Acronycine Analog: New Selective Synthesis of 6‐Methoxy‐3,3‐dimethyl‐3H,7H‐pyrano[2,3‐c]xanthen‐7‐one

A new, convenient, and selective route to the dimethylpyrano[2,3‐c]xanthen‐7‐one, analog of acronycine, via aromatization and dehydrogenation reactions from the corresponding saturated hexahydro intermediate is described.     

A novel electrochemical biosensor based on the hemin-graphene nano-sheets and gold nano-particles hybrid film for the analysis of hydrogen peroxide

Hydrogen peroxide is an important analyte in biochemical, industrial and environmental systems. Therefore, development of novel rapid and sensitive analytical methods is useful. In this work, a hemin-graphene nano-sheets (H-GNs)/gold nano-particles (AuNPs) electrochemical biosensor for the detection of hydrogen peroxide (H₂O₂) was researched and developed; it was constructed by consecutive, selective modification of the GCE electrode. Performance of the H-GNs/AuNPs/GCE was investigated by chronoamperometry, and AFM measurements suggested that the graphene flakes thickness was ∼1.3 nm and that of H-GNs was ∼1.8 nm, which ultimately indicated that each hemin layer was ∼0.25 nm. This biosensor exhibited significantly better electrocatalytic activity for the reduction of hydrogen peroxide in comparison with the simpler AuNPs/GCE and H-GNs/GCE; it also displayed a linear response for the reduction of H₂O₂ in the range of 0.3 μM to 1.8 mM with a detection limit of 0.11 μM (S N⁻¹ = 3), high sensitivity of 2774.8 μA mM⁻¹ cm⁻², and a rapid response, which reached 95% of the steady state condition within 5 s. In addition, the biosensor was unaffected by many interfering substances, and was stable over time. Thus, it was demonstrated that this biosensor was potentially suitable for H₂O₂ analysis in many types of sample.     

Quantitative monitoring of tamoxifen in human plasma extended to 40 metabolites using liquid-chromatography high-resolution mass spectrometry: new investigation capabilities for clinical pharmacology

Liquid-chromatography (LC) high-resolution (HR) mass spectrometry (MS) analysis can record HR full scans, a technique of detection that shows comparable selectivity and sensitivity to ion transitions (SRM) performed with triple-quadrupole (TQ)-MS but that allows de facto determination of “all” ions including drug metabolites. This could be of potential utility in in vivo drug metabolism and pharmacovigilance studies in order to have a more comprehensive insight in drug biotransformation profile differences in patients. This simultaneous quantitative and qualitative (Quan/Qual) approach has been tested with 20 patients chronically treated with tamoxifen (TAM). The absolute quantification of TAM and three metabolites in plasma was realized using HR- and TQ-MS and compared. The same LC-HR-MS analysis allowed the identification and relative quantification of 37 additional TAM metabolites. A number of new metabolites were detected in patients’ plasma including metabolites identified as didemethyl-trihydroxy-TAM-glucoside and didemethyl-tetrahydroxy-TAM-glucoside conjugates corresponding to TAM with six and seven biotransformation steps, respectively. Multivariate analysis allowed relevant patterns of metabolites and ratios to be associated with TAM administration and CYP2D6 genotype. Two hydroxylated metabolites, α-OH-TAM and 4′-OH-TAM, were newly identified as putative CYP2D6 substrates. The relative quantification was precise (<20 %), and the semiquantitative estimation suggests that metabolite levels are non-negligible. Metabolites could play an important role in drug toxicity, but their impact on drug-related side effects has been partially neglected due to the tremendous effort needed with previous MS technologies. Using present HR-MS, this situation should evolve with the straightforward determination of drug metabolites, enlarging the possibilities in studying inter- and intra-patients drug metabolism variability and related effects.

