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[Display omitted] Two-dimensional NOE (nuclear Overhauser effect) NMR spectroscopy was employed to investigate the dynamic properties of water within lyotropic bicontinuous lipidic cubic phases (LCPs) formed by monoolein (MO). Experiments observed categorically different effective residence times of water molecules: (i) in proximity to the glycerol moiety of MO, and (ii) adjacent to the hydrophobic chain towards the hydrocarbon tail of MO, as evidenced by the opposite signs of intermolecular NOE cross peaks between protons of water and those of MO in 2D 1H–1H NOESY spectra. Spectroscopic data delineating the different effective residence times of water molecules within both the gyroid (Q II G) and diamond (Q II D) phase groups corresponding to hydration levels of 35 and 40 wt%, respectively, are presented. Additionally, an increase in effective residence time of water molecules in proximity to the glycerol moiety of MO in LCPs was observed upon storage at ambient temperature and in the presence of an additive lipid, cholesterol. Atom-specific NOE build-up curves for protons of water and those of MO are also given. The results presented herein provide new insight into the physicochemical properties and behaviour of water in LCPs, and demonstrate an additional avenue for experimental study of water–lipid interactions and hydration dynamics in model membranes and nanomaterials using 2D NOE NMR spectroscopy. [ABSTRACT FROM AUTHOR]

Two new fully π-conjugated ethylene-linked COFs containing benzotrithiophene as functional group by Knoevenagel polycondensation reaction were sythesized to explore their differences in H 2 photogeneration activity. The donor-acceptor (D-A) type BTT-BpyDAN-COF exhibited the approximately enhanced 2.6-folds hydrogen evolution rate of 10.1 mmol g-1h−1 compared to a non-D-A COF (BTT-PDAN-COF) and gained an excellent apparent quantum efficiency of 4.83% under visible light irradiation. [Display omitted] Covalent organic frameworks (COFs) have a broad prospect to be used as a photocatalytic platform to convert solar energy into valuable chemicals due to their tunable structures and rich active catalytic sites. However, constructing COFs with tuned sp2 -carbon donor-acceptor moiety remains an enormous challenge. Herein, we synthesized two new fully π-conjugated cyano-ethylene-linked COFs containing benzotrithiophene as functional group by Knoevenagel polycondensation reaction. The accetpor 2,2′-bipyridine unit in BTT-BpyDAN-COF skeleton favored the formation of a intermolecular specific electron transport pathway with the donor benzotrithiophene, and thereby promoted charge separation and transfer efficiency. Specifically, a donor-acceptor (D-A) type BTT-BpyDAN-COF exhibited high hydrogen evolution rate of 10.1 mmol g-1h−1 and an excellent apparent quantum efficiency of 4.83 % under visible light irradiation. [ABSTRACT FROM AUTHOR]

[Display omitted] Diazirine is one of the smallest photo-sensitive moieties discovered to date. When incorporated in the structure of phospholipids, its minimal size has a low impact on the morphology of the resultant liposomes. A DMPC-diazirine analogue was designed and subsequently used to generate liposomes with a lower permeability and a lower phase-transition temperature compared to control DMPC liposomes. Contrary to control liposomes, in the absence of light, the photosensitive nanoparticles retained the cargo (calcein) for at least 10 days. However, upon irradiation, diazirine's conversion triggered the fluorophore release within minutes. The kinetics of the release could be tuned by the power and duration of the irradiation process. The same approach can be used on other nanomaterials, with the final goal of discovering a release profile appropriate not only for therapeutic applications, but also for agrochemicals delivery or cosmoceutics. [ABSTRACT FROM AUTHOR]

• Furan is used as a pro-reactive chemical handle to covalently capture an ODN target. • The electrophilic moiety that is generated in situ can react with naturally occurring targets. • DNA-DNA, DNA-RNA or DNA-Peptide crosslinking can be achieved with careful design of the probes. • Choice of the building block for the specific application is discussed. • Criteria for the optimal (photo)-oxidative activation of the furan are discussed. Oligonucleotides (ODNs) find applications as diagnostic and therapeutic tools due to their unique ability to interact, thanks to Watson-Crick base pairing, with a specific DNA or RNA target strand. Although most of the tools available today rely on mere hydrogen bond formation, chemical modifications to enable covalent interstrand-crosslinking (ICL) have been reported, and are gaining a place under the spotlight as they potentially offer a series of advantages over the state of the art, including a higher potency and selectivity. This methodological paper focuses on the use of a pro-reactive furan moiety and its subsequent oxidation for applications in ODN targeting. The design of effective capture and targeting probes to ensure high ICL yields is discussed and the mechanisms underlying the (photo)chemical oxidation of furan are explained. Furthermore, examples of furan-containing DNAs designed for different applications, including DNA-DNA or DNA-RNA ICL and DNA-peptide/protein targeting, are provided. The paper highlights the advantages of using different oxidative chemical triggers, such as N-bromosuccinimide or singlet oxygen, to offer additional selectivity control over the ICL reaction. [ABSTRACT FROM AUTHOR]

[Display omitted] • A series of flavylium polymethine derivatives of Flav7 was designed and synthesized. • Optical characterization of the new fluorophores was carried out. • New SWIR emitters were obtained, with FlavMorpho selected as the best compound. • The best SWIR emitter, FlavMorpho, was encapsulated in phosholipidic micelles. • FlavMorpho micelles emission was higher than Flav7 and ICG, exciting at their λ max. Imaging in the shortwave infrared (SWIR, 1000–1700 nm) region is gaining traction for biomedical applications, leading to an in-depth search for fluorophores emitting at these wavelengths. The development of SWIR emitters, to be used in vivo in biological media, is mostly hampered by the considerable lipophilicity of the structures, resulting from the highly conjugated scaffold required to shift the emission to this region, that limit their aqueous solubility. In this work, we have modulated a known SWIR emitter, named Flav7 , by adding hydrophilic moieties to the flavylium scaffold and we developed a new series of Flav7 -derivatives, which proved to be indeed more polar than the parent compound, but still not freely water-soluble. Optical characterization of these derivatives allowed us to select FlavMorpho , a new compound with improved emission properties compared to Flav7. Encapsulation of the two compounds in micelles resulted in water-soluble SWIR emitters, with FlavMorpho micelles being twice as emissive as Flav7 micelles. The SWIR emission extent of FlavMorpho micelles proved also superior to the tail-emission of Indocyanine Green (ICG), the FDA-approved reference cyanine, in the same region, by exciting the probes at their respective absorption maxima in phosphate buffered saline (PBS) solution. The availability of optical imaging devices equipped with lasers able to excite these dyes at their maximum of absorption in the SWIR region, could pave the way for implemented SWIR imaging results. [ABSTRACT FROM AUTHOR]

Biologics represent the fastest growing group of therapeutics, but many advanced recombinant protein moieties remain difficult to produce. Here, we identify metabolic engineering targets limiting expression of recombinant human proteins through a systems biology analysis of the transcriptomes of CHO and HEK293 during recombinant expression. In an expression comparison of 24 difficult to express proteins, one third of the challenging human proteins displayed improved secretion upon host cell swapping from CHO to HEK293. Guided by a comprehensive transcriptomics comparison between cell lines, especially highlighting differences in secretory pathway utilization, a co-expression screening of 21 secretory pathway components validated ATF4, SRP9, JUN, PDIA3 and HSPA8 as productivity boosters in CHO. Moreover, more heavily glycosylated products benefitted more from the elevated activities of the N- and O-glycosyltransferases found in HEK293. Collectively, our results demonstrate the utilization of HEK293 for expression rescue of human proteins and suggest a methodology for identification of secretory pathway components for metabolic engineering of HEK293 and CHO. • We report a first cross-species systems analysis of two of the most common mammalian cell factories, CHO and HEK293. • Comprehensive transcriptomic and productivity data set with 5 host cell lines and 24 human difficult to express proteins. • HEK293 can rescue the expression of several human proteins that are difficult to express in CHO. • Metabolic engineering of key secretory pathway bottleneck genes boosted bioproduction up to three-fold in CHO. • More heavily glycosylated proteins benefit from increased glycosyltransferase expression found in HEK293. [ABSTRACT FROM AUTHOR]

Glandular trichomes, known as metabolic cell factories, have been proposed as highly suitable for metabolically engineering the production of plant high-value specialized metabolites. Natural pyrethrins, found only in Dalmatian pyrethrum (Tanacetum cinerariifolium), are insecticides with low mammalian toxicity and short environmental persistence. Type I pyrethrins are esters of the monoterpenoid trans -chrysanthemic acid with one of the three rethrolone-type alcohols. To test if glandular trichomes can be made to synthesize trans -chrysanthemic acid, we reconstructed its biosynthetic pathway in tomato type VI glandular trichomes, which produce large amounts of terpenoids that share the precursor dimethylallyl diphosphate (DMAPP) with this acid. This was achieved by coexpressing the trans -chrysanthemic acid pathway related genes including TcCDS encoding chrysanthemyl diphosphate synthase and the fusion gene of TcADH2 encoding the alcohol dehydrogenase 2 linked with TcALDH1 encoding the aldehyde dehydrogenase 1 under the control of a newly identified type VI glandular trichome-specific metallocarboxypeptidase inhibitor promoter. Whole tomato leaves harboring type VI glandular trichomes expressing all three aformentioned genes had a concentration of total trans -chrysanthemic acid that was about 1.5-fold higher (by mole number) than the levels of β -phellandrene, the dominant monoterpene present in non-transgenic leaves, while the levels of β -phellandrene and the representative sesquiterpene β -caryophyllene in transgenic leaves were reduced by 96% and 81%, respectively. These results suggest that the tomato type VI glandular trichome is an alternative platform for the biosynthesis of trans -chrysanthemic acid by metabolic engineering. • Natural pyrethrins are efficient natural insecticides produced in Dalmatian pyrethrum. • trans -Chrysanthemic acid is the monoterpenoid acid moiety of type I pyrethrins. • The trans -chrysanthemic acid pathway was reconstructed in tomato type VI glandular trichomes. [ABSTRACT FROM AUTHOR]

