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The 57th SCS Conference on Stereochemistry, better known as the Bürgenstock Conference, brought together a diverse range of chemistry expertise in Brunnen, Switzerland., (© 2024 Wiley-VCH GmbH.)

The synthesis of enantioenriched α-substituted 1,3-dicarbonyls remains a contemporary challenge in synthesis due to their tendency to undergo racemization via keto-enol tautomerization. Herein, we report a method to access enantioenriched β-ketoamides by a chiral sulfinimine-mediated [3,3]-sigmatropic sulfonium rearrangement. The transformation displays good chirality transfer, as well as excellent chemoselectivity and functional group tolerance. Diastereoselective reduction of the ketone moiety, also achievable in one-pot fashion, affords enantioenriched β-hydroxyamides., (© 2024 The Author(s). Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

The dehydro-Diels-Alder (DDA) reaction is a powerful method for the construction of aromatic compounds. However, the enantioselective DDA reaction has been rarely developed, probably due to the competitive thermal reaction. Herein, we report a copper-catalyzed enantioselective DDA reaction through vinyl cation pathway. The reaction leads to the atom-economical synthesis of axially chiral phenyl and indolyl carbazoles in generally excellent yields with good to excellent atroposelectivities. This methodology represents the first example of non-noble metal-catalyzed enantioselective DDA reaction. Notably, new chiral ligand and organocatalyst derived from the constructed axially chiral carbazole are demonstrated to be useful in asymmetric catalysis., (© 2024 Wiley-VCH GmbH.)

The multi-substituted anilines are widely found in organic synthesis, medicinal chemistry and material science. The quest for robust and efficient methods to construct a diverse array of these compounds using readily accessible starting materials under simple reaction conditions is of utmost importance. Here, we report an unprecedented and efficient approach for the synthesis of 2,4-di and 2,4,6-trisubstituted anilines. With a simple molybdenum(VI) catalyst, a wide range of 2,4-di and 2,4,6-trisubstituted anilines were efficiently prepared in generally good to excellent yields from readily accessible ynones and allylic amines. The synthetic potential of this methodology was further underscored by its applications in several synthetic transformations, gram-scale reactions, and derivatization of bioactive molecules. Preliminary mechanistic studies suggested that this aniline formation might involve a cascade of aza-Michael addition, [1,6]-proton shift, cyclization, dehydration, 6π-electrocyclization, and aromatization. This novel strategy provided a robust, simple, and modular approach for the syntheses of various valuable di- or trisubstituted anilines, some of which were otherwise challenging to access., (© 2024 Wiley-VCH GmbH.)

Benzo[1,3,2]dithiazole-1,1,3-trioxides are bench-stable and easy-to-use reagents. In photoredox catalysis, they generate methyl and perdeuteromethyl radicals which can add to a variety of radical acceptors, including olefins, acrylamides, quinoxalinones, isocyanides, enol silanes, and N-Ts acrylamide. As byproduct, a salt is formed which can be regenerated to the original methylating agent. Flow chemistry provides an option for reaction scale-up further underscoring the synthetic usefulness of these methylation reagents. Mechanistic investigations suggest a single-electron transfer (SET) pathway induced by photoredox catalysis., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

A comprehensive study on the physicochemical properties of gem-fluorinated O-heterocyclic substituents is reported. Systematic additive effects of introducing O- and gem-CF2 group introduction on acidic properties (pKa) of the corresponding carboxylic acids / protonated primary amines was demonstrated. The impact of the O/CF2 moieties on lipophilicity (LogP) were found to be complex; significant mutual influence of the corresponding polar moieties governed the compound's overall properties in this case. Biological evaluation of MAPK kinase inhibitors incorporating the title substituents demonstrated their utility as promising fragments for bioisosteric replacements in drug discovery campaigns., (© 2024 Wiley‐VCH GmbH.)

In this study, several hydrogen-bonded arylamide foldamers (compounds 1--5) with the same degree of polymerization were designed and synthesized. The polyfluoroiodobenzene or iodoethynyl polyfluoroiodobenzene segment was modified as a halogen donor at the end of the monomer, and pyridine or pyridine oxynitride served as the corresponding halogen acceptor segment. The crystal structure of compound 1 indicates that the supramolecular double helices were constructed by stacking a P helix and an M helix in an antiparallel manner in the direction of intermolecular I···⁻O-N⁺ halogen bonding. The zig-zag-shaped linear structures of compounds 2 and 3 were generated under the induction of intermolecular I···N and I···⁻O-N⁺ halogen bonds. [1+1] near-planar bimolecular supramolecular macrocycles in compounds 4 and 5 were formed by multiple groups of effective intramolecular three-center hydrogen bonding and strong I···N and I···⁻O-N⁺ halogen bonds. Hirshfeld surface analysis and theoretical modelling of the halogen bonding energy were performed. The noncovalent interactions on the surface of the monomers and the halogen bonding energy were investigated in detail., (© 2024 Wiley‐VCH GmbH.)

The on-surface synthesis strategy has emerged as a promising route for fabricating well-defined two-dimensional (2D) BN-substituted carbon nanomaterials with tunable electronic properties. This approach relies on specially designed precursors and requires a thorough understanding of the on-surface reaction pathways. It promises precise structural control at the atomic scale, thus complementing chemical vapor deposition (CVD). In this study, we investigated a novel heteroatomic precursor, tetrabromoborazine, which incorporates a BN core and an OH group, on Ag(111) using low temperature scanning tunnelling microscopy/spectroscopy (LT-STM/STS) and X-ray photoelectron spectroscopy (XPS). Through sequential temperature-induced reactions involving dehalogenation and dehydrogenation, distinct tetrabromoborazine derivatives were produced as reaction intermediates, leading to the formation of specific self-assemblies. Notably, the resulting intricate supramolecular structures include a chiral kagomé lattice composed of molecular dimers exhibiting a unique electronic signature. The final product obtained was a random covalent carbon network with BN-substitution and embedded oxygen heteroatoms. Our study offers valuable insights into the significance of the structure and functionalization of BN precursors in temperature-induced on-surface reactions, which can help future rational precursor design. Additionally, it introduces complex surface architectures that offer a high areal density of borazine cores., (© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.)

