Search

Monitoring of human serum albumin (HSA) in a point-of-care fashion is urgently needed in particular for elderly or chronically ill patients. Herein, a dual-state emissive chalcone probe having the feature of aggregation-induced emission was designed and synthesized. The concentration of HSA can be evaluated by the ratios of emission from probes in aggregated and monomeric state, which gives a visually discernible red-to-green color change. A simple, portable paper-based analytical device have been fabricated by integration of the recognition probe in the detection pad and employed for HSA test using the whole blood samples. This paper-based assay shows the analytical capability comparable to the standard testing methods but is in a point-of-care fashion, providing a promising tool for at-home HSA detection and HSA-related disease diagnosis.

A potentially universal approach is presented for enzyme attachment to cellulose that significantly enhances enzyme stability while retaining high activity, and involves no chemical functionalization of cellulose. Bovine serum albumin (BSA) was interlocked in cellulose to form a protein-friendly surface (named BSA-Paper), while also providing COOH and NH2 groups for subsequent attachment of enzymes. The desired enzyme is then mixed with additional BSA and interlocked on BSA-Paper. The second BSA layer dilutes and crosslinks the enzyme for improved stability. Laccase was tested as a model enzyme for interlocking on BSA-Paper, and was found to retain over 100 % activity and was 240 times more stable at 25 °C (half life=180 d) than laccase. This new approach was also tested with a few other enzymes with encouraging results, thus providing a potentially universal method for stabilization of enzymes on cellulose with retention of high activities.

We report a general anion sensing platform based on a portable and cost-effective ion-selective optode and a smartphone detector equipped with a color analysis app. In contrast to traditional anion-selective optodes using a hydrophobic polymer and/or plasticizer to dissolve hydrophobic sensing elements, the new optode relies on hydrophilic cellulose paper. The anion ionophore and a lipophilic pH indicator are inkjet-printed and adsorbed on paper and form a “dry” hydrophobic sensing layer. Porous cellulose sheets also allow the sensing site to be modified with dried buffer that prevents any sample pH dependence of the observed color change. A highly selective fluoride optode using an Al(III)-porphyrin ionophore is examined as an initial example of this new anion sensing platform for measurements of fluoride levels in drinking water samples. In addition to Lewis acid-base recognition, hydrogen bonding recognition is also shown to be compatible with this sensing platform.

Here we report a self-powered origami paper analytical device (oPAD) that uses an aptamer to recognize an analyte, a glucose oxidase (GOx) tag to modify the relative concentrations of an electroactive redox couple, and a digital multimeter (DMM) to transduce the result of the assay. The sensor is self-powered in that it self-generates an electrical signal so that the read-out process is similar to testing a battery. The principle of the sensor is illustrated in Scheme 1. Briefly, the device is printed on a single piece of paper, folded into a three-dimensional (3D) configuration, and then laminated in plastic. An aliquot of sample is loaded at the inlet, split into two channels, and then directed to microbeads entrapped within the channels. In one channel, an aptamer immobilized on microbeads binds to the target and releases a GOx-labeled DNA strand that flows downstream. No aptamer is present on the microbeads in the other channel, which is used as a control. The split fluids terminate in an hour-glass-shaped, two-compartment electrochemical cell. The waist of the hour glass serves as a salt bridge between the two half cells. In one of the half cells, GOx catalyzes the oxidation of glucose, which in turn results in conversion of Fe(CN)63− to Fe(CN)64−.The difference in concentrations of Fe(CN)63− and Fe(CN)64− in the sensing half cell and control half cell results in a voltage that is used to charge a capacitor. When the switch (lower part of Scheme 1) is closed, the capacitor discharges through the DMM. The capacitor provides a high instantaneous current, in effect an amplified current, and hence a higher sensitivity than a direct current measurement.

