Stereocomplementary Routes to Hydroxylated Nitrogen Heterocycles: Total Syntheses of Casuarine,Australine, and 7‐epi‐Australine

Addition of lithiated 1‐benzyloxyallene to a D ‐arabinose‐derived cyclic nitrone occurred with perfect diastereoselectivity furnishing a bicyclic 1,2‐oxazine derivative, which is an excellent precursor for pyrrolizidine alkaloids hydroxylated at C‐7 with optional configuration at this stereogenic center. Depending on the stage of the N? O bond cleavage and ring re‐closure, 7‐hydroxypyrrolizidines with 7R or 7S configuration were obtained, as a result of completely selective addition reactions occurring complementarily at the bottom or top face of the endocyclic C? C double bond in six‐ and five‐membered B rings, respectively. Applicability of these stereodivergent routes to obtain polyhydroxy pyrrolizidine alkaloids is demonstrated by the efficient syntheses of casuarine and australine as examples of the two classes of diversely configured 7‐hydroxypyrrolizidine alkaloids. An alternative synthesis of australine and two strategies for the preparation of 7‐epi‐australine are also reported, which demonstrate that the stereoselectivity of hydride reduction of an exocyclic C? O double bond is independent of the ring size, occurring preferentially from the top face either in a six‐ or five‐membered ring.     

House-of-security approach to measurement in analytical chemistry: quantification of human error using expert judgments

A new technique for quantification of human errors in chemical analysis using expert judgments is described. This technique is based on the house-of-security approach developed recently in the field of safety and security for prevention of terrorist and criminal attacks against an organization. The following relative quantification parameters (expressed in %) are proposed in the technique: (a) likelihood score of human error in a chemical analytical measurement/testing method, (b) severity score of human error for reliability of the test results, (c) importance score of a component of a laboratory quality system, and (d) effectiveness score of the quality system as a whole in preventing/blocking human error. As an example, 34 scenarios of human error in pH measurement of groundwater are discussed and quantified.     

Exploring AuRh Nanoalloys: A Computational Perspective on the Formation and Physical Properties

We studied the formation of AuRh nanoalloys (between 20–150 atoms) in the gas phase by means of Molecular Dynamics (MD) calculations, exploring three possible formation processes: one-by-one growth, coalescence, and nanodroplets annealing. As a general trend, we recover a predominance of Rh@Au core-shell ordering over other chemical configurations. We identify new structural motifs with enhanced thermal stabilities. The physical features of those selected systems were studied at the Density Functional Theory (DFT) level, revealing profound correlations between the nanoalloys morphology and properties. Surprisingly, the arrangement of the inner Rh core seems to play a dominant role on nanoclusters’ physical features like the HOMO-LUMO gap and magnetic moment. Strong charge separations are recovered within the nanoalloys suggesting the existence of charge-transfer transitions.     

Light‐Controlled Regioselective Synthesis of Fullerene Bis‐Adducts

Multi‐functionalization and isomer‐purity of fullerenes are crucial tasks for the development of their chemistry in various fields. In both current main approaches—tether‐directed covalent functionalization and supramolecular masks—the control of regioselectivity requires multi‐step synthetic procedures to prepare the desired tether or mask. Herein, we describe light‐responsive tethers, containing an azobenzene photoswitch and two malonate groups, in the double cyclopropanation of [60]fullerene. The formation of the bis‐adducts and their spectroscopic and photochemical properties, as well as the effect of azobenzene photoswitching on the regiochemistry of the bis‐addition, have been studied. The behavior of the tethers depends on the geometry of the connection between the photoactive core and the malonate moieties. One tether lead to a strikingly different adduct distribution for the E and Z isomers, indicating that the covalent bis‐functionalization of C₆₀ can be controlled by light.     

Synthesis and Evaluation of Thymol-Based Synthetic Derivatives as Dual-Action Inhibitors against Different Strains of H. pylori and AGS Cell Line

Following a similar approach on carvacrol-based derivatives, we investigated the synthesis and the microbiological screening against eight strains of H. pylori, and the cytotoxic activity against human gastric adenocarcinoma (AGS) cells of a new series of ether compounds based on the structure of thymol. Structural analysis comprehended elemental analysis and ¹H/¹³C/¹⁹F NMR spectra. The analysis of structure–activity relationships within this molecular library of 38 structurally-related compounds reported that some chemical modifications of the OH group of thymol led to broad-spectrum growth inhibition on all isolates. Preferred substitutions were benzyl groups compared to alkyl chains, and the specific presence of functional groups at para position of the benzyl moiety such as 4-CN and 4-Ph endowed the most anti-H. pylori activity toward all the strains with minimum inhibitory concentration (MIC) values up to 4 µg/mL. Poly-substitution on the benzyl ring was not essential. Moreover, several compounds characterized by the lowest minimum inhibitory concentration/minimum bactericidal concentration (MIC/MBC) values against H. pylori were also tested in order to verify a cytotoxic effect against AGS cells with respect to 5-fluorouracil and carvacrol. Three derivatives can be considered as new lead compounds alternative to current therapy to manage H. pylori infection, preventing the occurrence of severe gastric diseases. The present work confirms the possibility to use natural compounds as templates for the medicinal semi-synthesis.     

