Search

We report herein a facile and generalized approach to the modification of solid surfaces with polymer brushes under ambient conditions: filter paper‐assisted surface‐initiated Cu0‐mediated controlled radical polymerization (PSI‐CuCRP). The polymerization solution wetted filter paper is sandwiched between a copper plate and an initiator‐modified substrate, which allows the creation of a surface‐initiated polymerization (SIP) “band‐aid” so that everyone can perform the surface grafting selectively with good control over the quality of the polymer brushes employing low concentration and microliter amounts of the monomer solution. The versatility of this method is demonstrated by grafting different homo‐, block‐, and multicomponent polymer brushes by using the same activation system and reaction conditions, the polymerization process can be precisely controlled to yield uniform polymers and show high chain‐end functionality which is exemplified by in situ tetra‐copolymerization. The combination of photolithography and paper cutting enables to prepare arbitrary three‐dimensional patterned polymer brushes on the surface., A facile and generalized approach is reported for the modification of solid surfaces with polymer brushes under ambient conditions: filter paper‐assisted surface‐initiated Cu0‐mediated controlled radical polymerization. A surface‐initiated “band‐aid” of the monomer solution wetted filter paper covered with a thin copper plate allows to perform the surface grafting selectively with polymer brushes.

This work reports on fully integrated “sample‐in‐signal‐out” microfluidic paper‐based analytical devices (μPADs) relying on bioluminescence resonance energy transfer (BRET) switches for analyte recognition and colorimetric signal generation. The devices use BRET‐based antibody sensing proteins integrated into vertically assembled layers of functionalized paper, and their design enables sample volume‐independent and fully reagent‐free operation, including on‐device blood plasma separation. User operation is limited to the application of a single drop (20–30 μL) of sample (serum, whole blood) and the acquisition of a photograph 20 min after sample introduction, with no requirement for precise pipetting, liquid handling, or analytical equipment except for a camera. Simultaneous detection of three different antibodies (anti‐HIV1, anti‐HA, and anti‐DEN1) in whole blood was achieved. Given its simplicity, this type of device is ideally suited for user‐friendly point‐of‐care testing in low‐resource environments.

Halide perovskite quantum dots (PQDs) are promising materials for diverse applications including displays, light‐emitting diodes, and solar cells due to their intriguing properties such as tunable bandgap, high photoluminescence quantum yield, high absorbance, and narrow emission peaks. Despite the prosperous achievements over the past several years, PQDs face severe challenges in terms of stability under different circumstances. Currently, researchers have overcome part of the stability problem, making PQDs sustainable in water, oxygen, and polar solvents for long‐term use. However, halide PQDs are easily degraded under continuous irradiation, which significantly limits their potential for conventional applications. In this study, an oleic acid/oleylamine (traditional surface ligands)‐free method to fabricate perovskite quantum dot papers (PQDP) is developed by adding cellulose nanocrystals as long‐chain binding ligands that stabilize the PQD structure. As a result, the relative photoluminescence intensity of PQDP remains over ≈90% under continuous ultraviolet (UV, 16 W) irradiation for 2 months, showing negligible photodegradation. This proposed method paves the way for the fabrication of ultrastable PQDs and the future development of related applications., Solid‐state perovskite quantum dot papers are fabricated using a unique vacuum filtration growth method without a purification process. The bonding between cellulose nanocrystals and perovskite quantum dots makes the hybrid structure stable, and record high UV stability and thermal stability are achieved for perovskite quantum dot papers.

The arrival of Cyber-physical systems provided space for a new emerging field of research oriented on this type of embedded systems. The aim of this paper is to provide a better understanding of this integrative research field focused on the concept, architecture and challenges in deployment of such systems within the concept of Industry 4.0. Cyber-physical systems represent an emerging area of research that attracts the interest of researchers around the world, because, in the field of design and development of future systems, they are expected to play a major role.

Following the fast spread of the coronavirus (Covid-19) across Europe and North America in March 2020, many people started stockpiling commodities like toilet paper. Despite the high relevance for public authorities to adequately address stockpiling behavior, empirical studies on the psychological underpinnings of toilet paper stockpiling are still scarce. In this study, we investigated the relation between personality traits, perceived threat of Covid-19, and stockpiling of toilet paper in an online survey (N = 996) across 22 countries. Results suggest that people who felt more threatened by Covid-19 stockpiled more toilet paper. Further, a predisposition towards Emotionality predicted the perceived threat of Covid-19 and affected stockpiling behavior indirectly. Finally, Conscientiousness was related to toilet paper stockpiling, such that individuals higher in Conscientiousness tended to stockpile more toilet paper. These results emphasize the importance of clear communication by public authorities acknowledging anxiety and, at the same time, transmitting a sense of control.

A novel paper‐based biofuel cell with a series/parallel array structure has been fabricated, in which the cell voltage and output power can easily be adjusted as required by printing. The output of the fabricated 4‐series/4‐parallel biofuel cell reached 0.97±0.02 mW at 1.4 V, which is the highest output power reported to date for a paper‐based biofuel cell. This work contributes to the development of flexible, wearable energy storage device.

H. Koga, N. Namba, T. Takahashi, M. Nogi, Y. Nishina. Renewable Wood Pulp Paper Reactor with Hierarchical Micro/Nanopores for Continuous‐Flow Nanocatalysis. ChemSusChem 2017, 10, 2560. https://doi.org/10.1002/cssc.201700576., Continuous-flow nanocatalysis based on metal nanoparticle catalyst-anchored flow reactors has recently provided an excellent platform for effective chemical manufacturing. However, there has been limited progress in porous structure design and recycling systems for metal nanoparticle-anchored flow reactors to create more efficient and sustainable catalytic processes. In this study, traditional paper is used for a highly efficient, recyclable, and even renewable flow reactor by tailoring the ultrastructures of wood pulp. The “paper reactor” offers hierarchically interconnected micro- and nanoscale pores, which can act as convective-flow and rapid-diffusion channels, respectively, for efficient access of reactants to metal nanoparticle catalysts. In continuous-flow, aqueous, room-temperature catalytic reduction of 4-nitrophenol to 4-aminophenol, a gold nanoparticle (AuNP)-anchored paper reactor with hierarchical micro/nanopores provided higher reaction efficiency than state-of-the-art AuNP-anchored flow reactors. Inspired by traditional paper materials, successful recycling and renewal of AuNP-anchored paper reactors were also demonstrated while high reaction efficiency was maintained.

