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Sulfonamides have many important biological applications, yet their synthesis often involves long reaction times under dry and non-ambient conditions. Here we report the synthesis of a large range of sulfonamides at room temperature using 4-nitrophenyl benzylsulfonate as a starting material. Sulfonamides were prepared from a wide range of aliphatic, linear, and cyclic amines, anilines, and N-methylanilines. The yields and reaction times observed here were comparable to or better than those reported previously, establishing sulfur-phenolate exchange as a viable alternative.

SuFEx chemistry has recently evolved as next-generation click chemistry. However, in most SuFEx syntheses, additional reagents/catalysts and carefully controlled conditions are still needed. Here, we aim to further generalize S(VI) exchange chemistry, using 4-nitrophenyl phenylmethanesulfonate as example, in which the nitrophenolate group is exchanged for a wide range of (substituted) phenols and alkyl alcohols. Quantitative yields were reached within 10 min under ambient conditions and required only filtering through silica as workup.

Ion channels, many expressed in insect neural and muscular systems, have drawn huge attention as primary targets of insecticides. With the recent technical breakthroughs in structural biology, especially in cryo-electron microscopy (cryo-EM), many new high-resolution structures of ion channel targets, apo or in complex with insecticides, have been solved, shedding light on the molecular mechanism of action of the insecticides and resistance mutations. These structures also provide accurate templates for structure-based insecticide screening and rational design. This review summarizes the recent progress in the structural studies of 5 ion channel families: the ryanodine receptor (RyR), the nicotinic acetylcholine receptor (nAChR), the voltage-gated sodium channel (VGSC), the transient receptor potential (TRP) channel, and the ligand-gated chloride channel (LGCC). We address the selectivity of the channel-targeting insecticides by examining the conservation of key coordinating residues revealed by the structures. The possible resistance mechanisms are proposed based on the locations of the identified resistance mutations on the 3D structures of the target channels and their impacts on the binding of insecticides. Finally, we discuss how to develop “green” insecticides with a novel mode of action based on these high-resolution structures to overcome the resistance.

With the ever-evolving cannabis industry, low-cost and high-throughput analytical methods for cannabinoids are urgently needed. Normally, (potentially) psychoactive cannabinoids, typically represented by Δ9-tetrahydrocannabinol (Δ9-THC), and nonpsychoactive cannabinoids with therapeutic benefits, typically represented by cannabidiol (CBD), are the target analytes. Structurally, the former (tetrahydrocannabinolic acid (THCA), cannabinol (CBN), and THC) have one olefinic double bond and the latter (cannabidiolic acid (CBDA), cannabigerol (CBG), and CBD) have two, which results in different affinities toward Ag(I) ions. Thus, a silica gel thin-layer chromatography (TLC) plate with the lower third impregnated with Ag(I) ions enabled within minutes a digital chromatographic separation of strongly retained CBD analogues and poorly retained THC analogues. The resolution (Rs) between the closest two spots from the two groups was 4.7, which is almost 8 times higher than the resolution on unmodified TLC. After applying Fast Blue BB as a chromogenic reagent, smartphone-based color analysis enabled semiquantification of the total percentage of THC analogues (with a limit of detection (LOD) of 11 ng for THC, 54 ng for CBN, and 50 ng for THCA when the loaded volume is 1.0 μL). The method was validated by analyzing mixed cannabis extracts and cannabis extracts. The results correlated with those of high-performance liquid chromatography with ultraviolet detection (HPLC-UV) (R2 = 0.97), but the TLC approach had the advantages of multi-minute analysis time, high throughput, low solvent consumption, portability, and ease of interpretation. In a desiccator, Ag(I)-TLC plates can be stored for at least 3 months. Therefore, this method would allow rapid distinction between high and low THC varieties of cannabis, with the potential for on-site applicability.

The ryanodine receptor (RyR) is one of the primary targets of commercial insecticides. The diamide insecticide family, including flubendiamide, chlorantraniliprole, cyantraniliprole, etc., targets insect RyRs and can be used to control a wide range of destructive agricultural pests. The diamide insecticides are highly selective against lepidopteran and coleopteran pests with relatively low toxicity for non-target species, such as mammals, fishes, and beneficial insects. However, recently mutations identified on insect RyRs have emerged and caused resistance in several major agricultural pests throughout different continents. This review paper summarizes the recent findings on the structure and function of insect RyRs as insecticide targets. Specifically, we examine the structures of RyRs from target and non-target species, which reveals the molecular basis for insecticide action and selectivity. We also examine the structural and functional changes of RyR caused by the resistance mutations. Finally, we examine the progress in RyR structure-based insecticide design and discuss how this might help the development of a new generation of green insecticides.

This work presents a novel route for creating metal-free antiviral coatings based on polymer brushes synthesized by surface-initiated photoinduced electron transfer-reversible addition-fragmentation chain transfer (SI-PET-RAFT) polymerization, applying eosin Y as a photocatalyst, water as a solvent, and visible light as a driving force. The polymer brushes were synthesized using N-[3-(decyldimethyl)-aminopropyl] methacrylamide bromide and carboxybetaine methacrylamide monomers. The chemical composition, thickness, roughness, and wettability of the resulting polymer brush coatings were characterized by X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), water contact angle measurements, and ellipsometry. The antiviral properties of coatings were investigated by exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and avian influenza viruses, with further measurement of residual viable viral particles. The best performance was obtained with Cu surfaces, with a ca. 20-fold reduction of SARS-Cov-2 and a 50-fold reduction in avian influenza. On the polymer brush-modified surfaces, the number of viable virus particles decreased by about 5-6 times faster for avian flu and about 2-3 times faster for SARS-CoV-2, all compared to unmodified silicon surfaces. Interestingly, no significant differences were obtained between quaternary ammonium brushes and zwitterionic brushes.

The efficient development of functional and sustainable polymers not only requires rapid formation under mild conditions but also a high degree of control over the polymer structure, as well as gentle degradation routes that do not diminish their function. A significant step forward was set by the groups of Wu and Sharpless, as outlined in ACS Central Science, in which they use sulfur exchange click chemistry to access polymers via a chain-growth mechanism and pave the way toward mild degradation and application as degradable gels.