[Display omitted] Fabricating high-efficiency catalysts of Pt nanoparticles coupled with single-atom sites (M N C) attracts intensive attention to accelerate the oxygen reduction reaction (ORR). Here we rationally design the low-Pt hybrid catalyst containing fine Pt nanoparticles coupled with Co-N x moieties via a microwave-assisted heating process. The well-dispersed Pt nanoparticles are anchored by Co N C supports because of the metal-support interaction. Furthermore, the Co-N x moiety acts as an electron donor to regulate the electronic structure of Pt through the electron synergistic effect, moderating the adsorption energy of oxygen intermediates on Pt sites, and then increasing the intrinsic activity of Pt. In addition, the overflow effect from Co N C to Pt facilitates a nearly four-electron process and enhances the kinetics of ORR. In acid media, the optimized 10% Pt/Co N C hybrid catalysts with Pt nanoparticles size (2.18 nm) exhibit improved ORR activity and robust durability, delivering a half-wave potential (E 1/2) of 0.886 V and negligible loss after accelerated durability test, exceeding the best-in-class commercial Pt/C. The finding of the synergy between Co N C supports and Pt nanoparticles offers a novel ideation to construct various low-loading Pt-based hybrid catalysts. [ABSTRACT FROM AUTHOR]

[Display omitted] • The first selective O -arylation of the 2-pyridone motif of Lycodine alkaloid under metal-free conditions. • Identification of 3 k and 3q as potent cholinergic anti-inflammatory pathway activators. • Significant IL-1β inhibitory potency and lower cytotoxicity compared with the clinical drugs. • Selectively block the initial phase of MSU-induced NLRP3 inflammasome activation. Lycodine alkaloids are important natural products with diverse biological effects. In this manuscript, we set out the first structural optimization of the 2-pyridone moiety of Lycodine alkaloid via selective O -arylation under metal-free conditions and obtained a series of potent bioactive molecules against monosodium urate (MSU)-induced IL-1β production. Further investigations demonstrated that these natural product derivatives could activate the neuro-immunomodulatory cholinergic anti-inflammatory pathway (CAP) to block the initial phase of NLRP3 inflammasome activation. Compared with the clinical drugs hydrocortisone and indomethacin, as well as commercially available CAP agonists GTS-21 and pnu282987, 3 k and 3q possessed greater potency against MSU-induced IL-1β production. Meanwhile, these molecules possessed less cytotoxicity against promonocytic THP-1 macrophages when compared with colchicine. This work reports a concise strategy for direct modification of 2-pyridone moiety from natural Lycodine alkaloids, and provides novel frameworks for discovering CAP activators and drugs for gout arthritis. [ABSTRACT FROM AUTHOR]

[Display omitted] • This study aimed at the complete elucidation of the mechanism of the Mukaiyama-type alkene epoxidation reaction using the [(salophen)CrIIICl] precatalyst, by combining spectroscopic (UV–visible and EPR) studies, catalytic reactivity and quantum chemical modeling. These studies performed in parallel allowed us to propose a detailed reaction scheme, in which two consecutive active species incorporating both {salophen(CrV = O)} moieties were formed in situ , resulting in two distinct catalytic regimes. This study aimed at the complete elucidation of the mechanism of the Mukaiyama-type alkene epoxidation reaction using the [(salophen)CrIIICl] precatalyst, by combining spectroscopic (UV–visible and EPR) studies, catalytic reactivity and quantum chemical modeling. These studies performed in parallel allowed us to propose a detailed reaction scheme, in which two consecutive active species incorporating both {salophen(CrV = O)} moieties were formed in situ , resulting in two distinct catalytic regimes. [ABSTRACT FROM AUTHOR]

[Display omitted] • Anthrax toxin translocates cytotoxic enzyme factors across membranes into host cells. • Protective antigen moiety forms a large oligomeric translocase channel. • Channel contains three peptide-clamp active sites that catalyze translocation. • Channel translocates β-sheet sequences via an extended-chain Brownian ratchet. • Channel translocates α-helical sequences via a helix-compression mechanism. Dedicated translocase channels are nanomachines that often, but not always, unfold and translocate proteins through narrow pores across the membrane. Generally, these molecular machines utilize external sources of free energy to drive these reactions, since folded proteins are thermodynamically stable, and once unfolded they contain immense diffusive configurational entropy. To catalyze unfolding and translocate the unfolded state at appreciable timescales, translocase channels often utilize analogous peptide-clamp active sites. Here we describe how anthrax toxin has been used as a biophysical model system to study protein translocation. The tripartite bacterial toxin is composed of an oligomeric translocase channel, protective antigen (PA), and two enzymes, edema factor (EF) and lethal factor (LF), which are translocated by PA into mammalian host cells. Unfolding and translocation are powered by the endosomal proton gradient and are catalyzed by three peptide-clamp sites in the PA channel: the α clamp, the ϕ clamp, and the charge clamp. These clamp sites interact nonspecifically with the chemically complex translocating chain, serve to minimize unfolded state configurational entropy, and work cooperatively to promote translocation. Two models of proton gradient driven translocation have been proposed: (i) an extended-chain Brownian ratchet mechanism and (ii) a proton-driven helix-compression mechanism. These models are not mutually exclusive; instead the extended-chain Brownian ratchet likely operates on β-sheet sequences and the helix-compression mechanism likely operates on α-helical sequences. Finally, we compare and contrast anthrax toxin with other related and unrelated translocase channels. [ABSTRACT FROM AUTHOR]

Prostatic acid phosphatase (PAP) is a glycoprotein that plays a crucial role in the hydrolysis of phosphate ester present in prostatic exudates. It is a well-established indicator for prostate cancer due to its elevated serum levels in disease progression. Despite its abundance in semen, PAP's influence on male fertility has not been extensively studied. In our study, we report a significantly optimized method for purifying human endogenous PAP, achieving remarkably high efficiency and active protein recovery rate. This achievement allowed us to better analyze and understand the PAP protein. We determined the cryo-electron microscopic (Cryo-EM) structure of prostatic acid phosphatase in its physiological state for the first time. Our structural and gel filtration analysis confirmed the formation of a tight homodimer structure of human PAP. This functional homodimer displayed an elongated conformation in the cryo-EM structure compared to the previously reported crystal structure. Additionally, there was a notable 5-degree rotation in the angle between the α domain and α/β domain of each monomer. Through structural analysis, we revealed three potential glycosylation sites: Asn94, Asn220, and Asn333. These sites contained varying numbers and forms of glycosyl units, suggesting sugar moieties influence PAP function. Furthermore, we found that the active sites of PAP, His44 and Asp290, are located between the two protein domains. Overall, our study not only provide an optimized approach for PAP purification, but also offer crucial insights into its structural characteristics. These findings lay the groundwork for further investigations into the physiological function and potential therapeutic applications of this important protein. • Optimized PAP purification strategy with highest yield and activity ever. • Determined the Cryo-EM structure of PAP in its physiological homodimer state. • Cryo-EM unveils human PAP homodimer with remarkable detail at 3.2 Å. [ABSTRACT FROM AUTHOR]

[Display omitted] • Pt-O 4 -In 2 O ensemble site for superior acetylene semi-hydrogenation. • Increased electron localization surrounding with Pt-O 4 moiety in the ensemble site. • Enhanced heterolytic dissociation of H 2 on Pt-O 4 -In 2 O ensemble site. • Favorable formation of oxygen vacancy on the Pt 1 -In 2 O 3 catalyst. Transition metal oxides are emerging as promising catalysts for selective hydrogenations, but elaborating oxides catalysts with excellent hydrogenation activity remains challenging, especially at atomic level. Here, we report a theoretical-guided atomic design strategy with experimental verification to fabricate an excellent In 2 O 3 -based catalyst with an Pt-O 4 -In 2 O ensemble site for acetylene semi-hydrogenation. Theoretical calculations reveal that the presence of Pt-O 4 moiety in the ensemble site increases the electron localization surrounding with the moiety and thus strengthens the frustrated Lewis pair of In-O within the In 2 O site adjacent to the moiety. These structure features contribute to a promoted activation of hydrogen on the ensemble site via heterolytic dissociation and enhanced acetylene semi-hydrogenation on the oxygen vacancy adjacent to the Pt-O 4 moiety. The Pt 1 -In 2 O 3 catalyst featured with the ensemble site was synthesized by atomic layer deposition technology and characterized by multiple technologies, including atomic-resolution electron microscopy, X-ray absorption spectroscopy, and H 2 -D 2 exchange experiments, to validate the theoretical predictions. As expected, the experimental results elucidate an enhanced activation of hydrogen, and a full conversion of acetylene with 91% of ethylene selectivity on the Pt 1 -In 2 O 3 catalyst, which is remarkably higher than those of the pristine In 2 O 3 catalyst. [ABSTRACT FROM AUTHOR]

