Here, we report that high-silica HY zeolite supported RuW alloy catalyst enables in situ refining of lignin, exclusively to benzene via coupling Bronsted acid catalyzed transformation of the Csp2-Csp3 bonds on the local structure of lignin molecule and RuW catalyzed hydrogenolysis of the Csp2-O bonds using the locally abstracted hydrogen from lignin molecule, affording a benzene yield of 18.8% on lignin weight basis in water system. The reaction mechanism is elucidated in detail by combination of control experiments and density functional theory calculations. The high-performance protocol can be readily scaled up to produce 8.5 g of benzene product from 50.0 g lignin without any saturation byproducts. This work opens the way to produce benzene using lignin as the feedstock efficiently.Benzene is a widely used commodity chemical, which is currently produced from fossil resources. Lignin, a waste from lignocellulosic biomass industry, is the most abundant renewable source of benzene ring in nature. Efficient production of benzene from lignin, which requires total transformation of C Efficient production of benzene from lignin is attractive and of great importance, but has not been realized. Here, the authors develop a strategy to transform lignin into benzene over a RuW/zeolite catalyst in water, and the yield of benzene can be as high as 18.8% on lignin weight basis. The global benzene demand is anticipated to grow with a rate of 2.9% annually in the next decade1 . Especially in the manufacturing industry, benzene is widely used in many sectors, where it is combined and processed with other basic chemicals (e.g. ethylene and propylene) to produce valuable consumer goods, such as clothing, packaging, car parts, building materials, pharmaceuticals, cosmetics, flame retardant, compact discs, eyeglass lenses, carpet, medical implants, foam insulation, adhesives, footwear, contact lens, dyes, agrochemicals , . Currently, benzene is dominantly produced from petroleum and coal via catalytic reforming, steam cracking and toluene disproportionation processes, as well as coal processing  and aromatic carbon–oxygen (Csp2–O) bonds functionalized on the benzene rings truly limited the abstraction of benzene from the lignin structure. In this context, further cleavage of the unbroken Csp2–Csp3/Csp2–O bonds in the above generated alkylbenzenes and alkylphenols for desired benzene product can only be realized via dealkylation, dealkenylation and reductive cleavage processes under quite harsh conditions 40. Moreover, such required reaction conditions often lead to inevitable side reactions33. For example, the concurrent hydrogenation of the benzene ring in the hydroprocessing stage of the lignin upgradation with exogenous hydrogen source always further reduces the benzene selectivity42. Thus, a key and great challenge for efficient lignin-to-benzene route would be to design practical strategy for combining the complicated refinements of the Csp2–Csp3/Csp2–O bonds into Csp2–H bonds via friendly catalysis, without multistep technological procedure and extra hydrogenation of benzene ring. In our previous work, we reported the hydrogenolysis of the aromatic Csp2–O(CH3) bond without need of any exogenous hydrogen or other reductants, termed as self-supported hydrogenolysis -1-propanol (1a) as the model compound because of its lignin-mimetic phenylpropanol structure [(CH3O)Ph-Csp3(OH)–] with only one methoxy group [Csp2–O(CH3)] and one 1-hydroxypropyl group [Csp2–Csp3(OH)] substituted on the benzene ring, which simplifies the study. After extensive screening of various conditions, we identified the optimized catalytic system and reaction conditions shown in Table 30, Si/Al ratio = 30) with supported RuW alloy component using water as the reaction medium at 180 °C under nitrogen atmosphere  in the blank experiment  was not reactive when only HY30 was used as the catalyst (Table 1b) via the SSH process of the Csp2–O bond (Table 1b) could be 97.3% with a remained anisole (1d) selectivity of 2.5% at 99.9% conversion of 1a over the RuW/HY30 catalyst under nitrogen atmosphere in water (Table 1H nuclear magnetic resonance (NMR) analysis of the aqueous phase  (Table 1e) and n-propylcyclohexane (1f) in respective selectivities of 35.8% and 3.9% (Table 1c), n-propylbenzene (1e) and n-propylcyclohexane (1f) under low pressure of exogenous H2 (Table α) position  catalysts , their selectivities of benzene were much lower than that over RuW/HY30 catalyst  without any benzene product, disclosing that the unique catalytic properties derived from the zeolitic aluminosilicate  frameworks can offer a particular way to tailor the Csp2–Csp3 bond into Csp2–H bond under mild conditions. The above control experiments showed that the HY30 zeolite and RuW alloy are respectively essential to realizing the transformations of the Csp2–Csp3 and Csp2–O bonds into Csp2–H bonds for producing benzene product (1b).We focused our in situ refining strategy studies initially on the overall transformation of the Cre Table . As expeer Table , and acc product   fitting  curve of the RuW/HY30 catalyst  possessed more acid sites, their strong Bronsted acid sites were in lower proportions   in quantity, albeit with limited selectivities of benzene over RuW/Beta  as the main product ] motif using the active hydrogen derived from the formaldehyde molecules generated during the SSH reaction of the Csp2–O bonds  was also resulted from the above hydrogenolysis of the hydroxyl group in [Csp2–Csp3(OH)] motif of 1a, but without SSH reaction of the Csp2–O bond proceeding yet. Aside from the catalytic properties, RuW/HY30 catalyst also exhibited excellent stability in the reaction, which was confirmed by reusing the catalyst  pattern of the as-synthesized RuW/HYyst Fig.  revealedata Fig. , the ranata Fig. . The Ru ing Fig.  exhibitsing Fig. , directlatios 3, , and 15 30 zeolite in the catalyst, where RuW NPs catalyzed hydrogenolysis of the Csp2–O bonds with the in situ abstracted hydrogen from the reactant can not only completely avoid the saturation of the benzene ring, but more importantly, allow the Csp2–Csp3 bonds to deconstruct promptly over the HY30 zeolite without the competition from the hydrogenolysis of the hydroxyl group in [Csp2–Csp3(OH)] motif. The pathway for the SSH reaction of Csp2–O bond on the RuW centers has been established and illustrated in Supplementary Fig. 243. We here focus on the study of the unique catalysis of Csp2–Csp3 into Csp2–H bond by means of the HY30 zeolite. Based on our experimental characterizations, we constructed the Bronsted acid model to represent the Csp2–Csp3 reaction center in the RuW/HY30 catalyst, and performed density functional theory (DFT) calculations to study the reaction path of the Csp2–Csp3 bond. As shown in Fig. α position is easily protonated on the Bronsted acid site, leading to the oxonium ion (structure I) that then transforms into a carbonium ion (structure II) by eliminating a molecule of H2O. Thermodynamically, the γ-methyl on the side chain is then shifted to the Cα position under the catalysis of the Bronsted acid center, evolving to the chemically adsorbed structure III with a migration barrier of 1.25 eV (TS-1), and subsequent proton abstraction by the Bronsted acid center delivers structure IV in a lower barrier of 0.89 eV (TS-2). Then, by a second protonation at the Cα position of structure V, the resulting carbonium ion V (structure V) would be formed by the trap of H2O, which gives tertiary alcohol geometry (structure VI) and concomitantly regenerate the Bronsted acid center with the proton. When the benzene ring of the tertiary alcohol (structure VI) is turned endothermically toward the Bronsted acid center, an appropriate geometry (structure VII) is formed to enable the protonation of the Csp2 position (structure VIII) with an effective barrier of 0.53 eV (TS-3). After that, the Csp2–Csp3 bond can be exothermically transformed into the desired Csp2–H bond via the ultimate β scission step36.On the basis of the above comparison tests Table , and givsp2–Csp3 bond into Csp2–H bond was proceeded via a stepwise protonated dehydroxylation, γ-methyl shift and Csp2–Csp3 β scission pathway. Although the dehydroxylation could also occur in the water-only system (Table 1h) was the sole product without other following steps, which provided compelling proof for the requisite catalysis worked in the desired refining of the Csp2–Csp3 bond. In terms of catalytic chemistry, highly active acid nature and chemical accessibility of the framework in the mesopore-rich HY30 innately enabled the aliphatic γ-methyl C (Cγ) atom to be activated on the Bronsted acid center, which could be illustrated by the spacing-filling models  and β2-C  atoms, which could be ascribed to the β3-C  atom shifted from the Cγ atom in