The products of the SuFEx reaction between sulfonimidoyl fluorides and phenols, sulfonimidates, are shown to display dynamic covalent chemistry with other phenols. This reaction was shown to be enantiospecific, finished in minutes at room temperature in high yields, and useful for both asymmetric synthesis and sustainable polymer production. Its wide scope further extends the usefulness of SuFEx and related click chemistries.

Click chemistry has been established rapidly as one of the most valuable methods for the chemical transformation of complex molecules. Due to the rapid rates, clean conversions to the products, and compatibility of the reagents and reaction conditions even in complex settings, it has found applications in many molecule-oriented disciplines. From the vast landscape of click reactions, approaches have emerged in the past decade centered around oxidative processes to generate in situ highly reactive synthons from dormant functionalities. These approaches have led to some of the fastest click reactions know to date. Here, we review the various methods that can be used for such oxidation-induced “one-pot” click chemistry for the transformation of small molecules, materials, and biomolecules. A comprehensive overview is provided of oxidation conditions that induce a click reaction, and oxidation conditions are orthogonal to other click reactions so that sequential “click-oxidation-click” derivatization of molecules can be performed in one pot. Our review of the relevant literature shows that this strategy is emerging as a powerful approach for the preparation of high-performance materials and the generation of complex biomolecules. As such, we expect that oxidation-induced “one-pot” click chemistry will widen in scope substantially in the forthcoming years.

The global rise of antimicrobial resistance (AMR) that increasingly invalidates conventional antibiotics has become a huge threat to human health. Although nanosized antibacterial agents have been extensively explored, they cannot sufficiently discriminate between microbes and mammals, which necessitates the exploration of other antibiotic-like candidates for clinical uses. Herein, two-dimensional boron nitride (BN) nanosheets are reported to exhibit antibiotic-like activity to AMR bacteria. Interestingly, BN nanosheets had AMR-independent antibacterial activity without triggering secondary resistance in long-term use and displayed excellent biocompatibility in mammals. They could target key surface proteins (e.g., FtsP, EnvC, TolB) in cell division, resulting in impairment of Z-ring constriction for inhibition of bacteria growth. Notably, BN nanosheets had potent antibacterial effects in a lung infection model by P. aeruginosa (AMR), displaying a 2-fold increment of survival rate. Overall, these results suggested that BN nanosheets could be a promising nano-antibiotic to combat resistant bacteria and prevent AMR evolution.

Herein, we describe the selective positioning of metal-organic framework (MOF) nanoparticles UiO-66 (Universitet i Oslo; Zr6O4(OH)4(bdc)6; bdc2- = benzene-1,4-dicarboxylate) and MIL-101 (Matérial Institut Lavoisier, Cr3O(OH) (H2O)2(bdc)3) at defined positions on a patterned substrate. For this purpose, patterned alkyne- and carboxylic acid-terminated self-assembled organic monolayer (SAM)-modified silicon surfaces were prepared by liquid immersion and microcontact printing (μCP). Preformed UiO-66 and MIL-101 nanometer-sized MOFs (NMOFs) were synthesized by solvothermal synthesis, and the nanocrystallite particles' exterior surface was functionalized in order to generate reactive sites (such as azides and amines) at the NMOFs. Copper-catalyzed alkyne azide cycloaddition and N-hydroxysuccinimide-mediated amide formation were used to selectively position the NMOFs at the surface of pre-patterned substrates. The resulting surfaces were thoroughly investigated by scanning electron microscopy, infrared spectroscopy, and X-ray photoelectron spectroscopy, confirming the validity of the presented approach. We hope that our research paves the way for microsystem integration of NMOFs, for example, in microfluidic devices/reactors, and further investigation of their enhanced catalytic activity.

In this work, we demonstrate that fine-grained, quantitative control over macroscopic dynamic material properties can be achieved using the Hammett equation in tuneable dynamic covalent polyimine materials. Via this established physical-organic principle, operating on the molecular level, one can fine-tune and control the dynamic material properties on the macroscopic level, by systematic variation of dynamic covalent bond dynamics through selection of the appropriate substituent of the aromatic imine building blocks. Five tuneable, crosslinked polyimine network materials, derived from dianiline monomers with varying Hammett parameter (σ) were studied by rheology, revealing a distinct correlation between the σ value and a range of corresponding dynamic material properties. Firstly, the linear correlation of the kinetic activation energy (Ea) for the imine exchange to the σ value, enabled us to tune the Ea from 16 to 85 kJ mol−1. Furthermore, the creep behaviour (γ), glass transition (Tg) and the topology freezing transition temperature (Tv), all showed a strong, often linear, dependence on the σ value of the dianiline monomer. These combined results demonstrate for the first time how dynamic material properties can be directly tuned and designed in a quantitative – and therefore predictable – manner through correlations based on the Hammett equation. Moreover, the polyimine materials were found to be strong elastic rubbers (G′ > 1 MPa at room temperature) that were stable up to 300 °C, as confirmed by TGA. Lastly, the dynamic nature of the imine bond enabled not only recycling, but also intrinsic self-healing of the materials over multiple cycles without the need for solvent, catalysts or addition of external chemicals., Controlling macroscopic material properties of dynamic covalent polyimines via the electronic effect of dianiline monomers based on the Hammett equation.

To investigate the dynamic stereochemical inversion behavior of pillar[5]arenes (P[5]s) in more detail, we synthesized a series of novel rim-differentiated P[5]s with various substituents and examined their rapid rotations by variable-temperature NMR (203–298 K). These studies revealed for the first time the barrier of “methyl-through-the-annulus” rotation (ΔG‡ = 47.4 kJ·mol–1 in acetone) and indicated that for rim-differentiated P[5]s with two types of alkyl substituents, the smaller rim typically determines the rate of rotation. However, substituents with terminal C=C or C≡C bonds give rise to lower inversion barriers, presumably as a result of attractive π–π interactions in the transition state. Finally, data on a rim-differentiated penta-methyl-penta-propargyl P[5] exhibited the complexity of the overall inversion dynamics.