Nutritional Value and Preventive Role of Nigella sativa L. and Its Main Component Thymoquinone in Cancer: An Evidenced-Based Review of Preclinical and Clinical Studies

In recent times, scientific attention has been paid to different foods and their bioactive components for the ability to inhibit the onset and progress of different types of cancer. Nigella sativa extract, powder and seed oil and its main components, thymoquinone and α-hederin, have showed potent anticancer and chemosensitizing effects against various types of cancer, such as liver, colon, breast, renal, cervical, lung, ovarian, pancreatic, prostate and skin tumors, through the modulation of various molecular signaling pathways. Herein, the purpose of this review was to highlight the anticancer activity of Nigella sativa and it constitutes, focusing on different in vitro, in vivo and clinical studies and projects, in order to underline their antiproliferative, proapoptotic, cytotoxic and antimetastatic effects. Particular attention has been also given to the synergistic effect of Nigella sativa and it constitutes with chemotherapeutic drugs, and to the synthesized analogs of thymoquinone that seem to enhance the chemo-sensitizing potential. This review could be a useful step towards new research on N. sativa and cancer, to include this plant in the dietary treatments in support to conventional therapies, for the best achievement of therapeutic goals.     

1H-NMR Profiling Shows as Specific Constituents Strongly Affect the International EVOO Blends Characteristics: The Case of the Italian Oil

Considering the growing number of extra virgin olive oil (EVOO) producers in the world, knowing the influence of olive oils with different geographical origins on the characteristics of the final blend becomes an interesting goal. The present work is focused on commercial organic EVOO blends obtained by mixing multiple oils from different geographical origins. These blends have been studied by ¹H-NMR spectroscopy supported by multivariate statistical analysis. Specific characteristics of commercial organic EVOO blends originated by mixing oils from Italy, Tunisia, Portugal, Spain, and Greece were found to be associated with the increasing content of the Italian component. A linear progression of the metabolic profile defined characteristics for the analysed samples—up to a plateau level—was found in relation to the content of the main constituent of the Italian oil, the monocultivar Coratina. The Italian constituent percentage appears to be correlated with the fatty acids (oleic) and the polyphenols (tyrosol, hydroxytyrosol, and derivatives) content as major and minor components respectively. These results, which highlight important economic aspects, also show the utility of ¹H-NMR associated with chemometric analysis as a powerful tool in this field. Mixing oils of different national origins, to obtain blends with specific characteristics, could be profitably controlled by this methodology.     

Neuroprotective Effects of Curcumin in Methamphetamine-Induced Toxicity

Curcumin (CUR), a natural polyphenol extracted from rhizome of the Curcuma longa L, has received great attention for its multiple potential health benefits as well as disease prevention. For instance, CUR protects against toxic agents acting on the human body, including the nervous system. In detail, CUR possesses, among others, strong effects as an autophagy activator. The present study indicates that CUR counteracts methamphetamine (METH) toxicity. Such a drug of abuse is toxic by disturbing the autophagy machinery. We profited from an unbiased, low variable cell context by using rat pheochromocytoma PC12 cell line. In such a system, a strong protection was exerted by CUR against METH toxicity. This was associated with increased autophagy flux, merging of autophagosomes with lysosomes and replenishment of autophagy vacuoles with LC3, which instead is moved out from the vacuoles by METH. This is expected to enable the autophagy machinery. In fact, while in METH-treated cells the autophagy substrates α-synuclein accumulates in the cytosol, CUR speeds up α-synuclein clearance. Under the effects of CUR LC3 penetrate in autophagy vacuoles to commit them to cell clearance and promotes the autophagy flux. The present data provide evidence that CUR counteracts the neurotoxic effects induced by METH by promoting autophagy.     

Color Stabilization of Apulian Red Wines through the Sequential Inoculation of Starmerella bacillaris and Saccharomyces cerevisiae

Mixed fermentation using Starmerella bacillaris and Saccharomyces cerevisiae has gained attention in recent years due to their ability to modulate the qualitative parameters of enological interest, such as the color intensity and stability of wine. In this study, three of the most important red Apulian varieties were fermented through two pure inoculations of Saccharomyces cerevisiae strains or the sequential inoculation of Saccharomyces cerevisiae after 48 h from Starmerella bacillaris. The evolution of anthocyanin profiles and chromatic characteristics were determined in the produced wines at draining off and after 18 months of bottle aging in order to assess the impact of the different fermentation protocols on the potential color stabilization and shelf-life. The chemical composition analysis showed titratable acidity and ethanol content exhibiting marked differences among wines after fermentation and aging. The 48 h inoculation delay produced wines with higher values of color intensity and color stability. This was ascribed to the increased presence of compounds, such as stable A-type vitisins and reddish/violet ethylidene-bridge flavonol-anthocyanin adducts, in the mixed fermentation. Our results proved that the sequential fermentation of Starmerella bacillaris and Saccharomyces cerevisiae could enhance the chromatic profile as well as the stability of the red wines, thus improving their organoleptic quality.