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The synthesis of crystalline self-assembled materials starting from building blocks with a large degree of freedom is challenging. Furthermore, incorporating redox-active moieties in self-assembled metal–organic polyhedra is of the utmost interest to modulate the properties of the cavity through redox stimuli. Herein is presented the synthesis of a novel electroactive ligand bearing four coordinating moieties around an S-alkylated tetrathiafulvalene (TTF) scaffold. The redox behavior of the ligand is similar to that of a tetra-S-alkylated TTF. In the solid state, it presents a densely packed H-bonded 1D polymeric structure. Upon reaction with Cu(OAc)2 in the presence of dimethylformamide or dimethylacetamide, two novel M4L4-type metal–organic polyhedra (MOPs) bearing paddlewheel metal clusters as connecting nodes are obtained. The structural features and electrochemical properties of the ligand and the MOPs are discussed. Both MOPs adopt the same structure characterized by a tetrahedral arrangement of the four TTF moieties. [ABSTRACT FROM AUTHOR]

We established an efficient photocatalyzed arylsilylation of alkenes, utilizing readily accessible silylboronates and (hetero)aryl nitriles in the presence of a base. This reaction proceeds through a photoredox-triggered cascade of single-electron transfers of base/silylboronate adducts and (hetero)aryl nitriles with the photocatalyst, leading to the formation of the silyl radicals and (hetero)aryl nitrile radical anions. This is followed by sequential coupling with alkenes, yielding valuable 1,1-diaryl derivatives with a silicon group at the β-position. This protocol features good functional group tolerance, mild reaction conditions, and broad substrate scopes, and thus can be applicable to the structural modification of bioactive molecules. [ABSTRACT FROM AUTHOR]

Recombinant Factor VIII-Fc fusion protein (rFVIIIFc) is an enhanced half-life therapeutic protein product used for the management of hemophilia A. Recent studies have demonstrated that rFVIIIFc interacts with Fc gamma receptors (FcγR) resulting in the activation or inhibition of various FcγR-expressing immune cells. We previously demonstrated that rFVIIIFc, unlike recombinant Factor IX-Fc (rFIXFc), activates natural killer (NK) cells via Fc-mediated interactions with FcγRIIIA (CD16). Additionally, we showed that rFVIIIFc activated CD16+ NK cells to lyse a FVIII-specific B cell clone. Here, we used human NK cell lines and primary NK cells enriched from peripheral blood leukocytes to study the role of the FVIII moiety in rFVIIIFc-mediated NK cell activation. Following overnight incubation of NK cells with rFVIIIFc, cellular activation was assessed by measuring secretion of the inflammatory cytokine IFNg by ELISA or by cellular degranulation. We show that anti-FVIII, anti-Fc, and anti-CD16 all inhibited indicating that these molecules were involved in rFVIIIFc-mediated NK cell activation. To define which domains of FVIII were involved, we used antibodies that are FVIII domain-specific and demonstrated that blocking FVIII C1 or C2 domain-mediated membrane binding potently inhibited rFVIIIFc-mediated CD16+ NK cell activation, while targeting the FVIII heavy chain domains did not. We also show that rFVIIIFc binds CD16 with about five-fold higher affinity than rFIXFc. Based on our results we propose that FVIII light chain-mediated membrane binding results in tethering of the fusion protein to the cell surface, and this, together with increased binding affinity for CD16, allows for Fc-CD16 interactions to proceed, resulting in NK cellular activation. Our working model may explain our previous results where we observed that rFVIIIFc activated NK cells via CD16, whereas rFIXFc did not despite having identical IgG1 Fc domains. [ABSTRACT FROM AUTHOR]

A simple, two‐step process was developed for the easy access of polycyclic pyrrolopyridine derivatives. The first step involves a multicomponent reaction of aryl glyoxal, cyclohexane‐1,3‐dione derivatives and 2‐amino‐1,4‐napthoquinone in AcOH: H2O (1 : 1 v/v) under reflux conditions which led to the formation of 1,5‐diketones in 15 min of reaction time. In the second step, the reaction of ammonium acetate with 1,5‐diketones in AcOH under reflux conditions resulted the formation of polycyclic pyrrolopyridine derivatives. All the products were characterized by FTIR, 1H NMR, 13C NMR and HRMS. The single crystal XRD of one compound was recorded to further confirm the structure of the product. The presence of several bioactive moieties in our product, simple reaction process, metal‐free reaction conditions, easy purification method, and good yields of the products are the notable features of this methodology. [ABSTRACT FROM AUTHOR]

The microenvironments of metal single‐atoms (SAs) have important effects on their physicochemical properties. However, the understanding of the relationship between the coordination configuration of SAs and their properties is insufficient. Here, a sacrificing template strategy is developed to anchor La‐SAs on interconnected graphene nanocages (La‐N‐Cl/GNC), where La‐SAs are located above the graphene plane and one La atom coordinated with four N atoms in the graphene plane and with one Cl atom along the axial direction. Theoretical calculations demonstrated that asymmetrically La‐SAs are more conducive to breaking local charge symmetry. Consequently, additional electrical dipoles along the axial direction are generated, leading to unprecedented dipolar polarization loss and strong electromagnetic wave absorption properties. Moreover, the film constructed by asymmetrically‐coordinated La‐N‐Cl/GNC with a mass density of 0.084 g cm−3 exhibits superior flexibility, excellent mechanical strength, and moderate thermal insulation properties, guaranteeing its practical applications in harsh environments. These findings not only shed light on the relationships between asymmetrically coordinated SAs and their dielectric properties at the atomic level but also provide an efficient method for preparing multifunctional films. [ABSTRACT FROM AUTHOR]

Alantolactone is a eudesmane-type sesquiterpene lactone containing an α-methylene-γ-lactone moiety. Previous studies showed that alantolactone inhibits the nuclear factor κB (NF-κB) signaling pathway by targeting the inhibitor of NF-κB (IκB) kinase. However, in the present study, we demonstrated that alantolactone selectively down-regulated the expression of tumor necrosis factor (TNF) receptor 1 (TNF-R1) in human lung adenocarcinoma A549 cells. Alantolactone did not affect the expression of three adaptor proteins recruited to TNF-R1. The down-regulation of TNF-R1 expression by alantolactone was suppressed by an inhibitor of TNF-α-converting enzyme. Alantolactone increased the soluble forms of TNF-R1 that were released into the culture medium as an ectodomain. The structure–activity relationship of eight eudesmane derivatives revealed that an α-methylene-γ-lactone moiety was needed to promote TNF-R1 ectodomain shedding. In addition, parthenolide and costunolide, two sesquiterpene lactones with an α-methylene-γ-lactone moiety, increased the amount of soluble TNF-R1. Therefore, the present results demonstrate that sesquiterpene lactones with an α-methylene-γ-lactone moiety can down-regulate the expression of TNF-R1 by promoting its ectodomain shedding in A549 cells. [ABSTRACT FROM AUTHOR]