reaction51. The above resolved signals were further supported by the solid-state two-dimensional (2D) 13C{1H} dipolar-mediated heteronuclear correlation (HETCOR) NMR analysis  and (–Cβ2H3) moieties in the intermediates II and III, respectively. The observed 13C and 1H signals at 13.5 and 1.0 ppm are assigned to the remained (–CγH3) moiety in the intermediate II. In line with the 13C NMR analysis  moiety in the intermediate III. It is the chemical bonding with the oxygen atom in the Bronsted acid [≡Al–O–Si≡] center that provided an inductive effect on the Cβ3 atom, which shifted its resonance downfield from that of the original Cβ1 and Cβ2 atoms, precisely supporting the Bronsted acid-catalyzed mechanism of the γ-methyl shift53. Echoing the chemical environment change of the reactant, such a chemical bonding in the [≡Al–O(Cβ3)–Si≡] unit also fed back to the tetrahedrally coordinated Al [Al(VI)] in the Bronsted acid center, which was further confirmed by 27Al multiple-quantum MAS (MQMAS)  signal, as expected, a resonance signal at 51.5 ppm (F2) was distinctly identified in the operating RuW/HY30 catalyst –Si≡] unit, where the charge compensation of the Cβ3 atom weakened the inductive effect of the O atom on the neighboring Al(VI) atom, and then reduced the Al–O–Si bond angel and lengthened the Al–O and Si–O bonds  Fig.  and 27Alyst Fig. , which hnds Fig. , shiftinies Fig. .sp2–Csp3/Csp2–O bonds equipped phenylpropanol derivatives were refined effectively and singly into desired benzene product, including those G (guaiacyl)-monomeric lignin model compounds , hydroxyl (3a) and isopropoxyl (4a) groups, as well as the S (syringyl)-monomers . The in situ refining strategy is not limited to the monomers, a range of G and S-monomer derived dimeric model compounds including those bearing the methoxyl groups  and the combinatorial groups of methoxyl and isopropoxyl , were all viable in the reactions with benzene as the single product. The catalytic performance observed here represented an important proof of the multifunctional centers on the RuW/HY30 catalyst, where the interlaced Csp2–Csp3 and Csp2–O bonds in the complex compounds could be efficiently tolerated and transformed into the Csp2–H bonds, respectively, demonstrating the feasibility of the in situ refining strategy  versus reaction time, which aimed to comprehensively understand the evolution of the Csp2–Csp3/Csp2–O bonds in the lignin-mimetic dimeric linkages  groups, and no active hydrogen was needed. With the ongoing refining process, the methoxyl derived Csp2–O(CH3) bonds in the above monomeric intermediates were gradually transformed into the Csp2–H bonds. Meanwhile, the phenolic Csp2–O bonds with higher bond energy could also be cleaved along with the Csp2–O(CH3) bond, which should be attributed to the RuW catalyzed hydrogenolysis of the phenolic hydroxyl group using the active hydrogen derived from the formaldehyde molecules generated during the SSH reaction of the Csp2–O(CH3) bond phenol was deconstructed over the HY30 component with phenol as the sole product, and the cleavage of the phenolic Csp2–O bond did not occur without the source of formaldehyde  bonds.With the optimized conditions established, we proceeded to study the scope of the in situ refining strategy. As shown in Fig. nds Fig.  bearing xyl Fig. , 10a–13aegy Fig. . As a fuegy Fig. a versus ups Fig. a and 9a ups Fig. a and 9a ups Fig. a and 9a ups Fig. a and 9a 11a , G (guaiacyl) and S (syringyl)-derived phenylpropanol building blocks in lignin   and quantitative 13C NMR analyses of the residue lignin oil showed a significant decrease in the signals of the above mentioned H, G, and S-derived phenylpropanol structures, which was accompanied by a simultaneous decrease in the quantity of the methoxy group  ] motif. In the scale-up experiment, 8.5 g of benzene can be produced from 50.0 g of lignin without any saturation byproducts. This in situ lignin refining strategy liberates the trapped benzene rings from the molecular structure of lignin, and paves a new way for sustainable production of benzene using lignin as the feedstock, which has great potential of practical application.In summary, we have developed an in situ refining strategy to the transformation of the C43. Prior to the impregnation, the used zeolites were pretreated by calcination at 550 °C for 4 h. In a typical preparation, ammonium metatungstate (AMT) (1.25 g) and RuCl3·xH2O (0.40 g) were dissolved in 15 mL of deionized water, respectively. Then, the precursor solutions containing AMT and Ru3+ ion were successively added dropwise to 70 mL deionized water with 2.0 g of zeolite at room temperature. The obtained mixture was vigorously stirred for 48 h, evaporated, and dried at 473 K for 16 h in an oven. The as-prepared sample was reduced in a continuous 10% H2/Ar flow, from room temperature to 400 °C at 5 °C min−1and then to 900 °C at 1 °C min−1, and maintained at 900 °C for 1 h. After being cooled to room temperature under Ar atmosphere, the reduced catalyst was exposed to 1% O2/Ar atmosphere for 1 h to form a passivation layer to prohibit against bulk oxidation before exposure to air. The passivated catalyst was kept under an inert atmosphere before testing and characterizations, and denoted as RuW/Zeolitex . For comparison, supported Ru/Zeolitex, W/Zeolitex and other catalysts were prepared by the same procedures for preparing the RuW/Zeolitex catalyst.Supported RuW/Zeolite catalysts were prepared by commonly used wet impregnation method2 adsorption-desorption of the samples were measured using a Micromeritics Tristar II 3020 at liquid nitrogen temperature. The specific surface areas were calculated by using the Brunauer–Emmett–Teller model. The pore size distribution of the sample was calculated using the Barret–Joyner–Halenda pore size model. XRD measurements were conducted on an X-ray diffractometer  operated at 40 kV and 200 mA with Cu Kα (λ = 0.154 nm) radiation. Rietveld refinements were performed applying the TOPAS program59 for the measured XRD profile of the RuW/HY30 catalyst. The XPS measurements were carried out on an ESCAL Lab 220i-XL spectrometer at a pressure of ~3 × 10−9 mbar (1 mbar = 100 Pa) using Al Kα as the excitation source (hν = 1486.6 eV) and operated at 15 kV and 20 mA. The X-ray absorption find structure (XAFS) spectra (Ru K-edge and W L3-edge) were collected at 1W1B station in Beijing Synchrotron Radiation Facility (BSRF). The storage ring of BSRF was operated at 2.5 GeV with a maximum current of 250 mA. Using Si (111) double-crystal monochromator, the data collection were carried out in transmission mode using ionization chamber. All spectra were collected in ambient conditions. The acquired EXAFS data were processed according to the standard procedures using the ATHENA module implemented in the IFEFFIT software packages. The k2-weighted EXAFS spectra were obtained by subtracting the post-edge background from the overall absorption and then normalizing with respect to the edge-jump step. Subsequently, k2-weighted χ(k) data of Ru K-edge and W L3 edge were Fourier transformed to real (R) space using a han-ning windows (dk = 1.0 Å−1) to separate the EXAFS contributions from different coordination shells. To obtain the quantitative structural parameters around central atoms, least-squares curve parameter fitting was performed using the ARTEMIS module of IFEFFIT software packages60. TEM and HRTEM images were obtained on a JEOL-2011F electron microscope operating at 200 kV. The contents of supported metals on the catalysts were determined by ICP.N2 to remove the air at room temperature and subsequently charged with 0.1 MPa of N2. Then, the autoclave was heated to 160 °C within 1 h. After that, the stirrer was started with a stirring speed of 600 rpm, and the reaction time was recorded. After 1 h, the autoclave was cooled down quickly, and the gas was released. The liquid was collected by a filtration process. The filter residue was washed three times with 200 mL of acetone/H2O (9:1), and the washing liquor was collected and combined with the filtrate liquid. After that, the liquid was concentrated under vacuum at 30 °C until the liquid became muddy and then dissolved again by 30 mL of acetone. Then, the concentrated lignin solution was slowly poured into the rapidly stirred 2000 mL of water, and the precipitate was filtered using a funnel with a pore size of 3–4 μm. Finally, the lignin solid was freeze-dried under vacuum for 24 h, and the extracted lignin was obtained. In addition, the solvent used in the above procedures were completely recovered along with the used wood powder (filter residue), and reused in the next extraction experiment. The obtained lignin was dissolved in 550 μl of dimethyl sulfoxide (DMSO)–d6 and characterized by 1H/13C 2D HSQC NMR and quantitative 13C NMR analyses