Double Chalcogen Bonding Recognition Arrays in Solution.

N-substituted pyridino-based congeners of Ebselen, named here as Pyrselen, incorporating proximal Se and N atoms, undergo dimerization in solution and in the solid state through a dual donor-acceptor arrangement of chalcogen bonding sites. Dimerization constants were measured within the 15-50 M-1 range. Computational studies on the dimers depict a notable charge-transfer contribution to the association, validating Pyrselen as an effective scaffold for designing chalcogen-bonding-based recognition motifs. Insert abstract text here.

Silica nanoparticle conjugation with gallic acid towards enhanced free radical scavenging capacity and activity on osteosarcoma cells in vitro.

Gallic acid (GA), derived from land plants, possesses diverse physiological benefits, including anti-inflammatory and anticancer effects, making it valuable for biomedical applications. In this study, GA was used to modify the surface of dendritic mesoporous silica nanoparticles (DMSNs) via carbamate (DMSN-NCO-GA) or amide (DMSN-NH-GA) bonds, using a post-grafting technique. To explore GA-conjugated materials' potential in modulating cancer cell redox status, three variants of osteosarcoma cells (U2-OS) were used. These variants comprised the wild-type cells (NEO), the cells overexpressing the wild-type human Golgi anti-apoptotic protein (hGAAP), and the null mutant of hGAAP (Ct-mut), as this protein was previously demonstrated to play a role in intracellular reactive oxygen species (ROS) accumulation and cell migration. In the absence of external ROS triggers, non-modified DMSNs increased intracellular ROS in Ct-mut and NEO cells, while GA-conjugated materials, particularly DMSN-NH-GA, significantly reduced ROS levels, especially pronounced with higher GA concentrations and notably in hGAAP cells with inherently higher ROS levels. Additionaly, NH-GA conjugates were less cytotoxic, more effective in reducing cell migration, and had higher ROS buffering capacity compared to DMSN-NCO-GA materials. However, in the presence of the external stressor tert-butyl-hydroperoxide (TBHP), NCO-GA conjugates showed more efficient reduction of intracellular ROS. These findings suggest that varying chemical decoration strategies of nanomaterials, along with the accessibility of functional groups to the cellular environment, significantly influence the biological response in osteosarcoma cells. Highlighting this, GA-conjugation is a promising method for implementing antioxidant properties and inhibiting cancer cell migration, warranting further research in anticancer treatment and drug development.

MANNosylation of Mesoporous Silica Nanoparticles Modifies TLR4 Localization and NF-κB Translocation in T24 Bladder Cancer Cells.

D-mannose is widely used as non-antibiotic treatment for bacterial urinary tract infections. This application is based on a well-studied mechanism of binding to the type 1 bacterial pili and, therefore, blocking bacteria adhesion to the uroepithelial cells. To implement D-mannose into carrier systems, the mechanism of action of the sugar in the bladder environment is also relevant and requires investigation. Herein, two different MANNosylation strategies using mesoporous silica nanoparticles (MSNs) are described. The impact of different chemical linkers on bacterial adhesion and bladder cell response is studied via confocal microscopy imaging of the MSN interactions with the respective organisms. Cytotoxicity is assessed and the expression of Toll-like receptor 4 (TLR4) and caveolin-1 (CAV-1), in the presence or absence of simulated infection with bacterial lipopolysaccharide (LPS), is evaluated using the human urinary bladder cancer cell line T24. Further, localisation of the transcription factor NF-κB due to the MANNosylated materials is examined over time. The results show that MANNosylation modifies bacterial adhesion to the nanomaterials and significantly affects TLR4, caveolin-1, and NF-κB in bladder cells. These elements are essential components of the inflammatory cascade/pathogens response during urinary tract infections. These findings demonstrate that MANNosylation is a versatile tool to design hybrid nanocarriers for targeted biomedical applications.

Decorating phenylalanine side-chains with triple labeled 13C/19F/2H isotope patterns.

We present an economic and straightforward method to introduce 13C-19F spin systems into the deuterated aromatic side chains of phenylalanine as reporters for various protein NMR applications. The method is based on the synthesis of [4-13C, 2,3,5,6-2H4] 4-fluorophenylalanine from the commercially available isotope sources [2-13C] acetone and deuterium oxide. This compound is readily metabolized by standard Escherichia coli overexpression in a glyphosate-containing minimal medium, which results in high incorporation rates in the corresponding target proteins.

