Synthesis of a new pyranoanthocyanin dimer linked through a methyl-methine bridge

Two new anthocyanin-derived compounds corresponding to the ethylpyranomalvidin-3-glucoside and the pyranomalvidin-3-glucoside dimer linked through a methyl-methine bridge were synthesized for the first time and their structure characterized by LC-DAD/MS and NMR spectroscopy. The latter was obtained in a hydroalcoholic model solution through the reaction of the carboxypyranomalvidin-3-glucoside with ethylpyranomalvidin-3-glucoside and displays a blue/green color in solution.     

A pericyclic cascade to the stereocontrolled synthesis of 9-cis-retinoids

A domino reaction that is pericyclic in nature is thought to be triggered upon treatment of alkenynol 10 with arylsulfenyl chlorides. The process comprises an ordered sequence of sigmatropic rearrangements: a reversible [2,3]-allyl sulfenate to allyl sulfoxide shift, followed by a [2,3]-propargyl sulfenate to allenyl sulfoxide rearrangement, and last a stereodifferentiating [1,5]-sigmatropic hydrogen migration leading to polyene 13. The occurrence of the C7 to C11 hydrogen migration has been demonstrated by labeling experiments. The double diastereoselection of the [1,5]-sigmatropic hydrogen shift to afford a single isomer of the final polyene 13 is thought to arise from a combination of the electronic effect of the sulfoxide at one terminus, and the steric effect imparted by the bulky trimethylcyclohexenyl substituent at the other terminus. The overall process thus constitutes a stereoselective synthesis of an E,Z,Z-triene fragment from an alkenynol and, in particular, a retinoid with the 7E,9Z,11Z,13E configuration on the conjugated polyenic side chain. Application of this method to the synthesis of retinoids, including labeled analogues, is straightforward.     

Delineating Binding Modes of Gal/GalNAc and Structural Elements of the Molecular Recognition of Tumor‐Associated Mucin Glycopeptides by the Human Macrophage Galactose‐Type Lectin

The human macrophage galactose‐type lectin (MGL) is a key physiological receptor for the carcinoma‐associated Tn antigen (GalNAc‐α‐1‐O‐Ser/Thr) in mucins. NMR and modeling‐based data on the molecular recognition features of synthetic Tn‐bearing glycopeptides by MGL are presented. Cognate epitopes on the sugar and matching key amino acids involved in the interaction were identified by saturation transfer difference (STD) NMR spectroscopy. Only the amino acids close to the glycosylation site in the peptides are involved in lectin contact. Moreover, control experiments with non‐glycosylated MUC1 peptides unequivocally showed that the sugar residue is essential for MGL binding, as is Ca²⁺. NMR data were complemented with molecular dynamics simulations and Corcema‐ST to establish a 3D view on the molecular recognition process between Gal, GalNAc, and the Tn‐presenting glycopeptides and MGL. Gal and GalNAc have a dual binding mode with opposite trend of the main interaction pattern and the differences in affinity can be explained by additional hydrogen bonds and CH–π contacts involving exclusively the NHAc moiety.     

Density Functional Study of Proline‐Catalyzed Intramolecular Baylis–Hillman Reactions

A rationalization of stereoselectivity : The mechanisms of proline‐catalyzed and imidazole‐co‐catalyzed intramolecular Baylis–Hillman reactions have been studied by using density functional theory methods. The computational data has allowed us to rationalize the experimental outcome, validating some of the mechanistic steps proposed in the literature, as well as to propose new ones that considerably change and improve our understanding of the full reaction path (see scheme).

     

Necrosis Depth and Photodynamic Threshold Dose with Redaporfin-PDT

Predicting the extent of necrosis in photodynamic therapy (PDT) is critical to ensure that the whole tumor is treated but vital structures, such as major blood vessels in the vicinity of the tumor, are spared. The models developed for clinical planning rely on empirical parameters that change with the nature of the photosensitizer and the target tissue. This work presents an in vivo study of the necrosis in the livers of rats due to PDT with a bacteriochlorin photosensitizer named redaporfin using both frontal illumination and interstitial illumination. Various doses of light at 750 nm were delivered 15 min postintravenous administration of redaporfin. Sharp boundaries between necrotic and healthy tissues were found. Frontal illumination allowed for the determination of the photodynamic threshold dose—1.5 × 10¹⁹ photons cm⁻³—which means that the regions of the tissues exposed to more than 11 mm of ROS evolved to necrosis. Interstitial illumination produced a necrotic radius of 0.7 cm for a light dose of 100 J cm⁻¹ and a redaporfin dose of 0.75 mg kg⁻¹. The experimental data obtained can be used to inform and improve clinical planning with frontal and interstitial illumination protocols.     