Nickel/photoredox dual catalyzed cross-coupling of aryl halides with alkylboron compounds is one of the effective methodologies for the construction of C(sp2)-C(sp3) bonds. Although elegant results have been achieved by using alkyl trifluoroborates as alkyl radical precursors, the generation of alkyl radicals from readily available alkyl boronic esters is still limited due to their high oxidation potential. We disclosed here that activation of alkyl boronic esters by MeOLi is highly efficient for the generation of alkyl radicals under photocatalysis conditions. The reaction featured with a wide substrate scope, high functional group tolerance, and late-stage modification of bioactive substances. In addition, the method was also successfully extended to alkyl boronic acids. Experimental and computational mechanistic studies indicated that the cross-coupling likely proceeds via a Ni(I)-catalyzed pathway., (© 2024 Wiley‐VCH GmbH.)

An enantioconvergent palladium-catalyzed Negishi cross-coupling with racemic secondary organozinc reagents has been developed, enabling access to enantioenriched 1,1-diarylalkane motifs in high yields and enantioselectivities. Computational data indicates that the racemization of organozinc compounds most likely occurs through a bridged bimolecular mechanism., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Starting from N-acyl sulfonimidamides, mechanochemically generated rhodium nitrenoids undergo intramolecular N-O couplings to provide unprecedented 1,3,2,4-oxathiadiazole 3-oxides in good to excellent yields. The cyclization proceeds efficiently with a catalyst loading of only 0.5 mol % in the presence of phenyliodine(III) diacetate (PIDA) as oxidant. Neither an inert atmosphere nor additional heating is required in this solvent-free procedure. Under heat or blue light, the newly formed five-membered heterocycles function as nitrene precursors reacting with sulfoxides as exemplified by the imidation of dimethyl sulfoxide., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Two diterpene synthases from the bacterium Chitinophaga pinensis were characterised. The first enzyme mainly produced the rearranged diterpene palmatol, a compound known from octocorals, while the second enzyme made the new coral-type eunicellane chitinol. The mechanisms of both enzymes were deeply studied through isotopic labelling experiments, DFT calculations, and with a substrate analog containing a saturated double bond, resulting in the formation of derailment products that gave additional insights into the nature of the cyclisation cascade intermediates. The formation of coral-type diterpenes poses interesting questions on the functions of these compounds in organisms as different as bacteria and corals., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

This work reports synthesis of a germylene based donor-acceptor molecule and its thermal excitation to a triplet state by coordination with a Lewis acid. Products have been characterized by single crystal X-ray diffraction, EPR spectroscopy, and SQUID measurement, in conjunction with DFT calculation. The singlet-triplet energy gap of the donor-acceptor molecule is dramatically reduced from -18.8 to -7.2 kcal/mol by the coordination with B(C 6 F 5 ) 3 (BCF), which enables an intramolecular single electron transfer from one germylene moiety to another upon heating, forming an intramolecular radical ion pair with diradical character. The work provides an approach to the formation of thermally populated open-shell species of heavier main group elements., (© 2024 Wiley-VCH GmbH.)

An air- and moisture-stable hydrocarbon radical with four six- and three five-membered rings alternately fused to a heptacycle was obtained by ortho fusion in a suitably ortho,ortho'-substituted diphenylfluorene and subsequent re-establishment of the conjugation. The radical was obtained in five consecutive steps from commercially available starting materials with a total yield of 34%; key steps are Suzuki couplings and cyclizing SEAr reactions. Mesityl substituents at the five-membered rings ensure the stability of the radical. This cyclopenta-fused polyaromatic hydrocarbon (CP-PAH) was characterized by EPR and UV/Vis spectroscopy and by cyclic voltammetry. Quantum chemical calculation disclosed further properties and led to simulated spectra (spin densities, aromaticity, orbital energies, and UV/Vis/NIR). This radical is best described with the unpaired electron centered in the outer five-membered rings; this resonance formula shows the largest number of fully intact benzene rings. Its triradical character was computed to be very small and can be neglected. The five-membered rings show notable antiaromatic character, especially in the central ring. The constitution of the radical could be further substantiated by X-ray crystallographic analysis of its direct precursor., (© 2024 Wiley‐VCH GmbH.)

Efficient fluorination reactions are key in the late-stage functionalization of complex molecules in medicinal chemistry, in upgrading chemical feedstocks, and in materials science. Radical C(sp 3 )-H fluorinations using Selectfluor ® - one of the most popular fluorination agents - allow to directly engage unactivated precursors under mild photochemical or thermal catalytic conditions. However, H-TEDA(BF 4 ) 2 to date is overlooked and discarded as waste, despite comprising 95% of the molecular weight of Selectfluor ® . We demonstrate that the addition of H-TEDA(BF 4 ) 2 at the start of fluorination reactions markedly promotes their rates and accesses higher overall yields of fluorinated products (~3.3 × higher on average across the cases studied) than unpromoted reactions. Several case studies showcase generality of the promotor, for photochemical, photocatalytic and thermal radical fluorination reactions. Detailed mechanistic investigations reveal the key importance of aggregation changes in Selectfluor ® and H-TEDA(BF 4 ) 2 to fill gaps of understanding in how radical C(sp 3 )-H fluorination reactions work. This study exemplifies an overlooked reaction waste product being upcycled for a useful application., (© 2024 The Authors. ChemSusChem published by Wiley-VCH GmbH.)

Most of the reported work focus on the development of O-, N-, C- and S-glycosylation methods. However, no study explores P(III)-glycosylation reaction. Herein we describe a convenient protocol to realize P(III)-glycosylation process. A simple β-phosphino ester is adopted as P(III)-transfer reagent for this new type of glycosylation via a nucleophilic substitution and release strategy. Diverse phosphine units are introduced to the anomeric center of various sugars efficiently and with excellent stereoselectivity. The value of this method is showcased by the prepared P(III)-sugars as novel linkers in bioactive molecule conjugation, new chiral ligands in metal-catalyzed asymmetric allylic substitutions and organocatalysts. Preliminary mechanistic studies corroborated the designed P(III)-transfer process., (© 2024 Wiley‐VCH GmbH.)