Glycopolymers are functional polymers with saccharide moieties on their side chains and are attractive candidates for biomaterials. Postpolymerization modification can be employed for the synthesis of glycopolymers. Activated esters are useful in various fields, including polymer chemistry and biochemistry, because of their high reactivity and ease of reaction. In particular, the formation of amide bonds caused by the reaction of activated esters with amino groups is of high synthetic chemical value owing to its high selectivity. It has been employed in the synthesis of various functional polymers, including glycopolymers. This paper reviews the recent advances in polymers bearing activated esters for the synthesis of glycopolymers by postpolymerization modification. The development of polymers bearing hydrophobic and hydrophilic activated esters is described. Although water-soluble activated esters are generally unstable and hydrolyzed in water, novel polymer backbones bearing water-soluble activated esters are stable and useful for postpolymerization modification for synthesizing glycopolymers in water. Dual postpolymerization modification can be employed to modify polymer side chains using two different molecules. Thiolactone and glycine propargyl esters on the polymer backbone are described as activated esters for dual postpolymerization modification. [ABSTRACT FROM AUTHOR]

The Diels–Alder equilibrium is a widely known process in chemistry that can be used to provide a thermoset structure with recyclability and reprocessability mechanisms. In this study, a commercial epoxy resin is modified through the integration of functional groups into the network structure to provide superior performance. The present study has demonstrated that it is possible to adapt the curing process to efficiently incorporate these moieties in the final structure of commercial epoxy-based resins. It also evaluates the impact that they have on the final properties of the cured composites. In addition, different approaches have been studied for the incorporation of the functional group, adjusting and adapting the stoichiometry of the system components due to the differences in reactivity caused by the presence of the incorporated reactive groups, with the objective of maintaining comparable ratios of epoxy/amine groups in the formulation. Finally, it has been demonstrated that although the Diels–Alder equilibrium responds under external conditions, such as temperature, different sets of parameters and behaviors are to be expected as the structures are integrated into the thermoset, generating new equilibrium temperatures. In this way, the present research has explored sustainable strategies to enable the recyclability of commercial thermoset systems through crosslinking control and its modification. [ABSTRACT FROM AUTHOR]

Pyrazolone moiety bearing an all‐carbon quaternary stereogenic center is frequent in biologically active products and pharmaceuticals. The catalytic route for the construction of quaternary carbon centers poses a formidable challenge. In this report, catalytic asymmetric Michael addition of 4‐monosubstituted‐pyrazol‐5‐ones to simple enones catalyzed by primary amine‐Brønsted acid composite has been developed. An array of pyrazolone derivatives bearing vicinal all carbon quaternary and tertiary stereocenters, were obtained in moderate to good diastereoselectivities (up to 92 : 8 dr) and good to excellent enantiomeric excess (up to 99 % ee). In addition, antipode for enantiomers of the pyrazolone derivatives were also realized in good to high stereoselectivities (up to 92 : 8 dr and up to 98 % ee). [ABSTRACT FROM AUTHOR]

Eleven derivatives of chalcones (PZ1–PZ11) were synthesized by incorporating N‐methyl piperazine on the para position of the aromatic B ring of chalcones. The A ring is substituted with different electron‐donating and withdrawing groups. All the final derivatives were evaluated for their monoamine oxidase A and B inhibition studies. From the series of compounds PZ‐7 was found to possess good MAO‐B inhibitory activity with an IC50 value of 2.60±0.22 μM, followed by PZ‐9 with an IC50 value of 3.44±0.20 μM, when compared with reference compound pargyline 2.69±0.48 μM. PZ‐7 also considerably reduced the cell mortality triggered by rotenone in SH‐SY5Y neuroblastoma cells. The docking study found that PZ‐7 showed a docking score of −10.809 kCal/mol, with a polar interaction with Gln206, and π‐π stacking interaction between the B ring of chalcone. A molecular dynamics simulation study showed higher stability of the protein–ligand complex. Overall, compound PZ‐7 could serve as a promising MAO‐B inhibitor with neuroprotective action. [ABSTRACT FROM AUTHOR]

Tröger's-based polymeric membranes have received tremendous attention for their inherent high free volume and excellent gas permeability. However, its selectivity was still unable to meet their industrial demand. In effort to achieve an optimization comprehensive performance, a set of homogeneous polymer chains was synthesized to fine-tune the free volume. These membranes were designed by copolymerization diamine moiety of 3, 3′-dimethylbiphenyl-4, 4′-diamine and 2, 2-bis [4-(4-aminophenoxy)phenyl] hexafluoropropane. Significant characterizations of their physical properties and chemical structures were carried out by FTIR, TGA, XRD, and mechanical strength. The effects of variation diamine content ratio were studied. An available simulation was carried out to elucidate the influence of introduced diamine. The permselectivity of membranes was evaluated by H 2 , CO 2 , O 2 , N 2 , and CH 4. The objective performances of feed gas pressure, test temperature, and aging stability on membranes were further studied. The exciting results demonstrated that our membranes exhibit improved gas performance. Notably, for H 2 separation, the H 2 /N 2 and H 2 /CH 4 selectivity was significantly enhanced by 125.7% (from 27.20 to 61.40) and 126.9% (from 30.41 to 69.02) with the addition of 30 mol% fluorinated diamine moiety while without much-compromising gas permeability was observed. These findings enlighten a facile and effective strategy in Tröger's-based polymer design towards high-purity gas separation. • Composite Tröger's-based polymeric membrane was prepared for gas separation. • Fluorinated aryl ether moiety diamine was used to tuning the free volume of membranes. • The H 2 /N 2 and H 2 /CH 4 selectivity was enhanced by 125.7 % and 126.9 % with the addition of 30 mol% diamine. • The attracted H 2 /CH 4 performance was very approached to the 2008 Robeson's upper bound. [ABSTRACT FROM AUTHOR]

Solution-state self-assemblies of block copolymers to form nanostructures are tremendously attractive for their tailorable morphologies and functionalities. While incorporating moieties with strong ordering effects may introduce highly orientational control over the molecular packing and dictate assembly behaviors, subtle and delicate driving forces can yield slower kinetics to reveal manifold metastable morphologies. Herein, we report the unusually convoluted self-assembly behaviors of a liquid crystalline block copolymer bearing triphenylene discotic mesogens. They undergo unusual multiple morphological transitions spontaneously, driven by their intrinsic subtle liquid crystalline ordering effect. Meanwhile, liquid crystalline orderedness can also be built very quickly by doping the mesogens with small-molecule dopants, and the morphological transitions are dramatically accelerated and various exotic micelles are produced. Surprisingly, with high doping levels, the self-assembly mechanism of this block copolymer is completely changed from intramolecular chain shuffling and rearrangement to nucleation-growth mode, based on which self-seeding experiments can be conducted to produce highly uniform fibrils. Assembly of block copolymers can be controlled to give varying morphologies and functionalities, but there are still aspects of the process that are not well understood. Here, the authors report convoluted self-assembly behaviours of block copolymers with discotic liquid crystalline moieties. [ABSTRACT FROM AUTHOR]