using Bruker Avance III 500WB and Bruker Avance 600, as described by other researchers57.In a typical experiment, 70 g of wood powder, 490 mL of acetone and 210 mL of water were loaded into a 1-L autoclave . The autoclave was sealed and purged with N2 for three times to remove the air at room temperature and subsequently charged with desired gas. Then the reactor was placed in a furnace at desired reaction temperature. When the reactor reached the desired reaction temperature, the stirrer was started with a stirring speed of 800 rpm, and the reaction time was recorded. After the reaction, the reactor was placed in ice water, and the gas was released, passing through the ethyl acetate. The reaction mixture in the reactor was transferred into a centrifuge tube. Then the reactor was washed with the ethyl acetate used for the gas filtration, which was finally combined with the reaction mixture. After centrifugation, the catalyst was separated from the reaction mixture. The quantitative analysis of the liquid products in the organic phase was conducted using a GC (Agilent 6820) equipped with a flame ionization detector and HP-5MS/HP-INNOWAX capillary columns . Identification of the products and reactant was performed using a GC-MS  and by comparing the retention time to respective standards in GC traces. Biphenyl was used as the internal standard to determine the conversions of substrates, selectivities and yields of the products. Identification of the products in the aqueous phase was conducted by 1H NMR analysis on a Bruker Avance III 400 HD with D2O as the solvent. The carbon balance for the reaction of the model compounds was calculated using Caromatics balance which was given relative to the aromatic products43. The Caromatics balances for the reaction of the model compounds were better than 99%. The recovered lignin residual solid were analyzed by1H/13C 2D HSQC NMR and quantitative13C NMR spectroscopy (Bruker Avance III 600 HD).The reaction was carried out in a Teflon-lined stainless-steel reactor of 20 mL with a magnetic stirrer. In a typical experiment, a suitable amount of reactant, catalyst, and water were loaded into the reactor. The reactor was sealed and purged with N30 catalyst was tested using the reaction of the model compound1-(4-methoxyphenyl)-1-propanol (1a). After the reaction, the reaction mixture in the reactor was transferred into a centrifuge tube. Then the reactor was washed with ethyl acetate, which was combined with the reaction mixture. Subsequently, the reaction mixture was centrifuged and the ethyl acetate layer was analyzed by GC. After that, the used RuW/HY30 catalyst was separated from the reaction mixture and successively washed with ethanol (5 × 10 mL) and water (5 × 10 ml). Then, the recovered catalyst was reused directly for the next run.The reusability of RuW/HY1a) (1 mmol), RuW/HY30 (0.40 g) and H2O (5.0 ml) were loaded into the reactor. The reactor was sealed and purged with N2 three times to remove the air at room temperature and subsequently charged with 0.1 MPa of N2. When the reactor was placed in a furnace and heated to 180 °C, the stirrer was started with a stirring speed of 800 rpm, and the reaction time was recorded. After 10 min, the reactor was transferred to a bath of liquid nitrogen very quickly. When the reaction mixture was frozen, the gas was released immediately. The reaction mixture was freeze-dried under vacuum for 12 h to remove the water. The detection of the intermediates in the dried sample was conducted by 13C NMR, solid-state 2D 13C{1H} dipolar-mediated HETCOR, 27Al MQMAS and 27Al NMR analyses on Bruker Avance III 400.The detection of intermediates was carried out in a Teflon-lined stainless-steel reactor of 20 mL with a magnetic stirrer. In the experiment, 1-(4-methoxyphenyl)-1-propanol ] and by comparing the retention time to standard benzene in GC. 1H and 13C NMR analyses (Bruker Avance III 400) were also performed to detect the benzene product in the organic layer.The scale-up reaction was performed in a 1-L autoclave . In the reaction, 50.0 g of lignin, 50.0 g of RuW/HYSupplementary InformationPeer Review File


Surprisingly, a tetra‐substituted flexible core, compound 11, also exhibited selective stabilization of G4 DNA over duplex DNA. The anticancer and antiparasitic activity of the library was also examined, with the lead compound 3 exhibiting nanomolar inhibition of Trypanosoma brucei with 78‐fold selectivity over MRC5 cells. The cellular localization of this compound was also studied via fluorescence microscopy. We found that uptake was time dependant, with localization outside the nucleus and kinetoplast that could be due to strong fluorescence quenching in the presence of small amounts of DNA.A facile imide coupling strategy for the one‐step preparation of G‐quadruplex ligands with varied core chemistries is described. The G‐quadruplex stabilization of a library of nine compounds was examined using FRET melting experiments, and CD, UV‐Vis, fluorescence and NMR titrations, identifying several compounds that were capable of stabilizing G‐quadruplex DNA with interesting selectivity profiles. The best G4 ligand was identified as compound  The rigid rules of G‐quadruplex stabilization: A library of amphiphiles has been synthesized in one step, using a simple imide condensation reaction. The G‐quadruplex stabilization, anti‐cancer and anti‐parasitic activity of the library has been investigated, uncovering the important factors that govern G‐quadruplex binding and selectivity, yielding a promising new core‐motif and a compound with potent trypanosomacidal activity. These motifs have garnered significant attention in recent years, as a wide variety of potential applications and functions continue to emerge.Whilst numerous small molecules have been reported to interact with G4 DNA for use as therapeutics,1 and 2  scaffold.3, due to the limited solubility of perylene‐3,4,9,10‐tetracarboxylic dianhydride. Purification of the resulting compounds by reverse‐phase flash chromatography (water+0.1 % trifluoroacetate (TFA)/MeCN, 9 : 1 to 5 : 95) was sufficient to protonate the methylpiperazine rings, yielding the final compounds as water soluble TFA salts.Previous work on G4 ligands3–9 were prepared in yields ranging from 16–79 % as di‐substituted bisimides, while tetra‐substituted compounds 10 and 11 were obtained serendipitously in the presence of an excess of amine in 40 and 75 % yield, respectively . There was no evidence of tri‐substituted species containing three amides and one carboxylic acid (expected MH22+=488). Analysis of LC‐MS data from the isolated fractions of 10 revealed the presence of multiple species with different core substitution patterns, amongst them the tri‐substituted species with an imide and two amides (MH22+=380) as well as the di‐substituted bisimide, and the bis(amide/carboxylic acid). Again, no evidence of the tri‐substituted species containing three amides and one carboxylic acid was found (expected MH22+=389). The presence of multiple species with a lower degree of substitution is in accordance with the lower yield obtained for compound 10 (40 %) compared to 11 (75 %) and indicates that this reaction proceeded to a lesser degree of completion. These results suggest that tetra‐substitution of 10 and 11 goes through the bisimide intermediate, which is presumably ring‐opened by further nucleophilic addition. The variation in isolated yields can be explained by several factors. Comparing the synthesis of PDI 3 (yield 39 %) with PIPER (yield 77 %), it is clear that water is a better solvent than molten imidazole for the synthesis of amphiphilic PDIs. The low yields for compounds 7 (yield 33 %) and 9 (yield 16 %) can be explained by competition between the desired di‐substituted product and undesired tri‐ and tetra‐substituted side products, which are removed during purification. Also in the case of 9, it would appear that DMSO/NEt3 are not favourable reaction conditions for imide condensation. The remaining variation in yield likely results from interplay between the sterics and electronics of the cores, though no obvious trends stand out.Compounds et. al.1 and 3–11 were tested against four model G4‐forming oligonucleotides and a hairpin duplex sequence to assess G4:Duplex selectivity as well as G4:G4 selectivity. The sequences examined (at 200 nM) were the human telomeric G4 in potassium buffer +, antiparallel G4),+, parallel G4),T. brucei ,+). Together, these sequences represent targets for therapeutic intervention to treat parasitic infections,3, 9 and 11 were capable of stabilizing G4 structures , spectral overlap between the PDI core and the FAM/TAMRA FRET pair in the 450–650 nm region prevents definitive conclusions about DNA stabilization from FRET melting experiments. Despite this, a significant difference was observed between the apparent ΔTm for G4 sequences and the duplex sequence. Compounds 9 and 11 also displayed some mild stabilization of G4 DNA, with minimal stabilization of the F10T duplex . Tetra‐substituted ligand 11 had superior stabilization over di‐substituted 9, in agreement with the number of basic residues being a primary driver for G4 stabilization.