La3B6O13(OH): The First Acentric High-Pressure Borate Displaying Edge-Sharing BO4 Tetrahedra

La₃B₆O₁₃(OH) was obtained by a high-pressure/high-temperature experiment at 6 GPa and 1673 K. The compound crystallizes in the space group P2₁ (no. 4) with the lattice parameters a=4.785(2), b=12.880(4), c=7.433(3) Å, and β=90.36(10)°, and is built up of corner- as well as edge-sharing BO₄ tetrahedra. It represents the first acentric high-pressure borate containing these B₂O₆ entities. The compound develops borate layers of „sechser“-rings with the La³⁺ cations positioned between the layers. Single-crystal and powder X-ray diffraction, vibrational and MAS NMR spectroscopy, second-harmonic generation (SHG) and thermoanalytical measurements, as well as computational methods were used to affirm the proposed structure and the B₂O₆ entities.     

Diversely Functionalised Cytochalasins through Mutasynthesis and Semi-Synthesis

Mutasynthesis of pyrichalasin H from Magnaporthe grisea NI980 yielded a series of unprecedented 4′-substituted cytochalasin analogues in titres as high as the wild-type system (≈60 mg L⁻¹). Halogenated, O-alkyl, O-allyl and O-propargyl examples were formed, as well as a 4′-azido analogue. 4′-O-Propargyl and 4′-azido analogues reacted smoothly in Huisgen cycloaddition reactions, whereas p-Br and p-I compounds reacted in Pd-catalysed cross-coupling reactions. A series of examples of biotin-linked, dye-linked and dimeric cytochalasins was rapidly created. In vitro and in vivo bioassays of these compounds showed that the 4′-halogenated and azido derivatives retained their cytotoxicity and antifungal activities; but a unique 4′-amino analogue was inactive. Attachment of larger substituents attenuated the bioactivities. In vivo actin-binding studies with adherent mammalian cells showed that actin remains the likely intracellular target. Dye-linked compounds revealed visualisation of intracellular actin structures even in the absence of phalloidin, thus constituting a potential new class of actin-visualisation tools with filament-barbed end-binding specificity.     

Terminal Alkyne Coupling Reactions Through a Ring: Effect of Ring Size on Rate and Regioselectivity

Terminal alkyne coupling reactions promoted by rhodium(I) complexes of macrocyclic NHC-based pincer ligands—which feature dodecamethylene, tetradecamethylene or hexadecamethylene wingtip linkers viz. [Rh(CNC-n)(C₂H₄)][BAr^F₄] (n=12, 14, 16; Ar^F=3,5-(CF₃)₂C₆H₃)—have been investigated, using the bulky alkynes HC≡CtBu and HC≡CAr’ (Ar’=3,5-tBu₂C₆H₃) as substrates. These stoichiometric reactions proceed with formation of rhodium(III) alkynyl alkenyl derivatives and produce rhodium(I) complexes of conjugated 1,3-enynes by C−C bond reductive elimination through the annulus of the ancillary ligand. The intermediates are formed with orthogonal regioselectivity, with E-alkenyl complexes derived from HC≡CtBu and gem-alkenyl complexes derived from HC≡CAr’, and the reductive elimination step is appreciably affected by the ring size of the macrocycle. For the homocoupling of HC≡CtBu, E-tBuC≡CCH=CHtBu is produced via direct reductive elimination from the corresponding rhodium(III) alkynyl E-alkenyl derivatives with increasing efficacy as the ring is expanded. In contrast, direct reductive elimination of Ar'C≡CC(=CH₂)Ar’ is encumbered relative to head-to-head coupling of HC≡CAr’ and it is only with the largest macrocyclic ligand studied that the two processes are competitive. These results showcase how macrocyclic ligands can be used to interrogate the mechanism and tune the outcome of terminal alkyne coupling reactions, and are discussed with reference to catalytic reactions mediated by the acyclic homologue [Rh(CNC-Me)(C₂H₄)][BAr^F₄] and solvent effects.     