Silicon (Si) is considered to be one of the most promising anode materials for next-generation lithium-ion batteries. However, the practical application of Si-based anodes is mainly hindered by the low intrinsic conductivity of Si and the large volume change upon lithiation/de-lithiation. Here, we prepared a composite material consisting of Si nanoparticles (NPs) and coconut silk bio-carbon (CSC) skeleton. The porous carbon skeleton derived from coconut silk with natural through-holes and ample micropores, which was used as the carrier of Si NPs. The continuous through-holes and well-distributed oxygen-containing functional groups of the CSC provided sufficient space and adsorption active sites for Si NPs, what's more, the good dispersion of Si NPs increased their contact with the surrounding carbon materials, which was conducive to electron transport. Meanwhile, the pore structure provided buffer space for the volume expansion of Si. The rich oxygen-containing functional groups can form a certain chemical force with silicon particles, and further stabilize the nano silicon particles. Hence, the CSC/Si electrode revealed an excellent capacity retention of 82.8% at 1 A g-1 after 100 cycles. This study provides a simple universal high-throughput method to obtain anode materials with outstanding electrochemical properties and promotes the further development of Si/C composites., (© 2024 Wiley‐VCH GmbH.)

Electrophilic activation of the aromatic cyclo-P 5 ligand in [Cp*Fe(η 5 -P 5 )] is demonstrated to drastically enhance its reactivity towards weak nucleophiles. Unprecedented functionalized, contracted as well as complexly aggregated polyphosphorus compounds are accessed utilizing [Cp*Fe(η 5 -P 5 Me)][OTf] (A), highlighting the great potential of this underexplored mode of reactivity. Addition of carbenes to A affords novel 1,2- or 1,1-difunctionalized cyclo-P 5 complexes [Cp*Fe(η 4 -P 5 (1-L)(2-Me)][OTf] (L=IDipp (1), Et CAAC (2), I i Pr (3 b)) and [Cp*Fe(η 4 -P 5 (1-I i Pr)(1-Me)][OTf] (3 a). For the first time, the much smaller IMe 4 leads to the contraction of the cyclo-P 5 ligand and formation of [Cp*Fe(η 4 -P 4 (1-IMe)(4-Me)] (4). DFT calculations shed light on the delicate mechanism of this type of reaction, which is reinforced by the experimental identification of key intermediates. Even the comparably weak nucleophile IDippCH 2 reacts with A to form [Cp*Fe(η 4 -P 5 (1-IDippCH 2 )(1/2-Me)][OTf] (6 a/b), highlighting its explicitly more reactive nature. Moreover, exposure of A to IDippEH (E=N, P) leads to a unique aggregation reaction affording [{Cp*Fe} 2 {μ 2 ,η 4:3:1 -P 10 Me 2 (IDippN)}][OTf] (8) and [{Cp*Fe} 2 {μ 2 ,η 4:1:1:1 -P 11 Me 2 (IDipp)}][OTf] (9), respectively., (© 2024 Wiley-VCH GmbH.)

This study investigates the hydrogen-bond geometry in six two-component solid systems composed of quinoline and chloro-nitrobenzoic acids. New X-ray diffraction studies were conducted using both the conventional independent-atom model and the more recent Hirshfeld atom-refinement method, with the latter providing precise hydrogen-atom positions. The systems can be divided into salts (the hydrogen atom transferred to the quinoline nitrogen), cocrystals (the hydrogen atom retained by the acid), and intermediate structures. Solid-state NMR experiments corroborated the X-ray diffraction-derived H-N distances. DFT calculations, using five functionals including hybrid B3LYP and PBE0, showed varying energy profiles for the hydrogen bonds, with notable differences across functionals. These calculations revealed different preferences for salt or cocrystal structures, depending on the functional used. Path-integral molecular dynamics simulations incorporating nuclear quantum effects demonstrated significant hydrogen-atom delocalization, forming a hydrogen-bond continuum, and provided average N-H distances in excellent agreement with experimental results. This comprehensive experimental and theoretical approach highlights the complexity of multicomponent solids. The study emphasizes that the classification into salts or cocrystals is frequently inadequate, as the hydrogen atom is often significantly delocalized in the hydrogen bond. This insight is crucial for understanding and predicting the behavior of such systems in pharmaceutical applications., (© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.)

Electrochemical transformations are considered a green alternative to classical redox chemistry as it eliminates the necessity for toxic and waste producing redox reagents. Typical electrochemical reactions require the addition of a supporting electrolyte - an ionic compound to facilitate reaction medium conductivity. However, this is often accompanied by an increase in the amount of produced waste. Here, we report an "in-situ electrolyte" concept for facile, transition-metal-free, additive-free one-pot electrochemical preparation of isoxazol(in)es, important scaffolds for biologically active natural and synthetic molecules, from the respective aldehydes. The protocol utilizes no halogenated solvents and no external oxidants, while salt side-products provide the ionic conductivity necessary for the electrosynthesis. The electrolysis is performed in an undivided cell, using the state-of-the-art electrodes for the chlor-alkali industry dimensionally stable and scalable mixed metal oxide anode and platinized titanium cathode of high durability. The cascade transformation comprises the condensation of aldehyde to oxime followed by its anodic oxidation and subsequent intra- and/or intermolecular [3+2] cycloadditions with an appropriate dipolarophile. Chemical yields up to 97 %, and good Faradaic efficiency, scalability, and stability are observed for most substrates in a broad scope., (© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.)

A (3+3)-cycloaddition to afford 2-azabiyclo[3.1.1]heptanes was realized by reacting highly strained aryl bicyclo[1.1.0]butane (BCBs) carboxylates with tosylated aziridines. Under Sc(OTf)3 catalysis the transformation proceeded smoothly under mild conditions to the corresponding bicyclic products bearing at the bridgeheads of the embedded four-membered ring aryl and ester moieties, respectively. This reaction is a rare example of a cycloaddition of two highly strained ring systems under Lewis acid catalysis. Mechanistic experiments provided insights into the reaction mechanism., (© 2024 Wiley‐VCH GmbH.)

