Carbene catalyzed umpolung of α,β-enals: a reactivity study of diamino dienols vs. azolium enolates,and the characterization of advanced reaction intermediates

Since their discovery by Bode and Glorius in 2004, N-heterocyclic carbene catalyzed conjugate umpolung reactions of α,β-enals have been postulated to involve the formation of diamino dienols (“homoenolates”) and/or azolium enolates (“enolates”), typically followed by addition to electrophiles, e.g. Michael-acceptors. In this article, we provide evidence, for the first time, for the postulated individual and specific reactivity patterns of diamino dienols (γ-C–C-bond formation) vs. azolium enolates (β-C–C-bond formation). Our study is based on the pre-formation of well defined diamino dienols and azolium enolates, and the in situ NMR monitoring of their reactivities towards enone electrophiles. Additionally, reaction intermediates were isolated and characterized, inter alia by X-ray crystallography.     

Detection of σ-alkane complexes of manganese by NMR and IR spectroscopy in solution: (η5-C5H5)Mn(CO)2(ethane) and (η5-C5H5)Mn(CO)2(isopentane)

Irradiation of CpMn(CO)₃ in liquid ethane at 135 K at 355 nm yields a photoproduct that exhibits ν(CO) bands in the IR spectrum shifted to low wavenumber with respect to CpMn(CO)₃ that are indicative of a Mn(i) dicarbonyl. Parallel experiments employing in situ irradiation within an NMR probe (133 K, 355 nm photolysis) reveal the ¹H NMR signals of this product and confirm its formulation as the σ-ethane complex CpMn(CO)₂(η²-C1–H-ethane). The resonance of its coordinated C–H group is observed at δ –5.84 and decays with lifetime of ca. 360 s. Analogous photolysis experiments in isopentane solution with IR detection produce CpMn(CO)₂(η²-C–H-isopentane) with similar IR bands to those of CpMn(CO)₂(η²-C–H-ethane). ¹H NMR spectra of the same species were obtained by irradiation of CpMn(CO)₃ in a 60 : 40 mixture of propane and isopentane; three isomers of CpMn(CO)₂(η²-C–H-isopentane) were detected with coordination of manganese at the two inequivalent methyl positions and at the methylene group, respectively. The lifetimes of these isomers are ca. 380 ± 20 s at 135 K and do not vary significantly from each other. These σ-complexes of manganese are far more reactive than those of related CpRe(CO)₂(alkane) complexes which are stable in solution at 170–180 K. The room temperature lifetimes of CpMn(CO)₂(η²-C–H-ethane) and CpMn(CO)₂(η²-C–H-isopentane), as determined by TRIR spectroscopy, are 2.0 ± 0.1 and 28 ± 1 μs, respectively.     

Palladium-catalyzed asymmetric allylic alkylation (AAA) with alkyl sulfones as nucleophiles

An efficient palladium-catalyzed AAA reaction with a simple α-sulfonyl carbon anion as nucleophiles is presented for the first time. Allyl fluorides are used as superior precursors for the generation of π-allyl complexes that upon ionization liberate fluoride anions for activation of silylated nucleophiles. With the unique bidentate diamidophosphite ligand ligated palladium as catalyst, the in situ generated α-sulfonyl carbon anion was quickly captured by the allylic intermediates, affording a series of chiral homo-allylic sulfones with high efficiency and selectivity. This work provides a mild in situ desilylation strategy to reveal nucleophilic carbon centers that could be used to overcome the pK_a limitation of “hard” nucleophiles in enantioselective transformations.

A variety of “hard” α-sulfonyl carbanions of aryl, heteroaryl and alkyl sulfones were successfully employed as nucleophiles in palladium-catalyzed asymmetric allylic alkylation with excellent enantioselectivities.     

Tandem sequential catalytic enantioselective synthesis of highly-functionalised tetrahydroindolizine derivatives

An isothiourea-catalysed enantioselective synthesis of novel tetrahydroindolizine derivatives is reported through a one-pot tandem sequential process. The application of 2-(pyrrol-1-yl)acetic acid in combination with either a trifluoromethyl enone or an α-keto-β,γ-unsaturated ester in an enantioselective Michael addition–lactonisation process, followed by in situ ring-opening and cyclisation, led to a range of 24 tetrahydroindolizine derivatives containing three stereocentres in up to >95 : 5 dr and >99 : 1 er.