Quantitative Assessment of Tip Effects in Single‐Molecule High‐Speed Atomic Force Microscopy Using DNA Origami Substrates

High‐speed atomic force microscopy (HS‐AFM) is widely employed in the investigation of dynamic biomolecular processes at a single‐molecule level. However, it remains an open and somewhat controversial question, how these processes are affected by the rapidly scanned AFM tip. While tip effects are commonly believed to be of minor importance in strongly binding systems, weaker interactions may significantly be disturbed. Herein, we quantitatively assess the role of tip effects in a strongly binding system using a DNA origami‐based single‐molecule assay. Despite its femtomolar dissociation constant, we find that HS‐AFM imaging can disrupt monodentate binding of streptavidin (SAv) to biotin (Bt) even under gentle scanning conditions. To a lesser extent, this is also observed for the much stronger bidentate SAv–Bt complex. The presented DNA origami‐based assay can be universally employed to quantify tip effects in strongly and weakly binding systems and to optimize the experimental settings for their reliable HS‐AFM imaging.     

Immunomodulatory Properties of Masticadienonic Acid and 3α-Hydroxy Masticadienoic Acid in Dendritic Cells

Dendritic cells are antigen-presenting cells, which identify and process pathogens to subsequently activate specific T lymphocytes. To regulate the immune responses, DCs have to mature by the recognition of TLR ligands, TNFα or IFNγ. These ligands have been used as adjuvants to activate DCs in situ or in vitro, with toxic effects. It has been shown that some molecules affect the immune system, e.g., Masticadienonic acid (MDA) and 3α-hydroxy masticadienoic acid (3α-OH MDA) triterpenes naturally occurring in several medicinal plants, since they activate the nitric oxide synthase in macrophages and induce T lymphocyte proliferation. The DCs maturation induced by MDA or 3a-OH MDA was determined by incubating these cells with MDA or 3α-OH MDA, and their phenotype was afterwards analyzed. The results showed that only 3α-OH MDA was able to induce DCs maturation. When mice with melanoma were inoculated with DCs/3α-OH MDA, a decreased tumor growth rate was observed along with an extended cell death area within tumors compared to mice treated with DCs incubated with MDA. In conclusion, it is proposed that 3α-OH MDA may be an immunostimulant molecule. Conversely, it is proposed that MDA may be a molecule with anti-inflammatory properties.     

Influence of Plant Extract Addition to Marinades on Polycyclic Aromatic Hydrocarbon Formation in Grilled Pork Meat

Marinating is one of the most common methods of pre-processing meat. Appropriate selection of marinade ingredients can influence the physicochemical properties of the meat and can reduce the level of polycyclic aromatic hydrocarbons (PAHs) in the final product. The effects of the inclusion of natural plant extracts such as bay leaf (BL), black pepper (BP), turmeric (TU), jalapeno pepper (JP) and tamarind paste (TA) in marinades on the physicochemical properties of grilled pork neck were studied. The addition of spice extracts to marinades increased the proportion of colour components L* and b*. The use of TU, TA, JP, MX and C marinades lowered the hardness and pH of the meat. The highest phenolic compound levels were observed in the case of the mixture of all extracts (MX) and JP marinades, and the highest total antioxidant capacity was exhibited by the BL and MX marinades. The highest PAH content was recorded in the CON marinade (Σ12PAH 98.48 ± 0.81 µg/kg) and the lowest in the JP marinade (4.76 ± 0.08 µg/kg), which had the strongest, statistically significant reducing effect (95% reduction) on PAH levels. Analysis of correlation coefficients showed a relationship between the total antioxidant capacity of the marinades and the PAH content in grilled pork.     