We demonstrate, for the first time, the multiplexed determination of microbial species from whole blood using the paper‐folding technique of origami to enable the sequential steps of DNA extraction, loop‐mediated isothermal amplification (LAMP), and array‐based fluorescence detection. A low‐cost handheld flashlight reveals the presence of the final DNA amplicon to the naked eye, providing a “sample‐to‐answer” diagnosis from a finger‐prick volume of human blood, within 45 min, with minimal user intervention. To demonstrate the method, we showed the identification of three species of Plasmodium, analyzing 80 patient samples benchmarked against the gold‐standard polymerase chain reaction (PCR) assay in an operator‐blinded study. We also show that the test retains its diagnostic accuracy when using stored or fixed reference samples.

Carbonaceous materials, especially with graphite‐layers structure, as anode for potassium‐ion batteries (PIBs), are the footstone for industrialization of PIBs. However, carbonaceous materials with graphite‐layers structure usually suffer from poor cycle life and inferior stability, not to mention freestanding and flexible PIBs. Here, a freestanding and flexible 3D hybrid architecture by introducing carbon dots on the reduced graphene oxide surface (CDs@rGO) is synthesized as high performance PIBs anode. The CDs@rGO paper has efficient electron and ion transfer channels due to its unique structure, thus enhancing reaction kinetics. In addition, the CDs provide abundant defects and oxygen‐containing functional groups, which can improve the electrochemical performance. This freestanding and flexible anode exhibits the high capacity of 310 mAh g−1 at 100 mA g−1, ultra‐long cycle life (840 cycles with a capacity of 244 mAh g−1 at 200 mA g−1), and excellent rate performance (undergo six consecutive currents changing from 100 to 500 mA g−1, high capacity 185 mAh g−1 at 500 mA g−1), outperforming many existing carbonaceous PIB anodes. The results may provide a starting point for high‐performance freestanding and flexible PIBs and promote the rapid development of next‐generation flexible batteries., A freestanding and flexible 3D hybrid architecture by introducing carbon dots on the reduced graphene oxide surface is synthesized as a high‐performance potassium‐ion battery anode. It may provide a starting point for high‐performance freestanding and flexible potassium‐ion battery and promote the rapid development of next‐generation flexible batteries.

Advanced carbon materials are important for the next-generation of energy storage apparatus, such as electrochemical capacitors. Here, the physical and electrochemical properties of carbonised filter paper (FP) were investigated. FP is comprised of pure cellulose and is a standardised material. After carbonisation at temperatures ranging from 600 to 1700 °C, FP was contaminant-free, containing only carbon and some oxygenated species, and its primary fibre structure was retained (diameter ≈20–40 μm). The observed enhancement in conductivity of the carbonised FP was correlated with the carbonisation temperature. Electrochemical capacitance in the range of ≈1.8–117 F g−1 was achieved, with FP carbonised at 1500 °C showing the best performance. This high capacitance was stable with >87 % retained after 3000 charge–discharge cycles. These results show that carbonised FP, without the addition of composite materials, exhibits good supercapacitance performance, which competes well with existing electrodes made of carbon-based materials. Furthermore, given the lower cost and renewable source, cellulose-based materials are the more eco-friendly option for energy storage applications.

We propose to use Twitter data as social-spatial sensors. This study deals with the question whether research papers on certain diseases are perceived by people in regions (worldwide) that are especially concerned by these diseases. Since (some) Twitter data contain location information, it is possible to spatially map the activity of Twitter users referring to certain papers (e.g., dealing with tuberculosis). The resulting maps reveal whether heavy activity on Twitter is correlated with large numbers of people having certain diseases. In this study, we focus on tuberculosis, human immunodeficiency virus (HIV), and malaria, since the World Health Organization ranks these diseases as the top three causes of death worldwide by a single infectious agent. The results of the social-spatial Twitter maps (and additionally performed regression models) reveal the usefulness of the proposed sensor approach. One receives an impression of how research papers on the diseases have been perceived by people in regions that are especially concerned by these diseases. Our study demonstrates a promising approach for using Twitter data for research evaluation purposes beyond simple counting of tweets.

In this study, we address the question whether (and to what extent, respectively) altmetrics are related to the scientific quality of papers (as measured by peer assessments). Only a few studies have previously investigated the relationship between altmetrics and assessments by peers. In the first step, we analyse the underlying dimensions of measurement for traditional metrics (citation counts) and altmetrics - by using principal component analysis (PCA) and factor analysis (FA). In the second step, we test the relationship between the dimensions and quality of papers (as measured by the post-publication peer-review system of F1000Prime assessments) - using regression analysis. The results of the PCA and FA show that altmetrics operate along different dimensions, whereas Mendeley counts are related to citation counts, and tweets form a separate dimension. The results of the regression analysis indicate that citation-based metrics and readership counts are significantly more related to quality, than tweets. This result on the one hand questions the use of Twitter counts for research evaluation purposes and on the other hand indicates potential use of Mendeley reader counts.

A novel ultra‐low‐cost biochemical analysis platform to quantify protein dissociation binding constants and kinetics using paper microfluidics is reported. This approach marries video imaging with one of humankind's oldest materials: paper, requiring no large, expensive laboratory equipment, complex microfluidics or external power. Temporal measurements of nanoparticle–antibody conjugates binding on paper is found to follow the Langmuir Adsorption Model. This is exploited to measure a series of antibody–antigen dissociation constants on paper, showing excellent agreement with a gold‐standard benchtop interferometer. The concept is demonstrated with a camera and low‐end smartphone, 500‐fold cheaper than the reference method, and can be multiplexed to measure ten reactions in parallel. These findings will help to widen access to quantitative analytical biochemistry, for diverse applications spanning disease diagnostics, drug discovery, and environmental analysis in resource‐limited settings.

With the rapid development of information technology, scientific social networks (SSNs) have become the fastest and most convenient way for researchers to communicate with each other. Many published papers are shared via SSNs every day, resulting in the problem of information overload. How to appropriately recommend personalized and highly valuable papers for researchers is becoming more urgent. However, when recommending papers in SSNs, only a small amount of positive instances are available, leaving a vast amount of unlabelled data, in which negative instances and potential unseen positive instances are mixed together, which naturally belongs to One-Class Collaborative Filtering (OCCF) problem. Therefore, considering the extreme data imbalance and data sparsity of this OCCF problem, a hybrid approach of Social and Content aware One-class Recommendation of Papers in SSNs, termed SCORP, is proposed in this study. Unlike previous approaches recommended to address the OCCF problem, social information, which has been proved playing a significant role in performing recommendations in many domains, is applied in both the profiling of content-based filtering and the collaborative filtering to achieve superior recommendations. To verify the effectiveness of the proposed SCORP approach, a real-life dataset from CiteULike was employed. The experimental results demonstrate that the proposed approach is superior to all of the compared approaches, thus providing a more effective method for recommending papers in SSNs.