Synthesis of 4-Deoxy-4-Fluoro-d-Sedoheptulose: A Promising New Sugar to Apply the Principle of Metabolic Trapping.

Fluorinated carbohydrates are important tools for understanding the deregulation of metabolic fluxes and pathways. Fluorinating specific positions within the sugar scaffold can lead to enhanced metabolic stability and subsequent metabolic trapping in cells. This principle has, however, never been applied to study the metabolism of the rare sugars of the pentose phosphate pathway (PPP). In this study, two fluorinated derivatives of d-sedoheptulose were designed and synthesized: 4-deoxy-4-fluoro-d-sedoheptulose (4DFS) and 3-deoxy-3-fluoro-d-sedoheptulose (3DFS). Both sugars are taken up by human fibroblasts but only 4DFS is phosphorylated. Fluorination of d-sedoheptulose at C-4 effectively halts the enzymatic degradation by transaldolase and transketolase. 4DFS thus has a high potential as a new PPP imaging probe based on the principle of metabolic trapping. Therefore, the synthesis of potential radiolabeling precursors for 4DFS for future radiofluorinations with fluorine-18 is presented.

Immobilization of Agaricus bisporus Polyphenol Oxidase 4 on mesoporous silica: Towards mimicking key enzymatic processes in peat soils.

HYPOTHESIS: The use of immobilized enzyme-type biocatalysts to mimic specific processes in soil can be considered one of the most promising alternatives to overcome the difficulties behind the structural elucidation of riverine humic-derived iron-complexes. Herein, we propose that the immobilization of the functional mushroom tyrosinase, Agaricus bisporus Polyphenol Oxidase 4 (AbPPO4) on mesoporous SBA-15-type silica could contribute to the study of small aquatic humic ligands such as phenols. EXPERIMENTS: The silica support was functionalized with amino-groups in order to investigate the impact of surface charge on the tyrosinase loading efficiency as well as on the catalytic performance of adsorbed AbPPO4. The oxidation of various phenols was catalyzed by the AbPPO4-loaded bioconjugates, yielding high levels of conversion and confirming the retention of enzyme activity after immobilization. The structures of the oxidized products were elucidated by integrating chromatographic and spectroscopic techniques. We also evaluated the stability of the immobilized enzyme over a wide range of pH values, temperatures, storage-times and sequential catalytic cycles. FINDINGS: This is the first report where the latent AbPPO4 is confined within silica mesopores. The improved catalytic performance of the adsorbed AbPPO4 shows the potential use of these silica-based mesoporous biocatalysts for the preparation of a column-type bioreactor for in situ identification of soil samples.

Constraining and Modifying Peptides Using Pd-Mediated Cysteine Allylation.

Over the past decades, several strategies for inducing and stabilizing secondary structure formation in peptides have been developed to increase their proteolytic stability and their binding affinity to specific interaction partners. Here, we report how our recently introduced chemoselective Pd-catalyzed cysteine allylation reaction can be extended to stapling and how the resulting alkene-containing staples themselves can be further modified to introduce additional probes into such stabilized peptides. The latter is demonstrated by introducing a fluorophore as well as a PEG moiety into different stapled peptides using bioorthogonal thiol-ene and Diels-Alder reactions. Furthermore, we investigated structural implications of our allyl staples when used to replace conformationally relevant disulfide bridges. To this end, we chose a selective binder of integrin α3 ß1 (LXY3), which is only active in its cyclic disulfide form. We replaced the disulfide bridge by different stapling reagents in order to increase stability and binding affinity towards integrin α3 ß1 .

Supramolecular Chalcogen-Bonded Semiconducting Nanoribbons at Work in Lighting Devices.

This work describes the design and synthesis of a π-conjugated telluro[3,2-ß][1]-tellurophene-based synthon that, embodying pyridyl and haloaryl chalcogen-bonding acceptors, self-assembles into nanoribbons through chalcogen bonds. The ribbons π-stack in a multi-layered architecture both in single crystals and thin films. Theoretical studies of the electronic states of chalcogen-bonded material showed the presence of a local charge density between Te and N atoms. OTFT-based charge transport measurements showed hole-transport properties for this material. Its integration as a p-type semiconductor in multi-layered CuI -based light-emitting electrochemical cells (LECs) led to a 10-fold increase in stability (38 h vs. 3 h) compared to single-layered devices. Finally, using the reference tellurotellurophene congener bearing a C-H group instead of the pyridyl N atom, a herringbone solid-state assembly is formed without charge transport features, resulting in LECs with poor stabilities (<1 h).