We synthesize supramolecular poly(disulfide) (CPS) containing covalently attached cucurbit[7]uril (CB[7]), which is exploited not only as a carrier to deliver plasmid DNA encoding destabilized Cas9 (dsCas9), but also as a host to include trimethoprim (TMP) by CB[7] moieties through the supramolecular complexation to form TMP@CPS/dsCas9. Once the plasmid is transfected into tumor cells by CPS, the presence of polyamines can competitively trigger the decomplexation of TMP@CPS, thereby displacing and releasing TMP from CB[7] to stabilize dsCas9 that can target and edit the genomic locus of PLK1 to inhibit the growth of tumor cells. Following the systemic administration of TMP@CPS/dsCas9 decorated with hyaluronic acid (HA), tumor‐specific editing of PLK1 is detected due to the elevated polyamines in tumor microenvironment, greatly minimizing off‐target editing in healthy tissues and non‐targeted organs. As the metabolism of polyamines is dysregulated in a wide range of disorders, this study offers a supramolecular approach to precisely control CRISPR/Cas9 functions under particular pathological contexts. [ABSTRACT FROM AUTHOR]

Developing an accessible and durable catalyst with minimal overpotentials to split water to produce both H 2 and O 2 is challenging. The hydrothermal-deposition precipitation route was adopted to synthesize α-Ag 2 WO 4 (20–80%) supported on α-Mn 3 O 4 (AgW/Mn). The 60%AgW/Mn catalyst, which is structurally made up of Mn platelets decorated with AgW nanoparticles, confirmed the existence of the MnO 2 (200) active sites, surpassing the Ag nanoparticles (54.3%), and the proportion of the birnessite Mn3+/4+ moieties. In comparison to other catalysts, it presented more selectivity for OER in 1.0 M KOH with a low overpotential (0.28 V) at 10 mA cm−2, a Tafel slope of 50.7 mV dec−1, an O 2 -equivelent amount of 221.5 mmolg−1, and a TOF of 1.17 s−1. Similarly, it produced HER at an overpotential of 0.089 V at η10, a Tafel slope of 73.35 mV dec−1, an H 2 -generated amount of 429.4 mmol g−1, and a TOF of 1.59 s−1. [Display omitted] • α-Ag 2 WO 4 (20–80%) supported on α-Mn 3 O 4 was synthesized by deposition precipitation. • Mn platelets including Mn3+, Mn4+, and Mn2+ decorated by Ag@α-Ag 2 WO 4 nanoparticles. • 60%AgW/Mn catalyst is an efficient water splitting electrocatalyst. • The overall splitting of the 60% catalyst indicates a potential of 1.54 V at η10. • The highest activity was based on the birnessite and Mn2+ ratio and Ag nanoparticles. [ABSTRACT FROM AUTHOR]

Polymers containing TEMPO moieties are effective catalysts for the electrochemical oxidation of alcohols. Such polymers, almost exclusively, are non‐commercial and are prepared using multi‐step synthetic procedures. Here we show that a commercially available TEMPO bearing polymer, Polyamine Immobilised Piperidinyl Oxyl (PIPO), is an effective homogeneous and surface‐confined polymeric catalyst for electrochemical alcohol oxidation at carbonaceous electrodes. We probe electrolytic conditions for effective and stable electrocatalytic alcohol oxidation showing that dichloromethane (DCM), containing tetrabutylammonium perchlorate (TBAP) and N‐methyl imidazole (NMI), is a suitable medium for homogeneous catalysis whilst carbonate buffer (pH 9.5) is better suited when PIPO is adsorbed at the electrode surface. These findings demonstrate the viability of PIPO as an effective and accessible catalyst for electrochemical alcohol oxidations. [ABSTRACT FROM AUTHOR]

A series of novel carboxamide compounds containing benzoxazole motif was synthesized through multiple steps, including electrophilic substitution, cyclization, reduction and amide formation. These processes utilized ortho-aminophenol and heptafluoro-2-iodopropane as starting materials. The structures of these compounds (4a–4r) were characterized by 1H NMR, 13C NMR, and HRMS. Bioassay results revealed that most of these compounds exhibited significant insecticidal activity against Mythimna separata at 500 mg/L. Among them, compound 6-chloro-N-(4-methoxy-3-(6-(perfluoropropan-2-yl)benzo[d]oxazol-2-yl)phenyl)-N-methylnicotinamide (4r) possessed the highest activity, even at 4 mg/L. Molecular docking predicted the binding modes of 4r. These novel carboxamide compounds containing benzoxazole motifs offer valuable insights for designing insecticidal compounds targeting GABA receptors, aiming to control lepidopteran pests effectively. [ABSTRACT FROM AUTHOR]

This study aims to comprehensively characterize 576 inhibitors targeting Spleen Tyrosine Kinase (SYK), a non-receptor tyrosine kinase primarily found in haematopoietic cells, with significant relevance to B-cell receptor function. The objective is to gain insights into the structural requirements essential for potent activity, with implications for various therapeutic applications. Through chemoinformatic analyses, we focus on exploring the chemical space, scaffold diversity, and structure-activity relationships (SAR). By leveraging ECFP4 and MACCS fingerprints, we elucidate the relationship between chemical compounds and visualize the network using RDKit and NetworkX platforms. Additionally, compound clustering and visualization of the associated chemical space aid in understanding overall diversity. The outcomes include identifying consensus diversity patterns to assess global chemical space diversity. Furthermore, incorporating pairwise activity differences enhances the activity landscape visualization, revealing heterogeneous SAR patterns. The dataset analysed in this work has three activity cliff generators, CHEMBL3415598, CHEMBL4780257, and CHEMBL3265037, compounds with high affinity to SYK are very similar to compounds analogues with reasonable potency differences. Overall, this study provides a critical analysis of SYK inhibitors, uncovering potential scaffolds and chemical moieties crucial for their activity, thereby advancing the understanding of their therapeutic potential. [ABSTRACT FROM AUTHOR]

1H-Indole-2,3-dione 3-[4-(4-sulfamoylphenyl)thiosemicarbazones] 6a-j were evaluated against para-influenza-3, reovirus-1, sindbis, coxsackie B4, and Punto Toro viruses. New 1-methyl-1H-indole-2,3-dione 3-[4-(4-sulfamoylphenyl) thiosemicarbazones] 7a-c were synthesized to evaluate the contribution of methyl substitution at position 1 of the indole ring to antiviral activity. The test results showed that 5-trifluoromethoxy substituted compound 6c (EC50 2-9 μM) and 5-bromo substituted 6f (EC50 2-3 μM) have non-toxic selective antiviral activity, while not all standards are active against reovirus-1. Molecular docking studies of 6c and 6f were carried out to determine the possible binding positions with reovirus-1. Trifluoromethoxy and bromine substitutions at position 5 of the indole ring provided selective antiviral activity, while methyl substitution at position 1 of the indole ring significantly decreased the activity against reovirus-1 and increased toxicity. [ABSTRACT FROM AUTHOR]

In this communication, a straighforward asymmetric synthesis of spiro‐indoline‐pyrazolone compounds is described. This methodology consists in a formal [4+1] cycloaddition reaction of 4‐bromopyrazolones and aza‐ortho‐quinone methides generated in situ catalyzed by a bisquinine‐derived squaramide in CHCl3 under basic conditions. A variety of chiral spirocyclic compounds bearing a pyrazolone and an indoline moieties were obtained in moderate to good yields (up to 68 %) and moderate to excellent enantioselectivities (up to 93 % ee). [ABSTRACT FROM AUTHOR]