[Display omitted] Specific interactions of yttrium and lanthanum ions with a fatty acid Langmuir monolayer were investigated using vibrational sum frequency spectroscopy. The trivalent ions were shown to interact with the charged form of the carboxylic acid group from nanomolar concentrations (<300 nM). Analysis of the spectral features from both the symmetric and the asymmetric carboxylate modes reveals the presence of at least three distinct coordination structures linked to specific binding configurations. Although the same species were identified for both La3+ and Y3+, they display a different concentration dependence, highlighting the ion-specificity of the interaction. From the analysis of the response of interfacial water molecules, the reversal of the surface charge, as well as the formation of yttrium hydroxide complexes, were detected upon increasing the amount of salt in solution. The binding interaction and kinetics of absorption are sensitive to the solution pH, showing a distinct ion speciation in the interfacial region when compared to the bulk. Changing the subphase pH or adding a monovalent background electrolyte that promotes deprotonation of the carboxylic acid headgroup could further improve the detection limit of La3+ and Y3+ to concentrations < 100 nM. These findings demonstrate that nM concentrations of trace metals contaminants, typically found on monovalent salts, can significantly influence the binding structure and kinetics in Langmuir monolayers. [ABSTRACT FROM AUTHOR]

[Display omitted] • PDA liposome-based biosensor system can detect and distinguish different pathogenic bacterial species and does not rely on the use of specific recognition elements coupled with PDA liposomes. • Increased levels of cholesterol in liposome assemblies greatly enhanced the sensitivity of liposomal system to bacterial strains in terms of detection limit and response time. • Varied protein toxins produced by bacteria causes specific chromatic color changes in different PDA liposomal systems comprising various concentration of cholesterol, leading to strikingly different chromatic color change signature. • The PDA-based biosensors are based on the diverse modes of membrane-damaging action of bacteria on artificial lipid membranes including pore-formation hemolysis and phospholipase hemolysis. Bacterial infections are considered as a critical healthcare concern worldwide. Timely infection detection is crucial to effective antibiotic administration which can reduce the severity of infection and the occurrence of antibiotic resistance. We have developed label–free polydiacetylene (PDA) liposome-based colorimetric biosensor to detect and identify bacterial cultures at the genus and species level with naked eyes by simple color change. We found that among the various liposomal systems, moderate concentration of PDA, phospholipids and cholesterol in liposome assemblies can greatly influence the sensitivity to different bacteria, exhibiting unique chromatic properties of each bacterial strain. The strikingly different chromatic color change was due to the various mechanisms of interactions between bacterial toxins and biomimetic lipid bilayers. Furthermore, increase of cholesterol in liposome assemblies greatly enhanced the sensitivity of bacterial strains related to membrane destruction mediated by pore-formation mechanism such as S. aureus and E.coli , whereas the detection of the two bacterial strains was believed to rely on the specific recognition elements coupled with PDA moiety. As a proof of concept, a colorimetric finger-print array for distinguishing 6 bacterial species was studied. Particularly, the proposed bacterial detection platform is achieved through the interaction between bacterially secreted toxins and liposome bilayers instead of specific recognition of receptors-ligands. The results of both response time and sensitivity of label-free-liposome-based system show superior to previous reports on chromatic bacterial detection assays. By combing these results, the label-free-liposome-based colorimetric sensing platform shows great importance as a bacterial-sensing and discrimination platform. [ABSTRACT FROM AUTHOR]

[Display omitted] The critical concentration above which micelles form from zwitterionic surfactant solutions and their thermodynamic stability is affected by the interaction with weak Brønsted polyacid chains (A n) via the formation of charged hydrogen bonds between the latter and anionic moieties. The interaction between zwitterionic micelles and polyacids capable of forming hydrogen bonds, and its dependence on the environmental pH and polymer structure, has been studied with constant–pH simulations and a restricted primitive model for all electrolytes. At low pH, the formation of polyacid/micelle complexes is witnessed independently of the polymer size or structure, so that the concentration above which micelles form is substantially decreased compared to polyacid–free cases. Upon rising pH, polymer desorption takes place within a narrow range of pH values, its location markedly depending on the size and structure of polyacids, and on the relative disposition between headgroup charged moieties. Thus, the desorption onset for long linear polyacids (A 60) interacting with sulphobetainic headgroups is roughly two pH units higher than for six decameric chains (6A 10) adsorbed onto micelles bearing phosphorylcholinic headgroups. This effect, together with the preferential desorption of chain ends at intermediate pH, may be exploited for drug delivery purposes or building advanced metamaterials. [ABSTRACT FROM AUTHOR]

1,2-β-Mannobiose phosphorylases (1,2-β-MBPs) from glycoside hydrolase 130 (GH130) family are important bio-catalysts in glycochemistry applications owing to their ability in synthesizing oligomannans. Here, we report the crystal structure of a thermostable 1,2-β-MBP from Thermoanaerobacter sp. X-514 termed Teth514_1789 to reveal the molecular basis of its higher thermostability and mechanism of action. We also solved the enzyme complexes of mannose, mannose-1-phosphate (M1P) and 1,4-β-mannobiose to manifest the enzyme-substrate interaction networks of three main subsites. Notably, a Zn ion that should be derived from crystallization buffer was found in the active site and coordinates the phosphate moiety of M1P. Nonetheless, this Zn-coordination should reflect an inhibitory status as supplementing Zn severely impairs the enzyme activity. These results indicate that the effects of metal ions should be taken into consideration when applying Teth514_1789 and other related enzymes. Based on the structure, a reliable model of Teth514_1788 that shares 61.7% sequence identity to Teth514_1789 but displays a different substrate preference was built. Analyzing the structural features of these two closely related enzymes, we hypothesized that the length of a loop fragment that covers the entrance of the catalytic center might regulate the substrate selectivity. In conclusion, these information provide in-depth understanding of GH130 1,2-β-MBPs and should serve as an important guidance for enzyme engineering for further applications. • Teth514_1789 is a thermostable GH130 1,2-β-mannobiose phosphorylase. • Crystal structure of Teth514_1789 and its complex with ligands were solved. • Enzyme-substrate interaction networks are revealed. • Structure-function relations contributing to substrate preference were proposed. [ABSTRACT FROM AUTHOR]

[Display omitted] • FeN x -HDC@Ru nanocomposites are designed for the LOBs. • The internal network-like hollow structure can enhance the charge transfer kinetics. • A low impedance Li 2 O 2 /catalysts contact interface could be earned by the Ru nanoparticles. • The formation and decomposition of Li 2 O 2 could be improved with the nanocomposites during the cycling. Owing to their high energy density, lithium-oxygen batteries (LOBs) have been drawn great attention as one of the promising electrochemical energy sources. However, the sluggish kinetics of oxygen reduction/evolution reaction (ORR/OER) hamper the widespread application of LOBs. Herein, an elaborate designed catalysts which are constructed by FeN x moieties dispersed on the network-like hollow dodecahedral carbon and then decorated with Ru nanoparticles (FeN x -HDC@Ru). Since the homogeneously dispersed FeN x moieties could promote ORR performance, and the Ru nanoparticles could facilitate OER capability, the FeN x -HDC@Ru nanocomposites used as cathode catalysts can significantly improve LOBs performance. A lower discharge and charge overpotentials of 0.15 V and 0.78 V can be detected in the first cycle, respectively, and an excellent cycle performance of 90 cycles at 200 mA g−1 and 89 cycles at 500 mA g−1 can be demonstrated. Herein, the charge transfer kinetics has been enhanced with the internal network-like hollow structure and a low impedance Li 2 O 2 /catalysts contact interface could be earned by the constructed Ru nanoparticles, these factors would lead to an efficient acceleration to the formation and decomposition of Li 2 O 2 during discharge and charge process. [ABSTRACT FROM AUTHOR]

[Display omitted] • A series of 2,4-diarylaminopyrimidine derivatives containing sulfonamide moiety were synthesized as FAK inhibitors. • Compound 7b exhibits potent FAK inhibitory activity with an IC 50 value of 0.27 nM. • Compound 7b arrests cell cycle at G2/M phase and induces cell apoptosis by production of ROS. • Compound 7b can inhibit the clone formation and migration of HCT-116 cells. • Compound 7b has better safety than TAE226. Two series of 2,4-diarylaminopyrimidine derivatives containing sulfonamide moiety were designed and synthesized for screening as inhibitors of focal adhesion kinase (FAK). Most compounds significantly inhibited the enzymatic activities of FAK, and the best compound was 7b (IC 50 = 0.27 nM). A majority of aminoethyl sulfonamide derivatives could effectively inhibit the proliferation of human cancer cell lines (HCT116, A549, MDA-MB-231 and Hela) expressing high levels of FAK. Particularly, compounds 7b , 7c , and 7o exhibited more significant efficacy against all of four cancer cell lines within concentrations of 1.5 μM. Furthermore, these three compounds displayed higher selectivity of cancer cells over normal cells (SI value > 14), compared to the positive control TAE226 (SI value = 1.63). Interestingly, introduction of dithiocarbamate moiety to the aminoethyl sulfonamide derivatives can indeed improve the antiproliferative activities against A549 cells. Especially, compound 8d demonstrated most significant cytotoxicity activity against A549 cells with an IC 50 value of 0.08 μM, which is 20-fold superior to parent compound 7k. Additionally, compound 7b , which display the best anti-FAK potency, can inhibit the clone formation and migration of HCT-116 cells, and cause cell cycle arrest at G2/M phase, inducing apoptosis by promoting ROS production. Overall, these results suggest that 7b is a valuable FAK inhibitor that deserves further optimization to improve its druggability. [ABSTRACT FROM AUTHOR]