This communication describes a simple method for patterning paper to create well-defined, millimeter-sized channels, comprising hydrophilic paper bounded by hydrophobic polymer. We believe that this type of patterned paper will become the basis for low-cost, portable, and technically simple multiplexed bioassays. We demonstrate this capability by the simultaneous detection of glucose and protein in 5 μL of urine. The assay system is small, disposable, easy to use (and carry), and requires no external equipment, reagents, or power sources. We believe this kind of system is attractive for uses in less-industrialized countries, in the field, or as an inexpensive alternative to more advanced technologies already used in clinical settings.[1-4] The analysis of biological fluids is necessary for monitoring the health of populations,[2] but these measurements are difficult to implement in remote regions such as those found in less-industrialized countries, in emergency situations, or in home health-care settings.[3] Conventional laboratory instruments provide quantitative measurements of biological samples, but they are unsuitable for these situations since they are large, expensive, and require trained personnel and considerable volumes of biological samples.[2] Other bioassay platforms provide alternatives to more expensive instruments,[5-7] but the need remains for a platform that uses small volumes of sample and that is sufficiently inexpensive to be used widely for measuring samples from large populations. We believe that paper may serve as a particularly convenient platform for running bioassays in the remote situations locations. As a prototype for a mthod we believe to be particularly promosing, we patterned photoresist onto chromatography paper to form defined areas of hydrophilic paper separated by hydrophobic lines or “walls”; these patterns provide spatial control of biological fluids and enable fluid transport, without pumping, due to capillary action in the millimeter-sized channels produced. This method for patterning paper makes it possible to run multiple diagnostic assays on one strip of paper, while still using only small volumes of a single sample. In a fully developed technology, patterned photoresist would be replaced by an appropriate printing technology, but patterning paper with photoresist is: i) convenient for prototyping these devices, and ii) a useful new micropatterning technology in its own right. We patterned chromatography paper with SU-8 2010 photoresist as shown in Figure 1a and as described below: we soaked a 7.5-cm diameter piece of chromatography paper in 2 mL of SU-8 2010 for 30 s, spun it at 2000 rpm for 30 s, and then baked it at 95 °C for 5 min to remove the cyclopentanone in the SU-8 formula. We then exposed the photoresist and paper to 405 nm UV light (50 mW/cm2) for 10 s through a photo-mask (CAD/Art Services, Inc.) that was aligned using a mask aligner (OL-2 Mask Aligner, AB-M, Inc). After exposure, we baked the paper a second time at 95 °C for 5 min to cross-link the exposed portions of the resist. The unpolymerized photoresist was removed by soaking the paper in propylene glycol monomethyl ether acetate (PGMEA) (5 min), and by washing the pattern with propan-2-ol (3 × 10 mL). The paper was more hydrophobic after it was patterned, presumably due to residual resist bound to the paper, so we exposed the entire surface to an oxygen plasma for 10 s at 600 millitorr (SPI Plasma-Prep II, Structure Probe, Inc) to increase the hydrophilicity of the paper (Figures 2a and 2b). Figure 1 Chromatography paper patterned with photoresist. The darker lines are cured photoresist; the lighter areas are unexposed paper. (a) Patterned paper after absorbing 5 μL of Waterman red ink by capillary action. The central channel absorbs the sample ... Figure 2 Assays contaminated with (a) dirt, (b) plant pollen, and (c) graphite powder. The pictures were taken before and after running an artificial urine solution that contained 550 mM glucose and 75 μM BSA. The particulates do not move up the channels ... The patterned paper can be derivatized for biological assays by adding appropriate reagents to the test areas (Figures 1b and ​and2b).2b). In this communication, we demonstrate the method by detecting glucose and protein,[8] but the surface should be suitable for measuring many other analytes as well.[7] The glucose assay is based on the enzymatic oxidation of iodide to iodine,[9] where a color change from clear to brown is associated with the presence of glucose.[10] The protein assay is based on the color change of tetrabromophenol blue (TBPB) when it ionizes and binds to proteins;[11] a positive result in this case is indicated by a color change from yellow to blue. For the glucose assay, we spotted 0.3 μL of a 0.6 M solution of potassium iodide, followed by 0.3 μL of a 1:5 horseradish peroxidase/glucose oxidase solution (15 units of protein per mL of solution). For the protein assay, we spotted 0.3 μL of a 250-mM citrate buffer (pH 1.8) in a well separate from the glucose assay, and then layered 0.3 μL of a 3.3 mM solution of tetrabromophenol blue (TBPB) in 95% ethanol over the citrate buffer. The spotted reagents were allowed to air dry at room temperature. This pre-loaded paper gave consistent results for the protein assay regardless of storage temperature and time (when stored for 15 d both at 0 °C and at 23 °C, wrapped in aluminum foil). The glucose assay was sensitive to storage conditions, and showed decreased signal for assays run 24 h after spotting the reagents (when stored at 23 °C); when stored at 0 °C, however, the glucose assay was as sensitive after day 15 as it was on day 1. We measured artificial samples of glucose and protein in clinically relevant ranges (2.5-50 mM for glucose and 0.38-7.5 μM for bovine serum albumin (BSA))[12, 13] by dipping the bottom of each test strip in 5 μL of a pre-made test solution (Figure 2d). The fluid filled the entire pattern within ca. one minute, but the assays required 10-11 min for the paper to dry and for the color to fully develop.[14] In all cases, we observed color changes corresponding roughly in intensity to the amount of glucose and protein in the test samples, where the lowest concentrations define the lower limits to which these assays can be used (Figure 2e). For comparison, commercially-available dipsticks detect glucose at concentrations as low as 5 mM[7, 9] and protein as low as 0.75 μM;[6, 15] these limits indicate that these paper-based assays are comparable in sensitivity to commercial dipstick assays. Our assay format also allows for the measurement of multiple analytes. This paper-based assay is suitable for measuring multiple samples in parallel and in a relatively short period of time. For example, in one trial, one researcher was able to run 20 different samples (all with 550 mM glucose and 75 μM BSA) within 7.5 min (followed by another 10.5 min for the color to fully develop). An 18-min assay of this type—one capable of measuring two analytes in 20 different sample—may be efficient enough to use in high-throughput screens of larger sample pools. In the field, samples will not be measured under sterile conditions, and dust and dirt may contaminate the assays. The combination of paper and capillary action provides a mechanism for separating particulates from a biological fluid. As a demonstration, we purposely contaminated the artificial urine samples with quantities of dirt, plant pollen, and graphite powder at levels higher than we might expect to see in the samples in the field. These particulates do not move up the channels under the action of capillary wicking, and do not interfere with the assay (Figure 3). Paper strips have been used in biomedical assays for decades because they offer an inexpensive platform for colorimetric chemical testing.[1] Patterned paper has characteristics that lead to miniaturized assays that run by capillary action (e.g., without external pumping), with small volumes of fluids. These methods suggest a path for the development of simple, inexpensive, and portable diagnostic assays that may be useful in remote settings, and in particular, in less-industrialized countries where simple assays are becoming increasingly important for detecting disease and monitoring health,[16, 17], for environmental monitoring, in veterinary and agricultural practice and for other applications.