We previously revealed that phosphine–boranes can function as molecular frameworks for biofunctional molecules. In the present study, we exploited the diversity of available phosphines to design and synthesize a series of B-(trifluoromethyl)phenyl phosphine–borane derivatives as novel progesterone receptor (PR) antagonists. We revealed that the synthesized phosphine–borane derivatives exhibited LogP values in a predictable manner and that the P–H group in the phosphine–borane was almost nonpolar. Among the synthesized phosphine–boranes, which exhibited PR antagonistic activity, B-(4-trifluoromethyl)phenyl tricyclopropylphosphine–borane was the most potent with an IC50 value of 0.54 μM. A docking simulation indicated that the tricyclopropylphosphine moiety plays an important role in ligand–receptor interactions. These results support the idea that phosphine–boranes are versatile structural options in drug discovery, and the developed compounds are promising lead compounds for further structural development of next-generation PR antagonists. [ABSTRACT FROM AUTHOR]

The synthesis of hybrid molecules is one of the current strategies of drug discovery for the development of new lead compounds. The 1,2,3-triazole moiety represents an important building block in Medicinal Chemistry, extensively present in recent years. In this paper, we presented the design and the synthesis of new 1,2,3-triazole hybrids, containing both an isatine and a phenolic core. Firstly, the non-commercial azide and the alkyne synthons were prepared by different isatines and phenolic acids, respectively. Then, the highly regioselective synthesis of 1,4-disubstituted triazoles was obtained in excellent yields by a click chemistry approach, catalyzed by Cu(I). Finally, a molecular docking study was performed on the hybrid library, finding four different therapeutic targets. Among them, the most promising results were obtained on 5-lipoxygenase, an enzyme involved in the inflammatory processes. [ABSTRACT FROM AUTHOR]

The plant-derived toxin ricin is classified as a type 2 ribosome-inactivating protein (RIP) and currently lacks effective clinical antidotes. The toxicity of ricin is mainly due to its ricin toxin A chain (RTA), which has become an important target for drug development. Previous studies have identified two essential binding pockets in the active site of RTA, but most existing inhibitors only target one of these pockets. In this study, we used computer-aided virtual screening to identify a compound called RSMI-29, which potentially interacts with both active pockets of RTA. We found that RSMI-29 can directly bind to RTA and effectively attenuate protein synthesis inhibition and rRNA depurination induced by RTA or ricin, thereby inhibiting their cytotoxic effects on cells in vitro. Moreover, RSMI-29 significantly reduced ricin-mediated damage to the liver, spleen, intestine, and lungs in mice, demonstrating its detoxification effect against ricin in vivo. RSMI-29 also exhibited excellent drug-like properties, featuring a typical structural moiety of known sulfonamides and barbiturates. These findings suggest that RSMI-29 is a novel small-molecule inhibitor that specifically targets ricin toxin A chain, providing a potential therapeutic option for ricin intoxication. [ABSTRACT FROM AUTHOR]

In the present work, the synthesis of new ethacrynic acid (EA) derivatives containing nitrogen heterocyclic, urea, or thiourea moieties via efficient and practical synthetic procedures was reported. The synthesised compounds were screened for their anti-proliferative activity against two different cancer cell lines, namely, HL60 (promyelocytic leukaemia) and HCT116 (human colon carcinoma). The results of the in vitro tests reveal that compounds 1–3, 10, 16(a–c), and 17 exhibit potent anti-proliferative activity against the HL60 cell line, with values of the percentage of cell viability ranging from 20 to 35% at 1 μM of the drug and IC50 values between 2.37 μM and 0.86 μM. Compounds 2 and 10 showed a very interesting anti-proliferative activity of 28 and 48% at 1 μM, respectively, against HCT116. Two PyTAP-based fluorescent EA analogues were also synthesised and tested, showing good anti-proliferative activity. A test on the drug-likeness properties in silico of all the synthetised compounds was performed in order to understand the mechanism of action of the most active compounds. A molecular docking study was conducted on two human proteins, namely, glutathione S-transferase P1-1 (pdb:2GSS) and caspase-3 (pdb:4AU8) as target enzymes. The docking results show that compounds 2 and 3 exhibit significant binding modes with these enzymes. This finding provides a potential strategy towards developing anticancer agents, and most of the synthesised and newly designed compounds show good drug-like properties. [ABSTRACT FROM AUTHOR]

Amphiphilic fluorocarbon substances are a trending topic of research due to their wide range of applications accompanied by an alarming environmental and health impact. In order to predict their fate in the environment, use them more economically, develop new water treatment methods, etc., a better understanding of their physicochemical behavior is required. Their hydrophobicity in water/oil systems is particularly sensitive to one key thermodynamic parameter: the free energy of transfer of a perfluoromethylene group from oil to water. However, for the –CF2– moiety, the transfer energy values reported in the literature vary by more than ±25%. Due to the exponential relationship between this energy and the adsorption constants or the partition coefficients, such an uncertainty can lead to orders of magnitude error in the predicted distribution of fluorinated species. We address this problem by presenting an experimental determination of the hydrophobic effect of a –CF2– moiety with a greater certainty than currently available. The transfer energy is determined by measuring the interfacial tension of water|hexane for aqueous solutions of short-chained fluorotelomer alcohols. The obtained results for the free energy of transfer of a –CF2– moiety from oil to water are 1.68 ± 0.02 × R T 0 , 1.75 ± 0.02 × R T 0 , and 1.88 ± 0.02 × R T 0 at 288.15 K, 293.15 K, and 303.15 K, respectively. [ABSTRACT FROM AUTHOR]

Significance: Reactive oxygen species (ROS), the reactive oxygen-carrying chemicals moieties, act as pleiotropic signal transducers to maintain various biological processes/functions, including immune response. Increased ROS production leads to oxidative stress, which is implicated in xenobiotic-induced adverse effects. Understanding the immunoregulatory mechanisms and immunotoxicity is of interest to developing therapeutics against xenobiotic insults. Recent Advances: While developmental studies have established the essential roles of ROS in the establishment and proper functioning of the immune system, toxicological studies have demonstrated high ROS generation as one of the potential mechanisms of immunotoxicity induced by environmental chemicals, including heavy metals, pesticides, aromatic hydrocarbons (benzene and derivatives), plastics, and nanoparticles. Mitochondrial electron transport and various signaling components, including NADH oxidase, toll-like receptors (TLRs), NF-κB, JNK, NRF2, p53, and STAT3, are involved in xenobiotic-induced ROS generation and immunotoxicity. Critical Issues: With many studies demonstrating the role of ROS and oxidative stress in xenobiotic-induced immunotoxicity, rigorous and orthogonal approaches are needed to achieve in-depth and precise understanding. The association of xenobiotic-induced immunotoxicity with disease susceptibility and progression needs more data acquisition. Furthermore, the general methodology needs to be possibly replaced with high-throughput precise techniques. Future Directions: The progression of xenobiotic-induced immunotoxicity into disease manifestation is not well documented. Immunotoxicological studies about the combination of xenobiotics, age-related sensitivity, and their involvement in human disease incidence and pathogenesis are warranted. Antioxid. Redox Signal. 40, 691–714. [ABSTRACT FROM AUTHOR]