This work presents a new method for the synthesis of antifouling polymer brushes using surface-initiated photoinduced electron transfer-reversible addition-fragmentation chain-transfer polymerization with eosin Y and triethanolamine as catalysts. This method proceeds in an aqueous environment under atmospheric conditions without any prior degassing and without the use of heavy metal catalysts. The versatility of the method is shown by using three chemically different monomers: oligo(ethylene glycol) methacrylate, N-(2-hydroxypropyl)methacrylamide, and carboxybetaine methacrylamide. In addition, the light-triggered nature of the polymerization allows the creation of complex three-dimensional structures. The composition and topological structuring of the brushes are confirmed by X-ray photoelectron spectroscopy and atomic force microscopy. The kinetics of the polymerizations are followed by measuring the layer thickness with ellipsometry. The polymer brushes demonstrate excellent antifouling properties when exposed to single-protein solutions and complex biological matrices such as diluted bovine serum. This method thus presents a new simple approach for the manufacturing of antifouling coatings for biomedical and biotechnological applications.

The realization of covalent adaptable networks with excellent mechanical and dynamic properties remains a major challenge. Herein, the acylsemicarbazide (ASC) moieties with dynamic reversibility and multiple hydrogen bonding were disclosed and used to prepare transparent, high modulus, and malleable polymer networks. It was found that the ASC moiety can reversibly generate isocyanate and hydrazide at elevated temperatures, that is, exhibiting dynamic reversibility. ASC can also produce the disordered multiple hydrogen bonds that contribute to superior mechanical strength for dynamic polymers. The hydrogen bonding in ASC moieties can diminish the energy barrier for the cleavage of dynamic covalent bonds, and the dissociation of ASC moieties further promotes the disruption of hydrogen bonds, showing the synergistic dynamic effects. ASC moieties provide a valuable molecular engineering opportunity toward high-performance dynamic polymer materials. The polymer containing ASC moieties possesses excellent optical transparency, superb mechanical performance (Young's modulus up to 1.7 GPa), together with malleable and healing properties.

Silicon nanoparticles (Si NPs) are a good alternative to conventional heavy metal-containing quantum dots in many applications, due to their low toxicity, low cost, and the high natural abundance of the starting material. Recently, much synthetic progress has been made, and crystalline Si NPs can now be prepared in a matter of hours. However, the passivation of these particles is still a time-consuming and difficult process, usually requiring high temperatures and/or harsh reaction conditions. In this paper, we report an easy method for the room-temperature functionalization of hydrogen-terminated Si NPs. Using silanol compounds, a range of functionalized Si NPs could be produced in only 1 h reaction time at room temperature. The coated NPs were fully characterized to determine the efficiency of binding and the effects of coating on the optical properties of the NPs. It was found that Si NPs were effectively functionalized, and that coated NPs could be extracted from the reaction mixture in a straightforward manner. The silanol coating increases the quantum yield of fluorescence, decreases the spectral width and causes a small (∼50 nm) blue-shift in both the excitation and emission spectra of the Si NPs, compared to unfunctionalized particles.

Novel methods to make synthetic chiral polymers are highly desirable given their potential in a rapidly increasing number of bio-inspired applications. The enantiospecific sulfur–fluorine exchange (SuFEx) reaction of chiral di-sulfonimidoyl fluorides (di-SFs) with diphenols, was used to produce high-molecular-weight chiral polymers with configurational backbone chirality. The resulting new class of polymers, polysulfonimidates, can be efficiently produced via this step-growth mechanism for a wide range of di-SFs and diphenols, yielding MnPS up to 283 kDa with a typical dispersity Đ around 1.6. The optical activity of the resulting chiral polymers is largely due to the intrinsic asymmetry of the S atoms (configurational chirality). Finally, the enantiospecificity (ee>98 %) of the polymerization reaction was demonstrated by the degradation of a disulfide-containing polysulfonimidate. This novel route towards configurational main-chain chirality opens up new approaches towards tailor-made chiral polymers with precisely defined properties.

Vektorielle Katalyse – die Steuerung von mehrstufigen Reaktionen in einer programmierten Abfolge und durch definierte räumliche Lokalisierung in einem mikroskaligen Reaktor – ist ein grundlegendes Ziel in der bioinspirierten Katalyseforschung. Die Übertragung von Konzepten aus der natürlichen Kaskaden-Biokatalyse zu künstlichen hierarchischen chemischen Systeme bleibt jedoch eine Herausforderung. Hier zeigen wir die Integration von zwei verschiedenen oberflächenverankerten, nanometergroßen metallorganischen Gerüsten (MOFs) in einem mikrofluidischen Reaktor zur Modellierung der vektoriellen Katalyse. Die Katalysatoren wurden an definierten Abschnitten entlang des Mikrokanals immobilisiert, dies ermöglichte eine zweistufige Kaskadenreaktion mit vollständiger Umsetzung nach 30 Sekunden und hohen Umsatzfrequenzen (TOF≈105 h−1).

A “rim-differentiated” pillar[6]arene (RD-P[6]) was obtained successfully, with the assistance of a dimeric silver trifluoroacetate template, among eight different constitutional isomers in a direct and regioselective manner. The solid-state conformation of this macrocycle could switch from the 1,3,5-alternate to a truly rim-differentiated one upon guest inclusion. This highly symmetric RD-P[6] not only hosts metal-containing molecules inside its cavity, but also can form a pillar[6]arene-C60 adduct through co-crystallization on account of donor-acceptor interactions. The development of synthetic strategies to desymmetrize pillararenes offers new opportunities for engineering complex molecular architectures and organic electronic materials.

Linear-bottlebrush-linear (LBBL) triblock copolymers are emerging systems for topologically-tunable elastic materials. In this paper, a new synthetic methodology is presented to synthesize LBBL polystyrene-block-bottlebrushpolydimethylsiloxane-block-polystyrene (PS-b-bbPDMS-b-PS) triblock copolymer via the “grafting onto” approach where the precursors are individually synthesized through living anionic polymerization and selective coupling reaction. In this two-step approach, polystyrene-block-polymethylvinylsiloxane (PS-b-PMVS) diblock copolymer with a low dispersity couples with another living PS block to form PS-b-PMVS-b-PS triblock copolymer. Secondly, this is followed by grafting of separately prepared monohydride-terminated PDMS chains with controllable grafting density through a hydrosilylation reaction. In addition to fully tunable architectural parameters, this approach permits a quantitative determination of the ratio of diblock and triblock bottlebrush copolymers and consistency between batches, highlighting the feasibility for scaled-up production. These LBBL triblock copolymers self-assemble into soft, low-modulus thermoplastic elastomers, and the precise knowledge of the composition is crucial for correlating microstructure to mechanical properties.