[Display omitted] • Sixteen new meroterpenoids were isolated from Atractylodes Chinensis by the LC/MS-based isolation. • Compound 1 has an unusual 6/6/6/6/5 pentacyclic ring system. • Compounds 2 and 3 possess a novel C 27 skeleton with a 6/6/5 tricyclic core. • Compounds 4 and 5 have a new C 32 skeleton with a rare scaffold of 3-(decahydronaphthalen-2-yl)-chromane. To mine fascinating molecules from the rhizomes of Atractylodes chinensis , the known molecular formula of atrachinenin A was used as a bait to search LC-HRMS data in different subfractions. Sixteen new meroterpenoids, atrachinenins D–S (1 – 16) including three unprecedented carbon skeletons (1 – 5) and eleven new oxygen-bridged hybrids (6 – 16) were obtained by the targeted isolation. Their structures and absolute configurations were elucidated by the spectroscopic data and electronic circular dichroism (ECD) calculations. The isolated compounds were evaluated for their inhibitory activity of NO production and compounds 1 , 4 , 8 , and 13 showed moderate anti-inflammatory activity. The proposed biosynthetic pathways of 1 – 5 were also discussed. [ABSTRACT FROM AUTHOR]

[Display omitted] • New compounds harboring the privileged thienopyrimidine scaffold were designed and synthesized. • They were tested for their inhibitory activity against carbonic anhydrase isoforms. • Compound 5r exhibited activity against CA II, CA IX and CA XII with Ki values of 8.6, 13.8, and 19 nM , respectively. • Molecular docking study was carried out to predict binding modes in the binding pockets of the four carbonic anhydrase isoforms. Eighteen novel compounds harboring the privileged thienopyrimidine scaffold (5a-q, and 6a) , were designed based on molecular hybridization strategy. These compounds were synthesized and tested for their inhibitory activity against four different carbonic anhydrase isoforms: CA I, II, IX, and XII. Microwave and conventional techniques were applied for their synthesis. Compounds 5b, 5g, 5l, and 5p showed the highest inhibition activity against the four CA isoforms. Compound 5p exhibited promising inhibitory activity against CA II, CA IX and CA XII with K I values of 8.6, 13.8, and 19 nM , respectively, relative to AAZ, where K I s = 12, 25, and 5.7 nM , respectively. Also, compound 5 l showed significant activity against the tumor-associated isoform CA IX with K I = 16.1 nM. All the newly synthesized compounds were also screened for their anticancer activity against NCI 60 cancer cell lines at a 10 µM concentration. Compound 5n showed 80.38, 83.95, and 87.39 % growth inhibition against the leukemic cell lines CCRF-CEM, HL-60 (TB), and RPMI-8226, respectively. Also, 5 h showed 87.57 % growth inhibition against breast cancer cell line MDA-MB-468; and 66.58 and 60.95 % inhibition against renal cancer cell lines UO-31, and ACHN, respectively. A molecular docking study was carried out to predict binding modes of our synthesized compounds in the binding pockets of the four carbonic anhydrase isoforms, and results revealed that compounds 5b, 5g, 5l , and 5p succeeded in mimicking the binding mode of AAZ through metal coordination with Zn+2 ion and binding to the amino acids Thr199, His94, and His96 that are critical for activity. [ABSTRACT FROM AUTHOR]

[Display omitted] • Multi-targetable chalcones bearing n -aryl piperazine moiety were designed synthesized, and evaluated for the treatment of AD. • Compound 41 identified as potential ligand and may be considered as promising "lead". • It ameliorated cognitive dysfunctions and signified memory improvement in the in-vivo behavioural studies. • Ex vivo biochemical analysis showed reduced AChE and increased ACh levels along with antioxidant potential. The multi-target directed ligand (MTDL) discovery has been gaining immense attention in the development of therapeutics for Alzheimer's disease (AD). The strategy has been evolved as an auspicious approach suitable to combat the heterogeneity and the multifactorial nature of AD. Therefore, multi-targetable chalcone derivatives bearing N -aryl piperazine moiety were designed, synthesized, and evaluated for the treatment of AD. All the synthesized compounds were screened for the in vitro activity against acetylcholinesterase (AChE), butylcholinesterase (BuChE), β-secretase-1 (BACE-1), and inhibition of amyloid β (Aβ) aggregation. Amongst all the tested derivatives, compound 41 bearing unsubstituted benzylpiperazine fragment and para -bromo substitution at the chalcone scaffold exhibited balanced inhibitory profile against the selected targets. Compound 41 elicited favourable permeation across the blood–brain barrier in the PAMPA assay. The molecular docking and dynamics simulation studies revealed the binding mode analysis and protein–ligand stability of the compound with AChE and BACE-1. Furthermore, it ameliorated cognitive dysfunctions and signified memory improvement in the in-vivo behavioural studies (scopolamine-induced amnesia model). The ex vivo biochemical analysis of mice brain homogenates established the reduced AChE and increased ACh levels. The antioxidant activity of compound 41 was accessed with the determination of catalase (CAT) and malondialdehyde (MDA) levels. The findings suggested that compound 41 , containing a privileged chalcone scaffold, can act as a lead molecule for developing AD therapeutics. [ABSTRACT FROM AUTHOR]

[Display omitted] • Chromone-thiazolidine-2,4-dione derivatives (5 ∼ 37) were synthesized. • All compounds presented potential PTP1B inhibitory activities and compound 9 displayed strongest inhibitory activity. • The binding of compound 9 with PTP1B led to conformational changes of PTP1B, resulting in the decrease on the catalytic activity of PTP1B. • Compound 9 recoveryed insulin resistance by regulation of IRSI and AKT. A series of chromone derivatives bearing thiazolidine-2,4-dione moiety (5 ∼ 37) were synthesized and evaluated for their PTP1B inhibitory activity, interaction analysis and effects on insulin pathway in palmitic acid (PA)-induced HepG2 cells. The results showed that all derivatives presented potential PTP1B inhibitory activity with IC 50 values of 1.40 ± 0.04 ∼ 16.83 ± 0.54 μM comparing to that of positive control lithocholic acid (IC 50 : 9.62 ± 0.14 μM). Among them, compound 9 had the strongest PTP1B inhibitory activity with the IC 50 value of 1.40 ± 0.04 μM. Inhibition kinetic study revealed that compound 9 was a reversible mixed-type inhibitor against PTP1B. CD spectra results confirmed that compound 9 changed the secondary structure of PTP1B by their interaction. Molecular docking explained the detailed binding between compound 9 and PTP1B. Compound 9 also showed 19-fold of selectivity for PTP1B over TCPTP. Moreover compound 9 could recovery PA-induced insulin resistance by increasing the phosphorylation of IRSI and AKT. CETSA results showed that compound 9 significantly increased the thermal stability of PTP1B. [ABSTRACT FROM AUTHOR]

s -triazine nucleus with various therapeutic applications. [Display omitted] This article summarizes the most recent advancements in the synthetic and pharmacological approaches along with the structure activity relationship towards the s -triazine and its derivatives. Much attention has been given to s -triazine core due to its facile synthesis, interesting pharmacology, high reactivity, and binding characteristics towards various enzymes. An array of biological applications has been demonstrated by s -triazines including antimalarial, anti-HIV, anti-viral, antimicrobial, anti-tuberculosis to name a few. In the present investigation s -triazine based molecular structures have been assembled in respect to their synthesis and medicinal properties. Further, the competence of s -triazine has been correlated and compared with the other heterocyclic moieties to substantiate s -triazine a privileged scaffold. From the literature it is revealed that nucleophilic substitution at 2, 4, and 6 positions is significant for various biological applications. This article would help in assisting the chemists in designing novel molecular entities with high medicinal value. [ABSTRACT FROM AUTHOR]

In this work, we for the first time conducted a detailed study on the structure, dynamics, and hybridization properties of N-benzimidazole group–bearing phosphoramide benzoazole oligonucleotides (PABAOs) that we developed recently. By circular dichroism we established that the introduction of the modifications does not disrupt the B conformation of the DNA double helix. The formation of complexes is approximated by a two-state model. Complexes of PABAOs with native oligodeoxriboynucleotides form efficiently, and the introduction of such modifications reduces thermal stability of short duplexes (8–10 bp) by ∼5°С per modification. Using UV-spectroscopy analysis, a neutral charge of the phosphate residue modified by the N-benzimidazole moiety in the pH range of 3–9.5 was found. The results confirm possible usefulness of PABAOs for both basic research and biomedical applications. [Display omitted] • Phosphoramidobenzoazole oligonucleotides (PABAOs) form B-form duplexes with DNA. • PABAO/DNA complexes have reduced thermal stability compared to DNA/DNA. • The conformational flexibility of PABAO/DNA complexes is close to that of native DNA/DNA. • PABAOs are a promising tool for basic research and various applications. [ABSTRACT FROM AUTHOR]