A water‐soluble hydrazone ligand bearing 2‐nicotinoylhydrazineylidene moiety, sodium 4‐hydroxy‐3‐([2‐nicotinoylhydrazineylidene]methyl) benzenesulfonate (NaH2NH), and its complexes with Co(II), Fe(III), and Mn(II) have been synthesized and characterized. The structure of the ligand and its complexes were analyzed using various spectroscopic techniques such as FT‐IR, 1H‐ and 13C‐NMR, EI‐mass, powder X‐ray diffraction, UV–visible spectra, and magnetic measurements. The infrared spectra indicated that the ligand behaves as a negatively charged bidentate ligand (ON) through the deprotonation of the enolic (OH) group and the azomethine (C=N) group in the [Co (NaHNH)2(H2O)4Cl2].3H2O complex. In the [Fe (NaNH)2(H2O)Cl].2H2O complex, the ligand behaves as bi‐negative tetradentate (O2N2) through the protonation of the enolic oxygen and the nitrogen atom of the azomethine group in two nicotinic hydrazone molecules. Another coordination type was observed for [Mn (NaNH)(H2O)3] complex in which NaH2NH acts as bi‐negative tridentate ONO through the nitrogen atom of the azomethine group, the protonated of enolic and phenolic groups. The fluorescence spectrum of the NaH2NH was found to be quenched upon addition of these Co(II) and Mn(II) ions. The antimicrobial results indicated that the Mn(II) complex exhibited the highest antibacterial potency against all targeted organisms. The results of antioxidants demonstrated that the complexes exhibited higher activity compared to the free ligand, indicating an enhancement of antioxidant activity through complexation. The tested substances established strong nuclease‐like activity at a high concentration of 7.5 mM, leading to the complete degradation of DNA as observed in agarose gel electrophoresis. This suggests that these compounds have the potential to serve as antitumor agents in vivo by inhibiting DNA replication in cancer cells and preventing tumor growth. The interaction of the isolated compounds with 1c14 and 6vj3 targets was discussed using molecular docking. [ABSTRACT FROM AUTHOR]

Selective alkaline and earth alkaline metal ion encapsulation by six different Lehn-type cryptands was predicted by DFT (B3LYP/LANL2DZp) computational chemistry. All cryptands contain three identical moieties connected by the aliphatic nitrogen atom, constructing a very structurally flexible system for accommodating different-sized metal cations. Inspiration for selected hosts was taken from already well-known Lehn-type Cryptand [phen.phen.phen] where one phenanthroline was substituted by 5H-cyclopenta[2,1-b:3,4b′]pyridine in which the CH2– group was replaced by a series of heteroatoms forming the selected series of investigated hosts. The ion selectivity and the ability of the hosts to adjust their structure to accommodate the metal cations successfully were based on energy and geometric criteria. Medium-size cations have been proven to be best fitted for the selected host series. [ABSTRACT FROM AUTHOR]

The effect of the gradually formed cross-linked structure on the thermal properties and swelling behaviour of modified poly(vinyl alcohol) was investigated. To this aim, the semi-crystalline polymer was functionalized with aldehyde and amino moieties to produce polymers with dynamic imine cross-links, and, thus, with self-healing or curing ability. With increasing degree of functionalization (0.89–7.12%), denser polymer networks cross-linked by dynamic imine bonds were formed, the samples systematically developed thermoset-like properties compared to the pristine, initially thermoplastic PVA. As a result, the introduction of new moieties into the initial PVA lowered the glass transition (from 65.3 to 35.0 °C) and melting temperatures (from 194 to 161 °C), however, a new peak (Tcrd) with growing enthalpy values appeared on the DSC curves, which indicates that more and more energy must be supplied in order to break the imine cross-links formed between the introduced aldehyde and amino groups. The significant impact of the degree of functionalization and cross-linking density on the polymer structure was also clearly demonstrated: the crystallinity decreased as the abundance of the introduced moieties increased and the formation of cross-links proceeded. At the same time, the water desorption enthalpies of the samples increased, suggesting a stronger, chemically cross-linked thermoset-like polymer network compared to the thermoplastic poly(vinyl alcohol). [ABSTRACT FROM AUTHOR]

Recombinant Cordyceps militaris lipase (rCML) expressed in Komagataella phaffii is more highly N -mannosylated (Man 8–11 GlcNAc 2) than the native lipase. The lipase activity of rCML was enhanced compared to its deglycosylated form (drCML), but the increases in the V max values of rCML for substrates with chain lengths of C4:0–C14:0 were 1.8 to 2.9-fold greater than those of drCML, whereas the difference was narrower for C16:0–C18:0. Changes in acyl chain length selectivity correlated with the conformational changes rather than hydrophobicity changes induced by N -mannosylation, which may have altered active site accessibility by shifting the favorable binding locations depending on acyl chain length. Nevertheless, high N -mannosylation did not significantly affect the melting temperature of rCML compared to that of drCML (55.5 °C and 57.0 °C, respectively) during thermal unfolding, but alleviated harsh deactivation in the thermal-transition state (60–70 °C). Furthermore, high N -mannosylation enhanced the long-term storage stability at –20 °C, and loss of activity was 5.2 ± 1.1% and 32.8 ± 1.2% for rCML and drCML, respectively. Overall, the introduction of yeast-derived high mannose moieties endowed short- to medium-chain selectivity and improved the biochemical properties of recombinant lipase. [Display omitted] • Recombinant Cordyceps militaris lipase (rCML) from Komagataella phaffii is highly mannosylated. • Lipase activity of rCML was higher than its deglycosylated form, regardless of acyl chain length. • Notable variations in acyl chain length-dependent kinetic parameters were observed. • N -Mannosylation enhanced selectivity for short- to medium-chain fatty acids. • N -Mannosylation enhanced stability during thermal processing and long-term storage. [ABSTRACT FROM AUTHOR]

Pd‐catalyzed cyclization of a fluorescent dimer in which two cores of the potent estrogenic estradiol are bridged by the 1,4‐diethynil benzene moiety led to a steroid dimer bearing the 1,4‐di(benzofuran‐2‐yl)benzene. The obtained compound showed an intense blue fluorescence characterized by a broad emission band between 350 and 550 nm, with four maxima at 384, 403, 435, and 456 nm. The benzofuran dimer showed an 18‐fold increased quantum yield compared with that of its synthetic precursor. [ABSTRACT FROM AUTHOR]