[1 also exhibited modest stabilization of the parasitic Febr1T‐K+ G4 . The lack of G4 stabilization of compounds 4–8 and 10 can likely be attributed to the increased conformational freedom and reduced hydrophobic aromatic surfaces present in many of the structures. Thus, our data suggests that aromatic π‐π stacking interactions and structural rigidity of the core motif are key driving forces for G‐quadruplex stabilization, and should be considered as important factors alongside the number and location of basic residues when designing optimum G‐quadruplex interactive compounds. More rigid cores not only provide hydrophobic and π‐π stacking interactions with terminal G‐tetrads, but also facilitate the correct orientation of side chains into the G4 grooves, leading to a lower entropic penalty for adopting the optimal conformation compared to more flexible cores. Interestingly, our approach also reveals that flexible cores with enough positively charged groups, such as in compound 11, can show G4 binding ability with a certain selectivity over duplex DNA.With the library in hand, we began our investigation into G4 stabilization by conducting a Förster resonance energy transfer (FRET) melting assay to assess DNA stabilization using the procedure outlined by De Cian 1, 3, 9, and 11, Circular Dichroism (CD) studies were conducted on four different oligonucleotide structures ,+ ,+ (which forms a mixed G4)+ (which forms a self‐complementary duplex). Together, these sequences cover a range of DNA topologies with therapeutic potential. The EBR1‐K+ G4 is specific to T. brucei, whilst the telomeric G4s (telo23‐K+ and telo22‐Na+) are common to both human and T. brucei genomes. Oligonucleotide concentrations were 5 μM in all cases, whilst ligand concentration was varied from 1 to 10 equivalents. Results from the titration of 1 with the EBR1‐K+ G4 and ds26‐K+ duplex revealed perturbation of both structures upon binding . This is similar to the G4 disruption previously observed for the perturbation of 1 with telo23‐K+ and telo22‐Na+G4’s.1, where a significant reduction in G4 stabilization was observed via FRET melting experiments when competitor duplex DNA was present.3 with each oligonucleotide revealed perturbations in the observed CD signal for every structure, and were more significant with the EBR1‐K+ G4 and ds26‐K+ duplex. It is interesting to note the presence of an induced CD band at 400–600 nm that is either due to induced CD from interaction with the oligonucleotide, or from the ligand itself, as PDIs are known to aggregate into helical structures with CD bands in this region.3 to the chiral DNA structures. Di‐substituted ligand 9 exhibited no effect on any DNA structure examined via CD . In contrast, tetra‐substituted ligand 11 modified the CD signal of the telo22‐Na+ G4 and the EBR1‐K+ G4 upon binding, showing no change when binding to the telo23‐K+ G4 or the ds26‐K+ duplex structure.To further probe the G4 and duplex DNA stabilization potential of ligands s Figure  and S8–91 and PDI 3 to the previously assessed G4 and duplex DNA structures, ultraviolet‐visible absorbance spectroscopy (UV‐Vis) titrations were conducted  were determined. Results from the titration of telo23‐K+, telo22‐Na+, EBR1‐K+ and ds26‐K+ oligonucleotides into a solution of NDI 1 .1 has with different topologies of the telomeric G4. Examples of G4 ligands with this level of discrimination between different G4 topologies are comparatively rare, and further examination of this apparent selectivity might yield useful insights into the future developments of compounds with interesting G4:G4 discrimination. Compound 1 also exhibited significant binding to the EBR1‐K+ G4 and ds26‐K+ duplex . These results confirm the significant binding to duplex DNA observed for compound 1, which is similar to its affinity for the EBR1‐K+ G4, and indicate that it is not as selective for G4 structures over duplex structures as FRET measurements suggest. Attempts to fit the observed binding isotherms to a 1 : 1 binding model were unsuccessful, resulting in poor fitted curves, whilst a 2 : 1 model described the data more convincingly. This is in agreement with the 2 : 1 stoichiometry observed via ITC for the telo23‐K+ G4 observed previously for compound 1,3 revealed a similar affinity for the telo23‐K+ G4 (Ka=2×106), but a much better selectivity profile, with 40‐fold selectivity over the ds26‐K+ duplex (Ka=5×104) and ∼7‐fold selectivity over the EBR1‐K+ G4 (Ka=3×105) versus 6‐fold and 3‐fold, respectively, for 1.To obtain quantitative information on the binding of NDI  Figure Ka were de Figure Ka were de Figure Ka were de1, PDI 3 displayed appreciable binding to the telo22‐Na+ G4 (Ka=8×105), indicating that the specific selectivity observed for 1 is not applicable to the larger PDI core of 3 [3 under aqueous conditions was further reinforced by comparing the NMR spectra of 3 in water with that in CDCl3 . In CDCl3, the spectrum is well resolved, with observable fine structure. In water, significant line‐broadening is observed, with a complete loss in fine structure which is in accordance with aggregated species.3 exhibiting well‐resolved vibrionic structure, resembling that of monomeric PDIs.[3 undergoes disaggregation in the presence of the DNA sequences examined here, leading to monomeric PDIs that are bound to G4 or duplex DNA. These results imply that the Ka for the binding of 3 to the G4 and duplex sequences examined here must be higher than the Ka for the self‐association of 3 which leads to aggregation. Thus, the presence of the G4/duplex sequences examined is sufficient to induce the disaggregation of PDI 3. This observation is in agreement with previous work by Kern et. al.[9 and 11 overlapped with the absorbance from the oligonucleotide (λabs <300 nm), preventing analysis via UV‐Vis titration.Unlike NDI ‐Na+ G4 Ka=8×105, ‐Na+ G4 Ka=8×105, ‐Na+ G4 Ka=8×105, ‐Na+ G4 Ka=8×105, ‐Na+ G4 Ka=8×105, ‐Na+ G4 Ka=8×105, ‐Na+ G4 Ka=8×105, ‐Na+ G4 Ka=8×105, ‐Na+ G4 Ka=8×105, ‐Na+ G4 Ka=8×105, ‐Na+ G4 Ka=8×105, 3, fluorescence titrations were conducted on the previously assessed G4 and duplex DNA structures . The concentration of 3 was kept constant at 1 μM, and the concentration of oligonucleotide was varied up to 1 μM. The results . This effect has been observed for other G4 ligands such as Neidle's diphenyl triazole ligands when binding to telo22‐Na+ or HIVPRO1 G4’s and has been attributed to unspecific binding.3 which shows concentration‐dependant aggregation, the high concentrations used in the NMR titration could alter the equilibrium between the PDI aggregates and binding to G4 DNA, favouring PDI aggregation and a weak association with the telo22‐Na+ G4. Similarly, di‐substituted 9 also exhibited minimal effects on the telo22‐Na+ G4 , which is in accordance with the minimal topological change upon binding revealed by the CD titrations, and also points to potential unspecific binding. In contrast, tetra‐substituted 11 exhibited small specific perturbations of imino protons G4 and G14 as well as aromatic protons both in the tetrads  and in the loops  or MTT assay (for L. major). Absolute EC50 values and selectivity indexes were then calculated from dose‐response curves . The efficacy and selectivity of 1, 3 and 11 for T. brucei over MRC5 was higher than for other typical G4 interactive compounds such as Pyridostatin and BRACO‐19  of 0.7 and 1.5, respectively).L. major, only compounds 1 and 11 displayed relevant toxicity . Whilst no correlation between G4 stabilization and anticancer activity was observed for these compounds, cytotoxicity towards T. brucei was correlated with G4 stabilization, with 1, 3 and 11 all exhibiting antiparasitic activity. Certainly, other mechanisms of action must also be considered and will be studied in the future.To investigate the potential anticancer and antiparasitic activity of compounds ompounds.6b, 9 es Table  and S14.3 enabled us to track its localization in both cells and parasites. Preliminary absorbance and fluorescence experiments indicated that 3 exists in H‐aggregated form in PBS at 25 μM . The ability of PDI 3 to undergo internalization into both HeLa  cells and T. brucei parasites was then assessed via fluorescence microscopy  for 30 minutes, limited uptake was observed , however greater uptake was detected after 120 minutes . The lack of colocalized fluorescence with DAPI staining suggested limited presence of compound 3 in the