The isothiourea-catalysed enantioselective synthesis of tetrahydroindolizine derivatives containing three stereocentres is reported through a one-pot tandem sequential process.     

Non-metal with metal behavior: metal-free coordination-insertion ring-opening polymerization

The “coordination-insertion” ring-opening polymerization (ROP) mechanism has so far been the monopoly of metal catalysts. In this work, we present a metal-free “coordination-insertion” ROP of trimethylene carbonate (TMC) and ε-caprolactone (ε-CL), as well as their sequential block copolymerization, with N-trimethylsilyl-bis (trifluoromethanesulfonyl)imide (TMSNTf₂) as the non-metallic initiator/catalyst. TMSNTf₂ was proposed to work through an unprecedented metal-free “coordination-insertion” mechanism, which involves the coordination of monomer to the Si atom of TMSNTf₂, the nucleophilic attack of the –NTf₂ group on the coordinated monomer, and the cleavage of the acyl–oxygen bond of the monomer. The proposed metal-free “coordination-insertion” ROP was studied by NMR, SEC, and MALDI-TOF analyses. In addition, the TMSNTf₂-mediated ROP of TMC and ε-CL led to linear and cyclic polymers following two-stage first-order polymerization processes, as evidenced by structural analyses and kinetics study, which further demonstrated the metal-free “coordination-insertion” mechanism.

The first metal-free “coordination-insertion” ROP of cyclic carbonate and lactones mediated by N-trimethylsilyl-bis(trifluoromethanesulfonyl)imide (TMSNTf₂) was proposed, which in the past was exclusively the monopoly of metal complex catalysts.     

From Combinations to Single-Molecule Polypharmacology—Cromolyn-Ibuprofen Conjugates for Alzheimer’s Disease

Despite Alzheimer’s disease (AD) incidence being projected to increase worldwide, the drugs currently on the market can only mitigate symptoms. Considering the failures of the classical paradigm “one target-one drug-one disease” in delivering effective medications for AD, polypharmacology appears to be a most viable therapeutic strategy. Polypharmacology can involve combinations of multiple drugs and/or single chemical entities modulating multiple targets. Taking inspiration from an ongoing clinical trial, this work aims to convert a promising cromolyn–ibuprofen drug combination into single-molecule “codrugs.” Such codrugs should be able to similarly modulate neuroinflammatory and amyloid pathways, while showing peculiar pros and cons. By exploiting a linking strategy, we designed and synthesized a small set of cromolyn–ibuprofen conjugates (4–6). Preliminary plasma stability and neurotoxicity assays allowed us to select diamide 5 and ethanolamide 6 as promising compounds for further studies. We investigated their immunomodulatory profile in immortalized microglia cells, in vitro anti-aggregating activity towards Aβ₄₂-amyloid self-aggregation, and their cellular neuroprotective effect against Aβ₄₂-induced neurotoxicity. The fact that 6 effectively reduced Aβ-induced neuronal death, prompted its investigation into an in vivo model. Notably, 6 was demonstrated to significantly increase the longevity of Aβ₄₂-expressing Drosophila and to improve fly locomotor performance.     

A Study of the Effect of Sintering Conditions of Mg0.95Ni0.05Ti3 on Its Physical and Dielectric Properties

Mg_0.95Ni_0.05TiO₃ ceramics were prepared by traditional solid-state route using sintering temperatures between 1300 and 1425 °C and holding time of 2–8 h. The sintered samples were characterized for their phase composition, micro-crystalline structure, unit–cell constant, and dielectric properties. A two-phase combination region was identified over the entire compositional range. The effect of sintering conditions was analyzed for various properties. Both permittivity (ε_r) and Q factor (Q_f) were sensitive to sintering temperatures and holding times, and the optimum performance was found at 1350 °C withholding time of 4 h. The temperature coefficient of resonant frequency (τ_f) in a range from −45.2 to −52 (ppm/°C) and unit–cell constant were not sensitive to both the sintering temperature and holding time. An optimized Q factor of 192,000 (GHz) related with a permittivity (ε_r) of 17.35 and a temperature coefficient (τ_f) of −47 (ppm/°C) was realized for the specimen sintered at 1350 °C withholding time of 4 h. For applications of 5G communication device (filter, antennas, etc.), Mg_0.95Ni_0.05TiO₃ is considered to be a suitable candidate for substrate materials.     

