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Dihydrodipicolinate synthase (DHDPS) catalyzes the first committed step in the diaminopimelate pathway of bacteria, yielding amino acids required for cell wall and protein biosyntheses. The essentiality of the enzyme to bacteria, coupled with its absence in humans, validates DHDPS as an antibacterial drug target. Conventional drug design efforts have thus far been unsuccessful in identifying potent DHDPS inhibitors. Here, we make use of contemporary molecular dynamics simulation and Markov state models to explore the interactions between DHDPS from the human pathogen Staphylococcus aureus and its cognate substrate, pyruvate. Our simulations recover the crystallographic DHDPS-pyruvate complex without a priori knowledge of the final bound structure. The highly conserved residue Arg140 was found to have a pivotal role in coordinating the entry of pyruvate into the active site from bulk solvent, consistent with previous kinetic reports, indicating an indirect role for the residue in DHDPS catalysis. A metastable binding intermediate characterized by multiple points of intermolecular interaction between pyruvate and key DHDPS residue Arg140 was found to be a highly conserved feature of the binding trajectory when comparing alternative binding pathways. By means of umbrella sampling we show that these binding intermediates are thermodynamically metastable, consistent with both the available experimental data and the substrate binding model presented in this study. Our results provide insight into an important enzyme-substrate interaction in atomistic detail that offers the potential to be exploited for the discovery of more effective DHDPS inhibitors and, in a broader sense, dynamic protein-drug interactions., Author Summary Interactions between proteins and ligands underpin many important biological processes, such as binding of substrates to their cognate enzymes in the process of catalysis. These interactions are complex, often requiring several intermediate steps to fully transition into the bound state. Here, we have used computational simulation to study binding of pyruvate to Dihydrodipicolinate synthase (DHDPS), an enzyme in the bacterial diaminopimelate pathway. In bacteria, such as the human pathogen S. aureus, DHDPS functions to make building blocks necessary for protein and bacterial cell wall biosyntheses. As the enzyme is absent in humans, yet essential for bacterial growth, DHDPS is a valid target for broad-range antibiotics. However, known DHDPS inhibitors show poor potency. One avenue that has not yet been taken into consideration for inhibitor design is the dynamics of DHDPS’s interaction with its reaction substrates (e.g. pyruvate). Using molecular dynamics simulation, we find that pyruvate binding to DHDPS must pass through a transition intermediate ‘hotspot’ in which the substrate is held in place by a dense network of noncovalent bonds. Given that many of the protein residues involved in this interaction are also shared by DHDPS from many pathogenic bacteria, this binding intermediate ‘hotspot’ may help in development of better broad-range DHDPS inhibitors.

The phototoxicity of photosensitizers (PSs) is a double-edged sword with one edge beneficial for destroying tumors while the other is detrimental to normal tissues, and the conventional "OFF-ON" strategy provides temporary inhibition so that phototoxicity would come sooner or later due to the inevitable retention and transformation of PSs in vivo. We herein put forward a strategy to convert "double-edged sword" PSs into "single-edged knife" ones with simultaneously persistent phototoxicity inhibition and alternative multiple therapeutical activation. The Chlorin e6 (Ce6) as the PS model directly assembles with Cu2+ ions into nanoscale frameworks (nFs) whose Cu2+-coordination includes both carboxyl groups and a porphyrin ring of Ce6 instead of Fe3+/Mn2+-coordination with only carboxyl groups. Compared to the high phototoxicity of Ce6, the nFs exhibit efficient energy transfer due to the dual-coordination of paramagnetic Cu2+ ions and the aggregation, achieving the persistent and high phototoxicity inhibition rate of >92%. Alternatively, the nFs not only activate a high photoacoustic contrast and near-infrared (NIR)-driven photothermal efficacy (3.5-fold that of free Ce6) due to the aggregation-enhanced nonradiative transition but also initiate tumor microenvironment modulation, structure disassembly, and chemodynamic effect by Cu2+ ions. Given these merits, the nFs achieve long-term biosecurity, no retina injury under sunlight, and a higher therapeutical output than the photodynamic effect of Ce6. This work presents a possibility of converting numerous highly phototoxic porphyrins into safe and efficient ones.