nucleus, although it can be observed in the rest of the cell. A similar scenario occurred for 3 when assayed in T. brucei. Uptake of 3 was observed after just 30 minutes incubation  was insufficient to induce DNA stabilization, however the tetra‐substituted analogue 11 exhibited selective stabilization of G4 DNA over duplex DNA, and interacted with specific residues at the top tetrad and on one of the groves of the telo22‐Na+ G4. The anticancer and antiparasitic activity of the library was also examined, with PDI 3 displaying potent toxicity towards T. brucei, and 78‐fold selectivity over control MRC5 cells. The potent antiparasitic activity of 3 correlated with strong stabilization of G4 DNA, although other modes of action could be operating. Compound 3 was internalized into both HeLa cells and T. brucei, and can be imaged at therapeutically relevant concentrations (5 μM) with uptake that is time dependent. No evidence for nuclear or kinetoplast uptake of 3 was found, which could be due to the fluorescence quenching of 3 in the presence of DNA. We hope this approach to diversify the core of future G4 ligands may inspire other library‐based convenient approaches to G4 interactive compounds that could help identify potent and selective G4 ligands with promising therapeutic activity.In conclusion, we have developed a practical strategy for the preparation of a diverse array of amphiphilic compounds using simple yet versatile imide coupling chemistry, examining their potential use as G4 ligands and as therapeutic agents. A library of nine compounds with different core motifs were produced in one step, from cheap, commercially available starting materials. We have examined the role of the core motif in facilitating G4 binding, highlighting the importance of core rigidity such as in the case of compounds Experimental Details, including further FRET melting experiments, CD experiments, UV‐Vis experiments, fluorescence experiments, NMR experiments, cytotoxicity studies and fluorescence microscopy is available in the supporting information.The authors declare no conflict of interest.As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re‐organized for online delivery, but are not copy‐edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors.SupplementaryClick here for additional data file.


The coating was formed using firing fusion technology on the powder composition. Oxidation resistance tests were carried out under static conditions in air at 1650 °C and under conditions of interaction with high-speed air plasma flows, with Mach numbers M = 5.5–6.0 and enthalpy 40–50 MJ/kg. The effectiveness of the protective action of the coating was confirmed at surface temperatures of wT = 1810–1820 °C for at least 920–930 s, at wT = 1850–1860 °C for not less than 510–520 s, at wT = 1900–1920 °C for not less than 280–290 s, and at wT = 1940–1960 °C for not less than 100–110 s. The values of the rate of loss of the coating mass and the rate constant of heterogeneous recombination of atoms and ions of air plasma on its surface were estimated. The performance of the coating was ensured by the structural-phase state of its main layer, and the formation and evolution on its surface during operation of a passivating heterogeneous oxide film. This film, in turn, is composed of borosilicate glass with titanium and calcium liquation inhomogeneities, reinforcing TiO2 microneedles and in situ Si2ON2 fibers. It was shown that at wT ≥ 1850–1860 °C, the generation of volatile silicon monoxide was observed at the “oxide layer–coating” interface, followed by the effects of boiling and breakdown degradation of the oxide film, which significantly reduced the lifespan of the protective action of the coating.The results of a study on the development and testing of a heat-resistant coating in a Si–TiSi Currently, carbon–carbon and carbon–ceramic composites are the most promising materials for use in thermal protection systems for airframes and flow paths of propulsion systems of atmospheric high-speed aircraft and reusable aerospace vehicles ,3,4,5,6.2–CrSi2  direction. Traces of titanite CaTiSiO5 (JCPDS card No. 25-0177) were also recorded in the oxide layer. Quantitative XRD analysis was impossible due to the different thickness of the formed oxide film and the change in the proportion of the amorphous and crystalline components of the SiO2 phase with increased distance from the epicenter of the flow, as well as due to differences in the roughness of the surface areas and revealed texture phenomena.The results of the XRD analysis performed from the surface of the samples after the firing experiments were in good qualitative agreement with the SEM and EDS data. In addition to the set of reflections characteristic of the coating in the initial state , a wide 2–MoSi2–TiB2–CaSi2 system with a high-speed air plasma flow, at temperatures up to wT = 1810–1820 °C, the surface is passivated, which prevents the development of active oxidation further into the coating. The oxidation processes of the coating components are described by the reactions:An analysis of the results obtained in this work, together with the results of earlier studies ,23,24,402 occurs during the oxidation of both free silicon, which is part of the eutectic of the main coating layer, and higher silicides MeSi2  and SiC carbide, forming a branched framework (reactions (3)–(6) and (8), (9), respectively). Oxidation of titanium-containing phases TiSi2 and TiB2 leads to the formation of needle-shaped crystals of TiO2 in the form of rutile (reactions (5), (7)), which are immiscible with silica. The oriented arrangement of TiO2 crystals leads to the appearance of the effect of “reinforcement” of the oxide film, and, consequently, to an additional increase in its resistance to mechanical entrainment in flows.The formation of a protective film based on SiOSimultaneously, with oxidation and the formation of a continuous outer oxide layer, segregation of calcium in its outer part occurs—initially uniformly distributed in the coating volume, apparently due to a high diffusion rate in viscous-plastic components (in eutectic and glass phase). Segregation of calcium is associated, on the one hand, with its surface activity in relation to silicon and titanium—characterized by a lower value of surface tension. On the other hand, calcium has a higher reactivity when interacting with oxygen than titanium, silicon and boron, as evidenced by comparative data on the differences in the values of relative electronegativities according to L.K. Pauling between oxygen and these elements.2O5 and CaTiSiO5 according to reactions (11) and (12), respectively. In this work, the distribution of boron in glass was not quantitatively estimated due to the low sensitivity of the EDS to light elements, especially with a low content (in reaction (10) y << x). The formation of solutions in the CaSi2O5–CaTiSiO5 system that are immiscible with the borosilicate glass phase confirmed the effect of liquid-phase separation in the SiO2–TiO2–CaO system, which was reported in [The interaction of primary oxidation products with each other, limited by the rate of diffusion mass transfer of reagents in a complex heterogeneous system, leads to the formation of: (i) borosilicate glass phase with a single anionic matrix according to reaction (10); and (ii) new crystalline phases CaSiorted in ,39,40.wT ~ 1850–1860 °C and a slowdown in the diffusion of oxygen into the coating volume through the growing heterogeneous oxide layer led to the interaction of free silicon and SiC with the SiO2 film at its inner boundary, and to the formation of gaseous products underneath the oxide film (at the boundaries of Si–SiO2 and SiC–SiO2) according to the reactions:An increase in the operating temperatures on the surface of up to 2 and N2 diffusing through a heterogeneous oxide film leads to an increase in the thickness of the SiO2 film from its lower boundary according to reaction (15) and in situ synthesis of silicon oxynitride Si2ON2 fibers according to reaction (16):As a result, cavities filled with gases, mainly silicon monoxide SiO, were formed under the oxide film b,c. More2 losses due to erosive entrainment from a surface streamlined by high-speed flows. The formation of Si2ON2 fibers in the oxide film contributes to its additional reinforcement, which increases the resistance to mechanical entrainment (erosion).Reaction (15) makes a positive contribution to the compensation of SiOAs the test duration increases at the indicated temperatures, gases accumulate under the oxide film, gas-filled cavities grow, and gaseous products penetrate the viscous borosilicate glass. The continuity of the oxide film is violated and intensive oxidation of free silicon and SiC begins according to the reactions:That is, the oxidation of the coating