A Combination of Structural, Genetic, Phenotypic and Enzymatic Analyses Reveals the Importance of a Predicted Fucosyltransferase to Protein O-Glycosylation in the Bacteroidetes.

Diverse members of the Bacteroidetes phylum have general protein O-glycosylation systems that are essential for processes such as host colonization and pathogenesis. Here, we analyzed the function of a putative fucosyltransferase (FucT) family that is widely encoded in Bacteroidetes protein O-glycosylation genetic loci. We studied the FucT orthologs of three Bacteroidetes species-Tannerella forsythia, Bacteroides fragilis, and Pedobacter heparinus. To identify the linkage created by the FucT of B. fragilis, we elucidated the full structure of its nine-sugar O-glycan and found that l-fucose is linked ß1,4 to glucose. Of the two fucose residues in the T. forsythia O-glycan, the fucose linked to the reducing-end galactose was shown by mutational analysis to be l-fucose. Despite the transfer of l-fucose to distinct hexose sugars in the B. fragilis and T. forsythia O-glycans, the FucT orthologs from B. fragilis, T. forsythia, and P. heparinus each cross-complement the B. fragilis ΔBF4306 and T. forsythia ΔTanf_01305 FucT mutants. In vitro enzymatic analyses showed relaxed acceptor specificity of the three enzymes, transferring l-fucose to various pNP-α-hexoses. Further, glycan structural analysis together with fucosidase assays indicated that the T. forsythia FucT links l-fucose α1,6 to galactose. Given the biological importance of fucosylated carbohydrates, these FucTs are promising candidates for synthetic glycobiology.

Evaporation-Induced Self-Assembly of Small Peptide-Conjugated Silica Nanoparticles.

Self-assembly processes guide disordered molecules or particles into long-range organized structures due to specific supramolecular interactions among the building entities. Herein, we report a unique evaporation-induced self-assembly (EISA) strategy for four different silica nanoparticle systems obtained through peptide functionalization of the particle surface. First, covalent peptide-silica coupling was investigated in detail, starting with the grafting of a single amino acid (L-serine) and expanded to specific small peptides (up to four amino acids) and transferred to different particle types (MCM-48-type MSNs, solid nanoparticles, and newly developed virus-like nanoparticles). These materials were investigated regarding their ability to undergo EISA, which was shown to be independent of particle type and amount of peptide anchored to their surface. This EISA-based approach provides new possibilities for the design of future advanced drug delivery systems, engineered hierarchical sorbents, and nanocatalyst assemblies.

Stereospecific Response of E/Z-isomers of N-Nitrososarcosine in LC-ESI-MS/MS.

The carcinogenic compound N-nitrososarcosine (NSAR) is found in foods and tobacco products, and its quantification is of great interest. Although the presence of two stereoisomers, E- and Z-NSAR, is well-known, individual investigation of the isomers has not been reported so far. The present study by liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) reveals that (i) the mass spectrometric responses of the isomers differ by a factor of approximately two and (ii) the isomer ratio is unstable in freshly prepared standard solutions. As a consequence, NSAR concentrations determined by LC-ESI-MS/MS are biased if those facts are not taken into account. The method described here overcomes the difficulty of stereospecific response by adjusting the isomer ratio and was applied to 100 tobacco products and fully validated for moist and dry snuff reference materials showing expanded measurement uncertainties of ~20% and limits of quantification of ~20 ng/g.

On the importance of the linking chemistry for the PEGylation of mesoporous silica nanoparticles.

The typical method for minimizing serum protein adsorption in biological settings and prolonging blood circulation time of nanoparticles, is to anchor hydrophilic polymers (e.g., poly(ethylene glycol), PEG) on the particle surface, which is most often done by covalent attachment (PEGylation). Herein, different PEGylation methods were realised and compared to functionalize mesoporous silica nanoparticles (MSNs). First, reactive groups were installed using post-grafting procedures with different functional silanes. Further, PEGs carrying a functional group and having different chain lengths and termini, were used. The grafting efficacy as well as the structural and physicochemical characteristics of the resulting particles were determined. Finally, the serum protein adsorption behaviour of these functionalized particles was investigated using thermogravimetric analysis. The type of selected coupling method was shown to strongly influence the grafting efficiency as well as the resulting protein adsorption. The results highlight the importance of the right choice of the linking chemistry when aiming at surface functionalization of nanoparticles.