A significant amount of attention has been given to the design and synthesis of co‐crystals by both industry and academia because of its potential to change a molecule's physicochemical properties. Yet, difficulties arise when searching for adequate combinations of molecules (or coformers) to form co‐crystals, hampering the efficient exploration of the target's solid‐state landscape. This paper reports on the application of a data‐driven co‐crystal prediction method based on two types of artificial neural network models and co‐crystal data present in the Cambridge Structural Database. The models accept pairs of coformers and predict whether a co‐crystal is likely to form. By combining the output of multiple models of both types, our approach shows to have excellent performance on the proposed co‐crystal training and validation sets, and has an estimated accuracy of 80 % for molecules for which previous co‐crystallization data is unavailable., An artificial neural network calculates whether two molecules are likely to form a co‐crystal. The approach shows excellent performance on the proposed co‐crystal training and validation sets, and has an estimated accuracy of 80 % for molecules for which previous co‐crystallization data is unavailable. The figure illustrates the prediction of the newly discovered drug–drug co‐crystal containing ketoprofen and carbamazepine.

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.

Drimane‐type sesquiterpenes exhibit various biological activities and are widely present in eukaryotes. Here, we completely elucidated the biosynthetic pathway of the drimane‐type sesquiterpene esters isolated from Aspergillus calidoustus and we discovered that it involves a drimenol cyclase having the same catalytic function previously only reported in plants. Moreover, since many fungal drimenol derivatives possess a γ‐butyrolactone ring, we clarified the functions of the cluster‐associated cytochrome P450 and FAD‐binding oxidoreductase discovering that these two enzymes are solely responsible for the formation of those structures. Furthermore, swapping of the enoyl reductase domain in the identified polyketide synthase led to the production of metabolites containing various polyketide chains with different levels of saturation. These findings have deepened our understanding of how fungi synthesize drimane‐type sesquiterpenes and the corresponding esters., Reported here is the complete elucidation of the biosynthetic pathway of drimane‐type sesquiterpene esters from Aspergillus calidoustus, including the first identified fungal drimenol cyclase. The cluster‐associated acyltransferase is then employed to transfer different lengths of ACP‐activated polyketides, but also very diverse CoA‐esters.

The longevity and reusability of N95‐grade filtering facepiece respirators (N95 FFRs) are limited by consecutive donning and disinfection treatments. Herein, we developed stable N97 nanofibrous respirators based on chemically modified surface to enable remarkable filtration characteristics via polarity driven interaction. This was achieved by a thin‐film coated polyacrylonitrile nanofibrous membrane (TFPNM), giving an overall long‐lasting filtration performance with high quality factor at 0.42 Pa−1 (filtration efficiency: over 97 %; pressure drop: around 10 Pa), which is higher than that of the commercial N95 FFRs (0.10–0.41 Pa−1) tested with a flow rate of 5 L min−1 and the 0.26 μm NaCl aerosol. A coxsackie B4 virus filtration test demonstrated that TFPNM also had strong virus capture capacity of 97.67 %. As compared with N95 FFRs, the TFPNM was more resistant to a wider variety of disinfection protocols, and the overall filtration characteristics remained N97 standard., A polarity‐driven air filtration approach is achieved based on the thin‐film coated PAN nanofibrous membranes (TFPNMs), possessing a superior filtration efficiency reaching to N97 grade with outstanding longevity and reusability compared with the N95 FFRs. The TFPNMs can be reused upon various disinfection treatments, giving great potential for personal health care.

Two homoleptic copper(II) complexes [Cu(L1)2] and [Cu(L2)2] with anionic redox‐active ligands were synthesised, one with urea azine (L1) and the other with thio‐urea azine (L2) ligands. One‐electron oxidation of the complexes initiates an unprecedented redox‐induced electron transfer process, leading to monocationic copper(I) complexes [Cu(L1)2]+ and [Cu(L2)2]+ with two oxidised ligands. While [Cu(L1)2]+ is best described as a CuI complex with two neutral radical ligands that couple antiferromagnetically, [Cu(L2)2]+ is a CuI complex with two clearly different ligand units in the solid state and with a magnetic susceptibility close to a diamagnetic compound. Further one‐electron oxidation of the complex with L1 ligands results in a dication [Cu(L1)2]2+, best described as a CuI complex with a twofold oxidised, monocationic ligand and a neutral radical ligand. The stability in at least three redox states, the accumulation of spin density at the ligands and the facile ligand‐metal electron transfer make these complexes highly attractive for a variety of applications; here the catalytic aerobic oxidation of alcohols to aldehydes is tested., Oxidation‐induced reduction: The oxidation of mononuclear CuII complexes with novel unsymmetric redox‐active urea azine or thio‐urea azine ligands leads to metal reduction and formation of complexes with intriguing electronic structures. The stability in several redox states is the basis for their first application in catalytic aerobic alcohol oxidation.