ORR: oxygen reduction reaction; SMSI: strong metal-support interaction; LABI: Lewis acid-base interaction. [Display omitted] • Residual Zn in various ZIF-8 derived carbons could reach ∼10 wt%. • ZnN x could act as 'spatial barriers' suppressing Pt forming ORR inactive PtN x. • ZnN x could serve as Zn source for the intermetallation of L1 0 -PtZn. • ZnN x could bring the SMSI between PtZn and support. • LABI between ZnN x and PtCl 6 2− could promote the dispersion of PtZn. ZIF-8 derived carbons demonstrate admirable application prospects in electrocatalytic fields, while ZnN x remaining in those materials are overlooked, crippling the validity of theoretic studies in researches. Herein, the residual Zn in ZIF-8 derived carbons are found could exceed 10 wt% even at carbonization temperatures over 900℃, and Zn-NCs with various Zn contents are adopted as supports to synthesize low-platinum ORR catalysts. Substantial characterizations manifest that ZnN x in Zn-NC can not only provide Zn source for L1 0 -PtZn intermetallic, but act as 'spatial barriers' to prevent the formation of inactive PtN x , elevating the active Pt proportion in catalyst by ∼104%. The resultant Zn-NC-Ar-PtZn exhibits a mass activity of 0.557 mA/g Pt and a peak density of 1.485 W/cm2. DFT calculations show the strong thermodynamic tendency of forming PtN 4 without the protection of ZnN 4 , and the superior durability and activity of Zn-NC-Ar-PtZn should be attributed to its Zn-derived ligand effects and the SMSI. [ABSTRACT FROM AUTHOR]

Supported molybdenum oxides have been widely employed as catalysts for variety of reactions including upgrading of bio-oil via hydrodeoxygenation. Herein, we perform spin-polarized density functional theory calculations to investigate the structures and reactivity of monomeric MoO x species supported on ZrO 2 in the absence and presence of hydroxyl(s). Monomeric molybdenum moieties were found to have a mono-oxo (one molybdenyl), di-oxo (two molybdenyls) or a pero-oxo (one molybdenyl and Mo coordinated to a peroxide) configuration. Based on the formation energies, we find that mono-oxo moieties are the most stable among the three. This is also true for the moieties in the presence of hydroxyls on the support. Further, the computed vibrational frequencies of a mono-oxo moiety on a hydroxylated support is a closer match to the peaks observed in experiments. A thermodynamic analysis of the molybdenum oxide moieties on a hydroxylated support indicated that the dehydroxylation is favoured at high temperatures and low partial pressures of water. On adsorption of hydrogen on the oxygen of the support, hydrogen loses its electron and reduces Mo of the monomeric moiety without making an oxygen vacancy. We studied the activity of this reduced site for deoxygenation of anisole to benzene. The overall barriers for this reaction are comparable to previously computed barriers for deoxygenation of bio-oil model compounds on an oxygen-vacant molybdenum oxide surfaces, suggesting that this may be an important mechanistic pathway during a hydro-deoxygenation process. [Display omitted] • Monomeric molybdenum oxide clusters supported on ZrO 2 have a mono-oxo configuration. • Vibrational peaks of mono-oxo cluster on hydroxylated ZrO 2 closely matches to experiments. • Hydrogen adsorbate forms a polaron on Mo, which becomes active for deoxygenation. [ABSTRACT FROM AUTHOR]

Paulomycins (PAUs) refer to a group of glycosylated antibiotics with attractive antibacterial activities against Gram-positive bacteria. They contain a special ring A moiety that is prone to dehydrate between C-4 and C-5 to a quinone-type form at acidic condition, which will reduce the antibacterial activities of PAUs significantly. Elucidation of the biosynthetic mechanism of the ring A moiety may facilitate its structure modifications by combinatorial biosynthesis to generate PAU analogues with enhanced bioactivity or stability. Previous studies showed that the ring A moiety is derived from chorismate, which is converted to 3-hydroxyanthranilic acid (3-HAA) by a 2-amino-2-deoxyisochorismate (ADIC) synthase, a 2,3-dihydro-3-hydroxyanthranilic acid (DHHA) synthase, and a DHHA dehydrogenase. Unfortunately, little is known about the conversion process from 3-HAA to the highly decorated ring A moiety of PAUs. In this work, we characterized Pau17 as an unprecedented 3-HAA 6-hydroxylase responsible for the conversion of 3-HAA to 3,6-DHAA by in vivo and in vitro studies, pushing one step forward toward elucidating the biosynthetic mechanism of the ring A moiety of PAUs. • Paulomycins (PAUs) are a group of glycoside antibiotics isolated from several Streptomyces strains. • PAUs are prone to dehydrate between C-4 and C-5 to form inactive PAU derivates with a quinone-type ring A. • Pau17 is an unprecedented 3-HAA 6-hydroxylase responsible for the conversion of 3-HAA to 3,6-DHAA in ring A biosynthesis. • Pau17 displays certain substrate promiscuity and can catalyze the hydroxylation of 2,3-dihydroxybenzoic acid. [ABSTRACT FROM AUTHOR]

Carbon-metal composites are promising multifunctional electrocatalysts, but it is still challenging to prepare carbon-metal composites with tunable structure and strong metal-carbon interactions. Here, we present a unique gas-foaming assembly strategy to prepare cytosine-Co chelate derived Co and N codoped carbon nanotube (Co-NCNT). The structure for Co-NCNTs could be easily controlled by regulating cytosine-Co coordination or the carbonization temperature. The optimal Co-NCNT possesses homogeneous distributed NCNTs (10 nm), CoO x (5 nm) and CoN x moieties to synergistically boost electrochemical processes, and offer mesoporous nanosheet architecture to guarantee fast mass migrate and electron transfer. As a result, Co-NCNT shows remarkable ORR performance (onset potential of 0.93 V in 0.1 M KOH electrolyte) along with significant OER and HER activity. More important, it was found that CoN x moieties are responsible for the remarkable electrocatalytic activity in Co-NCNTs, because CoN x could alter active center, enhance metal-carbon synergy, decrease interfacial resistance and reinforce the strength of composites. Therefore, this paper not just demonstrates an advanced multi-functional electrocatalyst, but could also give deep understanding on the designing of multifunctional electrocatalysts. [ABSTRACT FROM AUTHOR]

Simple zwitterions used as auxiliary agents might have the potential to change the zeta potential of oil-in-water (o/w) nanoemulsions on the mucosa. The zwitterion phosphorylated tyramine (p-Tyr) was synthesized by phosphorylation of Boc-tyramine (Boc-Tyr) using phosphoryl chloride (POCl 3). It was incorporated with 2% (m/v) in a self-emulsifying lipophilic phase comprising Captex 35, Cremophor EL, Capmul MCM and glycerol 85 at a ratio of 30:30:30:10 v/v. Phosphate release and resulting change in zeta potential were evaluated by incubating p-Tyr containing nanoemulsion with isolated intestinal alkaline phosphatase (AP). Mucus permeating behavior was evaluated across mucus obtained from porcine small intestinal mucosa. Subsequently, cellular uptake studies were accomplished on Caco-2 cells. The p-Tyr loaded nanoemulsion exhibited a mean droplet size of 43 ± 1.7 nm and zeta potential of −8.40 mV. Phosphate moieties were rapidly cleaved from p-Tyr loaded nanoemulsions after incubation with isolated AP resulting in a shift in zeta potential from −8.40 mV to +1.2 mV. p-Tyr loaded nanoemulsion revealed a significantly (p ≤ 0.001) improved mucus permeation compared to the same nanoemulsion having been pre-treated with AP. Cellular uptake of the zeta potential changing oily droplets was 2.4-fold improved. Phosphorylated zwitterions seem to be an alternative to cationic surfactants and considered as promising auxiliary agents for zeta potential changing nanoemulsions. [ABSTRACT FROM AUTHOR]

Many uses of emulsion droplets require precise control over droplet size and shape. Here we report a 'shape-memorable' micro-droplet formulation stabilized by a polyethylene glycol (PEG)-modified protein -surfactant, the droplets are stable against coalescence for months and can maintain non-spherical shapes for hours, depending on the surface coverage of PEGylated protein. Monodisperse droplets with aspect ratios ranging from 1.0 to 3.4 were controllably synthesized with a flow-focusing microfluidic device. Mechanical properties of the interfacial protein network were explored to elucidate the mechanism behind the droplet shape conservation phenomenon. Characterization of the protein film revealed that the presence of a PEG layer at interfaces alters the mechanical responses of the protein film, resulting in interfacial networks with improved strength. Taking advantage of the prolonged stabilization of non-spherical droplets, we demonstrate functionalization of the droplet interface with accessible biotins. The stabilization of micro-droplet shape with surface-active proteins that also serve as an anchor for integrating functional moieties, provides a tailorable interface for diverse biomimetic applications. [ABSTRACT FROM AUTHOR]

• SBA15-A-CD was facilely prepared via postsynthetic modification of SBA-15. • Multi-functionalization with β-CD and amine can enhance the methyl blue adsorption performance. • The maximum adsorption capacity of SBA15-A-CD2 for methyl blue was 1790.92 mg·g−1. • Adsorption mechanism was proposed through theoretical calculation and 2D NMR. To remove the bulky aqueous organic dye e.g. methyl blue (MB) from water, ordered mesoporous silica SBA-15 has been functionalized with β-cyclodextrin (β-CD) via amide linkage. The surface physical and chemical properties of the surface of the resulted β-CD-functionalized adsorbents (abbrev. SBA15-A-CD) were characterized systematically. The results indicate that the channels of SBA-15 were uniformly modified with amine groups and were further β-CD-terminated via amide linkages, without ruining its ordered mesoporous structure. The effects of contact time, pH, ionic strength, temperature and salt on the adsorption performance were explored. SBA15-A-CD showed maximum adsorption capacity for MB up to 1791 mg·g−1 combined with excellent recyclability. Besides, the adsorption behavior of MB onto SBA15-A-CD has been investigated by DFT calculation and two-dimensional NMR. Specifically, the enhanced adsorption capacity for MB stems from the tailored host–guest interaction between β-CD cavity and aromatic moiety of MB in combination with the electrostatic attraction between amine groups and sulfonated group of MB. These findings offer good opportunities for improving the ability of mesoporous silica in adsorption of bulky anion dyes in wastewater. [ABSTRACT FROM AUTHOR]