In order to overcome the problem of pesticide resistance, it is necessary to discover novel pesticides with new mechanisms of action. Herein, a series of novel pyrimidin‐4‐amine derivatives containing trifluoroethyl sulfide moiety were designed and synthesized. Bioassays indicated that the title compounds synthesized possessed excellent acaricidal activity against Tetranychus urticae and fungicidal activity against Erysiphe graminis and Puccinia sorghi. Especially, the acaricidal activity of 5‐chloro‐6‐(difluoromethyl)‐N‐(2‐(2‐fluoro‐4‐methyl‐5‐((2,2,2‐trifluoroethyl)thio)phenoxy)ethyl)pyrimidin‐4‐amine (compound T4, LC50 = 0.19 mg/L) against T. urticae was close to commercial acaricide cyenopyrafen, and the fungicidal activity of 5‐chloro‐6‐(difluoromethyl)‐2‐methyl‐N‐(2‐(3‐((2,2,2‐trifluoroethyl)thio)phenoxy)ethyl)pyrimidin‐4‐amine (compound T15, EC50 = 1.32 mg/L) against P. sorghi. was superior to commercial fungicide tebuconazole. The synthesis and characterization of these compounds were given and the structure–activity relationships were discussed. [ABSTRACT FROM AUTHOR]

The marine environment, contains plentiful renewable resources, e.g. macroalgae with unique polysaccharides, motivating search for enzymes from marine microorganisms to explore conversion possibilities of the polysaccharides. In this study, the first GH17 glucanosyltransglycosylase, Ml GH17B, from a marine bacterium (Muricauda lutaonensis), was characterized. The enzyme was moderately thermostable with Tm at 64.4 °C and 73.2 °C, but an activity optimum at 20 °C, indicating temperature sensitive active site interactions. Ml GH17B uses β-1,3 laminari-oligosaccharides with a degree of polymerization (DP) of 4 or higher as donors. Two glucose moieties (bound in the aglycone +1 and +2 subsites) are cleaved off from the reducing end of the donor while the remaining part (bound in the glycone subsites) is transferred to an incoming β-1,3 glucan acceptor, making a β-1,6-linkage, thereby synthesizing branched or kinked oligosaccharides. Synthesized oligosaccharides up to DP26 were detected by mass spectrometry analysis, showing that repeated transfer reactions occurred, resulting in several β-1,6-linked branches. The modeled structure revealed an active site comprising five subsites: three glycone (−3, −2 and −1) and two aglycone (+1 and +2) subsites, with significant conservation of substrate interactions compared to the only crystallized 1,3-β-glucanosyltransferase from GH17 (Rm Bgt17A from the compost thriving fungus Rhizomucor miehei), suggesting a common catalytic mechanism, despite different phylogenetic origin, growth environment, and natural substrate. Both enzymes lacked the subdomain extending the aglycone subsites, found in GH17 endo-β-glucanases from plants, but this extension was also missing in bacterial endoglucanases (modeled here), showing that this feature does not distinguish transglycosylation from hydrolysis, but may rather relate to phylogeny. [ABSTRACT FROM AUTHOR]

Xenograft bone granules are bone graft materials that are widely used to reconstruct bone tissue in clinical practice, and their clinical success requires aggregation with a biocompatible binder. While the catechol mussel bioadhesive has been used as a key universal biomedical glue moiety, the thiols in mussel adhesive proteins have recently been shown to play key roles in mussel wet adhesion. Here, pentaerythritol tris(3-mercaptopropionate)-di-catechol (PETMP-di-catechol), a catechol- and thiol-containing binder molecule that mimics mussel adhesive proteins, was used to aggregate xenograft bone granules and reconstruct bone tissue. The PETMP-di-catechol-aggregated xenograft bone granules were most resistive to compression stress when both the catechol and thiol moieties in PETMP-di-catechol were chemically oxidized with sodium periodate. The xenograft bone granules aggregated with the oxidized PETMP-di-catechol exhibited enhanced osteogenic cellular behavior in vitro and in vivo in a rat calvarial defect model, compared to the control group treated with catechol-conjugated chitosan, a catechol-containing polymer binder devoid of thiol moieties. Hence, the thiol-containing catechol-functionalized binder exhibits improved bone tissue reconstruction properties by mimicking mussel wet adhesion. In addition, our study suggests that PETMP-di-catechol is a potential biocompatible bone binder for use in clinical settings. [ABSTRACT FROM AUTHOR]

The base-catalyzed reaction between 4-phenyl-1H-imidazole-2-thiol and 1,5-diaryl-substituted (E)-pent-2-en-4-yn-1-ones proceeded with the involvement of the C≡CCH=CH moiety of the substrate and HS, HN groups of the reagents to give 5H-imidazo[2,1-b]-[1,3]thiazine derivatives (6-endo-trig cyclization). Under the same conditions, the reactions of these linearly conjugated enynones with 4,5-diphenyl-1H-imidazole-2-thiol proceeded with the furan ring closure (5-exo-dig cyclization). The difference in the reaction pathways involving 4-phenyl- and 4,5-diphenyl-substituted 1H-imidazole-2-thiols was explained by the steric effects arising in the transition state. [ABSTRACT FROM AUTHOR]

2,6-Di-tert-butyl-4-methylphenol reacted with an equimolar amount of benzyltrimethylammonium tribromide to give 4-bromomethyl derivative but not 4-hydroxymethyl derivative as was reported earlier. The present work is devoted to the synthesis of 4-bromomethylphenols with bulky tert-butyl and/or isobornyl moieties at positions 2 and 6. [ABSTRACT FROM AUTHOR]

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Burkholderia cepacia complex infections remain life-threatening to cystic fibrosis patients, and due to the limited eradication efficiency of current treatments, novel antimicrobial therapies are urgently needed. Surface proteins are among the best targets to develop new therapeutic strategies since they are exposed to the host's immune system. A surface-shaving approach was performed using Burkholderia cenocepacia J2315 to quantitatively compare the relative abundance of surface-exposed proteins (SEPs) expressed by the bacterium when grown under aerobic and microaerophilic conditions. After trypsin incubation of live bacteria and identification of resulting peptides by liquid chromatography coupled with mass spectrometry, a total of 461 proteins with ≥2 unique peptides were identified. Bioinformatics analyses revealed a total of 53 proteins predicted as localized at the outer membrane (OM) or extracellularly (E). Additionally, 37 proteins were predicted as moonlight proteins with OM or E secondary localization. B-cell linear epitope bioinformatics analysis of the proteins predicted to be OM and E-localized revealed 71 SEP moieties with predicted immunogenic epitopes. The protegenicity higher scores of proteins BCAM2761, BCAS0104, BCAL0151, and BCAL0849 point out these proteins as the best antigens for vaccine development. Additionally, 10 of the OM proteins also presented a high probability of playing important roles in adhesion to host cells, making them potential targets for passive immunotherapeutic approaches. The immunoreactivity of three of the OM proteins identified was experimentally demonstrated using serum samples from cystic fibrosis patients, validating our strategy for identifying immunoreactive moieties from surface-exposed proteins of potential interest for future immunotherapies development. [ABSTRACT FROM AUTHOR]