Well-defined silica supported aluminum hydride: another step towards the utopian single site dream?

Reaction of triisobutylaluminum with SBA15₇₀₀ at room temperature occurs by two parallel pathways involving either silanol or siloxane bridges. It leads to the formation of a well-defined bipodal [(SiO)₂Al–CH₂CH(CH₃)₂] 1a, silicon isobutyl [Si–CH₂CH(CH₃)₂] 1b and a silicon hydride [Si–H] 1c. Their structural identity was characterized by FT-IR and advanced solid-state NMR spectroscopies (¹H, ¹³C, ²⁹Si, ²⁷Al and 2D multiple quantum), elemental and gas phase analysis, and DFT calculations. The reaction involves the formation of a highly reactive monopodal intermediate: [SiO–Al–[CH₂CH(CH₃)₂]₂], with evolution of isobutane. This intermediate undergoes two parallel routes: transfer of either one isobutyl fragment or of one hydride to an adjacent silicon atom. Both processes occur by opening of a strained siloxane bridge, Si–O–Si but with two different mechanisms, showing that the reality of “single site” catalyst may be an utopia: DFT calculations indicate that isobutyl transfer occurs via a simple metathesis between the Al-isobutyl and O–Si bonds, while hydride transfer occurs via a two steps mechanism, the first one is a β-H elimination to Al with elimination of isobutene, whereas the second is a metathesis step between the formed Al–H bond and a O–Si bond. Thermal treatment of 1a (at 250 °C) under high vacuum (10^–5 mbar) generates Al–H through a β-H elimination of isobutyl fragment. These supported well-defined Al–H which are highly stable with time, are tetra, penta and octa coordinated as demonstrated by IR and ²⁷Al–¹H J-HMQC NMR spectroscopy. All these observations indicate that surfaces atoms around the site of grafting play a considerable role in the reactivity of a single site system.     

Can acyclic conformational control be achieved via a sulfur–fluorine gauche effect?

The gauche conformation of the 1,2-difluoroethane motif is known to involve stabilising hyperconjugative interactions between donor (bonding, σ_C–H) and acceptor (antibonding, σ*C–F) orbitals. This model rationalises the generic conformational preference of F–C_β–C_α–X systems (φ_FCCX ≈ 60°), where X is an electron deficient substituent containing a Period 2 atom. Little is known about the corresponding Period 3 systems, such as sulfur and phosphorus, where multiple oxidation states are possible. Conformational analyses of β-fluorosulfides, -sulfoxides and -sulfones are disclosed here, thus extending the scope of the fluorine gauche effect to the 3rd Period (F–C–C–S(O)_n; φ_FCCS ≈ 60°). Synergy between experiment and computation has revealed that the gauche effect is only pronounced in structures bearing an electropositive vicinal sulfur atom (S⁺–O^–, SO₂).     

Asymmetric C–H functionalization of cyclopropanes using an isoleucine-NH2 bidentate directing group

The systematic investigation of substrate-bound α-amino acid auxiliaries has resulted in catalytic asymmetric C–H functionalization of cyclopropanes enabled by amino acid amides as chiral bidentate directing groups. The use of an Ile-NH₂ auxiliary embedded in the substrate provided excellent levels of asymmetric induction (diastereomeric ratio of up to 72 : 1) in the Pd(ii)-catalyzed β-methylene C(sp³)–H bond activation of cyclopropanes and cross-coupling with aryl iodides.     

Oxygen deficient α-Fe2O3 photoelectrodes: a balance between enhanced electrical properties and trap-mediated losses

Intrinsic doping of hematite through the inclusion of oxygen vacancies (V_O) is being increasingly explored as a simple, low temperature route to preparing active water splitting α-Fe₂O_3–x photoelectrodes. Whilst it is widely accepted that the introduction of V_O leads to improved conductivities, little else is verified regarding the actual mechanism of enhancement. Here we employ transient absorption (TA) spectroscopy to build a comprehensive kinetic model for water oxidation on α-Fe₂O_3–x. In contrast to previous suggestions, the primary effect of introducing V_O is to block very slow (ms) surface hole – bulk electron recombination pathways. In light of our mechanistic research we are also able to identify and address a cause of the high photocurrent onset potential, a common issue with this class of electrodes. Atomic layer deposition (ALD) of Al₂O₃ is found to be particularly effective with α-Fe₂O_3–x, leading to the photocurrent onset potential shifting by ca. 200 mV. Significantly TA measurements on these ALD passivated electrodes also provide important insights into the role of passivating layers, that are relevant to the wider development of α-Fe₂O₃ photoelectrodes.     

