Reversible Light-Induced Dimerization of Secondary Face Azobenzene-Functionalized β-Cyclodextrin Derivatives

β-cyclodextrin (βCyD) derivatives equipped with aromatic appendages at the secondary face exhibit tailorable self-assembling capabilities. The aromatic modules can participate in inclusion phenomena and/or aromatic-aromatic interactions. Supramolecular species can thus form that, at their turn, can engage in further co-assembling with third components in a highly regulated manner; the design of nonviral gene delivery systems is an illustrative example. Endowing such systems with stimuli responsiveness while keeping diastereomeric purity and a low synthetic effort is a highly wanted advancement. Here, we show that an azobenzene moiety can be “clicked” to a single secondary O-2 position of βCyD affording 1,2,3-triazole-linked βCyD-azobenzene derivatives that undergo reversible light-controlled self-organization into dimers where the monomer components face their secondary rims. Their photoswitching and supramolecular properties have been thoroughly characterized by UV-vis absorption, induced circular dichroism, nuclear magnetic resonance, and computational techniques. As model processes, the formation of inclusion complexes between a water-soluble triazolylazobenzene derivative and βCyD as well as the assembly of native βCyD/βCyD-azobenzene derivative heterodimers have been investigated in parallel. The stability of the host-guest supramolecules has been challenged against the competitor guest adamantylamine and the decrease of the medium polarity using methanol-water mixtures. The collective data support that the E-configured βCyD-azobenzene derivatives, in aqueous solution, form dimers stabilized by the interplay of aromatic-aromatic and aromatic-βCyD cavity interactions after partial reciprocal inclusion. Photoswitching to the Z-isomer disrupts the dimers into monomeric species, offering opportunity for the spatiotemporal control of the organizational status by light.Ministerio de Ciencia e Innovación PID2019-105858RB-I00, PID2020-118403GB-I00, PID2020-118384GB-I00, PID2020-119130GB-I00Fondo Europeo de Desarrollo Regional PID2021-124247OB-C21Junta de Andalucía P20_00166, US-1380698, P12-FQM-1467Universidad de Sevilla FPU18/02922, FPU19/0436

Effects of inulin and di-D-fructose dianhydride-enriched caramels on intestinal microbiota composition and performance of broiler chickens

In vitro and in vivo experiments were designed to evaluate the effectiveness of laboratory-made di-D-fructose dianhydride (DFA)-enriched caramels. The DFA-enriched caramels were obtained from D-fructose (FC), D-fructose and sucrose (FSC), or D-fructose and β-cyclodextrin (FCDC). In the in vitro experiment, raftilose and all caramels increased (P < 0.05) L-lactate concentration and decreased (P < 0.05) pH. Total short-chain fatty acid concentration was higher (P < 0.05) than controls in tubes containing raftilose, FSC, FCDC and commercial sucrose caramel (CSC). Raftilose, and all caramels tested except FSC and FC (1%), increased (P < 0.01) lactobacilli log 10 number of copies compared with the non-additive control. FSC, FCDC and CSC increased (P < 0.01) the bifidobacteria number of copies as compared with controls. All additives, except FCDC, decreased (P < 0.01) Clostridium coccoides/ Eubacterium rectale log number of copies. Compared with controls, raftilose, FC and CSC led to lower (P < 0.01) EscherichiaShigella and enterobacteria. For the in vivo experiment, a total of 144 male 1-day-old broiler chickens of the Cobb strain were randomly assigned to one of the three dietary treatments for 21 days. Dietary treatments were control (commercial diet with no additive), inulin (20 g inulin/kg diet) and FC (20 g FC/kg diet). Final BW of birds fed FC diet was higher (P < 0.01) than controls or inulin-fed birds, although feed: gain values were not different. Feed intake of chickens fed FC was higher (P < 0.01) than that of inulin-fed birds but not statistically different from controls. Crop pH values were lower (P < 0.01) in birds fed FC diet as compared with control diet, with inulin-fed chickens showing values not different from control-or FC-fed birds. Lower (P < 0.05) lactobacilli number of copies was determined in the crop, ileum and caeca of birds fed the inulin diet compared with the control diet. Inulin supplementation also resulted in lower (P < 0.05) C. coccoides/E. rectale, bacteroides and total bacteria in caecal contents. Addition of FC to broiler diets gave place to lower (P < 0.05) enterobacteria and Escherichia-Shigella in crop and caecal contents compared with controls. The bacteroides number of copies increased (P < 0.05) as compared with controls in the ileum, but decreased (P < 0.05) in the caeca of chickens fed the FC diet. Energy, ADF, NDF and non-starch polysaccharides faecal digestibilities were greater (P < 0.05) than controls in chickens fed diets containing inulin or FC. Fat digestibility was higher (P < 0.05) in FC-fed birds compared with controls or inulin-fed chickens. In conclusion, DFA-enriched caramels tested here, particularly FC, may represent a type of new additives useful in poultry production

Trehalose-based siamese twin amphiphiles with tunable self-assembling, DNA nanocomplexing and gene delivery properties

An original family of multivalent vectors encompassing gemini and facial amphiphilicity, namely cationic Siamese twin surfactants, has been prepared fromthe disaccharide trehalose; molecular engineering lets us modulate the self-assembling properties and the topology of the nanocomplexes with plasmid DNA for efficient gene delivery in vitro and in vivo

sp2-Iminosugar glycolipids as inhibitors of lipopolysaccharide-mediated human dendritic cell activation in vitro and of acute inflammation in mice in vivo

Glycolipid mimetics consisting of a bicyclic polyhydroxypiperidine-cyclic carbamate core and a pseudoanomeric hydrophobic tail, termed sp2-iminosugar glycolipids (sp2-IGLs), target microglia during neuroinflammatory processes. Here we have synthesized and investigated new variants of sp2-IGLs for their ability to suppress the activation of human monocyte-derived dendritic cells (DCs) by lipopolysaccharide (LPS) signaling through Toll-like receptor 4. We report that the best lead was (1R)-1-dodecylsulfonyl-5N,6O-oxomethylidenenojirimycin (DSO2-ONJ), able to inhibit LPS-induced TNFα production and maturation of DCs. Immunovisualization experiments, using a mannoside glycolipid conjugate (MGC) that also suppress LPS-mediated DC activation as control, evidenced a distinct mode of action for the sp2-IGLs: unlike MGCs, DSO2-ONJ did not elicit internalization of the LPS co-receptor CD14 or induce its co-localization with the Toll-like receptor 4. In a mouse model of LPS-induced acute inflammation, DSO2-ONJ demonstrated anti-inflammatory activity by inhibiting the production of the pro-inflammatory interleukin-6. The ensemble of the data highlights sp2-IGLs as a promising new class of molecules against inflammation by interfering in Toll-like receptor intracellular signaling

Glyconanocavities: Cyclodextrins and beyond

International audienc

Glycochimie et thérapeutique: Les cyclodextrines en Pharmacie, perpectives pour le ciblage d'actifs thérapeutiques et le contrôle d'interactions membranaires

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