The ability to measure the concentration of metabolites in biological samples is important, both in the clinic and for home diagnostics. Here we present a nanopore‐based biosensor and automated data analysis for quantification of thiamine in urine in less than a minute, without the need for recalibration. For this we use the Cytolysin A nanopore and equip it with an engineered periplasmic thiamine binding protein (TbpA). To allow fast measurements we tuned the affinity of TbpA for thiamine by redesigning the π‐π stacking interactions between the thiazole group of thiamine and TbpA. This substitution resulted furthermore in a marked difference between unbound and bound state, allowing the reliable discrimination of thiamine from its two phosphorylated forms by residual current only. Using an array of nanopores, this will allow the quantification within seconds, paving the way for next‐generation single‐molecule metabolite detection systems., Quantification of small molecules in biological samples is challenging. Using the concentration‐dependent current fluctuations elicited by a thiamine binding protein inside a ClyA nanopore, we show the automated quantification of thiamine in urine in less than a minute. By swapping the internal biosensor, this principle can be applied for the development of multiple next‐generation home‐diagnostic small‐molecule sensors.

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.

Coccoliths are plates of biogenic calcium carbonate secreted by calcifying marine phytoplankton; annually these phytoplankton are responsible for exporting >1 billion tonnes (1015 g) of calcite to the deep ocean. Rapid and reliable methods for assessing the degree of calcification are technically challenging because the coccoliths are micron sized and contain picograms (pg) of calcite. Here we pioneer an opto‐eletrochemical acid titration of individual coccoliths which allows 3D reconstruction of each individual coccolith via in situ optical imaging enabling direct inference of the coccolith mass. Coccolith mass ranging from 2 to 400 pg are reported herein, evidencing both inter‐ and intra‐species variation over four different species. We foresee this scientific breakthrough, which is independent of knowledge regarding the species and calibration‐free, will allow continuous monitoring and reporting of the degree of coccolith calcification in the changing marine environment., Acid dissolution enables 3D image reconstruction of coccoliths, providing mass estimation in the range of 2 to 400 picograms.

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.

Threading intercalators bind DNA with high affinities. Here, we describe single‐molecule studies on a cell‐permeant luminescent dinuclear ruthenium(II) complex that has been previously shown to thread only into short, unstable duplex structures. Using optical tweezers and confocal microscopy, we show that this complex threads and locks into force‐extended duplex DNA in a two‐step mechanism. Detailed kinetic studies reveal that an individual stereoisomer of the complex exhibits the highest binding affinity reported for such a mono‐intercalator. This stereoisomer better preserves the biophysical properties of DNA than the widely used SYTOX Orange. Interestingly, threading into torsionally constrained DNA decreases dramatically, but is rescued on negatively supercoiled DNA. Given the “light‐switch” properties of this complex on binding DNA, it can be readily used as a long‐lived luminescent label for duplex or negatively supercoiled DNA through a unique “load‐and‐lock” protocol., Using single‐molecule optical tweezers and confocal microscopy we perform kinetic analysis of a novel dinuclear ruthenium(II) DNA imaging probe. Reversable binding is observed on relaxed DNA, however on stretching DNA, threading can occur, resulting in high affinity stable binding. Threading is highly stereoisomer specific and dependent on DNA supercoiling state. This DNA probe has exciting potential for DNA structure specific imaging.

Structural changes at the active site of an enzyme induced by binding to a substrate molecule can result in enhanced activity in biological systems. Herein, we report that the new hybrid ultramicroporous material sql‐SIFSIX‐bpe‐Zn exhibits an induced fit binding mechanism when exposed to acetylene, C2H2. The resulting phase change affords exceptionally strong C2H2 binding that in turn enables highly selective C2H2/C2H4 and C2H2/CO2 separation demonstrated by dynamic breakthrough experiments. sql‐SIFSIX‐bpe‐Zn was observed to exhibit at least four phases: as‐synthesised (α); activated (β); and C2H2 induced phases (β′ and γ). sql‐SIFSIX‐bpe‐Zn‐β exhibited strong affinity for C2H2 at ambient conditions as demonstrated by benchmark isosteric heat of adsorption (Q st) of 67.5 kJ mol−1 validated through in situ pressure gradient differential scanning calorimetry (PG‐DSC). Further, in situ characterisation and DFT calculations provide insight into the mechanism of the C2H2 induced fit transformation, binding positions and the nature of host‐guest and guest‐guest interactions., We introduce the new flexible physisorbent sql‐SIFSIX‐bpe‐Zn and reveal that it exhibits an induced fit structural change that results in extraordinary affinity for C2H2 that in turn enables high selectivity for separation of C2H2 over C2H4 and CO2.

[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.

Structurally authenticated free B‐alkyl boroles are presented and electronic implications of alkyl substitution were assessed. Deprotonation of a boron‐bound exocyclic methyl group in a B‐methyl borole yields the first 5‐boratafulvene anion—an isomer to boratabenzene. Boratafulvene was structurally characterized and its electronic structure probed by DFT calculations. The pK a value of the exocyclic B−CH3 in a set of boroles was computationally approximated and confirmed a pronounced acidic character caused by the boron atom embedded in an anti‐aromatic moiety. The non‐aromatic boratafulvene reacts as a C‐centered nucleophile with the mild electrophile Me3SnCl to give a stannylmethyl borole, regenerating the anti‐aromaticity. As nucleophilic synthons for boroles, boratafulvenes thus open an entirely new avenue for synthetic strategies toward this highly reactive class of heterocycles. Boratafulvene reacts as a methylene transfer reagent in a bora‐Wittig‐type reaction generating a borole oxide., The first boratafulvene was accessed by deprotonation of a B‐methyl borole. The boratafulvene is a new C‐nucleophilic synthon for substituted boroles and reacts with carbonyls in a bora‐Wittig‐type reaction transferring the methylene group.