Counterintuitive solvation effect of ionic-liquid/DMSO solvents on acidic C–H dissociation and insight into respective solvation

How would acidic bond dissociation be affected by adding a small quantity of a weakly polar ionic liquid IL (the “apparent” or “measured” dielectric constant ε of the IL is around 10–15) into a strongly polar molecular solvent (e.g., ε of DMSO: 46.5), or vice versa? The answer is blurred, because no previous investigation was reported in this regard. Toward this, we, taking various IL/DMSO mixtures as representatives, have thoroughly investigated the effects of the respective solvent in ionic–molecular binary systems on self-dissociation of C–H acid phenylmalononitrile PhCH(CN)₂via pK_a determination. As disclosed, in this category of binary media, (1) no linear correspondence exists between pK_a and molar fractions of the respective solvent components; (2) only ∼1–2 mol% of weakly polar ILs in strongly polar DMSO make C–H bonds even more dissociative than in neat DMSO; (3) a small fraction of DMSO in ILs (<10 mol%) can dramatically ease acidic C–H-dissociation; and (4) while the DMSO fraction further increases, its acidifying effect becomes much attenuated. These findings, though maybe counterintuitive, have been rationalized on the basis of the precise pK_a measurement of this work in relation to the respective roles of each solvent component in solvation.

The dependence of PhCH(CN)₂ pK_a on the molar fraction of ionic liquids in ionic–molecular binary mixtures showed a nonlinear three-fragment plot, which was rationalized for the first time by the respective roles of each solvent component for solvation.     

Synthesis of unstrained Criegee intermediates: inverse α-effect and other protective stereoelectronic forces can stop Baeyer–Villiger rearrangement of γ-hydroperoxy-γ-peroxylactones

How far can we push the limits in removing stereoelectronic protection from an unstable intermediate? We address this question by exploring the interplay between the primary and secondary stereoelectronic effects in the Baeyer–Villiger (BV) rearrangement by experimental and computational studies of γ-OR-substituted γ-peroxylactones, the previously elusive non-strained Criegee intermediates (CI). These new cyclic peroxides were synthesized by the peroxidation of γ-ketoesters followed by in situ cyclization using a BF₃·Et₂O/H₂O₂ system. Although the primary effect (alignment of the migrating C–R_m bond with the breaking O–O bond) is active in the 6-membered ring, weakening of the secondary effect (donation from the OR lone pair to the breaking C–R_m bond) provides sufficient kinetic stabilization to allow the formation and isolation of stable γ-hydroperoxy-γ-peroxylactones with a methyl-substituent in the C6-position. Furthermore, supplementary protection is also provided by reactant stabilization originating from two new stereoelectronic factors, both identified and quantified for the first time in the present work. First, an unexpected boat preference in the γ-hydroperoxy-γ-peroxylactones weakens the primary stereoelectronic effects and introduces a ∼2 kcal mol⁻¹ Curtin–Hammett penalty for reacquiring the more reactive chair conformation. Second, activation of the secondary stereoelectronic effect in the TS comes with a ∼2–3 kcal mol⁻¹ penalty for giving up the exo-anomeric stabilization in the 6-membered Criegee intermediate. Together, the three new stereoelectronic factors (inverse α-effect, misalignment of reacting bonds in the boat conformation, and the exo-anomeric effect) illustrate the richness of stereoelectronic patterns in peroxide chemistry and provide experimentally significant kinetic stabilization to this new class of bisperoxides. Furthermore, mild reduction of γ-hydroperoxy-γ-peroxylactone with Ph₃P produced an isolable γ-hydroxy-γ-peroxylactone, the first example of a structurally unencumbered CI where neither the primary nor the secondary stereoelectronic effect are impeded. Although this compound is relatively unstable, it does not undergo the BV reaction and instead follows a new mode of reactivity for the CI – a ring-opening process.