The analysis of catecholamines, such as dopamine, epinephrine and norepinephrine in urine can be used in the diagnosis of certain pathologies, such as hormone-producing tumors. Here, a fast and simple quantitative boronate affinity paper spray tandem mass spectrometric (PS-MS/MS) method is established, which can improve selectivity and reduce ion suppression without needing any instrumental chromatography. We use here the property of boronic acids, which can selectively bind ortho-diol-containing compounds under alkaline conditions. Paper tip modification and catechol enrichment protocols were developed to selectively bind, clean up and subsequently desorb such catecholamines. Standard catecholamine solutions, as well as human urine samples were analyzed with the PS-MS(/MS) method, which is fast, cheap and easy-to-operate compared to HPLC-MS/MS. Despite its high simplicity, boronate affinity PS-MS/MS exhibits good performance compared to HPLC-MS/MS in human urine analysis in terms of precision (2.1%–7.2% vs. 1.1%–2.9%) and accuracy (−10.2%–9.3% vs. −4.8%–5.1%), and a physiologically relevant limit of detection (0.027–0.12 μg mL−1). The boronate affinity PS-MS/MS clearly achieved the detection limits that would allow the fast analysis of urine samples for clinical purposes, such as screening for pheochromocytoma (exceeding 0.5 μg mL−1).

A common method to study protein complexes is immunoprecipitation (IP), followed by mass spectrometry (thus labeled: IP-MS). IP-MS has been shown to be a powerful tool to identify protein-protein interactions. It is, however, often challenging to discriminate true protein interactors from contaminating ones. Here, we describe the preparation of antifouling azide-functionalized polymer-coated beads that can be equipped with an antibody of choice via click chemistry. We show the preparation of generic immunoprecipitation beads that target the green fluorescent protein (GFP) and show how they can be used in IP-MS experiments targeting two different GFP-fusion proteins. Our antifouling beads were able to efficiently identify relevant protein-protein interactions but with a strong reduction in unwanted nonspecific protein binding compared to commercial anti-GFP beads.

The structures of hierarchically assembled supramolecular architectures are dictated characteristically by the encoded symmetries and geometries of the corresponding building blocks. In literature, assorted Platonic molecular polyhedra have been built out of highly symmetric macrocycles. Nonetheless, the synthesis of pillararene-based molecular cages remains challenging owing to the underlying shape and limited derivatization strategies of this macrocyclic scaffold. Herein, we report the assembly of AgnL2 metal-organic pillars from rim-differentiated pillar[5]arene-derived ligands, Lm and Lp, through [N···Ag+···N] coordinative bonds. These stereolabile macrocycles undergo chiral self-sorting during complexation. Although the meta-substituted Lm forms diastereoisomeric Ag5Lm2 complexes without stereocontrol in solution, only a meso-Ag4Lm2 complex with a Ag4 kernel was observed in the solid state. In contrast, the narcissistic coassembly of the para-substituted Lp with AgPF6 results in enantiomeric Ag5Lp2 complexes resembling twisted pentagonal prisms. This research paves the way for the construction of deep-cavity metallocavitands and nanochannels with unique molecular recognition and transportation properties.

We studied the mechanistic and biological origins of anti-inflammatory poly-unsaturated fatty acid-derived N-acylethanolamines using synthetic bifunctional chemical probes of docosahexaenoyl ethanolamide (DHEA) and arachidonoyl ethanolamide (AEA) in RAW264.7 macrophages stimulated with 1.0 μg mL-1lipopolysaccharide. Using a photoreactive diazirine, probes were covalently attached to their target proteins, which were further studied by introducing a fluorescent probe or biotin-based affinity purification. Fluorescence confocal microscopy showed DHEA and AEA probes localized in cytosol, specifically in structures that point toward the endoplasmic reticulum and in membrane vesicles. Affinity purification followed by proteomic analysis revealed peroxiredoxin-1 (Prdx1) as the most significant binding interactor of both DHEA and AEA probes. In addition, Prdx4, endosomal related proteins, small GTPase signaling proteins, and prostaglandin synthase 2 (Ptgs2, also known as cyclooxygenase 2 or COX-2) were identified. Lastly, confocal fluorescence microscopy revealed the colocalization of Ptgs2 and Rac1 with DHEA and AEA probes. These data identified new molecular targets suggesting that DHEA and AEA may be involved in reactive oxidation species regulation, cell migration, cytoskeletal remodeling, and endosomal trafficking and support endocytosis as an uptake mechanism.

Commonly, modification of surfaces with thermoresponsive polymers is performed using poly(N-isopropylacrylamide) (poly(NIPAM)). However, integration of poly(NIPAM) with a second polymer to obtain more complex copolymer structures has proven challenging due to inherently poorly controllable polymerization characteristics of acrylamides. In this study, (N-(2-methacryloyloxyethyl)pyrrolidone (NMEP) is synthesized and polymerized under controlled conditions from silicon oxide substrates via surface-initiated atom transfer radical polymerization (SI-ATRP) to produce thermoresponsive poly(NMEP) brushes. The livingness of the brushes is demonstrated by reinitiation of poly(NMEP) brushes using oligo(ethylene glycol) methyl ether methacrylate to obtain diblock copolymer brushes. Following extensive characterization, the reversible thermoresponsive behavior of these poly(NMEP) brushes is demonstrated using phase-controlled AFM topography measurements in an aqueous liquid environment. These measurements indicate that at 27 °C the poly(NMEP) brushes are solvated and extend away from the surface, whereas at 60 °C the polymers are insoluble and reside in a collapsed conformation. Finally, to investigate the potential applicability of poly(NMEP) brushes in biomedical devices, the antifouling properties of the coating are tested in aqueous media containing BSA, fibrinogen, or 10% diluted human serum using quartz crystal microbalance with dissipation monitoring (QCM-D). These measurements reveal very good antifouling properties, even when exposed to 10% diluted human serum.