Rhamnolipids (RLs) comprise a class of glycolipids produced by Pseudomonas aeruginosa under appropriate culture medium. They act as biosurfactants being composed by a hydrophilic head of either one (mono-RL) or two (di-RL) rhamnose moieties coupled to hydroxyaliphatic chains. It is well accepted that RLs present low biolitic activity as compared to other synthetic surfactants. However, their mechanisms of action in biological systems are not well defined yet. The interaction of RLs with lipid bilayers are here investigated to address how they impact on plasma membrane at molecular level. Our experimental approach was based on a deep analysis of optical microscopy data from giant unilamellar vesicles (GUVs) dispersed in aqueous solutions containing up to 0.5 mM of commercially available RLs (a mixture of mono-RL, 33–37 mol%, and di-RL, 63–67 mol%, cmc of 0.068 ± 0.005 mM). GUVs were made up of a single lipid POPC and a ternary system containing DOPC, sphingomyelin and cholesterol, which mimic lipid raft platforms. Our results demonstrate that RLs have a low partition in the lipid bilayer in respect to the total molecules in solution. We suppose that RLs insert in the outer leaflet with low propensity to flip-flop. In the case of POPC GUVs, the insertion of RL molecules in the outer leaflet impairs changes in spontaneous membrane curvature with incubation time. Then, small buds are formed that remain linked to the original membrane. No changes in membrane permeability have been detected. A remarkable result refers to the insertion of RLs in membranes containing liquid ordered ( L o ) - liquid disordered ( L d ) phase coexistence. The rate of interaction has been observed to be higher for L d phase than for L o phase (0.12 · 10 - 6 s−1 and 0.023 · 10 - 6 s−1 for L d and L o , respectively, at RL concentration of 0.5 mM). As a consequence, the preferential RL insertion in L d phase may also alter the membrane spontaneous curvature which, coupled to the change in the line tension associated to the domains boundary, conducted to L o domain protrusion. Even if it has been observed on a model system, such membrane remodelling might correlate to endocytic processes activated in cell membranes, regardless of the participation of specific proteins. Further, changes imposed by RLs in lipid rafts may affect the association of key proteins enrolled in cell signaling, which may perturb cell homeostasis. [ABSTRACT FROM AUTHOR]

The aim of the current study is to report a simple and efficient method to chemically modify chitosan in order to form S -nitroso-chitosan for antibacterial applications. Firstly, commercial chitosan (CS) was modified to form thiolated chitosan (TCS) based on an easy and environmental-friendly method. TCS was featured based on physicochemical and morphological techniques. Results have confirmed that thiol groups in TCS formed after CS's primary amino groups were replaced with secondary amino groups. Free thiol groups in TCS were nitrosated to form S -nitrosothiol moieties covalently bond to the polymer backbone (S -nitroso-CS). Kinetic measurements have shown that S -nitroso-CS was capable of generating NO in a sustained manner at levels suitable for biomedical applications. The antibacterial activities of CS, TCS and S -nitroso-CS were evaluated based on the minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and time-kill curves determined for Escherichia coli, Staphylococcus aureus and Streptococcus mutans. MIC/MBC values reached 25/25, 0.7/0.7 and 3.1/3.1 μg mL−1 for CS/TCS and 3.1/3.1, 0.1/0.2, 0.1/0.2 μg mL−1 for S -nitroso-CS, respectively. Decreased MIC and MBC values have indicated that S -nitroso-CS has higher antibacterial activity than CS and TCS. Time-kill curves have shown that the bacterial cell viability decreased 5-fold for E. coli and 2-fold for S. mutans in comparison to their respective controls, after 0.5 h of incubation with S -nitroso-CS. Together, CS backbone chemically modified with S -nitroso moieties have yielded a polymer capable of generating therapeutic NO concentrations with strong antibacterial effect. Image 1 • Chitosan was chemically modified with thioglycolic acid leading to thiolated chitosan. • Thiolated chitosan (TCS) was nitrosate to form S-nitroso moieties (S-nitroso-CS). • S-nitroso-CS spontaneously releases NO at concentrations suitable for biomedical applications. • S-nitroso-CS has a high antibacterial effect. [ABSTRACT FROM AUTHOR]

The effect of cationic head-group of ionic liquid on the structure and dynamics of phospholipid bilayer was studied to provide insights into the mechanism of ionic liquid-membrane interaction. The effect was observed using six ionic liquids containing benzimidazolium, imidazolium, pyrrolidinium, piperidinium, ammonium, and morpholinium based amphiphilic cations carrying a dodecyl alkyl chain. Unilamellar and multilamellar vesicles composed of zwitterionic 1-palmitoyl-2-oleoyl- sn - glycero -3-phosphocholine (POPC) were used. Permeability of POPC bilayer was found to have a strong dependence on ionic liquid head-group structure. To probe the structural details of interaction, 31P and 2H based solid-state NMR measurements were performed. The cations differed in terms of their effect on the orientation and disorder in the phosphocholine moiety in lipid head-group as revealed by chemical shift anisotropy of 31P. Cations carrying an unshielded charge like benzimidazolium, imidazolium, and ammonium result in strong reorientation of phosphocholine moiety in lipid head-group. Large sized cations like benzimidazolium and piperidinium result in enhanced lipid chain dynamics as revealed by order parameter calculations of deuterated lipid chains. Relatively polar head-group of morpholinium cation neither impacts the phospholipid head-group nor chain packing. Our results suggest that there exists a direct correlation between ionic liquid head-group induced structural changes in bilayer and their ability to permeabilize/disrupt the membrane and be cytotoxic. [ABSTRACT FROM AUTHOR]

The micellization behavior of nonionic surfactants is significantly influenced by substituting ethylene oxide (EO) units with CO 2 in the head group of nonionic C 12 EO j surfactants. Incorporating hydrophobic units has a major effect on the driving forces of the micellization process by a reduced hydration affinity. Hence, the incorporation of CO 2 moieties is favoring micellization and thereby adding a further tuning parameter. The micellization of the surfactants was characterized in terms of thermodynamics and the assembly properties on the water/air interface by isothermal titration calorimetry (ITC) and surface tension measurements. The incorporation of CO 2 moieties was compared to the effect of propylene oxide (PO) and propiolactone (PL) over the temperature range of 25–50 °C. From ITC measurements and the van't Hoff relation, we determined the thermodynamic parameters of micellization: enthalpy (ΔH mic), entropy (ΔS mic), and Gibbs free energy (ΔG mic). The incorporation of CO 2 moieties reduces the critical micellization concentration (cmc) and a transfer energy of −0.36 kT/CO 2 unit quantifies favored micellization for CO 2 surfactants. The presence of PO or CO 2 in the head group has a similar effect on the cmc, but for CO 2 ΔH mic is substantially decreased, resulting in a largely reduced temperature sensitivity of the micellization process and indicating a reduced hydration affinity. This thermodynamic analysis reveals that CO 2 and PO behave very differently concerning their effect on the micellization process. [ABSTRACT FROM AUTHOR]

DNA-encoded chemical libraries (DECLs) are powerful tools for modern drug discovery. A DECL is a pooled mixture of small molecule compounds, each of which is tagged with a unique DNA sequence which functions as a barcode. After incubation with a drug target and washing to remove non-binders, the bound molecules are eluted and submitted for DNA sequencing to determine which molecules are binding the target. While the DECL technology itself is ultra-high throughput, the following re-synthesis of identified compounds for orthogonal validation experiments remains the bottleneck. Using existing DNA-small molecule conjugates directly for affinity measurements, as opposed to complete compound resynthesis, could accelerate the discovery process. To this end, we have tested various geometries of fluorescently-labelled DNA constructs for fluorescence anisotropy (FA) experiments. Minimizing the distance between the fluorescent moiety and ligand can maximize the correlation between ligand-protein interaction and corresponding change in fluorophore rotational freedom, thus leading to larger, easier to interpret changes in FA values. However, close proximity can also cause artifacts due to potentially promiscuous interactions between fluorophore and protein. By balancing these two opposite effects, we have identified applicable fluorescently labelled DNA constructs displaying either a single ligand or pairs of fragments for affinity measurement using a FA assay. Fluorescently labelled DNA constructs of different geometry were optimized for their utility in DECL (DNA-Encoded Chemical Library) hit validation with fluorescence anisotropy assay. Image 1 [ABSTRACT FROM AUTHOR]