In dynamic covalent chemistry, reactions follow a thermodynamically controlled pathway through equilibria. Reversible covalent‐bond formation and breaking in a dynamic process enables the interconversion of products formed under kinetic control to thermodynamically more stable isomers. Notably, enantioselective catalysis of dynamic transformations has not been reported and applied in complex molecule synthesis. We describe the discovery of dynamic covalent enantioselective metal‐complex‐catalyzed 1,3‐dipolar cycloaddition reactions. We have developed a stereodivergent tandem synthesis of structurally and stereochemically complex molecules that generates eight stereocenters with high diastereo‐ and enantioselectivity through asymmetric reversible bond formation in a dynamic process in two consecutive Ag‐catalyzed 1,3‐dipolar cycloadditions of azomethine ylides with electron‐poor olefins. Time‐dependent reversible dynamic covalent‐bond formation gives enantiodivergent and diastereodivergent access to structurally complex double cycloadducts with high selectivity from a common set of reagents., A highly enantioselectively catalyzed dynamic covalent one‐pot‐tandem 1,3‐dipolar cycloaddition of azomethine ylides to α′‐alkylidene‐2‐cyclopentenones is described. Time‐dependend enantio‐ and diastereodivergent synthesis was achieved by using the same set of reagents. A reversible cycloaddition of the kinetically favored product enables the interconversion to its more stable thermodynamically favored product through a chiral complex‐mediated process.

Synthesis of a pentasil‐type zeolite with ultra‐small few‐unit‐cell crystalline domains, which we call FDP (few‐unit‐cell crystalline domain pentasil), is reported. FDP is made using bis‐1,5(tributyl ammonium) pentamethylene cations as structure directing agent (SDA). This di‐quaternary ammonium SDA combines butyl ammonium, in place of the one commonly used for MFI synthesis, propyl ammonium, and a five‐carbon nitrogen‐connecting chain, in place of the six‐carbon connecting chain SDAs that are known to fit well within the MFI pores. X‐ray diffraction analysis and electron microscopy imaging of FDP indicate ca. 10 nm crystalline domains organized in hierarchical micro‐/meso‐porous aggregates exhibiting mesoscopic order with an aggregate particle size up to ca. 5 μm. Al and Sn can be incorporated into the FDP zeolite framework to produce active and selective methanol‐to‐hydrocarbon and glucose isomerization catalysts, respectively., A simple di‐quaternary ammonium cation was used as structure‐directing agent to prepare few‐unit‐cell (ca. 10 nm) MFI type zeolite catalysts and adsorbents with a wide range of composition (pure silica, aluminosilicate and stannosilicate). The SDA design was selected based on simple heuristic arguments regarding contributions of its structural elements to early crystal growth characteristics of MFI.

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.

Covalent organic frameworks (COFs) have emerged as an important class of organic semiconductors and photocatalysts for the hydrogen evolution reaction (HER)from water. To optimize their photocatalytic activity, typically the organic moieties constituting the frameworks are considered and the most suitable combinations of them are searched for. However, the effect of the covalent linkage between these moieties on the photocatalytic performance has rarely been studied. Herein, we demonstrate that donor‐acceptor (D‐A) type imine‐linked COFs can produce hydrogen with a rate as high as 20.7 mmol g−1 h−1 under visible light irradiation, upon protonation of their imine linkages. A significant red‐shift in light absorbance, largely improved charge separation efficiency, and an increase in hydrophilicity triggered by protonation of the Schiff‐base moieties in the imine‐linked COFs, are responsible for the improved photocatalytic performance., Protonation of imine‐linked COFs yields significant variations of their (opto)electronic properties and results in a largely enhanced performance in photocatalytic hydrogen evolution from water. This is attributed to an enhanced light absorption ability, charge separation efficiency, and hydrophilicity of imine‐linked COFs upon protonation.

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.

Water oxidation to dioxygen is one of the key reactions that need to be mastered for the design of practical devices based on water splitting with sunlight. In this context, water oxidation catalysts based on first‐row transition metal complexes are highly desirable due to their low cost and their synthetic versatility and tunability through rational ligand design. A new family of dianionic bpy‐amidate ligands of general formula H2LNn− (LN is [2,2′‐bipyridine]‐6,6′‐dicarboxamide) substituted with phenyl or naphthyl redox non‐innocent moieties is described. A detailed electrochemical analysis of [(L4)Cu]2− (L4=4,4′‐(([2,2′‐bipyridine]‐6,6′‐dicarbonyl)bis(azanediyl))dibenzenesulfonate) at pH 11.6 shows the presence of a large electrocatalytic wave for water oxidation catalysis at an η=830 mV. Combined experimental and computational evidence, support an all ligand‐based process with redox events taking place at the aryl‐amide groups and at the hydroxido ligands., A family of Cu‐based complexes bearing dianionic bpy‐amidate ligands have been prepared and characterized by spectroscopic and electrochemical techniques. The new complexes are capable of performing water oxidation catalysis at overpotentials between 557–830 mV pH 11.6. A detailed electrocatalytic study in combination with computational calculations revealed the all ligand‐based nature of the electron transfer processes involved in the catalytic cycle.