Bempedoic acid is an ATP citrate lyase inhibitor approved for the treatment of hypercholesterolemia. The objective of this phase I study was to assess the pharmacokinetics (PKs) and safety of bempedoic acid in 24 subjects with normal renal function or mild, moderate, or severe renal impairment. All subjects received a single oral bempedoic acid 180-mg dose and PK parameters were monitored for up to 23 days. Resulting estimates of area under the concentration-time curve exposure following bempedoic acid treatment were 1.5-fold, 2.2-fold, and 2.2-fold higher in subjects with mild, moderate, or severe renal impairment, respectively, compared with subjects with normal renal function. With decreases in renal function, plasma free fraction was increased up to 20.1%, whereas total and unbound clearances were decreased by 55.2% and 62.6%, respectively, in subjects with severe renal impairment relative to those with normal renal function. These observed decreases in total and unbound oral clearance in subjects with decreased renal function are not explained by the increases in free fraction and might therefore also be attributable to changes in bioavailability or intrinsic clearance. Bempedoic acid was generally well-tolerated and the incidence and type of adverse events were not affected by the degree of renal impairment. In conclusion, bempedoic acid exposures in subjects with renal impairment were increased up to approximately two-fold with no safety signals identified, consistent with findings in phase III patients with mild or moderate renal impairment. No dose adjustments are necessary for patients with mild or moderate renal impairment.

C25.71H32.57N9.86O15P3S3Ru3, hexagonal, P63 (no. 173), a = 37.24213(9) Å, b = 37.24213(9) Å, c = 11.64828(3) Å, β = 90°, V = 13,991.40(8) Å3, Z = 14, R gt (F) = 0.0406, wR ref(F 2) = 0.1009, T = 100(2) K.

BACKGROUND Most dogs with primary hypoadrenocorticism (HA) have a mineralocorticoid deficiency, which decreases renal tubular sodium reabsorption and potassium excretion. Limited information is available concerning the clinical value of measuring urine electrolytes to aid in an HA diagnosis. OBJECTIVES We aimed to evaluate the diagnostic utility of urine electrolyte measurements in dogs with HA. METHODS Urine sodium and potassium concentrations were measured in 89 dogs, including 39 dogs with HA and 50 controls with nonadrenal illness. Fractional excretions of sodium (FENa ) and potassium (FEK ) were also calculated. Urine electrolytes and fractional excretion values were compared between the groups. Sensitivities and specificities were determined for various cut-points. RESULTS The median urine sodium to potassium (Na:K) ratio was twofold greater (P 90% sensitivity or specificity provided a corresponding specificity or sensitivity of >50%. When only dogs with abnormal serum or plasma electrolytes were included in the analyses, absolute urine electrolyte concentrations and FENa were not different between study populations (P > .05 for all comparisons), but the FEK was increased (P = .005) and the urine potassium:creatinine ratio was decreased (P

Fish is an important source of protein, however as human impacts on the environment through industrialization, mining and farming among others is resulting in increased concentration of toxic metals in them. The levels of copper (Cu), arsenic (As), zinc (Zn), lead (Pb), cadmium (Cd), mercury (Hg), and selenium (Se) were analysed in fish samples from the southwestern coast of Ghana using acid digestion and atomic absorption spectrophotometer method. A total of 71 fish species were sampled where 35 species were collected in the wet season (October, 2014) whereas 36 species were collected in the dry season (March, 2015). The average levels of heavy metals detected in the wet season were 1.08 mg/kg for Cu, 9.79 mg/kg for Zn, 4.80 mg/kg for Se, 0.06 mg/kg for Pb, 0.03 mg/kg for Hg, 0.02 mg/kg for As, and 0.01 mg/kg for Cd. The average values of heavy metals in fish samples analysed in the dry season were 2.17 mg/kg for Cu, 4.55 mg/kg for Zn, 8.13 mg/kg for Se, 0.06 mg/kg for Pb, 0.03 mg/kg for Hg, 0.09 mg/kg for As, and 0.005 mg/kg for Cd. The results showed that the average levels of toxic metals analysed in the wet season increased in the order of Cd < As