While aromatic diazonium salts are important reagents in organic synthesis, 'Diazonium ions generated from ordinary aliphatic primary amines are usually useless for preparative purposes, since they lead to a mixture of products giving not only substitution by any nucleophile present, but also elimination and rearrangements if the substrate permits.'[1] In this work, we report that the statement is no longer valid, and it is now possible to control diazotization of aliphatic amines by utilizing isopentyl nitrite in HFIP. This transformation enabled electrophilic aromatic substitution with these highly abundant and commercially available alkyl reagents, as well as transforming them into building blocks typically employed in organic synthesis. The methodology opens an avenue for reactions involving aliphatic amines, even such demanding substrates as amino acids, as a source of carbocations thus expanding the degree of chemical space., (© 2024 Wiley‐VCH GmbH.)

A preparation method for steroid-based difluoroboron complexes has been developed using lumiestrone as a steroid example. Previously inaccessible lumiestrone-based difluoroboron complexes annulated at positions 16 and 17 of the D ring have been prepared. Such difluoroboron complexes may have large synthetic potential for heterofunctionalization of steroids at the D ring. An application of a borylation mixture Ac 2 O-BF 3 ⋅OEt 2 significantly simplify the preparation of steroid "dimers" bearing two estrone moieties connected at positions 2 and 2' via a linker. Crystal structures of key representatives have been determined by X-ray diffraction., (© 2024 Wiley-VCH GmbH.)

The mechanical bond is emerging as a novel design element in catalyst development. Here, we report a series of 1,1'-binaphthyl-2,2'-diol (BINOL) based catalysts in which the number of interlocked macrocycles is varied. Unsurprisingly, the macrocycles have a profound steric influence on the catalytic performance of these molecules. However, in the enantioselective transformations examined, the macrocycles are detrimental to catalyst stereoselectivity whereas in lactide polymerization, they increase the molecular weight of the polymeric product., (© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.)

G-quadruplexes are noncanonical nucleic acid structures formed by stacked guanosine tetrads. Despite their functional and structural diversity, a single consensus model is typically used to describe sequences with the potential to form G-quadruplex structures. We are interested in developing more specific sequence models for G-quadruplexes. In previous work, we functionally characterized each sequence in a 496-member library of variants of a monomeric reference G-quadruplex for the ability to bind GTP, promote a model peroxidase reaction, generate intrinsic fluorescence, and to form multimers. Here we used NMR to obtain a broad overview of the structural features of this library. After determining the 1 H NMR spectrum of each of these 496 sequences, spectra were sorted into multiple classes, most of which could be rationalized based on mutational patterns in the primary sequence. A more detailed screen using representative sequences provided additional information about spectral classes, and confirmed that the classes determined based on analysis of 1 H NMR spectra are correlated with functional categories identified in previous studies. These results provide new insights into the surprising structural diversity of this library. They also show how NMR can be used to identify classes of sequences with distinct mutational signatures and functions., (© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.)

The use of Fpocket and virtual screening techniques enabled us to identify potential allosteric druggable pockets within the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). Of the compounds screened, compound 1 was identified as a promising inhibitor, lowering a SARS-CoV-2 RdRp activity to 57 % in an enzymatic assay at 10 μM concentration. The structure of compound 1 was subsequently optimized in order to preserve or enhance inhibitory activity. This involved the substitution of problematic ester and aromatic nitro groups with more inert functionalities. The N,N'-diphenylurea scaffold with two NH groups was identified as essential for the compound's activity but also exhibited high toxicity in Calu-3 cells. To address this issue, a scaffold hopping approach was employed to replace the urea core with potentially less toxic urea isosteres. This approach yielded several structural analogues with notable activity, specifically 2,2'-bisimidazol (in compound 55 with residual activity RA=42 %) and (1H-imidazol-2-yl)urea (in compounds 59 and 60, with RA=50 and 28 %, respectively). Despite these advances, toxicity remained a major concern. These compounds represent a promising starting point for further structure-activity relationship studies of allosteric inhibitors of SARS-CoV-2 RdRp, with the goal of reducing their cytotoxicity and improving aqueous solubility., (© 2024 The Authors. ChemMedChem published by Wiley-VCH GmbH.)

The transition metal-catalyzed direct coupling reactions involving electron-rich Fischer carbene species are largely underdeveloped and remain a big challenge. Here, a direct coupling reaction of azoles and azine N-oxides is reported with Fischer copper carbene species bearing an α-siloxy group i, which can be in situ generated from acylsilanes catalytically under photoirradiation and redox-neutral conditions. This coupling reaction between electron-rich α-siloxy Fischer Cu-carbene species with hard carbanion nucleophiles may undergo a bimetallic relay process, which is confirmed by the kinetic analysis and in situ NMR analysis. This reaction features mild conditions and remarkable heterocycle compatibility. Notably, this protocol tolerates a series of azole or azine N-oxide derivatives, including benzoxazole, benzothiazole, benzoimidazole, benzoisoxazole, oxazole, oxadiazole, triazolo[4,3-a]pyridine, purine, caffeine, pyridine N-oxide, quinoline N-oxide, pyrazine N-oxide, pyridazine N-oxide, etc. The synthetic value of this approach is demonstrated by the efficient synthesis of a histamine h4 receptor ligand and a marketed drug carbinoxamine., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Durable functionalization on polypropylene (PP) surfaces is always a key problem to besolved. Coatings with low surface energy peel off easily especially under extreme conditions, owing to their weak adhesion. In this paper, side groups of both polyhedral oligomeric silsesquioxane (POSS) and alkane are grafted to polypentafluorophenyl methacrylate (PFP), and then PP blends with these side-group modified PFP are obtained through a melt-blending process. It is found that POSS can result in surface segregation and provide hydrophobicity in blends. Microfibers are formed because of the orientation effect during the tensile testing, which furtherly promotes mechanical strength. Significantly, alkaneside-groups can be entangled with PP segments, which brings about cross linking. Therefore, with crosslinking and synchronous orientation of POSS, the elongation at the break of blends is greatly increased up to 974%. The final blend demonstrates quite durable hydrophobicity under many extreme conditions, such as repeated tape peeling, ultrasonic washing, strong friction, and soaking in strong acid (pH = 1), strong alkali (pH = 14) and alcohol. The heat and UV resistance of the blend are also obviously improved. This study will develop anovel and facile strategy to endow PP with durable hydrophobicity as well as greatly enhanced mechanical properties., (© 2024 Wiley‐VCH GmbH.)

