked and sustained accumulation of autophagosomes as the result of dysfunctional autophagic degradation. We also provide mechanistic insights showing that climacostol affects autophagosome turnover via p53-AMPK axis, although the mTOR pathway unrelated to p53 levels plays a role. In particular, climacostol activated p53 inducing the upregulation of p53 protein levels in the nuclei through effects on p53 stability at translational level, as for instance the phosphorylation at Ser15 site. Noteworthy, AMPKα activation was the major responsible of climacostol-induced autophagy disruption in the absence of a key role regulating cell death, thus indicating that climacostol effects on autophagy and apoptosis are two separate events, which may act independently on life/death decisions of the cell. Since the activation of p53 system is at the molecular crossroad regulating both the anti-autophagic action of climacostol and its role in the apoptosis induction, it might be important to explore the dual targeting of autophagy and apoptosis with agents acting on p53 for the selective killing of tumours. These findings also suggest the efficacy of ciliate bioactive molecules to identify novel lead compounds in drug discovery and development.
A potassium-containing hexaazamacrocyclic dication,
M
•H•K
2+
, is able to add in the gas phase mono- and dicarboxylate anions as well as inorganic anions by forming the corresponding monocharged ...adducts, the structure of which markedly depends on the basicity of the anion. With anions, such as acetate or fluoride, the neutral hexaazamacrocycle
M
acts as an acceptor of monosolvated K
+
ion. With less basic anions, such as trifluoroacetate or chloride, the protonated hexaazamacrocycle
M
•H
+
performs the unusual functions of an acceptor of contact K
+
/anion pairs.
Graphical Abstract
ᅟ
Protonated Hexaazamacrocycles as Selective K+ Receptors Fraschetti, Caterina; Filippi, Antonello; Crestoni, Maria Elisa ...
Journal of the American Society for Mass Spectrometry,
07/2015, Letnik:
26, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Protonated hexaazamacrocycle
M
•H
+
is able to detect K
+
ions present at ppb level in methanolic solutions containing 10
−5
M of Na
+
ions. The high sensitivity and selectivity of
M
•H
+
for K
+
...is ascribed to the favorable energy balance between the K
+
ion desolvation and its coordination to the
M
•H
+
macrocycle, which allows the formation of the corresponding adduct before the Coulombic explosion of the ESI-MS nanodroplets.
Graphical Abstract
ᅟ
The combination of cerium(III) chloride heptahydrate and sodium iodide supported on silica gel is known to promote Michael-type additions. Continuing our work on solvent-free conditions, the ...CeCl3.7H2O-NaI-SiO2 system catalyzes the addition of a variety of indoles and nitroalkenes, giving 2-indolyl-1-nitroalkane derivatives in good yields. Development of this method has resulted in a new protocol for the synthesis of 4-substituted beta-carbolines.
A headspace solid-phase microextraction coupled to gas chromatography with mass spectrometry and flame ionization detection (HS-SPME-GC-MS/FID) method has been developed for quantifying the main ...volatiles of the Italian sparkling red wine Vernaccia di Serrapetrona, leading to establish that the divinylbenzene/carboxen/polydimethylsiloxane-coated (gray) fiber, an equilibration time of 15 min, and an extraction time of 15 min at a temperature of 35 °C are the conditions representing the best compromise in terms of sensitivity and time expense, to carry out the analyses. Among the volatiles quantified, 2-phenylethanol, 3-methylbutyl acetate, and ethyl esters levels resulted to be above their odor thresholds, thus being probably responsible for the aroma of this wine with their positive attributes. Phenolic compounds, namely gallic acid, p-coumaric acid, caffeic acid, (+)-catechin, and (+)-epicatechin, were also quantified using high-performance liquid chromatography-MS, thus obtaining an overall characterization of molecules fundamental for both the sensory and the healthy characteristics of the wine. The total phenolic content was found to be in the range of 19.25–61.67 mg l⁻¹ with the most abundant compound being gallic acid (7.44–25.78 mg l⁻¹). Main differences in volatile and phenolic compounds between samples were discussed and analyzed by chemometric techniques as principal component analysis.
The clam Anadara inaequivalvis (Bruguière) is a bivalve mollusc now populating several areas of the Mediterranean Sea seafloor where it competes with other molluscs harvested as food. In fact, even ...though Anadara inaequivalvis has valuable nutritional properties, it has no commercial value in European countries. The aim of this study was to evaluate quantitatively and qualitatively fatty acid content in this bivalve mollusc and to compare 11 extraction methods: conventional procedures such as Folch, Bligh and Dyer, and Soxhlet with different solvents, as well as accelerated solvent extraction (ASE) and methods using low-toxicity solvents as substitutes for chloroform (CHCl₃) and methanol (MeOH). The best method was ASE CHCl₃-MeOH, affording yields of total lipids, total fatty acids, and polyunsaturated fatty acids (PUFAs) significantly higher than any other method. The estimated range of total lipids was 2.29%–6.99% (on the dry sample), and the range of fatty acids was 0.74%–1.78%. Yields of polyunsaturated fatty acids (PUFAs) ranged from 0.10% to 0.40%. The solvent mixture hexane—isopropanol as substitute for CHCl₃-MeOH did not afford good results. PUFAs were 22.5% in the total fatty acids and the ratio between PUFAs n-3 and PUFA n-6 was 2.74:1.
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