Cellulous-fiber papers are used as 3D structural templates for the assembly of graphene and graphitic carbon nitrate (g-C3N4) ultrathin nanosheets. The resultant materials, which possess highly active centers, rich porosity, and 3D conductive networks, can catalyze the oxygen evolution reaction with competitive activity and much better durability compared to the benchmark noble metal electrocatalysts (IrO2).

This position paper is intended to provide recommendations that will help lay the foundation for best practices for medical science liaisons (MSLs) and their activities. Its objective is to outline the roles and responsibilities expected of an MSL and provide clarity on the juxtaposition of MSLs and Sales representatives (SRs) when it comes to scientific exchange versus promotional messaging. It is of utmost importance that industry integrity and ethical standards are assured during external stakeholder engagement as well as medical and scientific communications. This guidance, delivered through the lens of APPA, IFAPP, MAPS and the MSLS executive committees, has been prepared primarily as a supportive resource to assist the Medical Affairs teams in the industry to develop their own set of standard operating procedures (SOPs), codes of conduct and policies within the framework of relevant industry regulations. We acknowledge that whilst there are guidelines already available that provide excellent directive to the MSL function, this paper is a review and distillation of these existing recommendations combined with the perspectives of four peak professional bodies to offer a practically focused resource to help MSLs interact, collaborate and exchange scientific information appropriately with external experts when out in the field.

Good scientific writing is essential to career development and to the progress of science. A well-structured manuscript allows readers and reviewers to get excited about the subject matter, to understand and verify the paper’s contributions, and to integrate these contributions into a broader context. However, many scientists struggle with producing high-quality manuscripts and typically get little training in paper writing. Focusing on how readers consume information, we present a set of 10 simple rules to help you get across the main idea of your paper. These rules are designed to make your paper more influential and the process of writing more efficient and pleasurable.

Background Little is known about how adverse events are summarised and reported in trials, as detailed information is usually considered confidential. We have acquired clinical study reports (CSRs) from the European Medicines Agency through the Freedom of Information Act. The CSRs describe the results of studies conducted as part of the application for marketing authorisation for the slimming pill orlistat. The purpose of this study was to study how adverse events were summarised and reported in study protocols, CSRs, and published papers of orlistat trials. Methods and Findings We received the CSRs from seven randomised placebo controlled orlistat trials (4,225 participants) submitted by Roche. The CSRs consisted of 8,716 pages and included protocols. Two researchers independently extracted data on adverse events from protocols and CSRs. Corresponding published papers were identified on PubMed and adverse event data were extracted from this source as well. All three sources were compared. Individual adverse events from one trial were summed and compared to the totals in the summary report. None of the protocols or CSRs contained instructions for investigators on how to question participants about adverse events. In CSRs, gastrointestinal adverse events were only coded if the participant reported that they were “bothersome,” a condition that was not specified in the protocol for two of the trials. Serious adverse events were assessed for relationship to the drug by the sponsor, and all adverse events were coded by the sponsor using a glossary that could be updated by the sponsor. The criteria for withdrawal due to adverse events were in one case related to efficacy (high fasting glucose led to withdrawal), which meant that one trial had more withdrawals due to adverse events in the placebo group. Finally, only between 3% and 33% of the total number of investigator-reported adverse events from the trials were reported in the publications because of post hoc filters, though six of seven papers stated that “all adverse events were recorded.” For one trial, we identified an additional 1,318 adverse events that were not listed or mentioned in the CSR itself but could be identified through manually counting individual adverse events reported in an appendix. We discovered that the majority of patients had multiple episodes of the same adverse event that were only counted once, though this was not described in the CSRs. We also discovered that participants treated with orlistat experienced twice as many days with adverse events as participants treated with placebo (22.7 d versus 14.9 d, p-value < 0.0001, Student’s t test). Furthermore, compared with the placebo group, adverse events in the orlistat group were more severe. None of this was stated in the CSR or in the published paper. Our analysis was restricted to one drug tested in the mid-1990s; our results might therefore not be applicable for newer drugs. Conclusions In the orlistat trials, we identified important disparities in the reporting of adverse events between protocols, clinical study reports, and published papers. Reports of these trials seemed to have systematically understated adverse events. Based on these findings, systematic reviews of drugs might be improved by including protocols and CSRs in addition to published articles., In a document analysis, Jeppe B. Schroll and colleagues seek insights into potential bias and underreporting in documentation of adverse events from the mid-1990s clinical trials of the anti-obesity drug orlistat., Author Summary Why Was This Study Done? Most drugs have adverse effects, or harms, that may become evident in clinical trials. Pharmaceutical companies seeking to market a new drug must report adverse effects observed in trial participants in the Clinical Study Reports (CSRs), which they provide to regulatory authorities. Additionally, investigators may report harms in published reports of their trials. We sought to understand the accuracy, and potential bias, in harms reporting for trials of orlistat, a slimming drug from Roche approved in Europe in 1998 and still marketed in Europe today. What Did The Researchers Do And Find? Using a Freedom of Information Act request to the European Medicines Agency (EMA), we obtained CSRs describing seven clinical trials of orlistat. We studied protocol instructions to investigators for reporting harms, the actual reporting of harms in individual CSR records versus summaries, and the final reporting of harms in published papers. We found that protocol instructions to trial investigators had the potential to dilute the appearance of drug-associated harms. Between 3% and 33% of the total adverse effects from CSR summaries were described in published papers. In one trial, we counted adverse events individually and found that both the number of adverse effects and the number of days with adverse effects in participants taking the drug were understated in the corresponding publication. What Do These Findings Mean? The reporting of trials of orlistat in the 1990s understated harms in the summarised results submitted to the EMA for drug approval and in the published papers. Based on the characteristics of harms observed and reported in these trials, we suggest that reports of harms include duration of adverse effects. We also suggest that systematic reviews of drugs might be improved by including protocols and CSRs in addition to published articles.

Cyclopropane rings are an important structural motif frequently found in many natural products and pharmaceuticals. Commonly, biocatalytic methodologies for the asymmetric synthesis of cyclopropanes rely on repurposed or artificial heme enzymes. Here, we engineered an unusual cofactor‐independent cyclopropanation enzyme based on a promiscuous tautomerase for the enantioselective synthesis of various cyclopropanes via the nucleophilic addition of diethyl 2‐chloromalonate to α,β‐unsaturated aldehydes. The engineered enzyme promotes formation of the two new carbon‐carbon bonds with excellent stereocontrol over both stereocenters, affording the desired cyclopropanes with high diastereo‐ and enantiopurity (d.r. up to 25:1; e.r. up to 99:1). Our results highlight the usefulness of promiscuous enzymes for expanding the biocatalytic repertoire for non‐natural reactions., Engineering of a promiscuous 4‐oxalocrotonate tautomerase (4‐OT) resulted in an unusual cofactor‐independent cyclopropanation enzyme that promotes the stereoselective addition of diethyl 2‐chloromalonate to substituted cinnamaldehydes to afford various cyclopropanes with high diastereo‐ and enantiopurity.