Campylobacter is a major cause of acute gastroenteritis in humans, and infections can be followed by inflammatory neuropathies and other sequelae. Handling or consumption of poultry meat is the primary risk factor for human campylobacteriosis, and C. jejuni remains highly prevalent in retail chicken in many countries. Control of Campylobacter in the avian reservoir is expected to limit the incidence of human disease. Toward this aim, we evaluated a glycoconjugate vaccine comprising the fibronectin-binding adhesin FlpA conjugated to up to ten moieties of the conserved N-linked heptasaccharide glycan of C. jejuni or with FlpA alone. The glycan dose significantly exceeded previous trials using FlpA with two N-glycan moieties. Vaccinated birds were challenged with C. jejuni orally or by exposure to seeder-birds colonised by C. jejuni to mimic natural transmission. No protection against caecal colonisation was observed with FlpA or the FlpA glycoconjugate vaccine. FlpA-specific antibody responses were significantly induced in vaccinated birds at the point of challenge relative to mock-vaccinated birds. A slight but significant antibody response to the N-glycan was detected after vaccination with FlpA-10×GT and challenge. As other laboratories have reported protection against Campylobacter with FlpA and glycoconjugate vaccines in chickens, our data indicate that vaccine-mediated immunity may be sensitive to host- or study-specific variables. [ABSTRACT FROM AUTHOR]

A series of novel pyrazole-dicarboxamides were synthesized from pyrazole-3,4-dicarboxylic acid chloride and various primary and secondary sulfonamides. The structures of the new compounds were confirmed by FT-IR, ¹H-NMR, 13C-NMR, and HRMS. Then the inhibition effects of newly synthesized molecules on human erythrocyte hCA I and hCA II isoenzymes were investigated. Ki values of the compounds were in the range of 0.024-0.496 µM for hCA I and 0.006-5.441µM for hCA II. Compounds 7a and 7i showed nanomolar level of inhibition of hCA II, and these compounds exhibited high selectivity for this isoenzyme. Molecular docking studies were performed between the most active compounds 7a, 7b, 7i, and the reference inhibitor AAZ and the hCAI and hCAII to investigate the binding mechanisms between the compounds and the isozymes. These compounds showed better interactions than the AAZ. ADMET and drug-likeness analyses for the compounds have shown that the compounds can be used pharmacologically in living organisms. [ABSTRACT FROM AUTHOR]

[Display omitted] 1-Alkylsulfanyl-4-X-2,3,5,6-tetrafluorobenzenes (X = CF 3 , H; alkyl = Me, Bn, CHF 2) upon reactions with nitromethane in the presence of DBU undergo replacement of 2 or 3-positioned fluorine atoms by a nitromethyl group to afford the corresponding (nitromethyl)trifluoroarenes. The calculations of the transition states using the DFT method correctly predict the ratios of reaction products. In the cases of relative sulfones, only 2-positioned fluorine atom undergoes substitution; however, the sulfonyl group can also be displaced by a nitromethyl moiety. [ABSTRACT FROM AUTHOR]

It is well established that an isolated benzene radical anion is not electronically stable. In the present study, we experimentally show that electron attachment to benzene clusters leads to weak albeit unequivocal occurrence of a C 6 H 6 − moiety. We propose here—based on electronic structure calculation—that this moiety actually corresponds to linear structures formed by the opening of the benzene ring via electron attachment. The cluster environment is essential in this process since it quenches the internal energy released upon ring opening, which in the gas phase leads to further dissociation of this anion. [ABSTRACT FROM AUTHOR]

An effective approach to 5‐triazolyl‐substituted 6,7‐dihydrobenzo[d]isoxazol‐4(5H)‐ones and 4,5,6,7‐tetrahydrobenzo[d]isoxazoles was developed. The approach included α‐keto bromination of 6,7‐dihydrobenzo[d]isoxazol‐4(5H)‐one followed by nucleophilic substitution of bromine with the azide group. For the preparation of 5‐azido‐6,7‐dihydrobenzo[d]isoxazol‐4(5H)‐one, the carbonyl group at position 4 was reduced to a methylene group under ionic hydrogenation conditions using triethylsilane as a reducing agent. Cu(I)‐catalyzed [2+3] cycloaddition of terminal alkynes to both obtained azides was used for the synthesis of two series of triazolyl derivatives. Compounds, which contain in their structures common for some Hsp90 inhibitors 2,4‐dihydroxy‐5‐isopropylphenyl fragment, were evaluated as antiproliferative agents against two breast cancer cell lines: hormone‐dependent MCF7 and HER2‐positive HCC1954. The lead compound showed half‐maximal inhibitory concentration (IC50) values below 5 μM and induced significant changes in the Hsp90 signaling pathways in HER2‐positive HCC1954 cells. It increased the expression of Hsp70 (used as a pharmacodynamic marker of Hsp90 inhibition) and inhibited the expression of HER2, p‐c‐Met, c‐Met, and p‐AKT. The combination of the selected isoxazole‐triazole hybrid molecule and the earlier described apoptosis inducer LCTA‐3344 demonstrated a significant antiproliferative effect against HCC1954 cells. The lead compound was revealed to be a promising candidate for future anticancer drug design, particularly against aggressive breast cancer positive for HER2. [ABSTRACT FROM AUTHOR]

Compared to their P,N-analogues, compounds combining P and Sb substituents remain less common. This contribution describes the synthesis of a new ferrocene phosphinostibine, Cy2PfcSbPh2 (3; fc = ferrocene-1,1′-diyl, Cy = cyclohexyl), and its derivatives modified at the phosphine and stibine moieties, viz., Cy2P(E)fcSbPh2 (E = BH3, O, S, AuCl), Cy2P(E)fcSbCl2Ph2 (E = BH3, S, AuCl) and stiboranes Cy2P(E)fcSb(O2C6Cl4)Ph2 (E = void, BH3, O, S and AuCl). The increased Lewis acidity of the Sb atom in the catecholatostiboranes Cy2PfcSb(O2C6Cl4)Ph2 and Cy2P(O)fcSb(O2C6Cl4)Ph2 resulted in intramolecular P → Sb and O → Sb dative interactions, which were not detected for the respective parent stibines or even in Cy2P(S)fcSb(O2C6Cl4)Ph2. While the P → Sb interaction in Cy2PfcSb(O2C6Cl4)Ph2 was stronger than that in the "all-phenyl" analogue Ph2PfcSb(O2C6Cl4)Ph2 due to the electron-donating effect of the cyclohexyl groups, the bonding situations in Cy2P(O)fcSb(O2C6Cl4)Ph2 and Ph2P(O)fcSb(O2C6Cl4)Ph2, where the substituent effect was only indirect, remained very similar according to DFT calculations. A coordination study with 3 resulted in isolation of phosphine ([AuCl(3-κP)]), P,Sb-bridging ([(μ(P,Sb)-3)(AuCl)2]), and P,Sb-chelate ([(arene)MCl(3-κ2P,Sb)]X, where (arene)M/X = (η6-p-cymene)Ru(II)/PF6, (η5-C5Me5)Rh(III)/Cl, and (η5-C5Me5)Rh(III)/PF6, and [MCl2(3-κ2P,Sb)], where M = Pd and Pt) complexes. For some of these compounds, structure determination revealed structural distortions suggesting weak intramolecular Cl–Sb interactions, which were confirmed by theoretical methods. [ABSTRACT FROM AUTHOR]