goes into an active stage. Abundant blistering of the coating is observed (the “boiling” effect), leading to a breakdown degradation of the oxide film –(9) and (15), (17) and (18) were recorded with the participation of molecular oxygen. The latter has a significantly lower reactivity than atomic oxygen. The presence of a predominant amount of atomic oxygen in the air plasma flow (air undergoes dissociation in a shock wave in front of the samples) leads to an acceleration of oxidative processes and an increase in the diffusion permeability of the oxidizer through the growing oxide layer.2 phase in the coating of the Si–TiSi2–MoSi2–TiB2–CaSi2 system and the degree of heterogeneity of oxide films formed during its oxidation led to an expansion of the temperature-time ranges of the protective action of the coating, in comparison with the coatings of the basic Si–TiSi2–MoSi2–TiB2–CaSi2 system. Thus, the performance of the coating of the Si–TiSi2–MoSi2–TiB2–CaSi2 system under the studied conditions of interaction with plasma flows was at least 920–930 s at wT = 1810–1820 °C, at least 510–520 s at wT = 1850–1860 °C, not less than 280–290 s at Tw = 1900–1920 °C, and not less than 100–110 s at wT = 1940–1960 °C. Under similar conditions, the coating of the Si–TiSi2–MoSi2–TiB2–CaSi2 system is efficient for no more than 50 s at wT ≥ 1800 °C. The results obtained in combination with the data of [2–MoSi2–TiB2–CaSi2 system and determine the need for parametric studies in the development of optimal concentration boundaries of compositions in the Si–TiSi2–MoSi2–TiB2–CaSi2 system.Thus, it was experimentally established that a simultaneous increase in the fraction of the refractory TiB data of ,24,40 coSystematic research aimed at the development and improvement of heat-resistant self-healing coatings based on silicide–boride systems has been continued. The coatings are designed to protect against high-temperature oxidation of carbon–carbon and carbon–ceramic composite materials, which are promising for use in thermal protection systems for airframes and flow paths of propulsion systems of atmospheric high-speed aircraft and reusable aerospace vehicles.2–MoSi2–TiB2–CaSi2 system was obtained by induction melting in a suspended state, followed by dispersion in a rotating ball mill. The phase composition of the powder included, wt%: 39.6 Ti0.8Mo0.2Si2, 33.6 TiB2, 17.8 CaSi2, 4.5 TiSi2, and 4.5 MoSi2. The powder was consolidated by hot pressing. The kinetics of static oxidation of compacts in air under thermal cycling conditions at 20 °C ↔ 1650 °C for 60 min was investigated. The total number of thermal cycles was 5. The oxidation process of compacts obeyed the power law with an exponent n = 2.695, which indicates a significant effect on the course of the process of evolutionary changes in the structure of the formed oxide film.A heterophase powder material of experimental composition in the Si–TiSif/C–SiC composite. The resulting powder, dosed with silicon in a mass ratio of 4: 1, was used as a starting material. Firing was carried out to a temperature of 1480 ± 5 °C with a residual pressure in the chamber of 8–9 MPa.Using the technology of firing deposition of layers, a thin-layer coating was formed on samples from a Cf/C–SiC composite with a coating of the Si–TiSi2–MoSi2–TiB2–CaSi2 system was carried out under conditions of aerogasdynamic flow and non-equilibrium heating by air plasma flows at Mach numbers M = 5.5–6.0 and enthalpy 40–50 MJ/kg. The coating remained operational at wT = 1810–1820 °C for at least 920–930 s, at wT = 1850–1860 °C for at least 510–520 s, at wT = 1900–1920 °C for at least 280–290 s, and at wT = 1940–1960 °C for not less than 100–110 s. The average values of the rate of loss of the coating mass in the indicated temperature ranges wT were, mg/(cm2·h): 30.1 ± 3.3, 83.5 ± 12.8, 145.3 ± 24.7, and 494.9 ± 71.8, respectively.Fire gas-dynamic tests of samples from a CwK of atoms and ions of the air plasma at the active centers of the coating surface was estimated. The average wK values in the above temperature ranges wT were m/s: 4.7 ± 1.3, 6.5 ± 1.5, 8.0 ± 2.0, and 9.0 ± 3.0, respectively.The rate constant of heterogeneous recombination 2ON2. A decrease in the vapor pressure in the “oxide film–coating” system with an increase in the degree of heterogeneity of the outer layer was experimentally confirmed. At wT ≥ 1850–1860 °C, intense gas formation was observed at the “oxide layer–coating” interface as a result of the generation of volatile silicon monoxide with the subsequent realization of the effects of boiling and breakdown degradation of the oxide film.It has been established that the performance of the coating was provided by the structural-phase state of its main layer, the formation and evolution on its surface during operation of a passivating heterogeneous oxide film composed of borosilicate glass with liquation inhomogeneities in titanium and calcium and reinforcing microneedles of titanium oxide in the form of rutile, and in situ by fibers of silicon oxynitride Si


These results revise the current understanding of nematicity in hole-doped iron-based superconductors.Electronic nematicity is often found in unconventional superconductors, suggesting its relevance for electronic pairing. In the strongly hole-doped iron-based superconductors, the symmetry channel and strength of the nematic fluctuations, as well as the possible presence of long-range nematic order, remain controversial. Here, we address these questions using transport measurements under elastic strain. By decomposing the strain response into the appropriate symmetry channels, we demonstrate the emergence of a giant in-plane symmetric contribution, associated with the growth of both strong electronic correlations and the sensitivity of these correlations to strain. We find weakened remnants of the nematic fluctuations that are present at optimal doping, but no change in the symmetry channel of nematic fluctuations with hole doping. Furthermore, we find no indication of a nematic-ordered state in the AFe AFe2As2  superconductors under elastic strain, and find no indication of a nematic ordered state.Whether the electronic nematicity is related to electronic pairing in strongly hole-doped iron-based superconductors remains controversial. Here, the authors perform transport measurements on  Furthermore, it has been theoretically suggested that nematic fluctuations may enhance pairing and therefore be an important ingredient for high-Tc superconductivity23.Nematicity, the breaking of rotational symmetry by electronic interactions, has by now been observed in a variety of unconventional superconductors. In addition to iron-based superconductors with almost ubiquitous nematicity2As2 because the stripe-type antiferromagnetic ground state inherently breaks the C4 rotational symmetry of the high-temperature tetragonal phase25, corresponding to a nematic degree of freedom. The accompanying structural distortion is in the Bg2 channel of the tetragonal Dh4 point group. In electron-doped BaFe2As2, the structural distortion occurs at a higher temperature than the antiferromagnetic state, creating a long-range, nematic-ordered phase. Nematic fluctuations of Bg2 symmetry are observed near optimal doping in both hole- and electron-doped BaFe2As227. Such fluctuations have frequently been studied using elastoresistance, the strain dependence of electrical resistivity29.In iron-based superconductors, nematicity has been intensively studied in the vicinity of the parent compound BaFe2As2 nominally has a 3d6 Fe configuration. With hole doping the Fe electron configuration begins to approach the half-filled 3d5, where a Mott insulating state is expected theoretically32. Indeed, signatures of strong electronic correlations and orbital-selective Mott behavior have been observed in the isoelectronic 3d5.5 series AFe2As2 , including an enhanced Sommerfeld coefficient and signs of a coherence–incoherence crossover35. On the basis of the strong increase of electronic correlations with increasing alkali ion size in AFe2As2 , it has further been proposed that these compounds lie near a quantum critical point (QCP) associated with the suppression of a (thus far unobserved) ordered phase, possibly related to the 3d5 Mott insulator37. Furthermore, the electronic correlations in AFe2As2 have been found to be highly sensitive to in-plane strain36.The parent compound BaFex1−KxFe2As2 series, the elastic softening associated with the Bg2 nematic fluctuations decreases with hole doping and is no longer observed for x ≥ 0.8227. Several recent studies have suggested a change to nematic fluctuations of Bg1 symmetry in the 3d5.5 compounds, in contrast to the pervasive Bg2 nematic fluctuations observed at optimal doping44. Furthermore, an ordered Bg1 nematic