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.

Crenarchaeol is a glycerol dialkyl glycerol tetraether lipid produced exclusively in Archaea of the phylum Thaumarchaeota. This membrane‐spanning lipid is undoubtedly the structurally most sophisticated of all known archaeal lipids and an iconic molecule in organic geochemistry. The 66‐membered macrocycle possesses a unique chemical structure featuring 22 mostly remote stereocenters, and a cyclohexane ring connected by a single bond to a cyclopentane ring. Herein we report the first total synthesis of the proposed structure of crenarchaeol. Comparison with natural crenarchaeol allowed us to propose a revised structure of crenarchaeol, wherein one of the 22 stereocenters is inverted., Total synthesis of the proposed structure of crenarchaeol and comparison with the natural isolate has led to a revised structure of crenarchaeol, wherein one of the 22 stereocenters is inverted. The synthesis featured an asymmetric intermolecular Tsuji–Trost‐type alkylation to access the unusual 5‐6‐ring motif as well as a late stage ring‐closing metathesis to access the 66‐membered macrocycle of crenarchaeol.

Supertetrahedral clusters have been reported in two generally different types so far: one type possessing an organic ligand shell, no or low charges, and high solubility, while the other cluster type is ligand‐free with usually high charges and low or no solubility in common solvents. The latter is a tremendous disadvantage regarding further use of the clusters in solution. However, as organic substituents usually broaden the HOMO–LUMO gaps, which cannot be overcompensated by the (limited) cluster sizes, a full organic shielding comes along with drawbacks regarding opto‐electronic properties. We therefore sought to find a way of generating soluble clusters with a minimum number of organic substituents. Here, we present the synthesis and full characterization of two salts of [Sn10O4S16(SBu)4]4− that are high soluble in CH2Cl2 or CH3CN, which includes first NMR and mass spectra obtained from solutions of such salts with mostly inorganic supertetrahedral clusters. The optical absorption properties of this new class of compounds indicates nearly unaffected band gaps. The synthetic approach and the spectroscopic findings were rationalized and explained by means of high‐level quantum chemical studies., Selective access to partially butylated supertetrahedral clusters [Sn10O4S16(SBu)4]4− was achieved by employing a di‐butylated ionic liquid as reaction medium and alkylation agent. In contrast to purely inorganic [Sn10O4S20]8−, the butylated analogs are soluble in solvents like CH2Cl2 or CH3CN, without losing the typical opto‐electronic properties. Solution‐NMR data were assigned with the help of newly developed all‐electron relativistic DFT methods.

A general protocol for the selective hydrogenation and deuteration of a variety of alkenes is presented. Key to success for these reactions is the use of a specific nickel‐graphitic shell‐based core–shell‐structured catalyst, which is conveniently prepared by impregnation and subsequent calcination of nickel nitrate on carbon at 450 °C under argon. Applying this nanostructured catalyst, both terminal and internal alkenes, which are of industrial and commercial importance, were selectively hydrogenated and deuterated at ambient conditions (room temperature, using 1 bar hydrogen or 1 bar deuterium), giving access to the corresponding alkanes and deuterium‐labeled alkanes in good to excellent yields. The synthetic utility and practicability of this Ni‐based hydrogenation protocol is demonstrated by gram‐scale reactions as well as efficient catalyst recycling experiments., Hydrogenation and deuteration of olefins made easy: A core–shell‐structured Ni‐nanocatalyst (Ni NPs@C) allows the selective hydrogenation and deuteration of alkenes under ambient conditions (1 bar H2/D2, room temperature).

Polymer brush surfaces that alter their physical properties in response to chemical stimuli have the capacity to be used as new surface‐based sensing materials. For such surfaces, detecting the polymer conformation is key to their sensing capabilities. Herein, we report on FRET‐integrated ultrathin (, FRET chemistry was integrated within stimuli‐responsive polymer brush layers on planar substrates for spatial sensing of changing polymer conformations. Sensing was demonstrated for a variety of liquid mixture compositions, including high‐resolution observation of lateral differences in polymer conformation at immiscible liquid interfaces (see picture), thus offering great potential to be leveraged for new surface‐based sensing devices.

The thiol group of the cysteine side chain is arguably the most versatile chemical handle in proteins. To expand the scope of established and commercially available thiol bioconjugation reagents, we genetically encoded a second such functional moiety in form of a latent thiol group that can be unmasked under mild physiological conditions. Phenylacetamidomethyl (Phacm) protected homocysteine (HcP) was incorporated and its latent thiol group unmasked on purified proteins using penicillin G acylase (PGA). The enzymatic deprotection depends on steric accessibility, but can occur efficiently within minutes on exposed positions in flexible sequences. The freshly liberated thiol group does not require treatment with reducing agents. We demonstrate the potential of this approach for protein modification with conceptually new schemes for regioselective dual labeling, thiol bioconjugation in presence of a preserved disulfide bond and formation of a novel intramolecular thioether crosslink., Enzymatic deprotection of a latent thiol under mild and physiological conditions expands the scope of classic thiol bioconjugation. New reaction schemes enable regioselective labeling and dual modifications for a variety of preparative applications and using the established and commercially available plethora of thiol‐directed reagents.