Semileptonic (Λ b → Λcev) decay in a field theoretic quark model

The semileptonic decay width of heavy baryons such as (Λ _b → Λcev) has been estimated in the framework of a nonrelativistic field theoretic quark model where four component quark field operators along with a harmonic oscillator wave function are used to describe translationally invariant hadronic states. The present estimation does not make an explicit use of heavy quark symmetry and has a reasonable agreement with the experimentally measured decay width, polarisation ratio and form factors with the harmonic oscillator radii and quark momentum distribution inside the hadron as free parameters.     

Residue-specific NH exchange rates studied by NMR diffusion experiments

We present a novel approach to the investigation of rapid (>2s(-1)) NH exchange rates in proteins, based on residue-specific diffusion measurements. (1)H, (15)N-DOSY-HSQC spectra are recorded in order to observe resolved amide proton signals for most residues of the protein. Human ubiquitin was used to demonstrate the proposed method. Exchange rates are derived directly from the decay data of the diffusion experiment by applying a model deduced from the assumption of a two-site exchange with water and the "pure" diffusion coefficients of water and protein. The "pure" diffusion coefficient of the protein is determined in an experiment with selective excitation of the amide protons in order to suppress the influence of magnetization transfer from water to amide protons on the decay data. For rapidly exchanging residues a comparison of our results with the exchange rates obtained in a MEXICO experiment showed good agreement. Molecular dynamics (MD) and quantum mechanical calculations were performed to find molecular parameters correlating with the exchangeability of the NH protons. The RMS fluctuations of the amide protons, obtained from the MD simulations, together with the NH coupling constants provide a bilinear model which shows a good correlation with the experimental NH exchange rates.     

Molecular interactions and CO2-philicity in supercritical CO2. A high-pressure NMR and molecular modeling study of a perfluorinated polymer in scCO2

The carbon and fluorine chemical shifts of mixtures of carbon dioxide and Krytox, a carboxylic acid end-capped perfluorinated polyether used as stabilizer for the dispersion polymerization of methyl methacrylate, have been studied using high-pressure, high-resolution nuclear magnetic resonance. 13C and 19F spectra were measured in the density region between 0.54 and 0.73 g.cm(-3) at 334 K for different solutions of Krytox in scCO2 (0.22, 1.13 and 1.72 w/w %). An in-house developed high-pressure apparatus with the capability to change in situ the sample composition was used for this purpose using a 10 mm polyether ketone NMR tube. The nature of CO2-Krytox interaction was assessed both by comparing the CO2 deltaC variation of neat CO2 with that of mixtures with increasing surfactant composition and by the analysis of Krytox 19F corrected chemical shifts in terms of medium magnetic susceptibility. Ab initio calculations, at the second-order M?ller-Plesset level of theory to include the effects of electron correlation, were performed to access and compare the nature of the interactions between CO2 and perfluorinated and nonfluorinated analogue model molecules. Both experimental 13C and 19F HP-NMR results and molecular modeling studies support a F...CO2 site-specific Lewis acid-Lewis base interaction model. A positive entropic variation for the formation of CO2-fluorinated solute complex is advanced as an explanation for the higher solubility of perfluorinated molecules when compared to the nonfluorinated analogues.     

Improved method for fatty acid analysis in herbage based on direct transesterification followed by solid-phase extraction

Direct transesterification (DT) and solvent extraction with acid or basic derivatization procedure for fatty acid (FA) analysis in herbage were compared. The highest total FA, alpha-linolenic and linoleic acid contents were obtained with DT. However, DT also produced the highest amount of interfering compounds, identified as phytadienes and sugar derivative products, which may co-elute with FA. An additional step based on solid-phase extraction to produce clean samples was proposed. This procedure is simple and gives good recoveries for the FA fortified samples. Additionally, structural characterization of 16:1 trans-3 was conducted by covalent adduct chemical ionization tandem mass spectrometry.