In this study, we present the synthesis and a versatile way to incorporate photoresponsive organic luminophores into polymeric materials using mesoporous silica nanoparticles (MSNs). The encapsulated thioethers within the MSNs were employed in polyvinyl alcohol (PVA) films, resin-based stereolithography, and electrospinning. Due to light-induced cyclization to dibenzothiophenes (DBTs), mmOC12 loaded materials were used to inscribe images using UV light. The DBTs formed from mmOC12 (mmDBTA/B) exhibit a long phosphorescence afterglow, which was investigated by steady-state and time-resolved photoluminescence spectroscopy. In addition, scanning electron microscopy (SEM) imaging, including energy dispersive X-ray spectroscopy (EDX), revealed the well-dispersed and intact MSNs in the polymeric materials. This approach shows a general way to incorporate non-polar organic luminophores into polymeric materials while retaining their unique emission properties., (© 2024 Wiley‐VCH GmbH.)

Halogenases are spurring a growing interest in the fields of biosynthesis and biocatalysis. Although various halogenases have been identified in numerous natural product biosynthetic pathways, the mechanisms for multiple halogenations and site-selectivity remain largely unclear. In this study, we biochemically characterized FasV, a flavin-dependent halogenase (FDH) that catalyzes five successive chlorinations in the biosynthesis of the naphthacene-containing aromatic polyketide naphthacemycin. This multiple halogenation reaction was elucidated to occur in an orderly fashion, as evidenced by enzyme kinetics, time-course assays, and computational simulations. Crystallographic analyses and mutagenesis studies revealed previously unrecognized amino acid residues, including T53, L81, F93, and I212, that are crucial for controlling regioselectivity and substrate specificity. Based on this, a I212T mutant was generated to exclusively catalyze selective monohalogenation. We propose a novel dual-activation mechanism and demonstrate that the larger binding pocket of FasV makes it a valuable biocatalyst for other substrates with diverse structures. Therefore, this study provides new insight into multi-site polyhalogenases and highlights the potential for engineering FasV-like FDHs for biocatalytic applications., (© 2024 Wiley-VCH GmbH.)

Sulfated cyclodextrins (CDs) are multiply negatively charged molecules widely used as chiral selectors in capillary electrophoresis (CE). In some of their applications, the effective charge numbers of their molecules were observed to be lower than the numbers of the attached sulfated groups due to strong binding of counterions. However, degree of reduction of the theoretical charge was not quantified. For that reason, in this study, capillary isotachophoresis (CITP) and capillary zone electrophoresis (CZE) were applied for the determination of the effective charge numbers and actual ionic mobilities of two kinds of sulfated CDs: single isomer sulfated α-, β-, and γ-CDs (SI-CDs) and randomly highly sulfated α-, β-, and γ-CDs (HS-CDs). The effective charge numbers of the SI-CDs and HS-CDs were determined from the length of their ITP zones, the ionic mobilities determined by CZE, and molar concentrations of their solutions applied for CITP analysis, and from the same parameters of reference compounds, formic acid for SI-CDs and dichloroacetic acid for HS-CDs. The determined effective charge numbers of the SI-CDs were equal to or only slightly lower than the numbers of sulfate groups in their molecules but the effective charge numbers of randomly HS-CDs were significantly (22.2%-27.8%) reduced as compared to the average numbers of sulfate groups in their molecules. In accordance with a lower number of sulfate groups in SI-CDs than in HS-CDs, the absolute values of the actual ionic mobilities of SI-CDs (35.5-37.5) × 10 -9  m 2  V -1  s -1 were lower than those of HS-CDs (43.5-44.1) × 10 -9  m 2  V -1  s -1 ., (© 2024 The Author(s). Electrophoresis published by Wiley‐VCH GmbH.)

Steroid hormones are C 18 -C 21 -sterane derivatives, featuring the typical 6-6-6-5 ring system. Here we report on a novel C 18 -steroid ring system named batrachane with a contracted A-ring resulting in a 5-6-6-5 ring arrangement. The isolation, structural elucidation, and total synthesis of three members of the novel batrachopolyene family occurring in the tropical frog genus Odontobatrachus is reported. The batrachopolyenes represent an entirely new collection of volatile steroidal natural products produced by anuran amphibians. Alongside the contracted A-ring, each member contains a Δ 16-17 double bond but differs in the central belt of the steroidal structure. To create these atypical structural features, syntheses featuring a combination of Breslow radical chain relay chlorination, Favorskii ring contraction, and Clemmensen reduction proved successful. The occurrence of such compounds in another distal anuran group, the Mantellinae, suggests a more widespread distribution of the batrachane-type compounds among frogs. The new structural steroid type raises questions concerning steroid biosynthesis and reception, as well as distribution in frogs in general and the structures of their hormones., (© 2024 The Author(s). Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Electrospun nanofibrous membranes made of chiral selectors (CSs) have shown their potential for efficient chiral resolutions via filtrations. It is thus of great importance to expand the number of electrospun membranes made of various CSs for the resolution of a wide range of chiral compounds. Here, the electrospinning of two benzyl carbamate derivatives of cellulose, namely cellulose benzyl carbamate (CBzC) and cellulose 4-chlorobenzyl carbamate (CCBzC), to form a new type of enantioselective membranes for chiral resolutions of racemic compounds, is reported. The morphology of the electrospun membranes is studied by optical microscopy and scanning electron microscopy in relation to the electrospinning process parameters. Liquid-liquid permeation experiments of the racemic compounds, (R,S)-1-(1-naphthyl)ethanol ((R,S)-NET), (R,S)-1,1'-bi-2-naphtol ((R,S)-BNP), (R,S)-naproxen ((R,S)-NAP), and (R,S)-benzoin ((R,S)-BNZ) through the membranes demonstrate preferable permeations of (R)- or (S)-enantiomers depending on the combinations between the CSs and the racemates. Molecular docking simulations indicate the differences in the binding type, number, and free energies between the CSs and the enantiomers., (© 2024 The Author(s). Macromolecular Bioscience published by Wiley‐VCH GmbH.)