phase has been proposed in RbFe2As2 based on a maximum in the elastoresistance39 and an anomaly in the zero-field nuclear spin lattice relaxation rate at a similar temperature44. In addition, asymmetries were observed in STM at low temperature40. However, the study of nematic fluctuations in these compounds is complicated by the emergence of the strong electronic correlations, which are sensitive to in-plane symmetric Ag1 strain45. In such a case, it is essential to properly decompose the contributions in different symmetry channels47. This symmetry decomposition was not performed in previous elastoresistance measurements on the strongly hole-doped iron-based superconductors39. In addition, the extreme thermal expansion of these samples  carried out in a piezoelectric-based strain cell capable of full control over the strain state of the sample. We find a monotonic increase of the Ag1 response with hole doping and increasing alkali ion size. In contrast, the Bg2 elastoresistance, a measure of the Bg2 nematic susceptibility, weakens with hole doping. The Bg1 elastoresistance shows no sign of divergence, and there is no indication of the emergence of a Bg1-type nematic instability with increasing hole doping. Furthermore, we find a clear correspondence between the low-temperature elastoresistance and the electronic Grüneisen parameter if the elastoresistance coefficient is defined based only on the temperature-dependent part of the resistance.In this work, we present comprehensive elastoresistance measurements on the hole-doped iron-based superconductors Ba2As2 obtained in this way are shown in Fig. The freestanding electrical resistance of our samples is displayed in Fig. mii,xx = (1/Rii)dRii/dϵxx, where i = x corresponds to the longitudinal and i = y corresponds to the transverse elastoresistance. The strain is applied along x∥[100] , both the longitudinal and transverse elastoresistance are positive at all temperatures.In Fig. 00] Fig. a–d or x∥10] Fig. e–h. In o2As2 and RbFe2As2  or the thermal expansion L(T) /dT and dL(T)/dT .From the Kadowaki–Woods relation, the increase of 2As2 and CsFe2As2, we find that the resistance at low temperature can be fit to R = R0 + ATn, but with an exponent n < 2 Tn. Consistently, we find that dR/dϵ can be fit to B + CTn with the same exponent n as the resistance and an intercept B consistent with zero. In this situation, if the elastoresistance is simply defined as m = (1/R)dR/dϵ as is commonly done Tn/(R0 + ATn). Clearly, m → 0 as T → 0, as shown in Fig. n. A similar approach has been applied in the analysis of elastoresistance data in YbRu2Ge250.In RbFe< 2 Fig. a. This iure Fig. c. Note tn = 2 where A ∝ γ2, A/dϵ)/A = (dγ2/dϵ)/γ2 = 2(dγ/dϵ)/γ, which is proportional to the Grüneisen parameter Γ ≡ (dγ/dϵ)/γ for the Sommerfeld coefficient γ. Γ is a measure of the strain dependence of an energy scale. Its divergence is a central characteristic of a strain-tuned QCP53, as previously discussed in these materials36.The redefined elastoresistance α represents the irreducible representation of the tetragonal Dh4 point group. These coefficients determine the resistance changes associated with the pure symmetric strains illustrated schematically in Fig. ϵ∥[100] (ϵ∥[110]) (see “Methods”). The resulting symmetry-decomposed elastoresistance coefficients are shown in Fig. 0.4K0.6Fe2As2 to KFe2As2 and further with chemical substitution from KFe2As2 to CsFe2As2. Furthermore, 2As2 has strong temperature dependence, with an increase on cooling and a broad peak near 30 K. This temperature dependence is reminiscent of the coherence–incoherence crossover observed in the thermal expansion coefficient of this material45. The coefficients 0.4K0.6Fe2As2. For all samples, 2As2, consistent with the observed sign change of resistivity anisotropy upon K substitution in Bax1−KxFe2As254. We also note that both 0.6K0.4Fe2As2 are similar in magnitude and sign to CaKFe4As4, which is isoelectronic to Ba0.5K0.5Fe2As256. The coefficient 2As2 and KFe2As2. In CsFe2As2 and Ba0.4K0.6Fe2As2, we observe an upturn at low temperature. The temperature dependence of Having understood the longitudinal and transverse elastoresistance data, we now calculate the symmetry-decomposed elastoresistance coefficients mentclass2pt{minimA1g Fig. a strongl45, the increase of 2As2 to CsFe2As2 indicates that the strain sensitivity of the electronic correlations increases as a result of this chemical substitution. This is consistent with the increase in the strain derivative of the Sommerfeld coefficient ∂γ/∂ϵ observed in thermodynamic measurements36. Therefore, the origin of the large Ag1 elastoresistance is the high-strain sensitivity of the electron correlations associated with the orbital-selective Mott behavior. As a consequence, the temperature and substitution dependence of the Ag1 coefficient show a strong similarity to that of the thermal expansion coefficient45 , 0.4K0.6Fe2As2 but has a similar temperature dependence, strongly suggesting that we are observing the remnants of the Bg2 nematic fluctuations found in lightly doped BaFe2As2. The temperature dependence of the coefficient 2As2  compounds are not near a Bg1 nematic instability. The evolution of Bg2 to Bg1 nematic fluctuations in hole-doped iron-based superconductors, in contrast to previous studies43. Further, nematic fluctuations of XY, as opposed to Ising, character have been proposed in the Bax1−RbxFe2As2 series in the 0.6 < x < 0.8 doping range39. Whereas we do find that 0.4K0.6Fe2As2 in our case), their distinct temperature dependence is inconsistent with XY nematic fluctuations.We turn now to the coefficients B2g Fig. b and \doB1g Fig. c correspBg1 nematic-ordered phase below 40 K has been proposed in RbFe2As2 based on a maximum in the longitudinal elastoresistance measured along [100]39. The symmetry decomposition of the elastoresistance reveals that such a maximum occurs in the Ag1 channel, which we associate with the coherence/incoherence crossover and not a phase transition. Consistently, the resistance and thermal expansion34 data show no sign of a phase transition in RbFe2As2  on the same horizontal axis. In all, 40 K is chosen so that the high-Tc sample can be included. The hashed region 0.6 < x < 0.8 denotes the doping range where a significant change of behavior has been observed, including a Lifshitz transition61 and proposed broken time-reversal symmetry in the superconducting state64, as well as the proposed XY nematic state in the Rb-doped series (Bax1−RbxFe2As2)39. Our results suggest that this doping range coincides with the emergence of an enhanced Ag1 elastoresistance. Recalling that a at low temperature, we plot Γa alongside Our results are summarized in Fig. Bg2 nematic fluctuations of the optimally doped regime even in fully substituted samples with 3d5.5 electronic configuration. We also observe signatures of possible weak nematic fluctuations in the Bg1 channel, but we do not observe a change from Bg2-dominant to Bg1-dominant nematic fluctuations with doping and we find no evidence for a bulk nematic state in any of our samples. These results revise the current understanding of nematicity in hole-doped iron-based superconductors and raise some new points. First, neither Bg1 nor Bg2 nematic fluctuations depend strongly on the alkali ion size in AFe2As2 . In contrast, the strong correlations related to the orbital-selective Mott behavior seen in the Ag1 channel increase dramatically with increasing alkali ion size. The contrasting behavior indicates that the orbital-selective Mott physics does not cause the nematic fluctuations. Second, we find that the Bg2 nematic fluctuations are surprisingly robust, persisting at high hole doping even beyond the Lifshitz transition where the electron pocket of the Fermi surface and the corresponding nesting properties are lost, and magnetic fluctuations become incommensurate.We stress that we observe, nevertheless, the remnant of the 0.4K0.6Fe2As2 with a sizeable nematic susceptibility, anisotropic strains change the measured resistance by favoring the resistance of one in-plane direction over the other, as nematic order causes a resistance anisotropy. In CsFe2As2, by contrast, symmetric strains directly modulate the strength of electron correlations and effective mass causing changes in average in-plane resistance.To conclude, we reflect on the different physical mechanisms responsible for the observed strain-induced resistance changes. In Ba2As2 were grown from solution using a Cs-rich self-flux in a sealed environment65. Cs, Fe, and As were weighted in molar ratio 8:1:11, respectively. All sample manipulations were performed in an argon glovebox (O2 content is < 0.5 ppm). Molten Cs together with a mixture of iron and arsenic powder were loaded into an alumina crucible. Typically 15–20 