In many technological applications, DNA is confined within nanoenvironments that are smaller than the size of the unconfined polymer in solution. However, the dependence of the diffusion coefficient on molecular weight and characteristic confinement dimension remains poorly understood in this regime. Here, convex lens-induced confinement (CLiC) was leveraged to examine how the diffusion of short DNA fragments varied as a function of slit height by using single-molecule fluorescence tracking microscopy. The diffusion coefficient followed approximate power law behavior versus confinement height, with exponents of 0.27 ± 0.01, 0.32 ± 0.02, and 0.42 ± 0.06 for 692, 1343, and 2686 base pair chains, respectively. The weak dependence on slit height suggests that shorter semiflexible chains may adopt increasingly rodlike conformations and therefore experience weaker excluded-volume interactions as the confinement dimension is reduced. The diffusion coefficient versus molecular weight also exhibited apparent power law behavior, with exponents that varied slightly (from -0.89 to -0.85) with slit height, consistent with hydrodynamic interactions intermediate between Rouse and Zimm model predictions.

Targeted protein degradation (TPD) using Proteolysis Targeting Chimeras (PROTACs) and molecular glue degraders has arisen as a powerful therapeutic modality for eliminating disease-causing proteins from cells. PROTACs and molecular glue degraders employ heterobifunctional or monovalent small molecules, respectively, to chemically induce the proximity of target proteins with E3 ubiquitin ligases to ubiquitinate and degrade specific proteins via the proteasome. While TPD is an attractive therapeutic strategy for expanding the druggable proteome, only a relatively small number of E3 ligases out of the >600 E3 ligases encoded by the human genome have been exploited by small molecules for TPD applications. Here, we review the existing E3 ligases that have thus far been successfully exploited for TPD and discuss chemoproteomics-enabled covalent screening strategies for discovering new E3 ligase recruiters. We also provide a chemoproteomic map of reactive cysteines within hundreds of E3 ligases which may represent potential ligandable sites that can be pharmacologically interrogated to uncover additional E3 ligase recruiters.

SARS-CoV-2 remains a global threat to human health particularly as escape mutants emerge. There is an unmet need for effective treatments against COVID-19 for which neutralizing single domain antibodies (nanobodies) have significant potential. Their small size and stability mean that nanobodies are compatible with respiratory administration. We report four nanobodies (C5, H3, C1, F2) engineered as homotrimers with pmolar affinity for the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. Crystal structures show C5 and H3 overlap the ACE2 epitope, whilst C1 and F2 bind to a different epitope. Cryo Electron Microscopy shows C5 binding results in an all down arrangement of the Spike protein. C1, H3 and C5 all neutralize the Victoria strain, and the highly transmissible Alpha (B.1.1.7 first identified in Kent, UK) strain and C1 also neutralizes the Beta (B.1.35, first identified in South Africa). Administration of C5-trimer via the respiratory route showed potent therapeutic efficacy in the Syrian hamster model of COVID-19 and separately, effective prophylaxis. The molecule was similarly potent by intraperitoneal injection., Neutralizing nanobodies (Nb) are of considerable interest as therapeutic agents for COVID-19 treatment. Here, the authors functionally and structurally characterize Nbs that bind with high affinity to the receptor binding domain of the SARS-CoV-2 spike protein and show that an engineered homotrimeric Nb prevents disease progression in a Syrian hamster model of COVID-19 when administered intranasally.

Dynamin belongs to the large GTPase superfamily, and mediates the fission of vesicles during endocytosis. Dynamin molecules are recruited to the neck of budding vesicles to assemble into a helical collar and to constrict the underlying membrane. Two helical forms were observed: the one-start helix in the constricted state and the two-start helix in the super-constricted state. Here we report the cryoEM structure of a super-constricted two-start dynamin 1 filament at 3.74 A resolution. The two strands are joined by the conserved GTPase dimeric interface. In comparison with the one-start structure, a rotation around Hinge 1 is observed, essential for communicating the chemical power of the GTPase domain and the mechanical force of the Stalk and PH domain onto the underlying membrane. The Stalk interfaces are well conserved and serve as fulcrums for adapting to changing curvatures. Relative to one-start, small rotations per interface accumulate to bring a drastic change in the helical pitch. Elasticity theory rationalizes the diversity of dynamin helical symmetries and suggests corresponding functional significance. Dynamin mediates the fission of vesicles during endocytosis. Here, the authors report the cryoEM structure of a super-constricted two-start dynamin 1 filament- one of the two known helical forms of dynamin, with insights into the molecular mechanisms of dynamin-mediated membrane scission.