para-Nitrophenyl (PNP) ethers of glycosides are important building blocks en route to functional carbohydrates. They are stable in neutral media, however, under basic conditions such as during the Zemplén deacylation of sugars, aryl migration is frequently observed. We have employed a library of O-PNP-substituted methyl glycosides of the manno-, galacto-, gluco- and altro-series to study the kinetics of aryl migration in MeOH/sodium methoxide using NMR spectroscopy revealing that migration between cis-oriented OH groups is faster than between trans-oriented ones. The rate constants of migration decrease in the order of Alt>Man>Gal>Glc and are related to the energy barriers of chair conformation inversion. The energy profile of the 3 to 4-PNP migration in methyl mannoside was calculated using DFT methods suggesting the Meisenheimer complex is an intermediate of PNP migration and that coordination of the sodium cation has a major impact on the energy profile., (© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.)

Here we present a highly versatile synthetic strategy based on twofold 6π-electrocyclization accompanied with HBr elimination as a novel approach towards centrosymmetric multi-heteroatom-doped nanographenes build around an electron-rich 1,4-dihydropyrrolo[3,2-b]pyrrole core. A straightforward synthesis from readily available substrates offers a unique possibility of fusing the 1,4-dihydropyrrolo[3,2-b]pyrrole subunit not only with carbocyclic building blocks, such as electron-deficient phenanthrenes, chrysenes, or [4]helicenes, but also with heterocyclic systems, such as benzo[b]furan and 5-thiatruxene. The clear advantage of this strategy is that there is no requirement to assemble complex scaffolds possessing bromoaryl units since bromine atom is introduced by bromination of 1,4-dihydropyrrolo[3,2-b]pyrrole core which, because of its exceptionally electron-rich character, is straightforward reaction. The obtained χ-shaped and S-shaped nanographenes containing 10 or more fused rings, exhibit visible-range emissions characterized by fluorescence quantum yields reaching 48 %. Computational studies of the reaction mechanism revealed that the 6π-electrocyclization is kinetically favourable over photo-induced direct arylation. Steady-state UV/Visible spectroscopy reveals that upon photoexcitation, the prepared S-shaped N-doped nanographenes undergo mostly radiative relaxation leading to large fluorescence quantum yields. We anticipate that this chemistry will empower the creation of new materials with various functionalities., (© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.)

With the rise of machine learning (ML), the modeling of chemical systems has reached a new era and has the potential to revolutionize how we understand and predict chemical reactions. Here, we probe the historic dependence on utilizing enantiomeric excess (ee) as a target variable and discuss the benefits of using relative Gibbs free activation energies (ΔΔG ≠ ), grounded firmly in transition-state theory, emphasizing practical benefits for chemists. This perspective is intended to discuss best practices that enhance modeling efforts especially for chemists with an experimental background in asymmetric catalysis that wish to explore modelling of their data. We outline the enhanced modeling performance using ΔΔG ≠ , escaping physical limitations, addressing temperature effects, managing non-linear error propagation, adjusting for data distributions and how to deal with unphysical predictions,in order to streamline modeling for the practical chemist and provide simple guidelines to strong statistical tools. For this endeavor, we gathered ten datasets from the literature covering very different reaction types. We evaluated the datasets using fingerprint-, descriptor-, and graph neural network-based models. Our results highlight the distinction in performance among varying model complexities with respect to the target representation, emphasizing practical benefits for chemists., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Deuterated and tritiated analogs of drugs are valuable compounds for pharmaceutical and medicinal chemistry. In this work, we present a novel hydrogen isotope exchange reaction of drugs using non-directed homogeneous Pd-catalysis. Aromatic C-H activation is achieved by a commercially available pyridine ligand. Using the most convenient and cheapest deuterium source, D 2 O, as the only solvent 39 pharmaceuticals were labelled with clean reaction profiles and high deuterium uptakes. Additionally, we describe the first application of non-directed homogeneous Pd-catalysis for H/T exchange on three different pharmaceuticals by using T 2 O as isotopic source, demonstrating the applicability to the synthesis of radiotracers., (© 2024 The Author(s). Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Covalent organic frameworks (COFs) have been demonstrated as promising photocatalysts for hydrogen peroxide (H 2 O 2 ) production. However, the construction of COFs with new active sites, high photoactivity, and wide-range light absorption for efficient H 2 O 2 production remains challenging. Herein, we present the synthesis of a novel azobenzene-bridged 2D COF (COF-TPT-Azo) with excellent performance on photocatalytic H 2 O 2 production under alkaline conditions. Notably, although COF-TPT-Azo differs by only one atom (-N=N- vs. -C=N-) from its corresponding imine-linked counterpart (COF-TPT-TPA), COF-TPT-Azo exhibits a significantly narrower band gap, enhanced charge transport, and prompted photoactivity. Remarkably, when employed as a metal-free photocatalyst, COF-TPT-Azo achieves a high photocatalytic H 2 O 2 production rate up to 1498 μmol g -1  h -1 at pH = 11, which is 7.9 times higher than that of COF-TPT-TPA. Further density functional theory (DFT) calculations reveal that the -N=N- linkages are the active sites for photocatalysis. This work provides new prospects for developing high-performance COF-based photocatalysts., (© 2024 Wiley-VCH GmbH.)