The first examples of monolithic crystalline host–guest hybrid materials are described. The reaction of 1,3,5‐benzenetricarboxylic acid (H3BTC) and Fe(NO3)3⋅9 H2O in the presence of decamethylcucurbit[5]uril ammonium chloride (MC5⋅2 NH4Cl⋅4 H2O) directly affords MC5@MIL‐100(Fe) hybrid monoliths featuring hierarchical micro‐, meso‐ and macropores. Particularly, this “bottle‐around‐ship” synthesis and one‐pot shaping are facilitated by a newly discovered Fe‐MC5 flowing gel formed by mechanochemistry. The designed MC5@MIL‐100(Fe) hybrid material with MC5 as active domains shows enhanced CH4 and lead(II) uptake performance, and selective capture of lead(II) cations at low concentrations. This shows that host–guest hybrid materials can exhibit synergic properties that out‐perform materials based on individual components., Mechanochemistry has been applied to achieve one‐pot fabrication of monolithic decamethylcucurbit[5]uril (MC5)‐encapsulating metal–organic frameworks. The designed MC5@MIL‐100(Fe) hybrid material with MC5 as active domains shows enhanced uptake, and selective capture of lead(II) cations at low concentrations. This work opens up the novel possibility of designing task‐specific porous host–guest hybrid materials on a macroscopic scale.

The clever one‐pot combination of two macromolecular concepts, ring‐opening polymerization (ROP) and step‐growth polymerization (SGP), is demonstrated to be a simple, yet powerful tool to design a library of sequence‐controlled polymers with diverse and spatially regulated degradability functions. ROP and SGP occur sequentially at room temperature when the organocatalytic conditions are switched from basic to acidic, and each allows the encoding of specific degradable bonds. ROP controls the sequence length and position of the degradability functions, while SGP between the complementary vinyl ether and hydroxyl chain‐ends enables the formation of acetal bonds and high‐molar‐mass copolymers. The result is the rational combination of cleavable bonds prone to either bulk or surface erosion within the same macromolecule. The strategy is versatile and offers higher chemical diversity and level of control over the primary structure than current aliphatic polyesters or polycarbonates, while being simple, effective, and atom‐economical and having potential for scalability., A dual polymerization approach creates new possibilities to access polymeric materials with sequence‐controlled primary structure and diverse degradable bonds. The methodology is overall simple and effective and involves an in situ organocatalyst switch, which leads to different polymerization mechanisms, and as a consequence, specific degradability functions are encoded.

The 1,3‐bis(tricyanoborane)imidazolate anion 1 was obtained in high yield from lithium imidazolate and B(CN)3−pyridine adduct. Anion 1 is chemically very robust and thus allowed the isolation of the corresponding H5O2 + salt. Furthermore, monoanion 1 served as starting species for the novel dianionic N‐heterocyclic carbene (NHC), 1,3‐bis(tricyanoborane)imidazoline‐2‐ylidenate anion 3 that acts as ditopic ligand via the carbene center and the cyano groups at boron. First reactions of this new NHC 3 with methyl iodide, elemental selenium, and [Ni(CO)4] led to the methylated imidazolate ion 4, the dianionic selenium adduct 5, and the dianionic nickel tricarbonyl complex 6. These NHC derivatives provide a first insight into the electronic and steric properties of the dianionic NHC 3. Especially the combination of properties, such as double negative charge, different coordination sites, large buried volume and good σ‐donor and π‐acceptor ability, make NHC 3 a unique and promising ligand and building block., Unprecedentedly stable salts of the 1,3‐bis(tricyanoborane)imidazolate ion with different types of counterions were obtained on large scale. Deprotonation of the imidazolate ion provided access to the corresponding dianionic NHC that acts as ditopic ligand.

Ir‐catalyzed asymmetric alkene hydrogenation is presented as the strategy par excellence to prepare saturated isoprenoids and mycoketides. This highly stereoselective synthesis approach is combined with an established 13C‐NMR method to determine the enantioselectivity of each methyl‐branched stereocenter. It is shown that this analysis is fit for purpose and the combination allows the synthesis of the title compounds with a significant increase in efficiency., Cyclo‐archaeol, iso‐caldarchaeol, caldarchaeol, and mycoketide are prepared by employing asymmetric hydrogenation to generate the multiple stereocenters.

Diethynyl phosphinates were developed as bisfunctional electrophiles for the site‐selective modification of peptides, proteins and antibodies. One of their electron‐deficient triple bonds reacts selectively with a thiol and positions an electrophilic moiety for a subsequent intra‐ or intermolecular reaction with another thiol. The obtained conjugates were found to be stable in human plasma and in the presence of small thiols. We further demonstrate that this method is suitable for the generation of functional protein conjugates for intracellular delivery. Finally, this reagent class was used to generate functional homogeneously rebridged antibodies that remain specific for their target. Their modular synthesis, thiol selectivity and conjugate stability make diethynyl phosphinates ideal candidates for protein conjugation for biological and pharmaceutical applications., Diethynyl phosphonites were found to react specifically with two thiols in aqueous buffer to give constructs that are stable under physiological conditions. This enables the facile generation of protein (double)‐conjugates. Moreover, these molecules can be used to rebridge the interchain disulfides of therapeutic IgG antibodies.

