Potential Risks of Plant Constituents in Dietary Supplements: Qualitative and Quantitative Analysis of Peganum harmala Seeds

The free online trading of herbal mixtures useful for various purposes facilitates the circulation of dangerous herbs or plant parts. This is the case, for example, of the illegal trade in seeds of Peganum harmala (Pgh), which contain alkaloids capable of inhibiting monoamine oxidase (MAO) and are therefore used in hallucinogenic preparations, such as the psychedelic drink ayahuasca. The precise identification of these seeds and their distinction from other very similar but not dangerous seeds are necessary for forensic purposes and represents an advance in avoiding the adulteration of mixtures. In this work, we show the qualitative identification of Pgh seeds by optical and electron microscopy and the parallel development of a real-time qPCR test, which reveals, in a species-specific manner, the presence of Pgh DNA up to quantities lower than 1 pg. In addition to the species specificity and high sensitivity, the reaction accurately quantifies the presence of seeds or parts of seeds of Pgh in complex herbal mixtures, thus giving an indication of the danger or otherwise of the product.     

Feynman Integrals and Motives of Configuration Spaces

We formulate the problem of renormalization of Feynman integrals and its relation to periods of motives in configuration space instead of momentum space. The algebro-geometric setting is provided by the wonderful compactifications [`(Conf)]_G(X){\overline{Conf}_\Gamma(X)} of arrangements of subvarieties associated to the subgraphs of a Feynman graph Γ, with X a (quasi)projective variety. The motive and the class in the Grothendieck ring are computed explicitly for these wonderful compactifications, in terms of the motive of X and the combinatorics of the Feynman graph, using recent results of Li Li. The pullback to the wonderful compactification of the form defined by the unrenormalized Feynman amplitude has singularities along a hypersurface, whose real locus is contained in the exceptional divisors of the iterated blowup that gives the wonderful compactification. A regularization of the Feynman integrals can be obtained by modifying the cycle of integration, by replacing the divergent locus with a Leray coboundary. The ambiguities are then defined by Poincaré residues. While these residues give periods associated to the cohomology of the exceptional divisors and their intersections, the regularized integrals give rise to periods of the hypersurface complement in the wonderful compactification.     

Oxidation of 2-hydroxynevirapine, a phenolic metabolite of the anti-HIV drug nevirapine: evidence for an unusual pyridine ring contraction

Nevirapine (NVP) is an anti-HIV drug associated with severe hepatotoxicity and skin rashes, which raises concerns about its chronic administration. There is increasing evidence that metabolic activation to reactive electrophiles capable of reacting with bionucleophiles is likely to be involved in the initiation of these toxic responses. Phase I NVP metabolism involves oxidation of the 4-methyl substituent and the formation of phenolic derivatives that are conceivably capable of undergoing further metabolic oxidation to electrophilic quinoid species prone to react with bionucleophiles. The covalent adducts thus formed might be at the genesis of toxic responses. As part of a program aimed at evaluating the possible contribution of quinoid derivatives of Phase I phenolic NVP metabolites to the toxic responses elicited by the parent drug, we have investigated the oxidation of 2-hydroxy-NVP with dipotassium nitroso-disulfonate (Frémy's salt), mimicking the one-electron oxidation involved in enzyme-mediated metabolic oxidations. We report herein the isolation and full structural characterization of a 1H-pyrrole-2,5-dione derivative as a major product, stemming from an unusual pyridine ring contraction.     

Codes as Fractals and Noncommutative Spaces

We consider the CSS algorithm relating self-orthogonal classical linear codes to q-ary quantum stabilizer codes and we show that to such a pair of a classical and a quantum code one can associate geometric spaces constructed using methods from noncommutative geometry, arising from rational noncommutative tori and finite abelian group actions on Cuntz algebras and fractals associated to the classical codes.     