The transition from weak (noncovalent) interactions to fully developed covalent bonds is examined using the quantum theory of atoms in molecules in a series of halogen-bonded (XB) complexes of bromosubstituted electrophiles, RBr, with 1,4-diazabicyclo[2.2.2]octane (DABCO) and Cl– and Br– anions. The gradual decrease in the XB lengths in these associations, dBr···Y (where Y = Cl–, Br–, or N), was accompanied by the exponential increase in the binding energies and charge transfer, as well as electron densities and magnitudes of the kinetic and potential energy densities at the bond critical points (BCPs) on the Br···Y bond path. These indices, as well as characteristics of the adjacent bonds in the XB donor, followed remarkably close trend lines when plotted against the normalized XB length RBrY = dBr···Y/(rBr + rY) (where rBr and rY are the van der Waals radii) regardless of the methods [MP2/6-311+G(d,p) or M062X/6-311+G(d,p)], media (gas phase or dichloromethane), and nucleophiles (Cl–, Br–, or DABCO). In the systems with an RBrY higher than about 0.78, the energy densities H(r) at BCPs at the Br···Y bond path were small and positive, and XBs did not substantially affect the characteristics of the adjacent R–Br covalent bond in the XB donor. Accordingly, the XB can be identified as noncovalent in this range. In the complexes with RBrY values between about 0.67 and 0.78, energy densities H(r) at Br···Y BCPs were negative, and their magnitudes increased with the decrease in the Br···Y separation. In this range, formation of XBs was accompanied by the increase in the R–Br bond length in the XB donor and the decrease in the magnitude of the (negative) H(r) values at the BCPs of the R–Br bonds. XBs can be classified as partially covalent in this RBrY range. At an RBrY less than about 0.67, electron densities were larger, and energy densities were more negative at BCPs of the Br···Y bond than those at BCPs of the R–Br bond in the XB donor. This indicates that Br···Y bonds were stronger than R–Br bonds, and these (Br···Y) XBs can be regarded as essentially covalent. The synchronous change of a variety of (R–Br and Br···Y) bonding characteristics with RBrY suggests that the normalized XB bond length can be used as a basic parameter in the identification of the type of intermolecular interaction. A continuity of these characteristics suggests an inherent relationship between limiting (covalent and noncovalent) types of XBs and thus an onset of molecular–orbital interactions in the weaker bonds.

Background The frequency with which multiple corticosteroid abnormalities occur in cats with aldosterone secreting adrenocortical tumors is unknown. Objectives To evaluate adrenal‐derived corticosteroids in cats in which blood samples were submitted for measure of aldosterone. Animals Two hundred ninety‐seven cats. Methods Retrospective study. Analysis of a convenience sample of previously submitted serum or plasma. Progesterone, corticosterone, and cortisol were measured in feline serum or plasma samples submitted to an endocrinology laboratory for aldosterone measurements. Demographics and clinical history were retrieved from submittal forms when provided. Statistical testing was performed to investigate associations among the adrenal corticosteroids. Results Progesterone and corticosterone concentrations were strongly correlated (ρ = 0.74; P