Understanding Selectivity of Mesoporous Silica-Grafted Diglycolamide-Type Ligands in the Solid-Phase Extraction of Rare Earths.

Rare earth elements (REEs) and their compounds are essential for rapidly developing modern technologies. These materials are especially critical in the area of green/sustainable energy; however, only very high-purity fractions are appropriate for these applications. Yet, achieving efficient REE separation and purification in an economically and environmentally effective way remains a challenge. Moreover, current extraction technologies often generate large amounts of undesirable wastes. In that perspective, the development of selective, reusable, and extremely efficient sorbents is needed. Among numerous ligands used in the liquid-liquid extraction (LLE) process, the diglycolamide-based (DGA) ligands play a leading role. Although these ligands display notable extraction performance in the liquid phase, their extractive chemistry is not widely studied when such ligands are tethered to a solid support. A detailed understanding of the relationship between chemical structure and function (i.e., extraction selectivity) at the molecular level is still missing although it is a key factor for the development of advanced sorbents with tailored selectivity. Herein, a series of functionalized mesoporous silica (KIT-6) solid phases were investigated as sorbents for the selective extraction of REEs. To better understand the extraction behavior of these sorbents, different spectroscopic techniques (solid-state NMR, X-ray photoelectron spectroscopy, XPS, and Fourier transform infrared spectroscopy, FT-IR) were implemented. The obtained spectroscopic results provide useful insights into the chemical environment and reactivity of the chelating ligand anchored on the KIT-6 support. Furthermore, it can be suggested that depending on the extracted metal and/or structure of the ligand and its attachment to KIT-6, different functional groups (i.e., C═O, N-H, or silanols) act as the main adsorption centers and preferentially capture targeted elements, which in turn may be associated with the different selectivity of the synthesized sorbents. Thus, by determining how metals interact with different supports, we aim to better understand the solid-phase extraction process of hybrid (organo)silica sorbents and design better extraction materials.

Indium-mediated allylation of disaccharides.

The indium-mediated allylation followed by ozonolysis has been applied for the elongation of different disaccharides such as cellobiose, lactose and maltose. This reaction sequence and per-O-acetylation produced the expected mixture of α/ß-pyranoid as well as α/ß-furanoid isomers. The main product in all cases adopted the ß-pyranose form and could be isolated and fully characterized with the help of NMR-spin simulations. Thorough investigation of the side products throughout optimization of the conditions for the ozonolysis resulted in the discovery of a novel 12 membered bridged disaccharide.

Methylated Xanthones from the Rootlets of Metaxya rostrata Display Cytotoxic Activity in Colorectal Cancer Cells.

The tree fern Metaxya rostrata (Kunth) C. Presl is common in the rainforests of Central and South America, where suspensions of the dried rhizome are traditionally used to treat intestinal diseases. Two compounds from this plant, 2-deprenyl-rheediaxanthone B (XB) and 2-deprenyl-7-hydroxy-rheediaxanthone B (OH-XB), have been shown to be biologically highly active against colorectal cancer (CRC) cells in previous studies. The current investigation resulted in the isolation of the previously undescribed methylated xanthones 2-deprenyl-6-O-methyl-7-hydroxy-rheediaxanthone B, 2-deprenyl-5-O-methyl-7-methoxy-rheediaxanthone B, 2-deprenyl-5-O-methyl- 7-hydroxy-rheediaxanthone B and 2-deprenyl-7-methoxy-rheediaxanthone B. All compounds were isolated by column chromatography, structures were elucidated by one- and two-dimensional NMR-experiments and the identities of the compounds were confirmed by LC-HRMS. In logarithmically growing SW480 CRC cell cultures, cytotoxicity by neutral red uptake and MTT assays as well as caspase activation was analyzed. Cellular targets were examined by Western blot, and topoisomerase I (topo I) inhibition potential was tested. Comparing the structure-activity relationship with XB and OH-XB, the monomethylated derivatives showed qualitatively similar effects/mechanisms to their nonmethylated analogues, while dimethylation almost abolished the activity. Inhibition of topo I was dependent on the presence of an unmethylated 7-OH group.

A Many-Faced Alkaloid: Polymorphism of (-)-Monophyllidin.