Dinuclear Co(III)/Co(III) and Co(II)/Co(III) mixed-valent complexes: synthetic control of the cobalt oxidation level

The reactivity of cobalt(II) salts towards H(3)L (2-(2-hydroxyphenyl)-1,3-bis[4-(2-hydroxyphenyl)-3-azabut-3-enyl]-1,3-imidazolidine) was studied in different reaction conditions. Accordingly, the interaction of cobalt(II) acetate with H(3)L in methanol gives rise to the discrete complex [Co(III)(2)L(OAc)(2)(OMe)]*1.5H(2)O.MeOH, 1. Reaction of cobalt(II) acetylacetonate with H(3)L in the presence of dicarboxylic acids was also investigated. Thus, when cobalt(II) acetylacetonate and H(3)L are mixed with terephthalic or malonic acid in 4 : 2 : 1 molar ratios, the mixed valent [Co(II/III)(2)L(acac)(p-O(2)CC(6)H(4)CO(2)H)][Co(II/III)(2)L(acac)(OH)]*2H(2)O*2MeOH, 2 and [Co(II/III)(2)L(acac)(O(2)CCH(2)CO(2)H)][Co(II/III)(2)L(acac)(OH)]*7H(2)O, complexes are isolated. Decreasing the pH of the medium, by addition of a second mol of dicarboxylic acid, leads to [Co(II/III)(2)L(O(2)CCH(2)CO(2))(MeOH)]*2MeOH, 4, while the reaction with terephthalic acid does not proceed. 1, 2 and 4 were crystallographically characterised and all the complexes are dinuclear, with hydrogen bonds that expand the initial nodes. The magnetic characterisation, as well as the NMR spectroscopy, indicates a diamagnetic nature for 1, in agreement with the presence of Co(III), showing the aerial oxidation suffered by the cobalt(II) ions. Nevertheless, are paramagnetic. Temperature variable magnetic measurements were recorded for the crystallographically characterised complexes 2 and 4 and these studies confirm the mixed valence Co(II)/Co(III) nature of the compounds. The best fits of the magnetic data give an axial distortion parameter Delta = 628.7 cm(-1) for 2 and 698.8 cm(-1) for 4, and spin-orbit coupling constant lambda = -117.8 cm(-1) for 2 and -107.0 cm(-1) for 4. Therefore, this study shows that the oxidation degree of the initial cobalt(ii) salt by atmospheric oxygen can be controlled according to the pH of the medium.     

Colorimetric characteristics of the phenolic fractions obtained from Tempranillo and Graciano wines through the use of different instrumental techniques

The aim of the present work was to determine whether there is any relationship between measurement by transmission and reflection (in the latter case, with and without contact with the sample). We also evaluated which methodology used would offer a better interpretation of the results in visual terms. For this purpose, different colorimetric techniques such as transmission spectrophotometry, diffuse reflectance spectrophotometry and spectroradiometry were applied. The samples consisted of increasing dilutions (0, 20, 40, 60, 80 and 100%) of the phenolic fractions obtained from 4 wines: Tempranillo (T) and Graciano (G) monovarietal wines, and two 80:20 mixtures: M (wine elaborated by blending grapes) and W (a blend of the T and G wines) (9 fractions per wine). Fractionation was performed using gel permeation chromatography with a Toyopearl HW-40S column, and the dilutions of the fractions were performed with synthetic wine (pH = 3.6). The spectroradiometric measurements permitted the differences due to the dilution effect on the fractions to be established more clearly than with the results obtained using diffuse reflectance and spectrophotometry. Thus, this technology is very suitable for use in comparative interpretations by the human eye. In turn, we assessed the changes in colour due to the effect of dilution on the fractions, observing that the effect of dilution led to an increase in the values of lightness (L*), while the chroma values (C*_ab) followed the opposite trend, in agreement with its role as a variable related to chromatic intensity or vividness of the sample. In contrast, hue (h_ab) did not seem to be affected by dilution of the fractions, in consonance with the qualitative nature of this parameter.     