Phlebotomine sand flies are vectors of Leishmania parasites that cause leishmaniases. Both sexes of sand flies feed on plants primarily for sugars, although the chemical cues that mediate attraction to host plants remain largely unknown. Previously, using coupled gas chromatography-mass spectrometry, the authors identified several volatile organic compounds (VOCs) common to preferred host plants for selected Afrotropical sand flies from the Fabaceae family. Of the identified volatiles, the significance of the monoterpenes linalool oxide, ocimene and p-cymene and the benzenoid m-cresol, p-cresol in sand fly behaviour is unknown. In olfactometer assays, the authors tested these compounds singly and in blends for their attractiveness to Phlebotomus duboscqi, cutaneous leishmaniasis vector in Kenya. In dose-response assays, single compounds increased the responses of males and females over controls, but their optimum attractive doses varied between the sexes. Two five-component blends, referred to as Blend-f and Blend-m for females and males respectively, were formulated and tested in dose-response assays against 1-octen-3-ol (positive control). The results of the present study showed that males and females were significantly attracted to varying levels of the two blends. In pairwise assays, the authors evaluated the most attractive of these blends to each sex (i.e., Blend Am for male against Blend Bf for female), revealing that males were attracted to both blends at varying levels, whereas females were indifferent. The study's results demonstrate that plant-derived VOCs can be exploited for sand fly management.

Triple pnictogen bonding refers to the ability of a pnictogen atom to engage in three simultaneous pnictogen bonds (PnBs) to a complementary partner through a single pnictogen atom. This supramolecular strategy was recently introduced as a unique facet of pnictogen bonding as compared to other named supramolecular interactions. Here, the ability of bismuth to participate in this phenomenon is demonstrated using Bi((NC9H7)3CH3). The study reveals that Bi engages in stronger PnBs than the analogous Sb system. The results have been contrasted with Bi systems that form strong coordination bonds, and analysis of the electron density along the bond path reveals key differences. The solution behavior of these newly synthesized supramolecules were studied by PFGSE NMR spectroscopy and they are found to remain intact in solution. Molecular design strategies that allow for triple pnictogen bonding should find use in the fields of molecular recognition and crystal engineering.

Activatable nanoscale drug delivery systems (NDDSs) are promising in maximizing cancer specificity and anticancer efficacy, and a multifunctional metal-organic nanomaterial is one of the new star NDDSs which requires further exploration. Herein, a novel DOX@MnCPs/PEG NDDSs were constructed by first synthesizing Mn3+-sealed coordination particles (MnCPs), modified with a targeted PEGylated polymer, and then loading anticancer drug doxorubicin (DOX). MnCPs were prepared from the assembly of Mn3+ ions and hematoporphyrin monomethyl ether (HMME) molecules. Furthermore, MnCPs had an average size of ∼100 nm and a large surface area (∼52.6 m2 g-1) and porosity (∼3.6 nm). After the loading of DOX, DOX@MnCPs/PEG exhibited a high DOX-loading efficacy of 27.2%, and they reacted with glutathione (GSH) to confer structural collapse, leading to the production of Mn2+ ions for enhanced magnetic resonance imaging (MRI), free HMME for augmented photodynamic effect, and free DOX for chemotherapy. As a consequence, these DOX@MnCPs/PEG NDDSs after intravenous injection showed efficient tumor homing and then exerted an obvious suppression for tumor growth rate by synergistic photodynamic-chemo therapy in vivo. Importantly, most of the DOX@MnCPs/PEG NDDSs could be gradually cleared through the renal pathway, and the remaining part could slowly be metabolized via the feces, enabling high biosafety. Therefore, this work provides a type of GSH-sensitive NDDS with biosafety, caner specificity, and multifunctionality for high synergistic treatment efficacy.

The growing prevalence of synthetically modified proteins in pharmaceuticals and materials has exposed the need for efficient strategies to enable chemical modifications with high site-selectivity. While genetic engineering can incorporate non-natural amino acids into recombinant proteins, regioselective chemical modification of wild-type proteins remains a challenge. Herein, we use photoredox catalysis to develop a site-selective tyrosine bioconjugation pathway that incorporates bioorthogonal formyl groups, which subsequently allows for the synthesis of structurally defined fluorescent conjugates from native proteins. A water-soluble photocatalyst, lumiflavin, has been shown to induce oxidative coupling between a previously unreported phenoxazine dialdehyde tag and a single tyrosine site, even in the presence of multiple tyrosyl side chains, through the formation of a covalent C–N bond. A variety of native proteins, including those with multiple tyrosines, can successfully undergo both tyrosine-specific and single-site-selective labelling. This technology directly introduces aldehyde moieties onto native proteins, enabling rapid product diversification using an array of well-established bioorthogonal functionalization protocols including the alkyne–azide click reaction. Regioselective chemical modification of wild-type proteins remains challenging. Now, by harnessing the varied SOMOphilicity of native tyrosine residues through photoredox catalysis, a site-selective bioconjugation method has been developed. This technology directly incorporates bioorthogonal formyl groups in one step, forming structurally defined fluorescent conjugates that can be rapidly diversified to biorelevant products.