In this work, we tuned the ion selectivity of a polyelectrolyte multilayer (PEM)-coated, cation-exchange membrane (CMX) in a membrane capacitive deionization (MCDI) process by carefully studying different operational modes, namely constant voltage (CV) and constant current (CC). The monovalent cation selectivity and its time-dependent behavior were monitored at different voltage and current values. Upon optimizing the current density (10 A/m2) and the number of polyelectrolyte bilayers (5.5) on the CMX membranes, a time-independent and nearly full monovalent cation selectivity was obtained for various feed solutions, provided a polycation-terminated PEM was applied. Furthermore, the selectivity values of several commercially available cation-exchange membranes were tested under the optimized conditions and compared with CMX and PEM-CMX, yielding the best performance for PEM-CMX, regardless the composition of feed solution. Before this optimization, this MCDI system showed a time-dependent selectivity, with a maximum of ρMgNa ≈3. The results were rationalized by applying an MCDI model based on the dynamic potential profile, describing the potential drops across the membrane and demonstrating a threshold for the current density.

Vectorial Catalysis - controlling multi-step reactions in a programmed sequence and by defined spatial localization in a microscale device - is an enticing goal in bio-inspired catalysis research. However, translating concepts from natural cascade biocatalysis into artificial hierarchical chemical systems remains a challenge. Herein, we demonstrate integration of two different surface-anchored nanometer-sized metal-organic frameworks (MOFs) in a microfluidic device for modelling vectorial catalysis. Catalysts immobilization at defined sections along the microchannel and a two-step cascade reaction was conducted with full conversion after 30 seconds and high turnover frequencies (TOF = ~10 5 h -1 ).

In this study, the build-up of polyelectrolyte multilayers (PEMs) containing 15-crown-5 (CE) groups and their interactions with various cations were studied by using quartz crystal microbalance with dissipation monitoring (QCM-D). First, poly(allylamine hydrochloride) (PAH) was modified with 4’-carboxybenzo-CE via carbodiimide chemistry. CE was chosen as its complexes with Na+ and K+ are reported to be more stable compared to those with other cations. The resulting functionalized polyelectrolyte (PAHCE) and poly(4-styrene sulfonic acid) (PSS) were used in the layer-by-layer build-up of a multilayer onto gold-coated quartz resonators, enabling their characterization with QCM-D. Compared to (PAH/PSS)4, (PAHCE/PSS)4 resulted in slightly thicker layers based on Voigt (65 ± 5 vs. 57 ± 3 nm) and Sauerbrey (45 ± 2 vs. 38 ± 3 nm) modelling of the QCM-D data. The same trend was found for the optical, dry thickness, as obtained with ellipsometry (15 ± 0.3 vs. 13 ± 1 nm). Next, the QCM-D characteristics of these PEMs were monitored in situ when exposed to various aqueous salt solutions (LiCl, NaCl, KCl, CsCl, RbCl, and MgCl2). Starting from Cs+, the frequency change of the (PAHCE/PSS)4 system upon changing to K+ and Na+ solutions was found to be ≈ 3 times larger than for (PAH/PSS)4. With a polycation (PAHCE) as the outermost PEM layer, the salt-exchange behavior was less visible due to increased charge rejection of cations. Therefore, we also modified a bio-based polyanion, pectin with 4’-aminobenzo-CE and built (PAH/pectinCE)4. Also in this case, the addition of CE increased the PEM layer thickness compared to (PAH/pectin)4, both in a wet state (Sauerbrey modelling, 447 ± 19 vs. 314 ± 17 nm) and when dry (115 ± 4 vs. 66 ± 3 nm). Again, we observed the largest QCM-D responses for K+ and Na+ solutions (≈ 6 and 12 times larger, respectively) compared to (PAH/pectin)4. The effect of CE is more prominent in pectin-based PEMs due their relatively higher thickness. Given the large toolbox of available polyelectrolytes and ionophores, we anticipate that functionalized PEMs can facilitate the further development of ion separation applications.

Surface modifications using responsive polymers give access to biomedical applications that rely on switchable properties, such as smart sensors and actuator systems. In this work, thermoresponsive polymer coatings are synthesized on silicon oxide surfaces using a facile and effective two-step grafting-to strategy. Briefly, the substrates are first functionalized with a poly(dopamine) (poly(DA)) primer layer. Subsequently, block copolymers of poly(glycidyl methacrylate) and poly(N-isopropylacrylamide) (poly(GMA)20-block-poly(NIPAM)n (n = 263, 528 and 705)) synthesized via reversible addition‑fragmentation chain‑transfer (RAFT) polymerization, are grafted to the poly(DA)-modified surfaces. Characterization using ellipsometry, X-ray photoelectron spectroscopy (XPS) and contact angle measurements confirmed polymer attachment with appreciable grafting densities. Quartz crystal microbalance with dissipation monitoring (QCM-D) is employed to investigate the thermoresponsive properties and degree of hydration of the polymers below and above their lower critical solution temperature (LCST). The longer the polymer chain, the more water is lost per repeating unit upon increasing the temperature above the LCST. The surfaces are exposed to diluted and undiluted human serum at 20 °C and 40 °C to demonstrate for all three polymer brushes switchable protein adsorption-repellence. In a broader perspective, this study presents a straightforward, robust and efficient procedure to modify virtually any surface type with a thermoresponsive coating.

Cyclooxygenase 2 (COX-2) plays a key role in the regulation of inflammation by catalyzing the oxygenation of PUFAs to prostaglandins (PGs) and hydroperoxides. Next to this, COX-2 can metabolize neutral lipids, including endocannabinoid-like esters and amides. We developed an LC-HRMS-based human recombinant (h)COX-2 screening assay to examine its ability to also convert n-3 PUFA-derived N-acylethanolamines. Our assay yields known hCOX-2-derived products from established PUFAs and anandamide. Subsequently, we proved that eicosapentaenoylethanolamide (EPEA), the N-acylethanolamine derivative of EPA, is converted into PGE3-ethanolamide (PGE3-EA), and into 11-, 14-, and 18-hydroxyeicosapentaenoyl-EA (11-, 14-, and 18-HEPE-EA, respectively). Interestingly, we demonstrated that docosahexaenoylethanolamide (DHEA) is converted by hCOX-2 into the previously unknown metabolites, 13- and 16-hydroxy-DHEA (13- and 16-HDHEA, respectively). These products were also produced by lipopolysaccharide-stimulated RAW267.4 macrophages incubated with DHEA. No oxygenated DHEA metabolites were detected when the selective COX-2 inhibitor, celecoxib, was added to the cells, further underlining the role of COX-2 in the formation of the novel hydroxylated products. This work demonstrates for the first time that DHEA and EPEA are converted by COX-2 into previously unknown hydroxylated metabolites and invites future studies toward the biological effects of these metabolites.