A MnI‐catalyzed hydroboration of terminal alkenes and a 1,2‐diboration of terminal alkynes with pinacolborane (HBPin) is described. For alkenes, anti‐Markovnikov hydroboration takes place; for alkynes the reaction proceeds with excellent trans‐1,2‐selectivity. The most active pre‐catalyst is bench‐stable alkyl bisphosphine MnI complex fac‐[Mn(dippe)(CO)3(CH2CH2CH3)]. The catalytic process is initiated by migratory insertion of a CO ligand into the Mn–alkyl bond to yield an acyl intermediate, which undergoes B−H bond cleavage of HBPin (for alkenes) and rapid C−H bond cleavage (for alkynes), forming the active MnI boryl and acetylide catalysts [Mn(dippe)(CO)2(BPin)] and [Mn(dippe)(CO)2(C≡CR)], respectively. A broad variety of aromatic and aliphatic alkenes and alkynes was efficiently and selectively borylated. Mechanistic insights are provided based on experimental data and DFT calculations revealing that an acceptorless reaction is operating involving dihydrogen release., A MnI‐catalyzed hydroboration of terminal alkenes and the 1,2‐diboration of terminal alkynes with pinacolborane is described. In the case of alkenes anti‐Markovnikov hydroboration takes place, while in the case of alkynes the reaction proceeds with trans‐1,2‐selectivity.

Herein we report unprecedented location‐dependent, size‐selective binding to designed lanthanide (Ln3+) sites within miniature protein coiled coil scaffolds. Not only do these engineered sites display unusual Ln3+ selectivity for moderately large Ln3+ ions (Nd to Tb), for the first time we demonstrate that selectivity can be location‐dependent and can be programmed into the sequence. A 1 nm linear translation of the binding site towards the N‐terminus can convert a selective site into a highly promiscuous one. An X‐ray crystal structure, the first of a lanthanide binding site within a coiled coil to be reported, coupled with CD studies, reveal the existence of an optimal radius that likely stems from the structural constraints of the coiled coil scaffold. To the best of our knowledge this is the first report of location‐dependent metal selectivity within a coiled coil scaffold, as well as the first report of location‐dependent Ln3+ selectivity within a protein., Location‐dependent size selectivity can be programmed into designed metallo coiled coils, allowing for the generation of near‐identical selective and promiscuous metal‐ion sites. The first crystal structure of a lanthanide bound within a coiled coil reveals that the existence of an optimal radius stems from the structural constraints of the peptide scaffold. Therefore, a selective site can in principle be designed de novo for any given Ln3+ ion.

Reduction of [SmIII(COT1,4‐SiiPr3)(BH4)(thf)] (COT1,4‐SiiPr3=1,4‐( i Pr3Si)3C8H6) with KC8 resulted in [SmIII/II/III(COT1,4‐SiiPr3)4], the first example of a homoleptic lanthanide quadruple‐decker. As indicated by an analysis of the bond metrics in the solid‐state, the inner Sm ion is present in the divalent oxidation state, while the outer ones are trivalent. This observation could be confirmed by quantum chemical calculations. Mechanistic studies revealed not only insight into possible formation pathways of [SmIII/II/III(COT1,4‐SiiPr3)4] but also resulted in the transformation to other mixed metal sandwich complexes with unique structural properties. These are the 1D‐polymeric chain structured [KSmIII(COT1,4‐SiiPr3)] n and the hexametallic species [(tol)K(COT1,4‐SiiPr3)SmII(COT1,4‐SiiPr3)K]2 which were initially envisioned as possible building blocks as part of different retrosynthetically guided pathways that we developed., The synthesis of the first well‐defined neutral and homoleptic (same metal, same ligand) all‐carbon‐based quadruple‐decker complexes [SmIII/II/III 3(COT1,4‐SiiPr3)4] (COT1,4‐SiiPr3=1,4‐( i Pr3Si)3C8H6) along with other unique sandwich complexes is shown.

The prezizane‐type sesquiterpene agarozizanol B was synthesized employing a photochemical cascade reaction as the key step. Starting from a readily available 1‐indanone with a tethered olefin, a strained tetracyclic skeleton was assembled which contained all carbon atoms of the sesquiterpene with the correct relative configuration. The conversion into the tricyclic prezizane skeleton was accomplished by a strategic cyclopropane bond cleavage. Prior to the cyclopropane ring opening an adaption of the oxidation state was required, which could be combined with a reductive resolution step. After removal of two functional groups, the natural product was obtained both in racemic form or, if resolved, as the (+)‐enantiomer which was shown to be identical to the natural product., Starting from a simple indanone derivative, diastereomerically pure intermediate 1 was formed in a photochemical cascade and served as precursor to agarozizanol B (2), either as racemate or as single enantiomer after a resolution step.

A series of novel heteroditopic halogen bonding (XB) receptor functionalised silica based materials, containing mono‐ and bis‐iodotriazole benzo‐15‐crown‐5 groups are investigated for the cooperative binding and extraction of sodium halide ion‐pair species from aqueous solution. Characterisation of the XB materials by CHN elemental analysis, 13C CP/MAS NMR and ATR‐FTIR spectroscopies confirms and quantifies the successful incorporation of the ion‐pair receptor frameworks to the silica material. ICP‐MS solid‐liquid extraction studies demonstrate the bidentate XB functionalised material is capable of NaI extraction from water. Importantly, cooperative XB‐mediated sodium halide ion‐pair binding is determined to be crucial to the material's extraction capabilities, impressively demonstrating a two‐fold enhancement in sodium iodide extraction efficiency relative to a heteroditopic hydrogen bonding receptor functionalised silica material analogue., A series of halogen bonding (XB) heteroditopic ion‐pair receptors comprising of benzo15‐crown‐5 cation binding moieties and iodotriazole XB donors are covalently integrated into silica QuadraSilTM based solid supports. Investigations into their sodium halide extraction capabilities demonstrated their ability as NaI extraction agents from water. Comparison with HB analogues demonstrate the crucial role of XB‐mediated NaI ion‐pair binding in the extraction performance.