Perfusion dynamics play a vital role in delivering essential nutrients and oxygen to tissues while removing metabolic waste products. Imaging techniques such as magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET) use contrast agents to visualize perfusion and clearance patterns; however, each technique has specific limitations. Hybrid PET/MRI combines the quantitative power and sensitivity of PET with the high functional and anatomical detail of MRI and holds great promise for precision in molecular imaging. However, the development of dual PET/MRI probes has been hampered by challenging synthesis and radiolabeling. Here, we present a novel PET/MRI probe, [ 18 F][Gd(FL 1 )], which exhibits excellent stability comparable to macrocyclic MRI contrast agents used in clinical practice. The unique molecular design of [ 18 F][Gd(FL 1 )] allows selective and expeditious radiolabeling of the gadolinium chelate in the final synthetic step. Leveraging the strengths of MRI and PET signals, the probe enables quantitative in vivo mapping of perfusion and excretion dynamics through an innovative voxel-based analysis. The diagnostic capabilities of [ 18 F][Gd(FL 1 )] were demonstrated in a pilot study on healthy mice, successfully detecting early cases of unilateral renal dysfunction, a condition that is typically challenging to diagnose. This study introduces a new approach for PET/MRI and emphasizes a streamlined probe design for practical synthesis and improved diagnostic accuracy., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Here we report the reaction of aryl thianthrenium salts that allows selective functionalization of the meta position of arenes. The combination of a site-selective thianthrenation with a Catellani reaction provides access to 3,5-dimethylated arenes. The developed reaction is complementary to the previously discovered reductive ipso-alkylation of aryl thianthrenium salts and extends the possibilities for late-stage methylation of arenes with a single aryl thianthrenium salt., (© 2024 The Author(s). Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Axially chiral tetrasubstituted alkenes are of increasing value and interest in chemistry-related areas. However, their catalytic asymmetric synthesis remains elusive, owing to the high steric repulsion and relatively low conformational stability. Herein, we disclose the straightforward construction of atropisomeric tetrasubstituted alkenes by effective enantiocontrol in a reaction with vinyl cation intermediates. This copper-catalyzed enantioselective C(sp 2 )-H functionalization of sterically hindered (hetero)arenes with vinyl cations enables the efficient and atom-economical preparation of axially chiral acyclic tetrasubstituted styrenes and pyrrolyl ethylenes with high atroposelectivities. Importantly, this reaction represents the first example of the assembly of axially chiral alkenes via vinyl cations. Computational mechanistic studies reveal the reaction mechanism, origin of regioselectivity, Z/E selectivity and enantioselectivity. The synthetic utility has been demonstrated by diverse product derivatizations, chiral organocatalyst synthesis, as well as further applications in asymmetric catalysis., (© 2024 Wiley-VCH GmbH.)

There is a perpetual need for efficient and mild methods to integrate deuterium atoms into carbon frameworks through late-stage modifications. We have developed a simple and highly effective synthetic route for hydrogen isotope exchange (HIE) in aromatic compounds under ambient conditions. This method utilizes catalytic amounts of hexafluorophosphate (PF 6 - ) in deuterated 1,1,1,3,3,3-hexafluoroisopropanol (HFIP-d 1 O. Phenols, anilines, anisoles, and heterocyclic compounds were converted with high yields and excellent deuterium incorporations, which allows for the synthesis of a wide range of deuterated aromatic compounds. Spectroscopic and theoretical studies show that an interactive H-bonding network triggered by HFIP-d 2 O. Phenols, anilines, anisoles, and heterocyclic compounds were converted with high yields and excellent deuterium incorporations, which allows for the synthesis of a wide range of deuterated aromatic compounds. Spectroscopic and theoretical studies show that an interactive H-bonding network triggered by HFIP-d 1 activates the typically inert P-F bond in PF 6 - for D 2 then triggers HIE, offering a new way to deuterated building blocks, drugs, and natural-product derivatives with high deuterium incorporation via the activation of strong bonds.2 F 2 then triggers HIE, offering a new way to deuterated building blocks, drugs, and natural-product derivatives with high deuterium incorporation via the activation of strong bonds., (© 2024 The Author(s). Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Organolithium reagents, known for their low cost, ready availability, and high reactivity, allow fast cross-coupling under ambient conditions. However, their direct cross-coupling with fluoroalkyl electrophiles remains a formidable challenge due to the easy formation of thermo-unstable fluoroalkyl lithium species during the reaction, which are prone to decomposition via rapid α/β-fluoride elimination. Here, we exploit heteroatom-stabilized allylic anions to harness the exceptional reactivity of organolithium reagents, enabling the compatibility of difluoroalkyl halides and facilitating versatile and precise fluorine functionality introduction under mild conditions. In this process, a nickel-catalyzed difluoroalkylation of β,γ-unsaturated α-amino nitrile derived lithium reagents (N-stabilized allyl lithium reagents) with various difluoroalkyl bromides has been developed, opening a new avenue to access fluorinated compounds through catalytic cross-coupling of organolithium reagents with fluoroalkyl electrophiles. This approach allows for the efficient and precise construction of secondary C(sp 3 )-CF 2 R bonds, previously challenging in transition-metal-catalyzed fluoroalkylation reactions due to β-hydride elimination. The rapid fluorine-editing of drugs demonstrates the synthetic versatility and utility of this protocol, showing the perspective in modern drug discovery., (© 2024 Wiley-VCH GmbH.)