Pillar[5]arenes, a type of novel macrocycles containing di-substituted hydroquinone units linked by methylene bridges in para-positions, have attracted extensive attention in supramolecular chemistry as interesting candidates to be used in the preparation of host-guest complexes. Functionalization by means of rim substitution and sustaining an ordered substituent arrangement on both sides of the rim is important for the development of new pillararene-based materials. In order to achieve this, the rim inversion process of rotating the hydroquinone units through the pillar[5]arenes has to be controlled. In this context we have studied the effect of different types of hydroquinone substituents on the rotational energy profile using density functional theory combined with the hybrid M06-2X functional. The influence of polar ([sbnd]CH2F, [sbnd]CH2Cl, [sbnd]CH2OH, [sbnd]CH2SH, [sbnd]CH2NH2) and nonpolar alkyl ([sbnd]CH3, [sbnd]CH2CH3, [sbnd]CH2CH2CH3, [sbnd]CH(CH3)2 and [sbnd]CH2CH2CH2CH3) substituents on the on the energy barriers of the rotation mechanism, and different local minima was investigated. The stabilization of the intermediate structures by non-covalent van der Waals and interactions and also by hydrogen bonds constitute a major factor affecting barrier heights. In case of polar substituents, the largest barriers were found for [sbnd]CH2OH and [sbnd]CH3 substitutions and the lowest ones for [sbnd]CH2SH and [sbnd]CH2NH2. For the alkyl series, the barrier decreased significantly up to propyl due to increasing stabilizing dispersion interactions while it increased again for n-butyl since the chain did not fit in well the cavity to rotate through.

[Image: see text] The development of an efficient synthetic route toward rim-differentiated C(5)-symmetric pillar[5]arenes (P[5]s), whose two rims are decorated with different chemical functionalities, opens up successive transformations of this macrocyclic scaffold. This paper describes a gram-scale synthesis of a C(5)-symmetric penta-hydroxy P[5] precursor, and a range of highly efficient reactions that allow functionalizing either rim at will via, e.g., sulfur(VI) fluoride exchange (SuFEx) reactions, esterifications, or Suzuki–Miyaura coupling. Afterward, BBr(3) demethylation activates another rim for similar functionalizations.

Dendrimers are interesting candidates for various applications because of the high level of control over their architecture, the presence of internal cavities, and the possibility for multivalent interactions. More specifically, zwitterionic dendrimers modified with an equal number of oppositely charged groups have found use in in vivo biomedical applications. However, the design and control over the synthesis of these dendrimers remains challenging, in particular with respect to achieving full modification of the dendrimer. In this work, we show the design and subsequent synthesis of dendrimers that are highly charged while having zero net charge, that is zwitterionic dendrimers that are potential candidates for biomedical applications. First, we designed and fully optimized the synthesis of charge-neutral carboxybetaine and sulfobetaine zwitterionic dendrimers. Following their synthesis, the various zwitterionic dendrimers were extensively characterized. In this study, we also report for the first time the use of X-ray photoelectron spectroscopy as an easy-to-use and quantitative tool for the compositional analysis of this type of macromolecules that can complement techniques such as nuclear magnetic resonance and gel permeation chromatography. Finally, we designed and synthesized zwitterionic dendrimers that contain a variable number of alkyne and azide groups that allow straightforward (bio)functionalization via click chemistry.

Self-healing polymer materials have drawn rapidly increasing interest over the last decade, and have been studied and used in an ever-increasing range of applications. Herein, we successfully make the covalent urea bond – a pinnacle of stability due to strong resonance effects – dynamic in nature through mediation of zinc salts. The dynamic covalent character of urea in the presence of zinc ions is confirmed through dissociation reaction experiments and quantum chemical calculations of small-molecule model urea compounds. In line with our experiments, the modelling results suggest that the presence of zinc ions speeds up the reaction of urea dissociation by two orders of magnitude via the formation of O-bound Zn complexes. Based on such dynamic covalent urea bonds, we then develop a novel class of self-healing polymer materials with excellent healing efficiencies. Different kinds of self-healing and reprocessable polyurea materials were prepared, with polymer properties that can be easily tuned by varying the degree of crosslinking and the molecular weight of the siloxane precursor. Since different kinds of self-healing polyurea materials could easily be prepared due to the commercial availability of a very wide range of amine and isocyanate monomers, this introduction of self-healing properties is expected to have significant potential in a range of applications, such as coatings, paints, and 3D printing. In addition, this introduces polyureas and other urea-containing polymers as a class of highly stable, yet easily reprocessable plastics, which is highly relevant given the globally desired more sustainable use of plastics.

This Feature Article focuses on recent advances in the bioconjugation of surface-bound zwitterionic polymers for biospecific antifouling surfaces. Various approaches for the functionalization of antifouling zwitterionic polymers are systematically investigated, such as chain-end and side-chain functionalization. Side-chain functionalization methods can be further classified as those that are achieved through homopolymerization of custom-synthesized zwitterionic monomers equipped with reactive groups, or those that are achieved via synthesis of random or block copolymers combining different monomers with antifouling functionality and others with reactive groups. Several of the pros and cons of these approaches are outlined and discussed. Finally, some perspective and future directions of research are presented toward long-term stable, generically repelling surfaces that strongly and specifically adhere to a single component in a complex mixture.