We have synthesized the first isolable geminal bisenolates L2K2Ge[(CO)R]2 (R=2,4,6‐trimethylphenyl (2 a,b), L=THF for (2 a) or [18]‐crown‐6 for (2 b)), a new synthon for the synthesis of organometallic reagents. The formation of these derivatives was confirmed by NMR spectroscopy and X‐ray crystallographic analysis. The UV/Vis spectra of these anions show three distinct bands, which were assigned by DFT calculations. The efficiency of 2 a,b to serve as new building block in macromolecular chemistry is demonstrated by the reactions with two different types of electrophiles (acid chlorides and alkyl halides). In all cases the salt metathesis reaction gave rise to novel Ge‐based photoinitiators in good yields., A convenient method to obtain geminal bisenolates L2K2Ge[(CO)R]2 (R=2,4,6‐trimethylphenyl (1 a,b), L=THF for (1 a) or [18]‐crown‐6 for (1 b)), a new synthon for the synthesis of organometallic reagents, is reported. Selected examples of electrophiles were used to display the efficiency of 1 a,b as new building blocks in organometallic chemistry.

Garsubellin A is a meroterpene capable of enhancing the enzyme choline acetyltransferase whose decreased level is believed to play a central role in the symptoms of Alzheimer's disease. Due to the potentially useful biological activity together with the novel bridged and fused cyclic molecular architecture, garsubellin A has garnered substantial synthetic interest, but its absolute stereostructure has been undetermined. We report here the first enantioselective total synthesis of (+)‐garsubellin A. Our synthesis relies on stereoselective fashioning of a cyclohexanone framework and double conjugate addition of 1,2‐ethanedithiol that promotes aldol cyclization to build the bicyclic [3.3.1] skeleton. The twelve‐step, protecting group‐free synthetic route has enabled the syntheses of both the natural (−)‐garsubellin A and its unnatural (+)‐antipode for biological evaluations., The first enantioselective total synthesis of garsubellin A establishes the absolute stereostructure of the plant‐derived meroterpene that enhances the choline acetyltransferase enzyme responsible for the biosynthesis of the neurotransmitter acetylcholine. The 12‐step, protecting group‐free synthesis features use of a dithiolane for efficient construction of the bridged and fused ring system.

Recent improvements in mRNA display have enabled the selection of peptides that incorporate non‐natural amino acids, thus expanding the chemical diversity of macrocycles beyond what is accessible in nature. Such libraries have incorporated non‐natural amino acids at the expense of natural amino acids by reassigning their codons. Here we report an alternative approach to expanded amino‐acid diversity that preserves all 19 natural amino acids (no methionine) and adds 6 non‐natural amino acids, resulting in the highest sequence complexity reported to date. We have applied mRNA display to this 25‐letter library to select functional macrocycles that bind human STING, a protein involved in immunoregulation. The resulting STING‐binding peptides include a 9‐mer macrocycle with a dissociation constant (K D) of 3.4 nM, which blocks binding of cGAMP to STING and induces STING dimerization. This approach is generalizable to expanding the amino‐acid alphabet in a library beyond 25 building blocks., In vitro selection of macrocyclic peptides from a library that uses a 25‐amino‐acid alphabet has allowed the identification of peptides that block binding of human STING to its natural ligand and induce dimerization of STING monomers. Our method splits multiple degenerate codons and reassigns them to non‐natural amino acids.

The reaction of a borylnitrene with carbon dioxide is studied under cryogenic matrix isolation conditions. Photogenerated CatBN (Cat=catecholato) reacts with CO2 under formation of the cycloaddition product CatBNCO2, a 3‐oxaziridinone derivative, after photoexcitation (>550 nm). The product shows Fermi resonances between the CO stretching and ring deformation modes that cause unusual 13C and 18O isotopic shifts. A computational analysis of the 3‐oxaziridinone shows this cyclic carbamate to be less strained than an α‐lactone or an α‐lactame., Triplet borylnitrene 1 reacts photochemically (λ>550 nm) under cryogenic matrix isolation conditions with CO2, which is known for its high thermodynamic and kinetic stability, to give a strained and unprecedented 3‐oxaziridinone motif 2.

The objective of this paper is to review and analyze existing literature on Public Private Dialogue (PPD) and the way it can be applied to address the issues of competitiveness at the city level. The paper aims to explain how traditional PPD approaches and techniques should be adjusted for application at the city level.

A visible light‐switchable buffer system based on a merocyanine photoacid is presented. Para‐substitution of the indolium side with a methoxy group affords a compound suitable for making hydrolytically stable aqueous buffers whose pH can be tuned between 7 and 4 using 500 nm light., We show that protonated merocyanines can act as reversible photoacids even when buffered with NaOH, attaining tunable and fully reversible jumps of up to 3 pH units between pH 7 and 4.

There is an urgent need to develop antiviral drugs and alleviate the current COVID‐19 pandemic. Herein we report the design and construction of chimeric oligonucleotides comprising a 2′‐OMe‐modified antisense oligonucleotide and a 5′‐phosphorylated 2′‐5′ poly(A)4 (4A2‐5) to degrade envelope and spike RNAs of SARS‐CoV‐2. The oligonucleotide was used for searching and recognizing target viral RNA sequence, and the conjugated 4A2‐5 was used for guided RNase L activation to sequence‐specifically degrade viral RNAs. Since RNase L can potently cleave single‐stranded RNA during innate antiviral response, degradation efficiencies with these chimeras were twice as much as those with only antisense oligonucleotides for both SARS‐CoV‐2 RNA targets. In pseudovirus infection models, chimera‐S4 achieved potent and broad‐spectrum inhibition of SARS‐CoV‐2 and its N501Y and/or ΔH69/ΔV70 mutants, indicating a promising antiviral agent based on the nucleic acid‐hydrolysis targeting chimera (NATAC) strategy., Based on the strategy of nucleic acid hydrolysis targeting chimera, 5′‐phosphorylated 2′‐5′‐poly(A)4‐modified chimeric oligonucleotides were developed for enhanced degradation of the envelope or spike RNA of SARS‐CoV‐2 in vitro. The oligonucleotides can recognize specific viral RNA sequences and 2′‐5′ poly(A)4 can activate RNase L to cleave them specifically.

This communication reports experimental and theoretical evidences of σ‐hole interactions in adducts between nitrogen or oxygen nucleophiles and tetroxides of osmium or other group 8 elements. Cocrystals between pyridine or pyridine N‐oxide derivatives and osmium tetroxide are characterized through various techniques and rationalized as σ‐hole interactions using DFT calculations and several other computational tools. We propose the term “osme bond” (OmB, Om=Fe, Ru, Os, (Hs)) for naming the noncovalent interactions wherein group 8 elements have the role of the electrophile. The word osme is the transcription of ὀσμή, the ancient Greek word for smell that was used to name the heaviest group 8 element in relation to the smoky odor of its tetroxide., σ‐Hole interactions in adducts between nitrogen or oxygen nucleophiles and tetroxides of osmium or other group 8 elements are reported. Cocrystals between pyridine or pyridine N‐oxide derivatives and osmium tetroxide are characterized through various techniques including computational tools. We propose the term “osme bond” (OmB, Om=Fe, Ru, Os, (Hs)) for naming the noncovalent interactions wherein group 8 elements have the role of the electrophile.