Copolymers are developed to enhance the overall physical and chemical properties of polymers. The surface nature of a copolymer is relevant to creating efficient materials to improve adhesion and biocompatibility. We hypothesize that the improved adhesion, as a surface property, is due to phase separation, surface segregation, and the overall molecular organization of different polymer components at the copolymer surface. The surface structure of a copolymer composed of 2-hydroxyethyl methacrylate (HEMA) monomer and 2-phenoxyethyl methacrylate (PhEMA) monomer was analyzed in comparison to the polyHEMA and polyPhEMA homopolymers using atomic force microscopy (AFM) and sum frequency generation (SFG) spectroscopy. The contrast in the phase images was due to the variance in the hydrophobic level provided by the hydroxyl and phenoxy modified monomers in the copolymer. The distribution of the adhesion values, supporting the presence of hydrophobic moieties, across the polymer surface defined the surface segregation of these two components. SFG spectra of the copolymer thin film showed combined spectral features of both polyHEMA and polyPhEMA thin films at the polymer surface. The tilt angles of the alpha-methyl group of homopolymers using the polarization intensity ratio analysis and the polarization mapping method were estimated to be in the range from 48° to 66°. [ABSTRACT FROM AUTHOR]

An O-acetyl sialic acid specific lectin was purified from the hemolymph of the marine crab Atergatis integerrimus by affinity chromatography using BSM (Bovine Submaxillary Mucin) coupled to cyanogen bromide activated Sepharose 4B and biospecific adsorption using formalinized buffalo erythrocytes. The purified AiL (Atergatis integerrimus lectin) showed an 1218 fold increase in specific activity when compared to the crude hemolymph agglutinin. The lectin, on non - denaturing PAGE showed a single band of 216 kDa and when subjected to SDS - PAGE, the lectin resolved into three subunits of molecular weight 70, 72 and 74 kDa. Physico chemical characterization revealed the lectin as pH and temperature sensitive, calcium dependent and sensitive to calcium chelators. Based on the calcium dependency of the lectin, AiL could be classified as a C-type lectin. The purified lectin agglutinated buffalo erythrocytes with greater avidity and was inhibited by the glycoproteins BSM, thyroglobulin, fetuin, PSM, and sugars raffinose, trehalose, l - fucose, α - Lactose, melibiose and GluNAc suggesting the affinity of the lectin to sialic acid. Reduction in HA with asialo buffalo erythrocytes and HAI titer with desialylated BSM, confirms the sialic acid specificity of the lectin. The reduction in HAI following de - O - acetylation confirms the specificity of the lectin for O - acetyl sialic acid. FTIR analysis confirms the purified lectin as a glycoprotein with spectral bands corresponding to amide bands and saccharides. Thus this study paves way to assess the therapeutic application of this lectin that could be targeted to modified sialic acid moieties that are expressed on the malignant cells and pathogenic microbes and also deduce the crystal structure of the lectin. • The marine crab, Atergatis integerrimus is the potent source of lectin. • A novel O-acetyl sialic acid specific lectin was isolated from this crab. • The molecular weight of the purified lectin was 216 kDa with three sub units. • The purified lectin agglutinated various erythrocytes with greater avidity. • It has wide application in determining sialic acid moieties on the malignant cells. [ABSTRACT FROM AUTHOR]

• A novel complex nanostructure of multipodal silica with a hollow cavity. • A region-selective control strategy to grow branched nanostructure. • A mechanism for precisely adjusting the number of the branched pods. Hypothesis: Hollow nanostructures, known as nanocapsules, have been the preferable candidates in the drug-delivery and control-release applications. To enhance the adherence and penetration into biological hosts for efficient drug delivery, constructing multiple pods on the hollow structure to form a tribulus-like branched architecture has been proven an effective strategy. However, the synthesis is challenging due to the simultaneous control of the branched podal morphology, the hollow architecture and the mesophase structures at the nanometer scale. Experiments: Polymer spheres with surface carboxyl moieties were first prepared by emulsion polymerization, which were partly coated by a type of basic silane. The left carboxyl moieties formed some seperated acid spots on the surface of polymer spheres, which could lead to the subsequent self-assembly of surfactant and silica within these acidic spots to grow a branched nanostructure. Findings: Radiolarian-like organic-inorganic hybrid hollow architecture with branched ordered mesoporous pods were obtained after removing the organic templates of the polymer spheres and surfactants by calcination. The ordered cylindrical mesoporous channels were along the central axis direction of the hexagonal-prism-like pods, which connected inside and outside of the hollow spheres. The number of the branched pods could be easily tuned at the range of one to four. [ABSTRACT FROM AUTHOR]

Flavonoids are generally glycosylated, and the glycan moieties of flavonoid glycosides are known to greatly affect their physicochemical and biological properties. Thus, the development of a variety of tools for glycan remodeling of flavonoid glycosides is highly desired. An endo-β- N -acetylglucosaminidase mutant Endo-CC N180H, which is developed as an excellent chemoenzymatic tool for creating sialylglycoproteins, was employed for the glycosylation of flavonoids. Endo-CC N180H transferred the sialyl biantennary glycans from the sialylglyco peptide to p NP-GlcNAc and narigenin-7- O -glucoside. The kinetic parameters of Endo-CC N180H towards SGP and p NP-GlcNAc were determined. Flavonoid glucosides harboring a 1,3-diol structure in the glucose moieties acted as substrates of Endo-CC N180H. We proposed that the sialyl biantennary glycan transfer to the flavonoid by Endo-CC N180H could pave the way for the improvement of the inherent biological functions of the flavonoids and creation of novel flavonoid glycoside derivatives for future human health benefits including foods and drugs. • Endo-CC N180H transferred the sialyl biantennary glycans to flavonoid glucoside. • The kinetic parameters of Endo-CC N180H towards SGP and p NP-GlcNAc were determined. • A 1,3-diol structure was important for the recognition by Endo-CC N180H. [ABSTRACT FROM AUTHOR]

Rhodopsin is the photosensitive protein, which binds to 11- cis -retinal as its chromophore. In the dark, rhodopsin exists as a stable complex between the opsin moiety and 11- cis -retinal. The absorption of a light photon converts 11- cis -retinal to all- trans -retinal and initiates our vision. As a result, the increase in the rate of dark activation of rhodopsin reduces its photosensitivity resulting in night blindness. The mutations, G90D and T94I are night blindness-causing mutations that exhibit completely different physicochemical characteristics associated with the dark activation of rhodopsin, such as a high rate of thermal isomerization of 11- cis -retinal and a slow pigment regeneration. To elucidate the molecular mechanism by which G90D and T94I mutations affect rhodopsin dark activation and regeneration, we performed light-induced difference FTIR spectroscopy on dark and primary photo-intermediate states of G90D and T94I mutants. The FTIR spectra clearly show that both charged G90D and hydrophobic T94I mutants alter the H-bond network at the Schiff base region of the chromophore, which weakens the electrostatic interaction with Glu113 counterion. Our results further show an altered water-mediated H-bond network around the central transmembrane region of mutant rhodopsin, which is reminiscent of the active Meta-II state. This altered water-mediated H-bond network may cause thermal isomerization of the chromophore and facilitate rhodopsin dark activation. Unlabelled Image [ABSTRACT FROM AUTHOR]

Cytidine deaminase (CDA) catalyzes the (deoxy)cytidine deamination to (deoxy)uridine, which involves in the catabolic and salvage pathways of pyrimidine nucleotides in plants. CDA serves as a prototype of the cytidine deaminase superfamily that contains a number of RNA editing enzymes. Arabidopsis thaliana has only one functional CDA, At CDA1. We solved the crystal structures of At CDA1, which is a dimeric zinc-containing enzyme and each protomer consists of an N-terminal zinc-binding catalytic domain and a C-terminal non-catalytic domain. Both domains adopt a typical α/β/α sandwich fold. In vitro biochemical assays showed that the ribose moiety of cytidine is required for ligand binding, and structural analyses revealed a conserved catalytic mechanism is adopted by At CDA1. • Crystal structure of At CDA1 is determined at 3.0 Å. • At CDA1 is a dimeric zinc-containing enzyme. • Hydrogen bonds are the major force in the formation of At CDA1 dimer. • The activities of At CDA1 depend on the N-terminal catalytic deaminase domain. • The ribose moiety of cytidine is required for ligand binding. [ABSTRACT FROM AUTHOR]

The widespread emergence of antibiotic resistance in pathogens necessitates the development of antibacterial agents inhibiting underexplored targets in bacterial metabolism. One such target is phospho-MurNAc-pentapeptide translocase (MraY), an essential integral membrane enzyme that catalyzes the first committed step of peptidoglycan biosynthesis. MraY has long been considered a promising candidate for antibiotic development in part because it is the target of five classes of naturally occurring nucleoside inhibitors with potent in vivo and in vitro antibacterial activity. Although these inhibitors each have a nucleoside moiety, they vary dramatically in their core structures, and they have different activity properties. Until recently, the structural basis of MraY inhibition was poorly understood. Several recent structures of MraY and its human paralog, GlcNAc-1-P-transferase, have provided insights into MraY inhibition that are consistent with known inhibitor activity data and can inform rational drug design for this important antibiotic target. Unlabelled Image • Antibiotics with new mechanisms of action are needed to combat antibiotic resistance. • MraY is an enzyme involved in bacterial membrane biosynthesis that has been historically regarded as an excellent target for antibiotic development; however, technical challenges associated with structural studies of this integral membrane protein have made it difficult to pursue. • Recent advances in the structural and functional understanding of MraY have regenerated interest in this target and have provided critical paths forward for the design of potent and selective MraY inhibitors. [ABSTRACT FROM AUTHOR]