During electrophoretic deposition of graphene oxide (GO) sheets on silicon substrates, not only deposition but also simultaneous anodic oxidation of the silicon substrate takes place, leading to a three-layered material. Scanning electron microscopy images reveal the presence of GO sheets on the silicon substrate, and this is also confirmed by X-ray photoelectron spectroscopy (XPS), albeit that the carbon portion increases with increasing emission angle, hinting at a thin carbon layer. With increasing applied potential and increasing conductivity of the GO solution, the carbon signal decreases, whereas the overall thickness of the added layer formed on top of the silicon substrate increases. Through XPS spectra in which the Si 2p peaks shifted under those conditions to 103–104 eV, we were able to conclude that significant amounts of oxygen are present, indicative of the formation of an oxide layer. This leads us to conclude that GO can be deposited using electrophoretic deposition, but that at the same time, silicon is oxidized, which may overshadow effects previously assigned to GO deposition. Published version

Tumor-derived extracellular vesicles (tdEVs) are promising blood biomarkers for cancer disease management. However, blood is a highly complex fluid that contains multiple objects in the same size range as tdEVs (30 nm-1 mu m), which obscures an unimpeded analysis of tdEVs. Here, we report a multi-modal analysis platform for the specific capture of tdEVs on antibody-functionalized stainless steel substrates, followed by their analysis using SEM, Raman spectroscopy and AFM, at the single EV level in terms of size and size distribution, and chemical fingerprint. After covalent attachment of anti-EpCAM (epithelial cell adhesion molecule) antibodies on stainless steel substrates, EV samples derived from a prostate cancer cell line (LnCAP) were flushed into a microfluidic device assembled with this stainless steel substrate for capture. To track the captured objects between the different analytical instruments and subsequent correlative analysis, navigation markers were fabricated onto the substrate from a cyanoacrylate glue. Specific capture of tdEVs on the antibody-functionalized surface was demonstrated using SEM, AFM and Raman imaging, with excellent correlation between the data acquired by the individual techniques. The particle distribution was visualized with SEM. Furthermore, a characteristic lipid-protein band at 2850-2950 cm(-1) was observed with Raman spectroscopy, and with AFM the size distribution and surface density of the captured EVs was assessed. Finally, correlation of SEM and Raman images enabled discrimination of tdEVs from cyanoacrylate glue particles, highlighting the capability of this multi-modal analysis platform for distinguishing tdEVs from contamination. The trans-instrumental compatibility of the stainless steel substrate and the possibility to spatially correlate the images of the different modalities with the help of the navigation markers open new avenues to a wide spectrum of combinations of different analytical and imaging techniques for the study of more complex EV samples.

Lignin is a highly abundant aromatic polymer in nature, but its controlled cleavage or cross-linking is a major challenge and currently hindering industrial applicability. Laccase (L) and laccase/mediator systems (LMS) are promising tools for enzymatic lignin modification, but to date, their overall reaction outcome is hard to predict and control. This research aimed to understand the reactivity of native and sulfonated β-O-4 linked lignin structures in L and LMS treatments. Trametes versicolor laccase, and the mediator hydroxybenzotriazole (HBT) were used, and reaction products were analyzed using UHPLC-MS n and MALDI-TOF-MS. Polymerization was observed for both the native and sulfonated phenolic compounds, suggesting that sulfonation does not affect radical coupling of the phenolic lignin subunits. In contrast, sulfonation of the non-phenolic lignin structure prevented C α oxidation and cleavage by L/HBT, which was explained by an increased C α -H bond dissociation energy of ∼10 kcal mol -1 upon sulfonation. Overall, our results indicate that lignin sulfonation drives the overall outcome of LMS incubations towards polymerization.

Correction to: Communications Biology https://doi.org/10.1038/s42003-021-02155-5, published online 9 June 2021. The original version of this Article contained an error in the spelling of the author Han Zuilhof, which was incorrectly given as Han T. Zuilhof. This has now been corrected in both the PDF and HTML versions of the Article.

Recently, ice with stacking disorder structure, consisting of random sequences of cubic ice (Ic) and hexagonal ice (Ih) layers, was reported to be more stable than pure Ih/Ic. Due to a much lower free energy barrier of heterogeneous nucleation, in practice, the freezing process of water is controlled by heterogeneous nucleation triggered by an external medium. Therefore, we carry out molecular dynamic simulations to explore how ice polymorphism depends on the lattice structure of the crystalline substrates on which the ice is grown, focusing on the primary source of atmospheric aerosols, carbon materials. It turns out that, during the nucleation stage, the polymorph of ice nuclei is strongly affected by graphene substrates. For ice nucleation on graphene, we find Ih is the dominant polymorph. This can be attributed to structural similarities between graphene and basal face of Ih. Our results also suggest that the substrate only affects the polymorph of ice close to the graphene surface, with the preference for Ih diminishing as the ice layer grows.

Sulfur(vi) fluoride exchange (SuFEx) is a category of click chemistry that enables covalent linking of modular units through sulfur(vi) connective hubs. The efficiency of SuFEx and the stability of the resulting bonds have led to polymer chemistry applications. Now, we report the SuFEx click chemistry synthesis of several structurally diverse SOF4-derived copolymers based on the polymerization of bis(iminosulfur oxydifluorides) and bis(aryl silyl ethers). This polymer class presents two key characteristics. First, the [–N=S(=O)F–O–] polymer backbone linkages are themselves SuFExable and undergo precise SuFEx-based post-modification with phenols or amines to yield branched functional polymers. Second, studies of individual polymer chains of several of these new materials indicate helical polymer structures. The robust nature of SuFEx click chemistry offers the potential for post-polymerization modification, enabling the synthesis of materials with control over composition and conformation. Sulfur(vi) fluoride exchange (SuFEx)—a type of click chemistry that generates SVI-centred covalent linkages—has previously been used for polymer synthesis. Now, modular SuFEx polymerization using SOF4 has been used to generate helical polymers. Unlike previous examples of SuFEx polymerization, the backbone retains SVI–F motifs and therefore is able to undergo further SuFEx click reactions, enabling facile and efficient post-polymerization modification.

A highly substituent-dependent rearrangement allows for the novel and SOCl2-induced divergent synthesis of 3-methylthioquinolin-2-ones and 3-methylthiospiro[4.5]trienones through intramolecular electrophilic cyclization of N-aryl propyamides. DMSO acts as both solvent and sulfur source, and use of DMSO-h6/d6 enables the incorporation of SCH3 or SCD3 moieties to the 3-position of the heterocyclic framework. Different para-substituents trigger divergent reaction pathways leading to the formation of quinolin-2-ones for mild substituents and spiro[4,5]trienones for both electron-withdrawing and -donating substituents, respectively. On the basis of both computational and experimental results, a new mechanism has been put forward that accounts for the exclusive spirolization/defluorination process and the surprising substituent effects.