A long-standing goal in the field of biotechnology is to develop and understand design rules for the stabilization of enzymes upon immobilization to materials. While immobilization has sometimes been successful as a strategy to stabilize enzymes, the design of synthetic materials that stabilize enzymes remains largely empirical. We sought to overcome this challenge by investigating the mechanistic basis for the stabilization of immobilized lipases on random copolymer brush surfaces comprised of poly(ethylene glycol) methacrylate (PEGMA) and sulfobetaine methacrylate (SBMA), which represent novel heterogeneous supports for immobilized enzymes. Using several related but structurally diverse lipases, including Bacillus subtilis lipase A (LipA), Rhizomucor miehei lipase, Candida rugosa lipase, and Candida antarctica lipase B (CALB), we showed that the stability of each lipase at elevated temperatures was strongly dependent on the fraction of PEGMA in the brush layer. This dependence was explained by developing and applying a new algorithm to quantify protein surface hydrophobicity, which involved using unsupervised cluster analysis to identify clusters of hydrophobic atoms. Characterization of the lipases showed that the optimal brush composition correlated with the free energy of solvation per enzyme surface area, which ranged from -17.1 kJ/mol·nm2 for LipA to -11.8 kJ/mol·nm2 for CALB. Additionally, using this algorithm, we found that hydrophobic patches consisting of aliphatic residues had a higher free energy than patches consisting of aromatic residues. By providing the basis for rationally tuning the interface between enzymes and materials, this understanding will transform the use of materials to reliably ruggedize enzymes under extreme conditions.

Bi nanoparticles (NPs) have been demonstrated as effective all-in-one type theranostic agent for imaging-guided photothermal therapy, but their applications have been limited by relatively low biocompatibility and target accumulation capacity. To address this issue, we report the camouflage of Bi NPs (size: ~42 ± 2 nm) by using the mouse colon cancer CT26 cells membrane (CT26 CCM). The camouflaging process confers the efficient coating of CCM shell layer with thickness of ~8 ± 2 nm on Bi NPs cores, which can be confirmed by TEM image, zeta potential and protein gel electrophoresis tests. Simultaneously, CCM shell has no side effects on the photoabsorption/photothermal effect. Importantly, Bi@CCM NPs retain significant features of CCM, including good biocompatibility and homologous targeting ability. When Bi@CCM dispersion was intravenously (i.v.) injected into mice, they exhibited higher blood circulation half-life (11.5 h, ~2.9 times) and accumulation amount (4.7 ± 0.56% ID/g, ~2.3 times) in homotypic CT26 tumor compared to those (4.0 h in blood and 2.03 ± 0.60% ID/g in tumor) from uncoated Bi NPs. After 808 nm laser irradiation, CT26 cancer cells could be effectively ablated after the photothermal therapy of high-accumulated Bi@CCM NPs, and then the tumor tends to be eradicated after 12 days. Thus, Bi NPs camouflaged with CT26 CCM have great potential for the targeted photothermal therapy of homotypic tumors.