Protecting stereoelectronic effects prevent Baeyer–Villiger rearrangement and stabilize γ-OX-γ-peroxylactones (X = H, OH), the previously elusive non-strained Criegee intermediates.     

Ferric Phosphate Hydroxide Microstructures Affect Their Magnetic Properties

Uniformly sized and shape-controlled nanoparticles are important due to their applications in catalysis, electrochemistry, ion exchange, molecular adsorption, and electronics. Several ferric phosphate hydroxide (Fe₄(OH)₃(PO₄)₃) microstructures were successfully prepared under hydrothermal conditions. Using controlled variations in the reaction conditions, such as reaction time, temperature, and amount of hexadecyltrimethylammonium bromide (CTAB), the crystals can be grown as almost perfect hyperbranched microcrystals at 180 °C (without CTAB) or relatively monodisperse particles at 220 °C (with CTAB). The large hyperbranched structure of Fe₄(OH)₃(PO₄)₃ with a size of ∼19 μm forms with the “fractal growth rule” and shows many branches. More importantly, the magnetic properties of these materials are directly correlated to their size and micro/nanostructure morphology. Interestingly, the blocking temperature (T_B) shows a dependence on size and shape, and a smaller size resulted in a lower T_B. These crystals are good examples that prove that physical and chemical properties of nano/microstructured materials are related to their structures, and the precise control of the morphology of such functional materials could allow for the control of their performance.     

Solid-State Structures and Photoluminescence of Lamellar Architectures of Cu(I) and Ag(I) Paddlewheel Clusters with Hydrogen-Bonded Polar Guests

Two hexanuclear paddlewheel-like clusters appending six carboxylic-acid pendants have been isolated with the inclusion of polar solvent guests: [Cu₆(Hmna)₆]·7DMF (1·7DMF) and [Ag₆(Hmna)₆]·8DMSO (2·8DMSO), where H₂mna = 2-mercaptonicotininc acid, DMF = N,N’-dimethylformamide, and DMSO = dimethyl sulfoxide. The solvated clusters, together with their fully desolvated forms 1 and 2, have been characterized by FTIR, UV–Vis diffuse reflectance spectroscopy, TG-DTA analysis, and DFT calculations. Crystal structures of two solvated clusters 1·7DMF and 2·8DMSO have been unambiguously determined by single-crystal X-ray diffraction analysis. Six carboxylic groups appended on the clusters trap solvent guests, DMF or DMSO, through H-bonds. As a result, alternately stacked lamellar architectures comprising of a paddlewheel cluster layer and H-bonded solvent layer are formed. Upon UV illumination (λ_ex = 365 nm), the solvated hexasilver(I) cluster 2·8DMSO gives intense greenish-yellow photoluminescence in the solid state (λ_PL = 545 nm, Φ_PL = 0.17 at 298 K), whereas the solvated hexacopper(I) cluster 1·7DMF displays PL in the near-IR region (λ_PL = 765 nm, Φ_PL = 0.38 at 298 K). Upon complete desolvation, a substantial bleach in the PL intensity (Φ_PL < 0.01) is observed. The desorption–sorption response was studied by the solid-state PL spectroscopy. Non-covalent interactions in the crystal including intermolecular H-bonds, CH⋯π interactions, and π⋯π stack were found to play decisive roles in the creation of the lamellar architectures, small-molecule trap-and-release behavior, and guest-induced luminescence enhancement.     

The Influence of HCl Concentration on the Rate of the Hydrolysis–Condensation Reaction of Phenyltrichlorosilane and the Yield of (Tetrahydroxy)(Tetraphenyl)Cyclotetrasiloxanes,Synthesis of All Its Geometrical Isomers and Thermal Self-Condensation of Them under “Pseudo”-Equilibrium Conditions