A reinvestigation of the linalool synthase from Chryseobacterium polytrichastri uncovered its diterpene synthase activity, yielding polytrichastrene A and polytrichastrol A with new skeletons, besides known wanju‐2,5‐diene and thunbergol. The enzyme mechanism was investigated by isotopic labeling experiments and DFT calculations to explain an unusual ethyl group formation. Rationally designed exchanges of active site residues showed major functional switches, resulting for I66F in the production of five more new compounds, including polytrichastrene B and polytrichastrol B, while A87T, A192V and the double exchange A87T, A192V gave a product shift towards wanju‐2,5‐diene., Linalool synthase from Chryseobacterium polytrichastri was found to have diterpene synthase activity and produced diterpenes with new skeletons containing a rare ethyl group. Its formation was mechanistically studied through isotopic labeling and DFT calculations. Exchange of active site residues resulted in a functional switch leading to additional novel diterpenes. This work lays the ground for future rational engineering of terpene synthases.

The first chemical total synthesis of the highly oxygenated polyketide enterocin has been accomplished. The key step of the synthesis was a late‐stage biomimetic reaction cascade involving two intramolecular aldol reactions in which each step proceeded in 52 % yield (averaged) and which established four of the seven stereogenic centers. The pivotal precursor for the cascade reaction was assembled from three readily available building blocks. A chiral dithioacetal with two stereogenic centers originating from L‐arabinose represented the core fragment to both ends of which the other building blocks were attached by aldol reactions. The remaining stereogenic center was installed by Davis oxygenation immediately prior to the key step., Entering Nature's Design Office: The highly oxygenated natural product enterocin, which has so far resisted total synthetic attempts, was obtained in a biomimetic key step from triketone 1, which in turn was assembled from an L‐arabinose‐derived core fragment with a defined absolute configuration.

[EN] HPM-16 is a highly porous germanosilicate zeolite with an interrupted framework that contains a three-dimensional system of 12+10 10(12) 12+10-membered ring (MR) pores. The 10(12) MR pore in the b direction is a 10 MR pore with long 12 MR stretches forming 30 long tubular supercages. Along one direction the 10 MR pores are fused, meaning that the separation between adjacent pores consists of a single tetrahedron that is, additionally, connected to only three additional tetrahedra (a Q3). These fused pores are thus decorated by T-OH groups along the whole diffusion path, creating a hydrophilic region embedded in an otherwise essentially hydrophobic environment. The structure is built from highly porous 12 12 12 MR uninterrupted layers that are connected to each other through Q3 producing a second system of 10 10 10 MRpores. This zeolite can be extensively degermanated yielding a material with high thermal stability, despite its interrupted nature., The authors are grateful for financial support to the Spanish Ministry of Science Innovation and Universities (MICIU) (PID2019-105479RB-I00 project, AEI, Spain and FEDER, EU). SRGB also thanks MICIU for a Juan de la Cierva- Formación Research Contract (FJC2018-035697-I code reference). Synchrotron experiments were performed at beamline BL04 (MSPD) at the Spanish ALBA Synchrotron with the collaboration of ALBA staff, and special thanks are due to A. Manj n and A. Missiul. Centro T cnico Inform tico-CSIC, Trueno cluster facility of SGAI-CSIC is acknowledged for running the calculations. We also deeply thank C. Márquez- Álvarez for his kind help in characterization. The cRED data were collected at the Electron Microscopy Center (EMC), Department of Materials and Environmental Chemistry (MMK) in Stockholm University with the support of Knut and Alice Wallenberg (KAW) foundation-financed project 3DEM-NATUR.

A big problem with the chemistry literature is that it is not standardized with respect to precise operational parameters, and real time corrections are hard to make without expert knowledge. This lack of context means difficult reproducibility because many steps are ambiguous, and hence depend on tacit knowledge. Here we present the integration of online NMR into an automated chemical synthesis machine (CSM aka. “Chemputer” which is capable of small‐molecule synthesis using a universal programming language) to allow automated analysis and adjustment of reactions on the fly. The system was validated and benchmarked by using Grignard reactions which were chosen due to their importance in synthesis. The system was monitored in real time using online‐NMR, and spectra were measured continuously during the reactions. This shows that the synthesis being done in the Chemputer can be dynamically controlled in response to feedback optimizing the reaction conditions according to the user requirements., A universal chemical synthesis platform was extended by online NMR to allow adjustments of the encoded reactions on the fly. The approach was demonstrated on the class of Grignard reactions showing robust analytical results under harsh conditions. Real‐time process analytics and the use of straightforward feedback control algorithm enhance the usability of available synthesis formula considering existing deviations.

Prussian blue analogs (PBAs) are considered as reliable and promising cathode materials for aqueous Zn‐ion batteries (AZIBs), but they suffer from low capacity and poor cycling stability due to insufficient active sites and structural damage caused by the ion insertion/extraction processes. Herein, a template‐engaged ion exchange approach has been developed for the synthesis of Co‐substituted Mn‐rich PBA hollow spheres (CoMn‐PBA HSs) as cathode materials for AZIBs. Benefiting from the multiple advantageous features including hollow structure, abundant active sites, fast Zn2+ ion diffusion, and partial Co substitution, the CoMn‐PBA HSs electrode shows efficient zinc ion storage properties in terms of high capacity, decent rate capability and prolonged cycle life., Co‐substituted Mn‐rich Prussian Blue Analog (PBA) hollow spheres (CoMn‐PBA HSs) are rationally designed and synthesized through an efficient self‐templating approach. Benefiting from the hollow structure and partial Co substitution, the CoMn‐PBA HSs electrode exhibits enhanced zinc ion storage performance with high capacity, favorable rate capability, and impressive cycling stability.

Resonance Raman optical activity (RROA) possesses all aspects of a sensitive tool for molecular detection, but its measurement remains challenging. We demonstrate that reliable recording of RROA of chiral colorful compounds is possible, but only after considering the effect of the electronic circular dichroism (ECD) on the ROA spectra induced by the dissolved chiral compound. We show RROA for a number of model vitamin B12 derivatives that are chemically similar but exhibit distinctively different spectroscopic behavior. The ECD/ROA effect is proportional to the concentration and dependent on the optical pathlength of the light propagating through the sample. It can severely alter relative band intensities and signs in the natural RROA spectra. The spectra analyses are supported by computational modeling based on density functional theory. Neglecting the ECD effect during ROA measurement can lead to misinterpretation of the recorded spectra and erroneous conclusions about the molecular structure., A strong influence of electronic circular dichroism on the measurement of resonance Raman optical activity of colorful chiral compounds is reported for a series of vitamin B12 derivatives. Neglecting this effect can lead to misinterpretation of recorded spectra, and seriously erroneous conclusions about molecular structure and chirality.