Fast approximate truncated SVD

This paper presents a new method for the computation of truncated singular value decomposition (SVD) of an arbitrary matrix. The method can be qualified as deterministic because it does not use randomized schemes. The number of operations required is asymptotically lower than that using conventional methods for nonsymmetric matrices and is at a par with the best existing deterministic methods for unstructured symmetric ones. It slightly exceeds the asymptotical computational cost of SVD methods based on randomization; however, the error estimate for such methods is significantly higher than for the presented one. The method is one‐pass, that is, each value of the matrix is used just once. It is also readily parallelizable. In the case of full SVD decomposition, it is exact. In addition, it can be modified for a case when data are obtained sequentially rather than being available all at once. Numerical simulations confirm accuracy of the method.     

Hamilton connectedness and the partially square graphs

Let G be a κ-connected graph on n vertices. The partially square graphG^* of G is obtained by adding edges uv whenever the vertices u,v have a common neighbor x satisfying the condition N_G(x)⊂N_G[u]∪N_G[v]. Clearly G⊆G^*⊆G², where G² is the square of G. In particular G^*=G² if G is quasi-claw-free (and claw-free). In this paper we prove that a κ-connected, (κ?3) graph G is either hamiltonian-connected or the independence number of G^* is at least κ. As a consequence we answer positively two open questions. The first one by Ainouche and Kouider and the second one by Wu et al. As a by-product we prove that a quasi-claw-free (and hence a claw-free) graph satisfying the condition α(G²)<κ is hamiltonian-connected.     

Minimal regularity of the solution of some boundary value problems of Signorini's type in polygonal domains

We study the regularity in Sobolev spaces of the solution of transmission problems in a polygonal domain of the plane, with unilateral boundary conditions of Signorini's type in a part of the boundary and Dirichlet or Neumann boundary conditions on the remainder part. We use a penalization method combined with an appropriated lifting argument to get uniform estimates of the approximated solutions in order to obtain some minimal regularity results for the exact solution. The same method allows us to consider problems with thin obstacles. It can be easily extended to 3D problems. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Singular solution to Special Lagrangian Equations

We prove the existence of non-smooth solutions to three-dimensional Special Lagrangian Equations in the non-convex case.     

Total synthesis,isolation, surfactant properties,and biological evaluation of ananatosides and related macrodilactone-containing rhamnolipids

Rhamnolipids are a specific class of microbial surfactants, which hold great biotechnological and therapeutic potential. However, their exploitation at the industrial level is hampered because they are mainly produced by the opportunistic pathogen Pseudomonas aeruginosa. The non-human pathogenic bacterium Pantoea ananatis is an alternative producer of rhamnolipid-like metabolites containing glucose instead of rhamnose residues. Herein, we present the isolation, structural characterization, and total synthesis of ananatoside A, a 15-membered macrodilactone-containing glucolipid, and ananatoside B, its open-chain congener, from organic extracts of P. ananatis. Ananatoside A was synthesized through three alternative pathways involving either an intramolecular glycosylation, a chemical macrolactonization or a direct enzymatic transformation from ananatoside B. A series of diasteroisomerically pure (1→2), (1→3), and (1→4)-macrolactonized rhamnolipids were also synthesized through intramolecular glycosylation and their anomeric configurations as well as ring conformations were solved using molecular modeling in tandem with NMR studies. We show that ananatoside B is a more potent surfactant than its macrolide counterpart. We present evidence that macrolactonization of rhamnolipids enhances their cytotoxic and hemolytic potential, pointing towards a mechanism involving the formation of pores into the lipidic cell membrane. Lastly, we demonstrate that ananatoside A and ananatoside B as well as synthetic macrolactonized rhamnolipids can be perceived by the plant immune system, and that this sensing is more pronounced for a macrolide featuring a rhamnose moiety in its native ¹C₄ conformation. Altogether our results suggest that macrolactonization of glycolipids can dramatically interfere with their surfactant properties and biological activity.

We show that macrolactonization of gluco- and rhamnolipids dramatically interfere with their surfactant properties and biological activity.