The rate of hydrolysis–condensation reaction of phenyltrichlorosilane in water-acetone solutions and the product yields were shown to significantly depend on the concentration of HCl (C_HCl) in the solutions. The main product of the reaction was all-cis-(tetrahydroxy)(tetraphenyl)cyclotetrasiloxane. This was different from the earlier published results of analogous reactions of m-tolylSiCl₃, m-ClPhSiCl₃, and α-naphtylSiCl, in which some products of other types were formed. For example, trans-1,1,3,3-tetrahydroxy-1,3-di-α-naphtyldisiloxane was obtained in the case of α-naphtylSiCl₃. All-cis-(tetrahydroxy)(tetraphenyl)cyclotetrasiloxane was treated in acetone with HCl to give the other three geometric isomers (cis-cis-trans-, cis-trans-, and all-trans-). The thermal self-condensation of these four isomers under “pseudo”-equilibrium conditions (under atmospheric pressure) was investigated in different solvents, in quartz or molybdenum glass flasks. The compositions of the products were monitored by APCI-MS and ²⁹Si NMR spectroscopy. It was shown that all-cis- and cis-cis-trans-isomers in toluene or anisole mostly gave the cage-like Ph-T_8,10,12,14 and uncompleted cage-like Ph-T_10,12OSi(HO)Ph compounds. In contrast to these two isomers, the cis-trans–isomer in toluene mainly formed dimers with the loss of one or two molecules of water. However, in acetonitrile, significant amounts of Ph-T_10,12 and Ph-T_10,12OSi(HO)Ph species were formed along with the dimers. All-trans-isomer did not enter into the reaction at all.     

Solvate sponge crystals of (DMF)3NaClO4: reversible pressure/temperature controlled juicing in a melt/press-castable sodium-ion conductor

A new type of crystalline solid, termed “solvate sponge crystal”, is presented, and the chemical basis of its properties are explained for a melt- and press-castable solid sodium ion conductor. X-ray crystallography and atomistic simulations reveal details of atomic interactions and clustering in (DMF)₃NaClO₄ and (DMF)₂NaClO₄ (DMF = N-N′-dimethylformamide). External pressure or heating results in reversible expulsion of liquid DMF from (DMF)₃NaClO₄ to generate (DMF)₂NaClO₄. The process reverses upon the release of pressure or cooling. Simulations reveal the mechanism of crystal “juicing,” as well as melting. In particular, cation–solvent clusters form a chain of octahedrally coordinated Na⁺–DMF networks, which have perchlorate ions present in a separate sublattice space in 3 : 1 stoichiometry. Upon heating and/or pressing, the Na⁺⋯DMF chains break and the replacement of a DMF molecule with a ClO₄⁻ anion per Na⁺ ion leads to the conversion of the 3 : 1 stoichiometry to a 2 : 1 stoichiometry. The simulations reveal the anisotropic nature of pressure induced stoichiometric conversion. The results provide molecular level understanding of a solvate sponge crystal with novel and desirable physical castability properties for device fabrication.

Stimuli-responsive “solvate-sponge”-(DMF)₃NaClO₄ exhibits linear chains of DMF–Na⁺ ions with ClO₄⁻ anions in the interstitial space. At increased pressure or temperature, DMF is expelled (reversibly), resulting in a new stoichiometry-(DMF)₂NaClO₄.     

GC-MS Metabolic Profile and α-Glucosidase-, α-Amylase-, Lipase-, and Acetylcholinesterase-Inhibitory Activities of Eight Peach Varieties

The inhibition of certain digestive enzymes by target food matrices represents a new approach in the treatment of socially significant diseases. Proving the ability of fruits to inhibit such enzymes can support the inclusion of specific varieties in the daily diets of patients with diabetes, obesity, Alzheimer’s disease, etc., providing them with much more than just valuable micro- and macromolecules. The current study aimed atidentifying and comparing the GC-MS metabolic profiles of eight peach varieties (“Filina”, “Ufo 4, “Gergana”, “Laskava”, “July Lady”, “Flat Queen”, “Evmolpiya”, and “Morsiani 90”) grown in Bulgaria (local and introduced) and to evaluate the inhibitory potential of their extracts towards α-glucosidase, α-amylase, lipase, and acetylcholinesterase. In order to confirm samples’ differences or similarities, principal component analysis (PCA) and hierarchical cluster analysis (HCA) were also applied to the identified metabolites. The results provide important insights into the metabolomic profiles of the eight peach varieties and represent a first attempt to characterize the peels of the peach varieties with respect to α-glucosidase-, α-amylase-, lipase-, and acetylcholinesterase-inhibitory activities. All of the studied peach extracts displayed inhibitory activity towards α-glucosidase (IC₅₀: 125–757 mg/mL) and acetylcholinesterase (IC₅₀: 60–739 mg/mL), but none of them affected α-amylase activity. Five of the eight varieties showed inhibitory activity towards porcine pancreatic lipase (IC₅₀: 24–167 mg/mL). The obtained results validate the usefulness of peaches and nectarines as valuable sources of natural agents beneficial for human health, although further detailed investigation should be performed in order to thoroughly identify the enzyme inhibitors responsible for each activity.     