Arsenic from geologic sources is widespread in groundwater within the United States (U.S.). In several areas, groundwater arsenic concentrations exceed the U.S. Environmental Protection Agency maximum contaminant level of 10 μg per liter (μg/L). However, this standard applies only to public-supply drinking water and not to private-supply, which is not federally regulated and is rarely monitored. As a result, arsenic exposure from private wells is a potentially substantial, but largely hidden, public health concern. Machine learning models using boosted regression trees (BRT) and random forest classification (RFC) techniques were developed to estimate probabilities and concentration ranges of arsenic in private wells throughout the conterminous U.S. Three BRT models were fit separately to estimate the probability of private well arsenic concentrations exceeding 1, 5, or 10 μg/L whereas the RFC model estimates the most probable category ≤5, >5 to ≤10, or >10 μg/ L). Overall, the models perform best at identifying areas with low concentrations of arsenic in private wells. The BRT 10 μg/L model estimates for testing data have an overall accuracy of 91.2%, sensitivity of 33.9%, and specificity of 98.2%. Influential variables identified across all models included average annual precipitation and soil geochemistry. Models were developed in collaboration with public health experts to support U.S.-based studies focused on health effects from arsenic exposure.

The intramolecular "inverse" frustrated Lewis pairs (FLPs) of general formula 1-BR2 -2-[(Me2 N)2 C=N]-C6 H4 (3-6) [BR2 =BMes2 (3), BC12 H8 , (4), BBN (5), BBNO (6)] were synthesized and structurally characterized by multinuclear NMR spectroscopy and X-ray analysis. These novel types of pre-organized FLPs, featuring strongly basic guanidino units rigidly linked to weakly Lewis acidic boryl moieties via an ortho-phenylene linker, are capable of activating H-H, C-H, N-H, O-H, Si-H, B-H and C=O bonds. 4 and 5 deprotonated terminal alkynes and acetylene to form the zwitterionic borates 1-(RC≡C-BR2 )-2-[(Me2 N)2 C=NH]-C6 H4 (R=Ph, H) and reacted with ammonia, BnNH2 and pyrrolidine, to generate the FLP adducts 1-(R2 HN→BR2 )-2-[(Me2 N)2 C=NH]-C6 H4 , where the N-H functionality is activated by intramolecular H-bond interactions. In addition, 5 was found to rapidly add across the double bond of H2 CO, PhCHO and PhNCO to form cyclic zwitterionic guanidinium borates in excellent yields. Likewise, 5 is capable of cleaving H2 , HBPin and PhSiH3 to form various amino boranes. Collectively, the results demonstrate that these new types of intramolecular FLPs featuring weakly Lewis acidic boryl and strongly basic guanidino moieties are as potent as conventional intramolecular FLPs with strongly Lewis acidic units in activating small molecules.

Insects are known plant pests, and some of them such as Trichoplusia ni feed on a variety of crops. In this study, Trichoplusia ni was fed distinct diets of leaves of Arabidopsis thaliana or Solanum lycopersicum as well as an artificial diet. After four generations, the microbial composition of the insect gut was evaluated to determine if the diet influenced the structure and function of the microbial communities. The population fed with A. thaliana had higher proportions of Shinella, Terribacillus and Propionibacterium, and these genera are known to have tolerance to glucosinolate activity, which is produced by A. thaliana to deter insects. The population fed with S. lycopersicum expressed increased relative abundances of the Agrobacterium and Rhizobium genera. These microbial members can degrade alkaloids, which are produced by S. lycopersicum. All five of these genera were also present in the respective leaves of either A. thaliana or S. lycopersicum, suggesting that these microbes are acquired by the insects from the diet itself. This study describes a potential mechanism used by generalist insects to become habituated to their available diet based on acquisition of phytochemical degrading gut bacteria.

Trimethoprim (TMP) is an active pharmaceutical ingredient with poor aqueous solubility. Here, we describe the cocrystallization of TMP with five co-formers, three bipyridines and two monopyridines....

The formation of a self-interpenetrated honeycomb molecular network based upon 4,6-dichlororesorcinol (4,6-diCl res), a water molecule, and the photoproduct rtct-tetrakis(pyridin-4-yl)cyclobutane ( rtct -TPCB) is reported. Interestingly, only three of the four pyridine rings on the central cyclobutane ring are found to engage in O—H...N hydrogen bonds with either the 4,6-diCl res or an included water molecule, resulting in a three-connected net. Notably, the solid (4,6-diCl res)·( rtct -TPCB)·(H2O), C6H4Cl2O2·C24H20N4·H2O, contains channels that run along the crystallographic b axis, which are found to be interpenetrated. Although rtct -TPCB has been employed as a bridging ligand in the formation of numerous metal–organic materials, surprisingly neither the single-component X-ray structure nor any multi-component molecular solids based upon this stereoisomer have been reported previously. Lastly, the single-crystal X-ray structure of the photoproduct rtct -TPCB is also reported.