The synthesis of the alkaloid (-)-monophyllidin is described. The molecule is a hybrid of xanthoxyline and (S)-proline, accessible in one-step through a Mannich reaction. In the solid-state, defined structural arrangements with different physical properties are formed. Single crystal X-ray diffraction revealed structures of six distinct polymorphs. In the crystalline state, the alkaloid can host small polar molecules (preferably water), while the (S)-proline moiety is present in the zwitterionic state. Combined with the chelate, which is already present in the xanthoxyline substructure, an ideal disposition for multiple hydrogen bond networks evolve. Therefore, highly water-soluble polymorphs of monophyllidin can form. This structural flexibility explains the many faces of the molecule in terms of structure as well as analytical data. Furthermore, speculations about the biological role of the molecule, with regard to the manifold interactions with water, are presented.

Indium-mediated C-allylation of melibiose.

The indium-mediated allylation reaction has been applied to melibiose, a disaccharidic substrate. This elongation methodology allows for a short, efficient and diastereoselective approach towards complex glycosylated carbohydrate structures. The stereochemical outcome of the key intermediates, allylated disaccharides, has been determined by X-ray analysis. Ozonolysis of the introduced double bond yielded the unprotected elongated disaccharides in the equilibrium of the pyranoid as well as furanoid isomers in both anomeric forms, respectively. Per-O-acetylation has been performed to facilitate separation of the isomeric mixture for structural identification. The main product revealed to adopt a ß-pyranoid form of the elongated unit at the reducing end of the disaccharide.

Waste-Derived Low-Cost Mycelium Nanopapers with Tunable Mechanical and Surface Properties.

Mycelium, the vegetative growth of filamentous fungi, has attracted increasing commercial and academic interest in recent years because of its ability to upcycle agricultural and industrial wastes into low-cost, sustainable composite materials. However, mycelium composites typically exhibit foam-like mechanical properties, primarily originating from their weak organic filler constituents. Fungal growth can be alternatively utilized as a low-cost method for on-demand generation of natural nanofibrils, such as chitin and chitosan, which can be grown and isolated from liquid wastes and byproducts in the form of fungal microfilaments. This study characterized polymer extracts and nanopapers produced from a common mushroom reference and various species of fungal mycelium grown on sugarcane byproduct molasses. Polymer yields of ∼10-26% were achieved, which are comparable to those of crustacean-derived chitin, and the nanopapers produced exhibited much higher tensile strengths than the existing mycelium materials, with values of up to ∼25 MPa (mycelium) and ∼98 MPa (mushroom), in addition to useful hydrophobic surface properties resulting from the presence of organic lipid residues in the nanopapers. HCl or H2O2 treatments were used to remove these impurities facilitating tuning of mechanical, thermal, and surface properties of the nanopapers produced. This potentially enables their use in a wide range of applications including coatings, membranes, packaging, and paper.

Size-Selective Separation of Rare Earth Elements Using Functionalized Mesoporous Silica Materials.

The separation and preconcentration of rare earth elements (REEs) from mineral concentrates in an economically and environmentally sustainable manner are difficult tasks due to their similar physicochemical properties. Herein, a series of tetradentate phenylenedioxy diamide (PDDA) ligands were synthesized and grafted on large-pore three-dimensional KIT-6 mesoporous silica. In solid-phase extraction, the hybrid sorbents enable a size-selective separation of REEs on the basis of the bite angles of the ligands. In particular, smaller REE3+ ions are preferentially extracted by KIT-6-1,2-PDDA, whereas light REEs with larger ionic radius are favored by KIT-6-1,3-PDDA. The exposure of bauxite residue digestion solution containing REEs as well as a number of types of competitive ions (including Th and U) to the sorbents results in selective recovery of target REEs. The possibility of regenerating the mesoporous sorbents through a simple loading-stripping-regeneration process is demonstrated over up to five cycles with no significant loss in REE extraction capacity, suggesting adequate chemical and structural stability of the new sorbent materials.

Ovalbumin Epitope SIINFEKL Self-Assembles into a Supramolecular Hydrogel.

Here we show that the well-known ovalbumin epitope SIINFEKL that is routinely used to stimulate ovalbumin-specific T cells and to test new vaccine adjuvants can form a stable hydrogel. We investigate properties of this hydrogel by a range of spectroscopic and imaging techniques demonstrating that the hydrogel is stabilized by self-assembly of the peptide into nanofibres via stacking of ß-sheets. As peptide hydrogels are known to stimulate an immune response as adjuvants, the immunoactive properties of the SIINFEKL peptide may also originate from its propensity to self-assemble into a hydrogel. This finding requires a re-evaluation of this epitope in adjuvant testing.