Transition metal π-arene complexes enable the dearomatization of benzene rings to access diversified unsaturated carbocycles through multistep synthetic procedures involving sequential addition of nucleophiles and electrophiles. This work details a single-step dearomatization process by reaction of Ru(η 6 -arene) complexes with enolates derived from α-halo or α-(tosyloxy)esters to directly transform π-coordinated arenes to ring-expanded cycloheptatrienes., (© 2024 The Author(s). Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

The reducing power of iodide anion is an underexplored property that can be used for the cross-electrophile coupling of organic molecules. Herein we harness this trait for the preparation of tertiary amines through the combination of two simple reagents: an electrophilic-carbon precursor and an iminium iodide in a dual role - both as nitrogen-containing building block and as reducing agent. The underlying mechanism of this new C-C bond-formation paradigm is explored through a combination of experiment and quantum chemical calculations., (© 2024 The Author(s). Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Poly(ɛ-caprolactone) (PCL) is a biocompatible, biodegradable, and highly mechanically resilient FDA-approved material (for specific biomedical applications, e.g. as drug delivery devices, in sutures, or as an adhesion barrier), rendering it a promising candidate to serve bone tissue engineering. However, in vivo monitoring of PCL-based implants, as well as biodegradable implants in general, and their degradation profiles pose a significant challenge, hindering further development in the tissue engineering field and subsequent clinical adoption. To address this, photo-cross-linkable mechanically resilient PCL networks are developed and functionalized with a radiopaque monomer, 5-acrylamido-2,4,6-triiodoisophthalic acid (AATIPA), to enable non-destructive in vivo monitoring of PCL-based implants. The covalent incorporation of AATIPA into the crosslinked PCL networks does not significantly affect their crosslinking kinetics, mechanical properties, or thermal properties, but it increases their hydrolysis rate and radiopacity. Complex and porous 3D designs of radiopaque PCL networks can be effectively monitored in vivo. This work paves the way toward non-invasive monitoring of in vivo degradation profiles and early detection of potential implant malfunctions., (© 2024 Wiley‐VCH GmbH.)

Herein, a copper(I)-catalyzed asymmetric 1,4-hydroarsination of β-substituted α,β-unsaturated esters is achieved in moderate to excellent yields with high to excellent enantioselectivity, based on the proposed nucleophilic [Cu]-AsPh 2 species. As for α-substituted α,β-unsaturated esters, a 1,4-hydroarsination/enantioselective protonation event occurs smoothly in satisfying results. Furthermore, β-substituted α,β-unsaturated ketone, α,β-unsaturated amide, and α,β-unsaturated phosphine sulfide are well applied in the present catalytic system. Finally, some control experiments show that HAsPh 2 is activated through coordination with the copper(I) catalyst and HAsPh 2 exhibits inferior soft Lewis basicity to HPPh 2 in the presence of a copper(I)-bisphosphine complex., (© 2024 Wiley-VCH GmbH.)

Liquid-crystallization-driven self-assembly (LCDSA) has recently emerged as an efficient strategy to create uniform one-dimensional (1-D), 2-D and 3-D nanostructures in a controlled manner. However, the examples of generation of uniform multi-morphology nanostructures from solution self-assembly of one single polymer sample are rare. Herein, we report the first example of preparation of multi-morphology fried-egg-like nanostructures consisting of an inner spherical/bowl-like core of uniform size and platelets protruded from the core by LCDSA of PAMAM-Azo 6 (PAMAM=polyamidoamine, Azo=azobenzene) in methanol. It is disclosed that the different aggregation rates for PAMAM-Azo 6 with varying contents of Azo units spontaneously separated nucleation and growth stages, which led to the formation of inner spherical/bowl-like cores ("seeds") firstly, followed by the formation of platelets protruded from the edges of inner core to give "imperfect" fried-egg-like nanostructures. Additional annealing of initially formed "imperfect" fried-egg-like micelles will promote the rearrangement of Azo units to give thermodynamically-favored "perfect" fried-egg-shaped micelles with a uniform dimension both in the core and whole structure. This work not only provides an efficient strategy to create uniform multi-morphology fried-egg-shaped nanostructures, but also reveals the essential impact of aggregation kinetics of liquid-crystalline-coil BCPs in the formation of multi-morphology nanostructures., (© 2024 Wiley-VCH GmbH.)

A series of aryl-substituted ortho-quinone methides (oQMs) was synthesised and structurally characterised. Kinetic studies of the nucleophilic additions of carbanions (reference nucleophiles) to oQMs were used to determine second-order rate constants k 2 for the carbon-carbon bond forming reactions (20 °C, DMSO) at the oQMs' exocyclic π-bond. Analysing the kinetic data by the linear free energy relationship lg k 2 =s N (N+E) revealed the Mayr electrophilicities E of the oQMs. The electrophilicities E of oQMs correlate linearly with Hammett substituent constants and experimentally determined reduction potentials E p as well as with quantum-chemically calculated methyl anion affinities (MAAs), which provides valuable tools for prediciting the reactivity of further types of oQMs. Embedding the oQMs in Mayr's reactivity scales enables to predict novel nucleophilic reaction partners for oQMs and can productively be used to prepare simple Michael adducts as well as 4+2 or 4+1 cyclisation products as demonstrated in this work by several novel reactions with neutral or negatively charged C-, N-, and S-nucleophiles.red as well as with quantum-chemically calculated methyl anion affinities (MAAs), which provides valuable tools for prediciting the reactivity of further types of oQMs. Embedding the oQMs in Mayr's reactivity scales enables to predict novel nucleophilic reaction partners for oQMs and can productively be used to prepare simple Michael adducts as well as 4+2 or 4+1 cyclisation products as demonstrated in this work by several novel reactions with neutral or negatively charged C-, N-, and S-nucleophiles., (© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.)

Uranium is a critical resource in the development of nuclear energy, and its extraction from natural seawater has been identified as a potential solution to address uranium resource shortages. In this study, hierarchical meso-/micro- porous metal-organic framework functionalized with phytic acid (PA) microspheres (denoted H-UiO-66-PA) are rationally synthesized for efficient uranium extraction. This unique design allowed for a large adsorption capacity and fast adsorption kinetics, making it a promising material for uranium extraction. Due to the hierarchically porous structure, H-UiO-66-NH 2 materials not only provide more sites for grafting PA, and thus enhance the adsorption capacity, but also facilitate the rapid diffusion of uranyl ions which can quickly and effectively access the interior of the H-UiO-66-PA adsorbent. Therefore, the obtained H-UiO-66-PA can achieve an impressive absorption efficiency of 6.76 mg g -1 in actual seawater within 15 days. Meanwhile, the H-UiO-66-PA possesses a good adsorption capacity for uranyl ions in the five adsorption/desorption cycles. This work proposes a feasible strategy for constructing functional hierarchical porous MOFs for uranium removal., (© 2024 Wiley‐VCH GmbH.)