Modeling procyanidin self-association processes and understanding their micellar organization: a study by diffusion NMR and molecular mechanics

The colloidal behavior of eight synthetic procyanidins (three monomers, four dimers, and a trimer) has been investigated in water or in a winelike medium using DOSY NMR spectroscopy and molecular dynamics simulations. Different behavior was observed for monomers and oligomers. Monomers self-associate with a high affinity constant (37-53 M(-1)) to form micelles at low cmc (critical micelle concentration) values (1-5 g.L(-1)). These micelles undergo a time-dependent coalescence process to form hazes and precipitates. As for dimers and the trimer, self-association also occurs but with a lower affinity (approximately 6 M(-1)) and at higher cmc values (10-20 g.L(-1)) to form small micelles (<5 nm) that remain stable throughout the experiment. The presence of 10% ethanol does not significantly affect the self-association constant for monomers and oligomers but increases their cmc values by approximately 50% and decreases the micelle size by a factor 2. However, the presence of 20 mM NaCl appears to negate the effect of ethanol. This study helps to clarify the role of procyanidin monomers versus oligomers in wine turbidity and demonstrates that procyanidin oligomers are fully available to interact with saliva proteins.     

Room‐Temperature,Ligand‐ and Base‐Free Heck Reactions of Aryl Diazonium Salts at Low Palladium Loading: Sustainable Preparation of Substituted Stilbene Derivatives

The Pd(OAc)₂‐catalyzed Heck reaction of aryl diazonium salts with 2‐arylacrylates led to cis‐stilbenes with good to excellent stereoselectivity. The environmentally friendly protocol developed in this work features low palladium loading in technical‐grade methanol at room temperature under base‐, additive‐, and ligand‐free conditions. The same protocol applied to simple Heck coupling of aryl diazonium salts with methyl acrylate allows astonishingly low palladium loading, down to 0.005 mol %. The stereoselectivity experimentally observed for the synthesis of cis‐stilbenes has been rationalized by DFT calculations. Moreover, the role of methanol in promoting the reaction has been clarified by a computational study.     

A Useful,Reliable and Safer Protocol for Hydrogenation and the Hydrogenolysis of O‐Benzyl Groups: The In Situ Preparation of an Active Pd0/C Catalyst with Well‐Defined Properties

A simple, highly reproducible protocol for the hydrogenation of alkenes and alkynes and for the hydrogenolysis of O‐benzyl ethers has been developed. The method features the in situ preparation of an active Pd⁰/C catalyst from Pd(OAc)₂ and charcoal, in methanol. The mild reaction conditions (25 °C) and low catalyst loading required (0.025 mol %), as well as the absence of contamination of the product by palladium residues (<4 ppb), make this a sustainable, useful process for organic chemists. Alternatively, the protocol can be carried out under microwave activation, to shorten the reaction times, with cyclohexene as the hydrogen source.     

Distinction and quantitation of sugar isomers in ternary mixtures using the kinetic method

Quantitative isomeric analysis of fructose, galactose, and glucose was achieved using electrospray ionization and trimeric ion dissociation with data analysis by the kinetic method. Several L-amino acids and divalent metal cations were tested to select the best systems for isomeric distinction and quantitation of each monosaccharide. High discrimination could be achieved for most tested systems, and serine/Cu²⁺ and aspartic acid/Mn²⁺ were selected for quantitative analysis due to their ability to strongly distinguish the three analytes and to allow long-term reproducible measuring conditions. Accurate quantitative results were obtained for all isomers using three-point corrected calibration curves, which account for the competition effects evidenced to occur between sugars for the formation of the trimeric complexes. As a result, the relative proportion of one isomer in the liquid and in the gas phase depends on the sugar mixture composition. However, for a given reference/metal system, the extent of competition effects was shown to be constant within a given pair of sugars. The correction factors could thus be established based on data obtained from binary mixtures and successfully used for ternary sample analysis.     

Isomeric Distinction of Small Oligosaccharides: A Bottom-Up Approach Using the Kinetic Method

Isomeric distinction of di- and tri-saccharides could be efficiently achieved by using data previously obtained while performing experiments aimed at discriminating monosaccharides using trimeric ion dissociation with data analysis by the kinetic method. This study shows that effects observed for lower homologues when one of the partners is changed in the metal/reference system (typically a transition metal divalent cation associated to amino acids) can be extrapolated to upper homologues, at least for the tested analyte series. Systems allowing galactose, glucose, and fructose distinction were used as starting conditions to resolve cellobiose, lactose, maltose, and saccharose disaccharides. When a unique dissociation reaction was observed from the trimeric clusters, a new reference was selected based on its propensity to favor the analyte or the reference release, as revealed from monosaccharide experiments, depending on the desired effect. The same approach could be implemented from data obtained for disaccharides to select efficient metal/reference systems to distinguish cellotriose, isomaltotriose, maltotriose, and panose trisaccharides. As a result, method optimization is greatly improved due to an enhanced rationalization of the search for discriminant systems. While 40 systems had to be tested for monosaccharides, by screening five transition metals and eight amino acids, the proposed approach allowed efficient metal/reference systems to be found for disaccharides after testing 18 combinations; then, only four systems had to be scrutinized to achieve trisaccharide distinction. Accurate quantitative analyses could be performed in binary mixtures using three-point calibration curves to correct for competition effects between analytes for the formation of the trimeric clusters.     

Colloidal behavior of wine galloylated tannins

Tannins are one of the four key components determining wine organoleptic quality. First, they play an important gustative role since they are responsible for wine astringency and/or bitterness. Second, they act as a structuring compound directly linked to red wine turbidity and stability. This second role is the consequence of their colloidal behavior. In the present work, we demonstrate that wine tannins exhibit different colloidal behaviour whether they are or not galloylated. Procyanidins, when galloylated, are more inclined to form micelles than their non-galloylated form, letting us suggest that they could act as structuring agent in wine. However, the size of the formed micelles is of the nanometer range suggesting that procyanidins, up to trimers, are not involved alone in wine turbidity.     

Structural and conformational analysis of two native procyanidin trimers

The structure and conformation of two native procyanidin trimers in water have been determined using 2D NMR and molecular mechanics. The results show the existence of four rotameric forms, one of which is predominant (60 to 80%). These four rotamers are shown to be in slow to intermediate exchange on the NMR timescale. Both trimers, whose structures vary owing to a different substitution of one carbon atom, adopt conformations in which stacking between different phenolic rings is favored.