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The unsaponifiable lipid fraction of plant-based foods is a potential source of bioactive components such as phytosterols, squalene, and tocopherols. The objective of the present study was to determine the levels of phytosterols, and squalene, as well as tocopherols (alpha and beta + gamma) in selected grains, seeds, and legumes. The method comprised acid hydrolysis and lipid extraction followed by alkaline saponification, prior to analysis by HPLC. In addition, the fatty acid profile of the foods was determined via total lipid extraction, fatty acid derivitisation and GC analysis. In general, beta-sitosterol was the most prevalent phytosterol, ranging in concentration from 24.9 mg/100 g in pumpkin seed to 191.4 mg/100 g in peas. Squalene identified in all foods examined in this study, was particularly abundant in pumpkin seed (89.0 mg/100 g). The sum of alpha- and beta+ gamma-tocopherols ranged from 0.1 mg/100 g in rye to 15.9 mg/100 g in pumpkin seeds. Total oil content ranged from 0.9% (w/w) in butter beans to 42.3% (w/w) in pumpkin seed and the type of fat, in all foods examined, was predominantly unsaturated. In conclusion, seeds, grains, and legumes are a rich natural source of phytosterols. Additionally, they contain noticeable amounts of squalene and tocopherols, and in general, their fatty acid profile is favorable.

Potatoes, tomatoes, and aubergines are all species of the Solanum genus and contain a vast array of secondary metabolites including calystegine alkaloids, phenolic compounds, lectins, and glycoalkaloids. Glycoalkaloids have been the subject of many literature papers, occur widely in the human diet, and are known to induce toxicity. Therefore, from a food safety perspective further information is required regarding their analysis, toxicity, and bioavailability. This is especially important in crop cultivars derived from wild species to prevent glycoalkaloid-induced toxicity. A comprehensive review of the bioactivity of glycoalkaloids and their aglycones of the Solanum species, particularly focused on comparison of their bioactivities including their anticancer, anticholesterol, antimicrobial, anti-inflammatory, antinociceptive, and antipyretic effects, toxicity, and synergism of action of the principal Solanum glycoalkaloids, correlated to differences of their individual molecular structures is presented.

Nuts contain bioactive constituents that elicit cardio-protective effects including phytosterols, tocopherols and squalene. The objective of the present study was to determine the total oil content, peroxide value, fatty acid composition and levels of tocopherols, squalene and phytosterols in oil extracted from freshly ground brazil, pecan, pine, pistachio and cashew nuts. The total oil content of the nuts ranged from 40.4 to 60.8% (w/w) while the peroxide values ranged from 0.14 to 0.22 mEq O2/kg oil. The most abundant monounsaturated fatty acid was oleic acid (C18:1), while linoleic acid (C18:2) was the most prevalent polyunsaturated fatty acid. The levels of total tocopherols ranged from 60.8 to 291.0 mg/g. Squalene ranged from 39.5 mg/g oil in the pine nut to 1377.8 mg/g oil in the brazil nut. beta-Sitosterol was the most prevalent phytosterol, ranging in concentration from 1325.4 to 4685.9 mg/g oil. In conclusion, the present data indicate that nuts are a good dietary source of unsaturated fatty acids, tocopherols, squalene and phytosterols.

BackgroundMany computational chemistry analyses require the generation of conformers, either on-the-fly, or in advance. We present Confab, an open source command-line application for the systematic generation of low-energy conformers according to a diversity criterion.ResultsConfab generates conformations using the 'torsion driving approach' which involves iterating systematically through a set of allowed torsion angles for each rotatable bond. Energy is assessed using the MMFF94 forcefield. Diversity is measured using the heavy-atom root-mean-square deviation (RMSD) relative to conformers already stored. We investigated the recovery of crystal structures for a dataset of 1000 ligands from the Protein Data Bank with fewer than 1 million conformations. Confab can recover 97% of the molecules to within 1.5 Å at a diversity level of 1.5 Å and an energy cutoff of 50 kcal/mol.ConclusionsConfab is available from http://confab.googlecode.com.

Type of publicationArticle ( 1 This is the pre-peer reviewed version of the following article: Deadman, B. J., Benjamin J. Deadman, [a] Stuart G. Collins [a] and Anita R. Maguire* [b] 2 This is the pre-peer reviewed version of the following article: Deadman, B. J., , Taming Hazardous Chemistry in Flow: The Continuous Processing of Diazo and Diazonium Compounds. Chem. Eur. J. which has been published in final form at http://dx.doi.org/10.1002/chem.201404348 DOI: 10.1002/chem.201404348 IntroductionDiazo and diazonium compounds are extremely versatile intermediates and reagents in organic synthesis. Diazoalkanes are important alkylating reagents, [1,2] while α-diazocarbonyls are important for their role in generating carbenes and metal carbenoids, [1,[3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] and also for providing access to reactive ketene and heteroanalogous intermediates via the Wolff rearrangement. [21][22][23][24][25][26] Diazo compounds are also important 1,3-dipoles for heterocycle-forming cycloaddition reactions. [27][28][29][30][31][32] The diazonium ion moiety is an important leaving group in Sandmeyer, [33][34][35] Meerwein, [36,37] Balz-Schiemann [38,39] and palladium catalysed cross coupling [40][41][42] chemistry; and is an essential reagent for the preparation of azo compounds, the backbone of the synthetic dye industry. [42,43] The versatility of the diazo and diazonium moieties is matched only by their fearsome reputation. Diazoalkanes are highly toxic due to their potent alkylation of DNA. [44] Furthermore, diazo and diazonium compounds are highly energetic by nature and explosions can be triggered by shock, heat or exposure to concentrated acids. [44,45] α-Diazocarbonyls are considerably more stable than diazoalkanes and diazoniums due to the resonance stabilisation of adjacent carbonyls but detonation is still possible under more forcing conditions. [44,46] These safety concerns necessitate caution when using diazo and diazonium intermediates in the laboratory, and have limited their use on scale in industry. The synthetic utility of these hazardous compounds has led to a recent interest in developing safer alternative methods for their preparation and use. [1,44] Continuous processing is rapidly growing in the academic, pharmaceutical and fine chemical sectors due to its favourable safety profile among other benefits such as efficient mixing, enhanced heat and mass transfer, access to extreme reaction conditions, reproducibility and scale up, in-line workups and automated operation. [47][48][49][50][51][52][53][54] The safety profile offered by continuous processing is perhaps the most compelling reason for its popularity in recent years. Sensitive and toxic reaction intermediates can be generated and consumed during a single flow process without the need for stockpiling hazardous quantities of material. Furthermore, the high surface area-tovolume ratio of tubular flow reactors also ensures rapid dissipation of heat and reduces the risk of reaction runaway.Continuou...