Biomimetic nanochannels for the discrimination of sialylated glycans via a tug-of-war between glycan binding and polymer shrinkage

Sialylated glycans that are attached to cell surface mediate diverse cellular processes such as immune responses, pathogen binding, and cancer progression. Precise determination of sialylated glycans, particularly their linkage isomers that can trigger distinct biological events and are indicative of different cancer types, remains a challenge, due to their complicated composition and limited structural differences. Here, we present a biomimetic nanochannels system integrated with the responsive polymer polyethyleneimine-g-glucopyranoside (Glc-PEI) to solve this problem. By using a dramatic “OFF–ON” change in ion flux, the nanochannels system achieves specific recognition for N-acetylneuraminic acid (Neu5Ac, the predominant form of sialic acid) from various monosaccharides and sialic acid species. Importantly, different “OFF–ON” ratios of the conical nanochannels system allows the precise and sensitive discrimination of sialylated glycan linkage isomers, α2–3 and α2–6 linkage (the corresponding ion conductance increase ratios are 96.2% and 264%, respectively). Analyses revealed an unusual tug-of-war mechanism between polymer-glycan binding and polymer shrinkage. The low binding affinity of Glc-PEI for the α2–6-linked glycan caused considerable shrinkage of Glc-PEI layer, but the high affinity for the α2–3-linked glycan resulted in only a slight shrinkage. This competition mechanism provides a simple and versatile materials design principle for recognition or sensing systems that involve negatively charged target biomolecules. Furthermore, this work broadens the application of nanochannel systems in bioanalysis and biosensing, and opens a new route to glycan analysis that could help to uncover the mysterious and wonderful glycoworld.

A glycan-responsive polymer-modified nanochannels system enables the precise discrimination of sialylated glycan linkage isomers via the different “OFF–ON” changes resulting from a “tug-of-war” between polymer-glycan binding and polymer shrinkage.     

Highly Oxygenated Triterpenoids and Diterpenoids from Fructus Rubi (Rubus chingii Hu) and Their NF-kappa B Inhibitory Effects

During a phytochemical investigation of the unripe fruits of Rubus chingii Hu (i.e., Fructus Rubi, a traditional Chinese medicine named “Fu-Pen-Zi”), a number of highly oxygenated terpenoids were isolated and characterized. These included nine ursane-type (1, 2, and 4–10), five oleanane-type (3, 11–14), and six cucurbitane-type (15–20) triterpenoids, together with five ent-kaurane-type diterpenoids (21–25). Among them, (4R,5R,8R,9R,10R,14S,17S,18S,19R,20R)-2,19α,23-trihydroxy-3-oxo-urs-1,12-dien-28-oic acid (rubusacid A, 1), (2R*,4S*,5R*,8R*,9R*,10R*,14S*,17S*, 18S*,19R*,20R*)-2α,19α,24-trihydroxy-3-oxo-urs-12-en-28-oic acid (rubusacid B, 2), (5R,8R,9R,10R, 14S,17R,18S,19S)-2,19α-dihydroxy-olean-1,12-dien-28-oic acid (rubusacid C, 3), and (3S,5S,8S,9R, 10S,13R,16R)-3α,16α,17-trihydroxy-ent-kaur-2-one (rubusone, 21) were previously undescribed. Their chemical structures and absolute configurations were elucidated on the basis of spectroscopic data and electronic circular dichroism (ECD) analyses. Compounds 1 and 3 are rare naturally occurring pentacyclic triterpenoids featuring a special α,β-unsaturated keto-enol (diosphenol) unit in ring A. Cucurbitacin B (15), cucurbitacin D (16), and 3α,16α,20(R),25-tetrahydroxy-cucurbita-5,23- dien-2,11,22-trione (17) were found to have remarkable inhibitory effects against NF-κB, with IC₅₀ values of 0.08, 0.61, and 1.60 μM, respectively.