MINIEMULSION FORMATION BY TRANSITIONAL INVERSION

Very fine emulsions with droplet size in the sub-micron range, often called miniemulsions, are prepared by the moderate (magnetic) stirring of a system undergoing a dynamic transitional inversion driven by a continuous change in physicochemical formulation (here temperature). Near optimum formulation for three-phase systems, the ultralow interfacial tension favors the drop breaking rate, and fine emulsions can be made. However, this region is also known for its rapid coalescence rate. Thus, a high enough stability can be attained only by shifting the formulation away from optimum as soon as the emulsion is made. Moreover, a rapid change in formulation through the three-phase region also results in a separation phenomenon that can be harnessed to produce ultra fine droplets.

The phase behavior of surfactant-oil-water systems and emulsion properties (type, droplet size and stability) are studied as a function of surfactant concentration (2 wt.% and 6 wt.%), for two different nonionic surfactants (polyoxyethylene tri-terbutyl ethers and sorbitan derivatives) with HLB ranging from 4 to 16. Kerosene and paraffin oil are used as oil phases. The transitional inversion form W/O to O/W is induced by a rapid cooling of the stirred systems from above to below the optimum temperature for three-phase behavior.

Miniemulsions are attained when the surfactant concentration is high enough, and when the temperature quenching span covers an appropriate range related to phase behavior.     

A general phosphoric acid-catalyzed desymmetrization of meso-aziridines with silylated selenium nucleophiles

The first example of meso-aziridine desymmetrization with selenium nucleophiles is reported. The reaction, promoted by VAPOL-hydrogen phosphate using (phenylseleno)trimethylsilane as the nucleophile, proves to be very general and highly enantioselective (84-99% ee).     

Cyclodextrin-mediated crystallization of acid β-glucosidase in complex with amphiphilic bicyclic nojirimycin analogues

Cyclodextrin-based host-guest chemistry has been exploited to facilitate co-crystallization of recombinant human acid β-glucosidase (β-glucocerebrosidase, GlcCerase) with amphiphilic bicyclic nojirimycin analogues of the sp(2)-iminosugar type. Attempts to co-crystallize GlcCerase with 5-N,6-O-[N'-(n-octyl)iminomethylidene]nojirimycin (NOI-NJ) or with 5-N,6-S-[N'-(n-octyl)iminomethylidene]-6-thionojirimycin (6S-NOI-NJ), two potent inhibitors of the enzyme with promising pharmacological chaperone activity for several Gaucher disease-associated mutations, were unsuccessful probably due to the formation of aggregates that increase the heterogeneity of the sample and affect nucleation and growth of crystals. Cyclomaltoheptaose (β-cyclodextrin, βCD) efficiently captures NOI-NJ and 6S-NOI-NJ in aqueous media to form inclusion complexes in which the lipophilic tail is accommodated in the hydrophobic cavity of the cyclooligosaccharide. The dissociation constant of the complex of the amphiphilic sp(2)-iminosugars with βCD is two orders of magnitude higher than that of the corresponding complex with GlcCerase, allowing the efficient transfer of the inhibitor from the βCD cavity to the GlcCerase active site. Enzyme-inhibitor complexes suitable for X-ray analysis were thus grown in the presence of βCD. In contrast to what was previously observed for the complex of GlcCerase with the more basic derivative, 6-amino-6-deoxy-5-N,6-N-[N'-(n-octyl)iminomethylidene]nojirimycin (6N-NOI-NJ), the β-anomers of both NOI-NJ and 6S-NOI-NJ were seen in the active site, even though the α-anomer was exclusively detected both in aqueous solution and in the corresponding βCD:sp(2)-iminosugar complexes. Our results further suggest that cyclodextrin derivatives might serve as suitable delivery systems of amphiphilic glycosidase inhibitors in a biomedical context.