Phytosterols contain an unsaturated ring structure and therefore are susceptible to oxidation under certain conditions. Whilst the cytotoxicity of the analogous cholesterol oxidation products (COP) has been well documented, the biological effects of phytosterol oxidation products (POP) have not yet been fully ascertained. The objective of the present study was to examine the cytotoxicity of b-sitosterol oxides and their corresponding COP in a human monocytic cell line (U937), a colonic adenocarcinoma cell line (CaCo-2) and a hepatoma liver cell line (HepG2). 7b-Hydroxysitosterol, 7-ketositosterol, sitosterol3b,5a,6b-triol and a sitosterol-5a,6a-epoxide-sitosterol-5b,6b-epoxide (6:1) mixture were found to be cytotoxic to all three cell lines employed; the mode of cell death was by apoptosis in the U937 cell line and necrosis in the CaCo-2 and HepG2 cells. 7b-Hydroxysitosterol was the only b-sitosterol oxide to cause depletion in glutathione, indicating that POP-induced apoptosis may not be dependent on the generation of an oxidative stress. A further objective of this study was to assess the ability of the antioxidants a-tocopherol, g-tocopherol and b-carotene to modulate POP-induced cytotoxicity in U937 cells. Whilst a/g-tocopherol protected against 7b-hydroxycholesterol-induced apoptosis, they did not confer protection against 7b-hydroxysitosterolor 7-ketositosterol-induced toxicity, indicating that perhaps COP provoke different apoptotic pathways than POP. b-Carotene did not protect against COPor POP-induced toxicity. In general, results indicate that POP have qualitatively similar toxic effects to COP. However, higher concentrations of POP are required to elicit comparable levels of toxicity.

Polymerases have a structurally highly conserved negatively charged amino acid motif that is strictly required for Mg 2+ cation-dependent catalytic incorporation of (d)NTP nucleotides into nucleic acids. Based on these characteristics, a nucleoside monophosphonate scaffold, α-carboxy nucleoside phosphonate (α-CNP), was designed that is recognized by a variety of polymerases. Kinetic, biochemical, and crystallographic studies with HIV-1 reverse transcriptase revealed that α-CNPs mimic the dNTP binding through a carboxylate oxygen, two phosphonate oxygens, and base-pairing with the template. In particular, the carboxyl oxygen of the α-CNP acts as the potential equivalent of the α-phosphate oxygen of dNTPs and two oxygens of the phosphonate group of the α-CNP chelate Mg 2+ , mimicking the chelation by the β-and γ-phosphate oxygens of dNTPs. α-CNPs (i) do not require metabolic activation (phosphorylation), (ii) bind directly to the substrate-binding site, (iii) chelate one of the two active site Mg 2+ ions, and (iv) reversibly inhibit the polymerase catalytic activity without being incorporated into nucleic acids. In addition, α-CNPs were also found to selectively interact with regulatory (i.e., allosteric) Mg 2+ -dNTP-binding sites of nucleos(t)ide-metabolizing enzymes susceptible to metabolic regulation. α-CNPs represent an entirely novel and broad technological platform for the development of specific substrate active-or regulatory-site inhibitors with therapeutic potential. The polymerization of nucleotides by Escherichia coli DNA polymerase I represents a general model for catalytic action of nucleic acid polymerases (SI Appendix, Fig. S1) (1, 2). According to this model, there is a universal role for the Mg 2+ cation to interact with three phosphate oxygens of dNTP. The highly conserved consensus motifs in every polymerase active site consist of either aspartate or glutamate residues that chelate Mg 2+ through three additional coordination bonds during polymerization (2, 3). The crucial role of the metal cofactor and structurally conserved active site architecture in polymerases has also been demonstrated by validating Mg 2+ as a target for the design of antiviral drugs, not only against HIV RT but also, among others, against HIV integrase, HIV ribonuclease H (RNase H), and influenza-encoded endonuclease (4, 5). Hence, it should be feasible to design a universal but simplified (d)NTP mimic that binds efficiently to a wide variety of DNA/RNA polymerases.It was hypothesized that a universal nucleoside triphosphate mimic should contain three major indispensable entities: (i) a nucleobase part (i.e., to achieve optimal Watson-Crick basepairing with the template overhang), (ii) a replacement of the triphosphate moiety that should enable efficient Mg 2+ -directed coordination, and (iii) a variable linker between the nucleobase and the modified triphosphate to mimic the pentose entity present in natural (d)NTPs. For the triphosphate part, we chose an α-carboxy phosphonate entity that is chemically stable in physiolog...