Molecules forming directed intermolecular hydrogen bonds, such as the well-known benzene- 1 , 3 , 5 -tricarboxamides (BTA) motif, are known to self-assemble into long fibrous structures. However, only a few of these systems have so far demonstrated the ability to form such anisotropic nanostructures, if they are combined with hydrophilic polymers to create an amphiphilic material. Here, we designed BTA-polymer conjugates to investigate whether the directionality of the hydrogen bonds or the ratio of hydrophobic to hydrophilic parts of the molecule, and thus the packing parameter, is decisive for obtaining anisotropic supramolecular structures in water. Poly(ethylene glycol) was conjugated to BTA moieties with varying lengths of hydrophobic alkyl spacers ranging from two to twelve methylene units. The resulting amphiphilic materials were characterized in aqueous solution by light and small-angle neutron scattering, analytical ultracentrifugation, and cryo-transmission electron microscopy. While spherical micelles were observed for C 6 and C 10 alkyl spacers, anisotropic structures were only present in case of the C 12 spacer. The comparison to an analogous material, which lacks the directed hydrogen bonds, revealed that the BTA motif cannot provide a sufficient driving force to induce anisotropic structures, but increases the packing density in the hydrophobic part. Therefore, the packing parameter governs the appearance of anisotropic aggregates. [ABSTRACT FROM AUTHOR]

[Display omitted] • Modified TBAs were synthesized by linking naphthalendiimides (N) and 3-hydroxypropylphosphate (p) at the ends. • Their physico-chemical properties, serum resistance and anticoagulant activity were evaluated. • The analogue named N -TBA-p proved to be > 11 times more effective than unmodified TBA. The limitations associated with the in vivo use of the thrombin binding aptamer (TBA or TBA 15) have dramatically stimulated the search of suitable chemically modified analogues in order to discover effective and reversible inhibitors of thrombin activity. In this context, we previously proposed cyclic and pseudo-cyclic TBA analogues with improved stability that proved to be more active than the parent aptamer. Herein, we have investigated a novel library of TBA derivatives carrying naphthalene diimide (NDI) moieties at the 3′- or 5′-end. In a subset of the investigated oligonucleotides, additional 3-hydroxypropylphosphate (HPP) groups were introduced at one or both ends of the TBA sequence. Evaluation of the G-quadruplex thermal stability, serum nuclease resistance and in vitro anticoagulant activity of the new TBA analogues allowed rationalizing the effect of these appendages on the activity of the aptamer on the basis of their relative position. Notably, most of the different TBA analogues tested were more potent thrombin inhibitors than unmodified TBA. Particularly, the analogue carrying an NDI group at the 5′-end and an HPP group at the 3′-end, named N-TBA-p , exhibited enhanced G-quadruplex thermal stability (ΔT m + 14° C) and ca. 10-fold improved nuclease resistance in serum compared to the native aptamer. N-TBA-p also induced prolonged and dose-dependent clotting times, showing a ca. 11-fold higher anticoagulant activity compared to unmodified TBA, as determined by spectroscopic methods. Overall, N-TBA-p proved to be in vitro a more efficient thrombin inhibitor than all the best ones previously investigated in our group. Its interesting features, associated with its easy preparation, make it a very promising candidate for future in vivo studies. [ABSTRACT FROM AUTHOR]

M13 phages possessing filamentous phage genomes offer the benefits of selective display of molecular moieties and delivery of therapeutic agent payloads with a tolerable safety profile. M13 phage-displayed technology for resembling antigen portions led to the discovery of mimetic epitopes that applied to antibody-based therapy and could be useful in the design of anticancer vaccines. To date, the excremental experiences have engaged the M13 phage in the development of innovative biosensors for detecting biospecies, biomolecules, and human cells with an acceptable limit of detection. Addressing the emergence of antibiotic-resistant bacteria, M13 phages are potent for packaging the programmed gene editing tools, such as CRISPR/Cas, to target multiple antimicrobial genes. Moreover, their display potential in combination with nanoparticles inspires new approaches for engineering targeted theragnostic platforms targeting multiple cellular biomarkers in vivo. In this review, we present the available data on optimizing the use of bacteriophages with a focus on the to date experiences with M13 phages, either as monoagent or as part of combination regimens in the practices of biosensors, vaccines, bactericidal, modeling of specific antigen epitopes, and phage-guided nanoparticles for drug delivery systems. Despite increasing research interest, a deep understanding of the underlying biological and genetic behaviors of M13 phages is needed to enable the full potential of these bioagents in biomedicine, as discussed here. We also discuss some of the challenges that have thus far limited the development and practical marketing of M13 phages. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • Carbonylative double cyclization leading to benzothienofuranones and benzothienopyranones. • First example of carbonylative S -cyclization of 3-(2-(methylthio)phenyl)prop-2-yn-1-ols. • First example of carbonylative S -cyclization of 4-(2-(methylthio)phenyl)but-3-yn-1-ols. • Structure of four representative products confirmed by XRD analysis. • Products formed in 40–83% isolated yields over 23 examples. 3-(2-(Methylthio)phenyl)prop-2-yn-1-ols have been successfully converted in one synthetic step into benzo[4,5]thieno[2,3-c]furan-1-ones by a PdI 2 /KI-catalyzed oxidative carbonylative double cyclization process, performed in MeCN under relative mild conditions (1–10 mol % PdI 2 , 7 equiv of KI, 80 °C, 60 atm of a 4:1 mixture CO–air). The process takes place through an ordered sequence of steps, involving 5- endo - dig S -cyclization, iodide-promoted demethylation of the ensuing sulfonium salt, CO insertion, a second cyclization (possibly, through the formation of a palladacycle intermediate followed by reductive elimination), and Pd(0) reoxidation by oxygen (from air) used as external benign oxidant. Under similar conditions, 4-(2-(methylthio)phenyl)but-3-yn-1-ols, bearing a butynol moiety ortho to the methylthio group, led to a mixture of double cyclization and dicarbonylation products, however, by slightly tuning the reaction conditions, dihydrobenzo[4,5]thieno[3,2-c]pyran-1-ones could be selectively obtained with no formation of the dicarbonylated byproduct. The structures of four representative products, including two tetracyclic derivatives, have been confirmed by XRD analysis. [ABSTRACT FROM AUTHOR]

Abstract The insertion of phenylbutylamine into a layered perovskite of formula H 2 Bi 0.1 Sr 0.85 Ta 2 O 7 (HST) has been investigated as a function of the synthesis conditions. For short reactions times (1.5 h), achieved using microwave assisted reactions, a short interlayer distance (2.2 nm) is obtained (PBA1-HST) whereas for long reaction times (18 h) achieved using classical solvothermal reaction, a much larger interlayer distance is obtained (3.0 nm) (PBA3-HST). The compounds are well crystallized despite a more pronounced disorder of the organic moiety for PBA1-HST , evidenced by IR spectroscopy. The organic loading is very similar for both phases, and no difference in the 13C CP/MAS solid state NMR spectra could be evidenced. 1D electron density profiles established from XRD patterns allow to precise the organization of the molecules within the interlayer space. More subtle variations of the reaction parameters tend to show that there is a gradual evolution from the kinetic product, PBA1-HST , to the thermodynamic one, PBA3-HST , but it has not been possible to isolate a monophasic intermediate phase. Yet a compound with an intermediate interlayer distance could be isolated as a pure phase, using a prefunctionalized precursor as starting material (PBA2-HST , 2.7 nm). It was finally shown that it is possible to realize a mutual conversion of PBA2-HST and PBA3-HST by post-synthesis solvent treatment. This work completes the emerging studies on microwave-assisted functionalization of layered oxides and paves the way to a fine tailoring of hybrid materials with specific structures and properties. Graphical abstract Phenylbutylamine has been successfully inserted into a layered perovskite H 2 Bi 0.1 Sr 0.85 Ta 2 O 7 , with different arrangements depending on the reaction conditions. fx1 [ABSTRACT FROM AUTHOR]

[Display omitted] • SIRAH is one of the most complete force fields for coarse-grained and multiscale simulations of complex biological systems. • Its implementation in popular molecular dynamics simulation packages provides plug&play solution for coarse-grained simulations. • This review provides a comprehensive outlook of the development strategies and illustrate the future of the force field. The different combinations of molecular dynamics simulations with coarse-grained representations have acquired considerable popularity among the scientific community. Especially in biocomputing, the significant speedup granted by simplified molecular models opened the possibility of increasing the diversity and complexity of macromolecular systems, providing realistic insights on large assemblies for more extended time windows. However, a holistic view of biological ensembles' structural and dynamic features requires a self-consistent force field, namely, a set of equations and parameters that describe the intra and intermolecular interactions among moieties of diverse chemical nature (i.e., nucleic and amino acids, lipids, solvent, ions, etc.). Nevertheless, examples of such force fields are scarce in the literature at the fully atomistic and coarse-grained levels. Moreover, the number of force fields capable of handling simultaneously different scales is restricted to a handful. Among those, the SIRAH force field, developed in our group, furnishes a set of topologies and tools that facilitate the setting up and running of molecular dynamics simulations at the coarse-grained and multiscale levels. SIRAH uses the same classical pairwise Hamiltonian function implemented in the most popular molecular dynamics software. In particular, it runs natively in AMBER and Gromacs engines, and porting it to other simulation packages is straightforward. This review describes the underlying philosophy behind the development of SIRAH over the years and across families of biological molecules, discussing current limitations and future implementations. [ABSTRACT FROM AUTHOR]