Nucleotide Analogues Bearing a C2′ or C3′-Stereogenic All-Carbon Quaternary Center as SARS-CoV-2 RdRp Inhibitors

The design of novel nucleoside triphosphate (NTP) analogues bearing an all-carbon quaternary center at C2′ or C3′ is described. The construction of this all-carbon stereogenic center involves the use of an intramoleculer photoredox-catalyzed reaction. The nucleoside analogues (NA) hydroxyl functional group at C2′ was generated by diastereoselective epoxidation. In addition, highly enantioselective and diastereoselective Mukaiyama aldol reactions, diastereoselective N-glycosylations and regioselective triphosphorylation reactions were employed to synthesize the novel NTPs. Two of these compounds are inhibitors of the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2, the causal virus of COVID-19.     

Phenylalanine-Based AMPA Receptor Antagonist as the Anticonvulsant Agent with Neuroprotective Activity—In Vitro and In Vivo Studies

Trying to meet the multitarget-directed ligands strategy, a series of previously described aryl-substituted phenylalanine derivatives, reported as competitive antagonists of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, were screened in vitro for their free-radical scavenging and antioxidant capacity in two different assays: ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity fluorescent (ORAC-FL) assays. The most active antioxidants 1 and 8 were further examined to evaluate their neuroprotective properties in vitro. In this study, compound 1 showed a significant neuroprotective effect against the neurotoxin 6-hydroxydopamine in neuroblastoma SH-SY5Y and IMR-32 cell lines. Both compounds also showed prevention from high levels of reactive oxygen species (ROS) in SH-SY5Y cells. Furthermore, the desired monoamine oxidase B (MAO-B) inhibition effect (IC₅₀ = 278 ± 29 nM) for 1 was determined. No toxic effects up to 100 µM of 1 and 8 against neuroblastoma cells were observed. Furthermore, in vivo studies showed that compound 1 demonstrated significant anticonvulsant potential in 6-Hz test, but in neuropathic pain models its antiallodynic and antihyperalgesic properties were not observed. Concluding, the compound 1 seems to be of higher importance as a new phenylalanine-based lead candidate due to its confirmed promise in in vitro and in vivo anticonvulsant activity.     

Electrochemical Oxidation of Nitrogen towards Direct Nitrate Production on Spinel Oxides

Nitrates are widely used as fertilizer and oxidizing agents. Commercial nitrate production from nitrogen involves high‐temperature‐high‐pressure multi‐step processes. Therefore, an alternative nitrate production method under ambient environment is of importance. Herein, an electrochemical nitrogen oxidation reaction (NOR) approach is developed to produce nitrate catalyzed by ZnFe_xCo_2?xO₄ spinel oxides. Theoretical and experimental results show Fe aids the formation of the first N?O bond on the *N site, while high oxidation state Co assists in stabilizing the absorbed OH^? for the generation of the second and third N?O bonds. Owing to the concerted catalysis, the ZnFe_0.4Co_1.6O₄ oxide demonstrates the highest nitrate production rate of 130±12 μmol h^?1 g_MO^?1 at an applied potential of 1.6 V versus the reversible hydrogen electrode (RHE).     

A Review of Surface Functionalized Amine Terminated Dendrimers for Application in Biological and Molecular Sensing

Dendrimers are three dimensional nanosized synthetic molecules that have internal cavities and numerous surface groups. In recent times they have received increased attention in sensing applications. For dendrimers to be used as sensors, they most commonly require functionalization at their surface. This is because the surface is generally the first point of contact between the dendrimer and the outside world, hence surface functionalization serves to selectively home in on the target analyte. Further, sensor signals may be transmitted through surface functionalities e.g. fluorochromic molecules. It is therefore important to document surface functionalization approaches. Dendrimers with amine surface groups have the advantage of being able to be conjugated to other molecules via an amide linkage, which is one of the most fundamental and widespread chemical bonds in nature. In this paper we demonstrate the properties of dendrimers that make them so applicable to sensing. We review several methods for functionalizing dendrimers via an amide linkage, as well as present a review of surface functionalized polyamidoamine, polyamine, and polypeptide dendrimers that have been employed for biological, chemical and molecular sensing.