Selective removal of ions from water via capacitive deionization (CDI) is relevant for environmental and industrial applications like water purification, softening, and resource recovery. Prussian blue analogs (PBAs) are proposed as an electrode material for selectively removing cations from water, based on their size. So far, PBAs used in CDI are selective toward monovalent ions. Here, vanadium hexacyanoferrate (VHCF), a PBA, is introduced as a new electrode material in a hybrid CDI setup to selectively remove divalent cations from water. These electrodes prefer divalent Ca2+over monovalent Na+, with a separation factor, βCa/Na≈3.5. This finding contrasts with the observed monovalent ion selectivity by PBA electrodes. This opposite behavior is understood by density functional theory simulations. Furthermore, coating the VHCF electrodes with a conducting polymer (poly-pyrrole, doped with poly-styrenesulphonate) prevents the contamination of the treated water following the degradation of the electrode. This facile and modular coating method can be effortlessly extended to other PBA electrodes, limiting the extent of treated water contamination during repeated cycling. This study paves the way for tunable selectivity while extending the library of electrodes that can be successfully used in (selective) CDI.

Induced phase separation extraction (IPSE) is an efficient sample clean-up technique that can replace liquid-liquid extraction (LLE). The purpose of this study was to miniaturize IPSE by carrying it out in a microfluidic chip. An IPSE chip was designed and evaluated for its ability to separate and purify samples on a microscale. The 5 &times, 2 cm chip was fed with a solution of polar to non-polar model compounds in acetonitrile-water (1:1). In the 100 &micro, m wide and 40 &micro, m deep microchannels, the sample solution was efficiently separated into two immiscible phases by adding a hydrophobic solvent as inducer. Analytes present in the sample solution each migrated to their own favorable phase upon phase separation. After optimization, extraction and fractionation were easily and efficiently achieved. The behavior of analytes with a pH-dependent partitioning could be influenced by adjusting the pH of the sample solution. Scutellaria baicalensis extract, used in Traditional Chinese Medicine (TCM), was successfully separated in aglycones and glycosides. In this microscale system, the sample and solvent consumption is reduced to microliters, while the time needed for the sample pretreatment is less than one minute. Additionally, the extraction efficiency can reach up to 98.8%, and emulsion formation is avoided.

Organosilicon compounds are ubiquitous in everyday use. Application of some of these compounds in food, cosmetics and pharmaceuticals is widespread on the assumption that these materials are not systemically absorbed. Here the interactions of various organosilicon compounds (simeticone, hexamethyldisilazane and polydimethylsiloxane) with cell membranes and models thereof were characterized with a range of analytical techniques, demonstrating that these compounds were retained in or on the cell membrane. The increasing application of organosilicon compounds as replacement of other plastics calls for a better awareness and understanding of these interactions. Moreover, with many developments in biotechnology relying on organosilicon materials, it becomes important to scrutinize the potential effect that silicone leaching may have on biological systems., Beekman et al. investigate whether low molecular weight organosilicon compounds leaching out of commonly used biological laboratory materials and household items can interact with molecules found in cellular membranes. The results suggest this is a passive process by physicochemical forces rather than active uptake.

In this work, we show two different routes to synthesize polymer-dendrimer hybrids by the coupling of poly( l -lysine) and zwitterionic dendrimers (ZIDs). Poly( l -lysine) (PLL) is used because of its advantageous self-assembly properties onto silicon oxide by charged-based interactions between the lysine groups and the negatively charged surface, whilst the coupled ZIDs provide antifouling properties. The first route yields network-like structures in which PLL and ZIDs are crosslinked by multiple amide bonds. By using different ratios of PLL and ZID, we vary the size of the formed networks. A more defined, linear PLL-ZID macromolecule is formed via coupling of multiple ZIDs to PLL in a controlled way by a copper-catalyzed azide/alkyne cycloaddition (CuAAC) “click” reaction. Following synthesis and characterization of the two different types of PLL-ZID macromolecules, they are self-assembled on silicon oxide surfaces from aqueous solutions in a single step, to form thin, hydrophilic coatings. Their potential use as antifouling coatings is tested by fluorescence microscopy and quartz crystal microbalance (QCM) with foulants such a single proteins and diluted human serum. Finally, by performing an on-surface biofunctionalization step by biotin we demonstrate it is possible to use these polymer-dendrimer hybrids for selective detection of target analytes (here: streptavidin), while the underlying coating maintains its antifouling properties. This method presents a new, straightforward approach for the manufacturing of PLL-ZID based coatings that can be pre-synthesized partly or fully and applied as coating in a single self-assembly step. Both steps can take place in aqueous solution and under ambient conditions, and result in stable coatings that not only display antifouling properties but also maintain the possibility of further functionalization.

The chemistry of strained unsaturated cyclic compounds has experienced remarkable growth in recent years via the development of metal–free click reactions. Among these reactions, the cycloaddition of cyclopropenes and their analogues to ortho-quinones has been established as a highly promising click reaction. The present work investigates the mechanism involved in the cycloaddition of strained dienes to ortho-quinones and structural factors that would influence this reaction. For this purpose, we use B97D density functional theory calculations throughout, and for relevant cases, we use spin component–scaled MP2 calculations and single–point domain-based local pair natural orbital coupled cluster (DLPNO-CCSD(T)) calculations. The outcomes are analyzed in detail using the distortion/interaction model, and suggestions for future experimental work are made.

Over the past years, laccase/mediator systems (LMS) have received a lot of attention as potential sustainable tools for biocatalytic lignin degradation. Nevertheless, it has often been reported that Cα-oxidation, rather than ether bond cleavage, is the main result of LMS treatments, which limits the overall efficiency and effectiveness. Remarkably few studies have attempted to influence this product profile and thereby enhance the effectivity of LMS-catalyzed lignin degradation. Here, we studied the influence of buffer properties on the product profile of a β-O-4′ linked lignin model dimer upon conversion by a laccase/hydroxybenzotriazole system. We show that the ratio between β-O-4′ ether cleavage and Cα-oxidation can be substantially increased by using unconventional buffer properties (i.e., highly concentrated buffers at near-neutral pH). Whereas