Copolymers are the answer to property limitations of homopolymers. In order to use the full variety of monomers available, catalysts active in more than one polymerization mechanism are currently investigated. Iron guanidine catalysts have shown to be extraordinarily active in ROP of lactide and herein prove their versatility by also promoting ATRP of styrene. The presented iron complex is the first polymerizing lactide and styrene simultaneously to a defined block copolymer in a convenient one‐pot synthesis. Both mechanisms work hand in hand with ROP using the dominantly present FeII species on the dormant side of the ATRP equilibrium. This orthogonal copolymerization by a benign iron catalyst opens up new pathways to biocompatible polymerization procedures broadening the scope of ATRP applications., Orthogonal catalysis combining two polymerization mechanisms in a one‐pot synthesis enables facile production routes to block copolymers. An iron guanidine catalyst is able to copolymerize styrene via ATRP and lactide via ROP simultaneously. By using the FeII species on the dormant side of the ATRP equilibrium for ROP both mechanisms proceed in a controlled manner without interference.

We present a computational analysis of hexaphenylethane derivatives with heavier tetrels comprising the central bond. In stark contrast to parent hexaphenylethane, the heavier tetrel derivatives can readily be prepared. In order to determine the origin of their apparent thermodynamic stability against dissociation as compared to the carbon case, we employed local energy decomposition analysis (LED) and symmetry‐adapted perturbation theory (SAPT) at the DLPNO‐CCSD(T)/def2‐TZVP and sSAPT0/def2‐TZVP levels of theory. We identified London dispersion (LD) interactions as the decisive factor for the molecular stability of heavier tetrel derivatives. This stability is made possible owing to the longer (than C−C) central bonds that move the phenyl groups out of the heavily repulsive regime so they can optimally benefit from LD interactions., Carbon‐Carbon bonds are exceptional as demonstrated for the hexaphenylditetrels where attractive London dispersion interactions are the decisive factor for the thermodynamic stabilities of tetrels other than carbon. Structural and energetic comparisons show that even though hexaphenylethane displays the largest dispersion energy between the two molecular halves, it has remained elusive because of even larger Pauli repulsion of the phenyl moieties that are forced in close contact due to the C−C bond that is the shortest in this series.

Herein, we disclose a recyclable, hybrid manganese catalyst for site‐selective azine C−H activation by weak amide assistance. The novel, reusable catalyst enabled C3–H arylation and C3–H alkylation with ample scope, and was characterized by detailed transmission electron microscopy analysis., A recyclable hybrid‐manganese catalyst was developed for site‐selective azine C−H activation by weak amide‐assistance with ample substrate scope. The heterogeneous catalyst proved to be reusable, and was analyzed in detail by spectroscopy, spectrometry and transmission electron microscopy.

Cyclophane structures can control steric pressure in the otherwise open spaces of square‐planar d8‐metal catalysts. This elegant concept was so far limited to symmetrical coordinated metals. We report how a cyclophane motif can be generated in ligands that chelate via two different donors. An ancillary second imine in the versatile κ2‐N,O‐salicylaldiminato catalyst type enables ring closure via olefin metathesis and selective double bond hydrogenation to yield a 30‐membered ring efficiently. Experimental and theoretical analyses show the ancillary imine is directed away from the active site and inert for catalysis. In ethylene polymerization the cyclophane catalyst is more active and temperature stable vs. an open structure reference, notably also in polar solvents. Increased molecular weights and decreased degrees of branching can be traced to an increased energy of sterically demanding transition states by the encircling cyclophane while chain propagation remains highly efficient., We demonstrate how a cyclophane structure can be generated in square‐planar complexes with two different chelating donors (N,O). An ancillary second imine function in the versatile κ 2‐N,O‐salicylaldiminato catalyst type enables ring closure between two symmetrical 4′,4′′‐diallyl substituted terphenyl motifs.

Radical polymerization with reversible addition‐fragmentation chain transfer (RAFT polymerization) has been successfully applied to generate polymers of well‐defined architecture. For RAFT polymerization a source of radicals is required. Recent work has demonstrated that for minimal side‐reactions and high spatio‐temporal control these should be formed directly from the RAFT agent or macroRAFT agent (usually carbonothiosulfanyl compounds) thermally, photochemically or by electrochemical reduction. In this work, we investigated low‐energy electron attachment to a common RAFT agent (cyanomethyl benzodithioate), and, for comparison, a simple carbonothioylsulfanyl compound (dimethyl trithiocarbonate, DMTTC) in the gas phase by means of mass spectrometry as well as quantum chemical calculations. We observe for both compounds that specific cleavage of the C−S bond is induced upon low‐energy electron attachment at electron energies close to zero eV. This applies even in the case of a poor homolytic leaving group (.CH3 in DMTTC). All other dissociation reactions found at higher electron energies are much less abundant. The present results show a high control of the chemical reactions induced by electron attachment., Electron attachment leads to the efficient dissociation of carbonothioylsulfanyl molecules which are relevant for Reversible Addition‐Fragmentation chain Transfer (RAFT) polymerization. We show that the preferred C−S bond cleavage can be initiated by an electron with almost no kinetic energy, in contrast to other dissociation reactions. This feature leads to a pronounced control of bond dissociation upon electron attachment.

Atropo‐enantioselective biaryl coupling through C−H bond functionalization is an emerging technology allowing direct construction of axially chiral molecules. This approach is largely limited to electrophilic coupling partners. We report a highly atropo‐enantioselective C−H arylation of tetralone derivatives paired with aryl boronic esters as nucleophilic components. The transformation is catalyzed by chiral cyclopentadienyl (Cpx) iridium(III) complexes and enabled by oxidatively enhanced reductive elimination from high‐valent cyclometalated Ir‐species., A highly atropo‐enantioselective C−H arylation of tetralone derivatives paired with aryl boronic esters as nucleophilic components is presented. The transformation is catalyzed by chiral cyclopentadienyl (Cpx) iridium(III) complexes and enabled by oxidatively enhanced reductive elimination from high‐valent cyclometalated Ir‐species.