A novel approach has been developed for the efficient synthesis of the unsymmetrical (2-aminopyrrolidin-1-yl)carboxamidine alkaloidal core found in cernumidine (1) and its analogs (20a, 20c, 20f, 20i–o). The key transformation in this process involves the utilization of the Curtius rearrangement, which plays a pivotal role in constructing the aminal moiety. One of the major challenges encountered during this synthesis was the instability of the free aminal core intermediate. Furthermore, a noteworthy observation during the synthesis was the racemization process that occurred during the isocyanate trapping by organometallic reagents. Detailed DFT calculations shed light on this phenomenon, revealing a neighboring coordination-induced mechanism. The resulting compounds were subjected to evaluation for their anti-inflammatory properties using lipopolysaccharide-stimulated human THP1 cells. Notably, compounds featuring the guanidine moiety and electron-donating groups exhibited significant anti-inflammatory activity. These findings suggest that these compounds hold promise as potential candidates for further development as anti-inflammatory agents. [ABSTRACT FROM AUTHOR]

Nickel complexes with a two‐electron reduced CO2 ligand (CO22−, "carbonite") are investigated with regard to the influence alkali metal (AM) ions have as Lewis acids on the activation of the CO2 entity. For this purpose complexes with NiII(CO2)AM (AM=Li, Na, K) moieties were accessed via deprotonation of nickel‐formate compounds with (AM)N(iPr)2. It was found that not only the nature of the AM ions in vicinity to CO2 affect the activation, but also the number and the ligation of a given AM. To this end the effects of added (AM)N(R)2, THF, open and closed polyethers as well as cryptands were systematically studied. In 14 cases the products were characterized by X‐ray diffraction and correlations with the situation in solution were made. The more the AM ions get detached from the carbonite ligand, the lower is the degree of aggregation. At the same time the extent of CO2 activation is decreased as indicated by the structural and spectroscopic analysis and reactivity studies. Accompanying DFT studies showed that the coordinating AM Lewis acidic fragment withdraws only a small amount of charge from the carbonite moiety, but it also affects the internal charge equilibration between the LtBuNi and carbonite moieties. [ABSTRACT FROM AUTHOR]

Background: Degradation via enzymatic processes for the production of valuable β-1,3-glucooligosaccharides (GOS) from curdlan has attracted considerable interest. CBM6E functions as a curdlan-specific β-1,3-endoglucanase, composed of a glycoside hydrolase family 128 (GH128) module and a carbohydrate-binding module (CBM) derived from family CBM6. Results: Crystallographic analyses were conducted to comprehend the substrate specificity mechanism of CBM6E. This unveiled structures of both apo CBM6E and its GOS-complexed form. The GH128 and CBM6 modules constitute a cohesive unit, binding nine glucoside moieties within the catalytic groove in a singular helical conformation. By extending the substrate-binding groove, we engineered CBM6E variants with heightened hydrolytic activities, generating diverse GOS profiles from curdlan. Molecular docking, followed by mutation validation, unveiled the cooperative recognition of triple-helical β-1,3-glucan by the GH128 and CBM6 modules, along with the identification of a novel sugar-binding residue situated within the CBM6 module. Interestingly, supplementing the CBM6 module into curdlan gel disrupted the gel's network structure, enhancing the hydrolysis of curdlan by specific β-1,3-glucanases. Conclusions: This study offers new insights into the recognition mechanism of glycoside hydrolases toward triple-helical β-1,3-glucans, presenting an effective method to enhance endoglucanase activity and manipulate its product profile. Furthermore, it discovered a CBM module capable of disrupting the quaternary structures of curdlan, thereby boosting the hydrolytic activity of curdlan gel when co-incubated with β-1,3-glucanases. These findings hold relevance for developing future enzyme and CBM cocktails useful in GOS production from curdlan degradation. [ABSTRACT FROM AUTHOR]

To improve their properties or to introduce entirely new functionalities, the intriguing scaffolds of nucleic acids have been decorated with various modifications, most recently also organometallic ones. While challenging to introduce, organometallic modifications offer the potential of expanding the field of application of metal-dependent functionalities to metal-deficient conditions, notably those of biological media. So far, organometallic moieties have been utilized as probes, labels and catalysts. This Feature Article summarizes recent efforts and predicts likely future developments in each of these lines of research. [ABSTRACT FROM AUTHOR]

As an effective and non‐invasive treatment modality for cancer, photodynamic therapy (PDT) has attracted considerable interest. With the recent advances in the photosensitizing agents, the fiber‐optic systems, and other aspects, its application is extended to a wide range of superficial and localized cancers. However, for the few clinically used photosensitizers, most of them suffer from the drawback of causing prolonged photosensitivity after the treatment. As a result, post‐PDT management is also a crucial issue. Herein, a facile bioorthogonal approach is reported that can effectively suppress this common side effect of PDT in nude mice. It involves the use of an antidote that contains a black‐hole quencher BHQ‐3 conjugated with a bicyclo[6.1.0]non‐4‐yne (BCN) moiety and a tetrazine‐substituted boron dipyrromethene‐based photosensitizer. By using tumor‐bearing nude mice as an animal model, it is demonstrated that after PDT with this photosensitizer, the administration of the antidote can effectively quench the photodynamic activity of the residual photosensitizer by bringing the BHQ‐3 quencher close to the photosensitizing unit through a rapid click reaction. It results in substantial reduction in skin damage upon light irradiation. The overall results demonstrate that this simple and facile strategy can provide an effective means for minimizing the photosensitivity after PDT. [ABSTRACT FROM AUTHOR]

A boron trifluoride–pyridyl Lewis adduct is reported, which exhibits various types of chromism and high solid-state photoluminescence quantum yields, as well as excitation-dependent emission in the mechanically ground form. The facile synthetic approach offers a simple and potentially versatile strategy for inducing chromism in pyridyl ligands with donor moieties. We envisage this approach as having a dual benefit: simplicity and extensive applicability. [ABSTRACT FROM AUTHOR]

N-Acetylglucosamine (GlcNAc), a fundamental amino sugar moiety, is essential for protein glycosylation, glycolipid, GPI-anchor protein, and cell wall components. Uridine diphosphate-GlcNAc (UDP-GlcNAc), an active form of GlcNAc, is synthesized through the hexosamine biosynthesis pathway (HBP). Although HBP is highly conserved across organisms, the enzymes involved perform subtly distinct functions among microbes, mammals, and plants. A complete block of HBP normally causes lethality in any life form, reflecting the pivotal role of HBP in the normal growth and development of organisms. Although HBP is mainly composed of four biochemical reactions, HBP is exquisitely regulated to maintain the homeostasis of UDP-GlcNAc content. As HBP utilizes substrates including fructose-6-P, glutamine, acetyl-CoA, and UTP, endogenous nutrient/energy metabolites may be integrated to better suit internal growth and development, and external environmental stimuli. Although the genes encoding HBP enzymes are well characterized in microbes and mammals, they were less understood in higher plants in the past. As the HBPrelated genes/enzymes have largely been characterized in higher plants in recent years, in this review we update the latest advances in the functions of the HBP-related genes in higher plants. In addition, HBP’s salvage pathway and GlcNAc-mediated two major co- or post-translational modifications, N-glycosylation and O-GlcNAcylation, are also included in this review. Further knowledge on the function of HBP and its product conjugates, and the mechanisms underlying their response to deleterious environments might provide an alternative strategy for agricultural biofortification in the future. [ABSTRACT FROM AUTHOR]