A long‐term goal in realizing a sustainable biocatalysis and organic synthesis is the direct use of the greenhouse gas CO2 as feedstock for the production of bulk and fine chemicals, such as pharmaceuticals, fragrances and food additives. Here we developed a modular in vitro platform for the continuous conversion of CO2 into complex multi‐carbon compounds, such as monoterpenes (C10), sesquiterpenes (C15) and polyketides. Combining natural and synthetic metabolic pathway modules, we established a route from CO2 into the key intermediates acetyl‐ and malonyl‐CoA, which can be subsequently diversified through the action of different terpene and polyketide synthases. Our proof‐of‐principle study demonstrates the simultaneous operation of different metabolic modules comprising of up to 29 enzymes in one pot, which paves the way for developing and optimizing synthesis routes for the generation of complex CO2‐based chemicals in the future., Coupling of a synthetic CO2‐fixing cycle and a natural glyoxylate assimilation cycle with different biosynthetic pathways enables the sustainable production of terpenes and polyketides. Demonstration of this modular, multi‐enzyme in vitro platform sets the stage for a diversified synthesis of pharmaceuticals and commodity chemicals directly from CO2.

Novel anticancer compounds and their precision delivery systems are actively developed to create potent and well‐tolerated anticancer therapeutics. Here, we report the synthesis of a novel anthracycline, Utorubicin (UTO), and its preclinical development as an anticancer payload for nanocarriers. Free UTO was significantly more toxic to cultured tumor cell lines than the clinically used anthracycline, doxorubicin. Nanoformulated UTO, encapsulated in polymeric nanovesicles (polymersomes, PS), reduced the viability of cultured malignant cells and this effect was potentiated by functionalization with a tumor‐penetrating peptide (TPP). Systemic peptide‐guided PS showed preferential accumulation in triple‐negative breast tumor xenografts implanted in mice. At the same systemic UTO dose, the highest UTO accumulation in tumor tissue was seen for the TPP‐targeted PS, followed by nontargeted PS, and free doxorubicin. Our study suggests potential applications for UTO in the treatment of malignant diseases and encourages further preclinical and clinical studies on UTO as a nanocarrier payload for precision cancer therapy., Utorubicin (UTO) is a novel anthracycline with higher anticancer activity than doxorubicin in cultured cancer cells. Nanoencapsulation of UTO in polymeric vesicles functionalized with tumor‐penetrating peptides increases the cytotoxicity of the drug in receptor‐positive cells in vitro and, after systemic administration into mice bearing triple‐negative tumors, potentiates UTO accumulation in malignant tissue.

A 12‐step total synthesis of the natural product dysiherbol A, a strongly anti‐inflammatory and anti‐tumor avarane meroterpene isolated from the marine sponge Dysidea sp., was elaborated. As key steps, the synthesis features an enantioselective Cu‐catalyzed 1,4‐addition/enolate‐trapping opening move, an Au‐catalyzed double cyclization to build up the tetracyclic core‐carbon skeleton, and a late installation of the C5‐bridgehead methyl group via proton‐induced cyclopropane opening associated with spontaneous cyclic ether formation. The obtained pentacyclic compound (corresponding to an anhydride of the originally suggested structure for dysiherbol A) showed identical spectroscopic data as the natural product, but an opposite molecular rotation. CD‐spectroscopic measurements finally confirmed that both the constitution and the absolute configuration of the originally proposed structure of (+)‐dysiherbol A need to be revised., In a key step of the first enantioselective total synthesis of the anti‐inflammatory marine meroterpene dysiherbol A, the tetra‐carbocyclic core skeleton is set‐up in a unique gold‐catalyzed double cyclization, and the ether bridge of the pentacyclic target structure is spontaneously formed under cyclopropane opening upon deprotection of a late intermediate.

Layered double hydroxides (LDHs) are among the most active and studied catalysts for the oxygen evolution reaction (OER) in alkaline electrolytes. However, previous studies have generally either focused on a small number of LDHs, applied synthetic routes with limited structural control, or used non‐intrinsic activity metrics, thus hampering the construction of consistent structure–activity‐relations. Herein, by employing new individually developed synthesis strategies with atomic structural control, we obtained a broad series of crystalline α‐MA(II)MB(III) LDH and β‐MA(OH)2 electrocatalysts (MA=Ni, Co, and MB=Co, Fe, Mn). We further derived their intrinsic activity through electrochemical active surface area normalization, yielding the trend NiFe LDH > CoFe LDH > Fe‐free Co‐containing catalysts > Fe‐Co‐free Ni‐based catalysts. Our theoretical reactivity analysis revealed that these intrinsic activity trends originate from the dual‐metal‐site nature of the reaction centers, which lead to composition‐dependent synergies and diverse scaling relationships that may be used to design catalysts with improved performance., Catalytic activities for oxygen evolution on crystalline 3d transition metal layered double hydroxides are derived using electrochemical surface area based normalization. Density functional calculations reveal a dual‐metal‐site feature of the reaction centers that provides opportunities to design new catalysts with improved performance.