Dysregulation of post‐translational modifications (PTMs) like phosphorylation is often involved in disease. NMR may elucidate exact loci and time courses of PTMs at atomic resolution and near‐physiological conditions but requires signal assignment to individual atoms. Conventional NMR methods for this base on tedious global signal assignment that may often fail, as for large intrinsically disordered proteins (IDPs). We present a sensitive, robust alternative to rapidly obtain only the local assignment near affected signals, based on FOcused SpectroscopY (FOSY) experiments using selective polarisation transfer (SPT). We prove its efficiency by identifying two phosphorylation sites of glycogen synthase kinase 3 beta (GSK3β) in human Tau40, an IDP of 441 residues, where the extreme spectral dispersion in FOSY revealed unprimed phosphorylation also of Ser409. FOSY may broadly benefit NMR studies of PTMs and other hotspots in IDPs, including sites involved in molecular interactions., A new suite of 2D FOSY experiments focuses on one coupled nuclear spin system at a time, that is, a PTM site or a structural hotspot in general, with 3–5 known frequencies. With higher sensitivity and versatility than achievable by traditional experiments, FOSY solves the spectral dispersion problem and obtains only the relevant local NMR signal assignment in a few hours, as demonstrated for two phosphorylation sites in the 441‐residue IDP Tau.

Post‐synthetic modification (PSM) of the interpenetrated diamondoid metal–organic framework (Me2NH2)[In(BDC‐NH2)2] (BDC‐NH2=aminobenzenedicarboxylate) SHF‐61 proceeds quantitatively in a single‐crystal‐to‐single‐crystal manner to yield the acetamide derivative (Me2NH2)[In(BDC‐NHC(O)Me)2] SHF‐62. Continuous breathing behaviour during activation/desolvation is retained upon PSM, but pore closing now leads to ring‐flipping to avert steric clash of amide methyl groups of the modified ligands. This triggers a reduction in the amplitude of the breathing deformation in the two dimensions associated with pore diameter, but a large increase in the third dimension associated with pore length. The MOF is thereby converted from predominantly 2D breathing (in SHF‐61) to a distinctly 3D breathing motion (in SHF‐62) indicating a decoupling of the pore‐width and pore‐length breathing motions. These breathing motions have been mapped by a series of single‐crystal diffraction studies., Post‐synthetic modification of diamondoid MOF SHF‐61 generates its methylamide analogue [(Me2NH2)[In(BDC‐NH(CO)Me)], SHF‐62, as single crystals. Resulting ligand steric demands and H‐bonding capability lead to a change in dimensionality of the MOF breathing behaviour from 2D breathing (pore width) to 3D breathing (pore width and length), which has been mapped by single‐crystal X‐ray diffraction.

We report the functionalization of cysteine residues with lipophilic alkynes bearing a silyl group or an alkyl chain using amphiphilic ethynylbenziodoxolone reagents (EBXs). The reactions were carried out in buffer (pH 6 to 9), without organic co‐solvent or removal of oxygen, either at 37 °C or room temperature. The transformation led to a significant increase of peptide lipophilicity and worked for aromatic thiols, homocysteine, cysteine, and peptides containing 4 to 18 amino acids. His6‐Cys‐Ubiquitin was also alkynylated under physiological conditions. Under acidic conditions, the thioalkynes were converted into thioesters, which could be cleaved in the presence of hydroxylamine., Amphiphilic hypervalent iodine reagents enable the alkynylation of cysteine residues in peptides with lipophilic groups in water. The reaction proceeds in neutral standard buffers with high efficiency for a broad range of peptides and one protein. The thioalkynes can be converted into cleavable thioesters under acidic conditions.

DNA polymerase β (Pol β) is a frequently overexpressed and/or mutated bifunctional repair enzyme. Pol β possesses polymerase and lyase active sites, that are employed in two steps of base excision repair. Pol β is an attractive therapeutic target for which there is a need for inhibitors. Two mechanistically inspired covalent inhibitors (1, IC50=21.0 μM; 9, IC50=18.7 μM) that modify lysine residues in different Pol β active sites are characterized. Despite modifying lysine residues in different active sites, 1 and 9 inactivate the polymerase and lyase activities of Pol β. Fluorescence anisotropy experiments indicate that they do so by preventing DNA binding. Inhibitors 1 and 9 provide the basis for a general approach to preparing domain selective inhibitors of bifunctional polymerases. Such molecules could prove to be useful tools for studying the role of wild type and mutant forms of Pol β and other polymerases in DNA repair., A single synthesis and screening strategy yields covalent inhibitors that inactivate bifunctional DNA polymerase β by modifying lysine residues in different active site domains and prevent DNA binding.

Trifluoromethoxylated (hetero)arenes are of great interest for several disciplines, especially in agro‐ and medicinal chemistry. Radical C−H trifluoromethoxylation of (hetero)arenes represents an attractive approach to prepare such compounds, but the high cost and low atom economy of existing .OCF3 radical sources make them unsuitable for the large‐scale synthesis of trifluoromethoxylated building blocks. Herein, we introduce bis(trifluoromethyl)peroxide (BTMP, CF3OOCF3) as a practical and efficient trifluoromethoxylating reagent that is easily accessible from inexpensive bulk chemicals. Using either visible light photoredox or TEMPO catalysis, trifluoromethoxylated arenes could be prepared in good yields under mild conditions directly from unactivated aromatics. Moreover, TEMPO catalysis allowed for the one‐step synthesis of valuable pyridine derivatives, which have been previously prepared via multi‐step approaches., Bis(trifluoromethyl)peroxide (BTMP) is introduced as a new reagent for the C−H trifluoromethoxylation of arenes and heteroarenes. Readily accessed from inexpensive bulk chemicals, BTMP serves as a practical source of •OCF3 radicals upon activation through either visible light photoredox or TEMPO catalysis. Both methods deliver valuable fluorine‐containing building blocks in a single step from (hetero)aromatic feedstocks.

Linear or branched 1,3‐diketone‐linked thymidine 5′‐O‐mono‐ and triphosphate were synthesized through CuAAC click reaction of diketone‐alkynes with 5‐azidomethyl‐dUMP or ‐dUTP. The triphosphates were good substrates for KOD XL DNA polymerase in primer extension synthesis of modified DNA. The nucleotide bearing linear 3,5‐dioxohexyl group (HDO) efficiently reacted with arginine‐containing peptides to form stable pyrimidine‐linked conjugates, whereas the branched 2‐acetyl‐3‐oxo‐butyl (PDO) group was not reactive. Reaction with Lys or a terminal amino group formed enamine adducts that were prone to hydrolysis. This reactive HDO modification in DNA was used for bioconjugations and cross‐linking with Arg‐containing peptides or proteins (e.g. histones)., Arginine‐specific 1,3‐diketone‐linked reactive nucleotides are reported for the enzymatic construction of DNA probes and cross‐linking with peptides and proteins.