Radiation-grafted anion-exchange membranes (RG-AEM) are being developed to evaluate a range of chemistries that have relevance to a variety of electrochemical applications including reverse electrodialysis (RED) salinity gradient power. RG-AEMs are typically fabricated using an electron-beam activated (peroxidated) polymer substrate film. These activated films are first grafted with a monomer, such as vinylbenzyl chloride (VBC) and then reacted with a variety of tertiary amines to yield the desired RG-AEMs. The amination process forms covalently bound quaternary ammonium (QA) head-groups that allow the RG-AEMs to conduct anions such as Cl−. RG-AEMs are of interest as they exhibit high conductivities (100 mS cm−1 at elevated temperatures when containing Cl− anions). However, the current generation of RG-AEMs have two main Achilles' heels: (1) they exhibit low permselectivities; and (2) they exhibit a high degree of swelling in water. Introducing covalent crosslinking into ion-exchange membranes is a well-known strategy to overcome these issues but it often comes with a price – a significantly lowered conductivity (raised in situ resistance). Therefore, the level of crosslinking must be carefully optimised. RG-AEMs can be primarily crosslinked using two methods: (1) introduction of a divinyl monomer into the monomer mixture used during grafting; or (2) introduction of a diamine agent into the amination process. This study looks into both methods where either divinylbenzene (DVB) is added into the grafting mixture or N,N,N′,N′-tetramethylhexane-1,6-diamine (TMHDA) is added into the amination mixture. We show that on the balance of two application-relevant properties (resistances in aqueous NaCl (0.5 mol dm−3) solution and permselectivity), the diamine crosslinking method is the most effective for RG-AEMs being used in RED cells.

Pedal motion or static disorder in single-component solids containing imine groups is demonstrated. Unique solid-state behaviors including colossal biaxial positive thermal expansion in one solid and a temperature-dependent phase transition in another are discussed. Imines exhibit torsional flexibility, which differs from the isoelectronic azo and olefin groups and influences solid-state behaviors.

Argentophilic forces are formed in a coordination complex based on silver(I) trifluoromethanesulfonate and 4-stilbazole as a ligand. The forces are absent at low temperature and form as a result of an order–disorder phase transition that occurs upon heating. Colossal positive thermal expansion also precedes the phase transition.

In this work, we present a strategy for the preparation of functionalized 2,3-dihydrobenzofuran derivatives via the Cs2CO3-catalyzed domino annulation of enantiopure chiral salicyl N-phosphonyl imines with bromo malonates, which offers an avenue for the construction of 2,3-dihydrobenzofurans. Nineteen examples were synthesized in impressive chemical yields and diastereoselectivity. The products were purified simply by washing the crude mixtures with hexanes following group-assisted purification chemistry/technology to bypass traditional separation methods which often result in a loss of product. The absolute configuration was unambiguously assigned by X-ray structural analysis.

The BINOL supported 1,3,2-dioxaborepines [C10H12O2BC6F5(THF)] [(R)-1], [C10H12O2BC6F5(OPEt3)] [(R)-3], [C10H12O2BC6F5]2 [(R,R)-2], [C10H12O2B(OPEt3)2]+[B(O2C10H12)2]− [(R)-6], and [C10H12O2B(OSMe2)2]+[B(O2C10H12)2]− [(R)-7] have been prepared.

Utilizing an intramolecular frustrated Lewis pair (FLP) decorated with a strongly donating guanidino moiety enabled the formation of a thermally remarkably stable FLP-CO adduct, which at 120 °C underwent CO migration to form an acyl borane. Both compounds underwent rapid CO cleavage in the presence of strong electrophiles leading to the selective formation of a range of new 1,2- and 1,3-benzazaboroles in good yields under mild conditions.