g of a mixture of Cs, Fe, and As were used for each crystal growth experiment. The alumina crucible with a lid was placed inside a stainless steel container and encapsulated. This was done by welding a stainless screw cap to one end of the container. This has the advantage that stainless steel does not corrode due to Cs vapor at high temperatures. The stainless steel container was placed in a tube furnace, which was evacuated at 5–10 mbar and slowly heated up to 200 °C. The sample was kept at this temperature for 10 h and subsequently heated up to 980 °C in 8 h. The furnace temperature was kept constant at 980 °C for 5 h and slowly cooled to 760 °C in 14 days, and then the furnace was canted to separate the excess flux. After cooling to room temperature, shiny plate-like crystals were easily removed from the remaining ingot. Refined crystallographic data have been presented elsewhere45. KFe2As2 and RbFe2As2 single crystals were obtained under similar conditions using an alkali metal/As-rich flux34.Single crystals of CsFe0.4K0.6Fe2As2 were grown by a self-flux technique, using FeAs fluxes, in alumina crucibles sealed in iron cylinders using very slow cooling rates of 0.2–0.4 °C/h. The crystals were annealed in situ by further slow cooling to room temperature.High-quality single crystals of BaElastoresistance measurements were performed in a commercial strain cell (Razorbill Instruments CS-120). The samples were cut with edges along the tetragonal in-plane directions [100] or [110], with typical dimensions of 3.0 × 1.0 × 0.06 mm. The samples were fixed in the strain cell using DevCon 5 Minute Epoxy with an effective strained sample length of 2.0 mm. The epoxy thickness was controlled to be 50 μm below the sample and ~30 μm above the sample. Cigarette paper was used to ensure the electrical insulation of the sample from the titanium mounting plates. The sample strain was measured via a built-in capacitive displacement sensor and readout on an Andeen Hagerling 2550A capacitance bridge. Resistance was measured using a four-point method on a Lake Shore 372 resistance bridge. Hans Wolbring Leitsilber 200N was used to make the electrical contacts, as contacts made with DuPont 4929N silver paint were found to be mechanically unstable on strain application.66. From a comparison with established elastoresistance data on BaFe2As2, we estimate that the true strain is ~60% of the nominal strain in our setup, as shown in Supplementary Fig. We note that the true strain experienced by a sample in the strain cell is less than the nominal strain read by the capacitance sensor2As2, the sample is expected to experience ~0.7% tension at base temperature. In contrast, the parent compound BaFe2As2 has a thermal expansion nearly identical to titanium. This is also true for lightly doped compounds66. Elastoresistance has typically been measured by gluing the sample directly onto the side of a piezoelectric stack, which has a small thermal expansion, similar to titanium. The success of previous elastoresistance measurements on lightly doped BaFe2As2 samples thus depended on the fortunately similar thermal expansion of the piezoelectric stack and the sample. However, this method is unreliable for the 3d5.5 superconductors45.Due to the large thermal expansion mismatch between our samples and the titanium body of the strain cell, the samples will experience tension on cooling Fig. b. In the45.To keep the sample in an unstrained state on cooling, we progressively reduce the distance between the sample mounting plates by an amount calculated based on the known thermal expansion difference between the sample and titanium, and the measurement of a titanium calibration sampleα of the Dh4 point group, we note that the symmetric strains ϵα are given in terms of ϵxx by εx ≡ εxx. Similar expressions apply relating Rα with Rxx. The symmetry-decomposed elastoresistance coefficients are then defined as mα = (1/Rα)dRα/dεα. In terms of the experimental data, these coefficients are given byTo express the elastoresistance in terms of the irreducible representations ν is the sample’s Poisson ratio, which relates the strain along different directions, ν[100] = − ε[010]/ε[100], and ν is sample and temperature-dependent and anisotropic (ν[100] ≠ ν[110]). The elastoresistance coefficients in the notation of irreducible representations are given in terms of the elastoresistance coefficients in the usual Voigt notation asAg1 channel, c-axis compression (tension) which accompanies the symmetric in-plane biaxial tension (compression) because of the Poisson effect.The quantity 2As2 are larger in this paper than in our previous work45. This results from a difference in the ratio between real and nominal strain in the two studies. Our previous work was conducted with a Razorbill CS-100 cell, which has a smaller maximum displacement than the CS-120 cell used here. According to the documentation provided with our strain cells by Razorbill Instruments, due to the deformation of the strain device itself by a stiff sample, the capacitance sensor will overread the applied displacement according toks is the sample spring constant, and hs is the sample mounting height above the top of the apparatus. The remaining parameters are properties of the strain cell itself: kτ is the torsional spring constant, ha is the height of the top surface above the moving block rotation center, and hc is the height of the top surface above the center of the capacitor. The parameters kτ, ha and hc are different between the two strain cells. In addition, the sample spring constants ks in this work were typically ~2 N/μm, compared with ~4 N/μm in our previous work. The smaller ks allows for a transmitted strain closer to the nominal value determined from the capacitance sensor, producing a greater measured elastoresistance in our current work. Due to these issues, we chose to re-measure CsFe2As2 in the CS-120 cell to make sure the results were comparable in all presented samples.We note that the reported elastoresistance coefficients for CsFeνx = − ϵyy/ϵxx and cij are given byThe sample Poisson ratios 36. The phonon dispersions and corresponding interatomic force constants were calculated via density functional perturbation theory and the elastic constants were then extracted via the method of long waves. For Ba0.4K0.6Fe2As2, we used values calculated for Ba0.5K0.5Fe2As2 in a virtual-crystal approximation. The numerical values of elastic constants and Poisson ratios calculated therefrom are given in Table To obtain rough estimates of the elastic constants, we performed ab initio calculations in the framework of the generalized gradient approximation using a mixed-basis pseudopotential methodSupplementary InformationPeer Review File


F) via synergetic photoredox and copper catalysis. This method readily converts primary and secondary alkyl carboxylic acids into the corresponding polyfluoroaryl compounds, which could have a wide range of F‐content (2F‐5F) and variable F‐substitution patterns on the aryl groups. Broad scope and good functional group compatibility were achieved, including on substrates derived from natural products and pharmaceuticals. Mechanistic study revealed that a [Cu‐(ArF)2] species could be responsible for the transfer of polyfluoroaryl groups to the alkyl radicals.Polyfluoroarenes are an important class of compounds in medical and material chemistry. The synthesis of alkylated polyfluoroarenes remains challenging. Here we describe a decarboxylative coupling reaction of N‐hydroxyphthalimide esters of aliphatic carboxylic acids with polyfluoroaryl zinc reagents  and variable F‐substitution patterns. F and anion–πF interactions, which lead to widespread applications in pharmaceuticalsAr reactionsPolyfluoroarenes can form special intermolecular interactions,F, H‐ArF and M‐ArF, where X is a halide, M is a metal), on the other hand, provides a more general and versatile approach to the synthesis of polyfluoroaryl compounds  were not suitable substrates, likely because the ArF−H bonds of the low‐F‐content arenes were less acidic and resistant to base‐assisted C−H metalation. The reaction also has relatively harsh conditions and suffers from the regioselectivity problem of C−H activation for many substrates.Metal catalyzed C−C cross‐coupling of polyfluoroaryl reagents  and alkyl carboxylic acids (Scheme F reagentsF groups with a wide range of F‐content (2F‐5F) and with varied F‐substitution patterns. Although the coupling reaction of NHPI esters is well established with many organometallic reagents,F‐Zn reagents is hitherto unknown. Compared to the method of Ritter,Here we describe a metallophotoredox approachs Scheme . Unlike 6F5)2 (b1) as the source of ‐ArF, which could be obtained as a stable solid from a simple reaction of pentafluoroiodobenzene with diethylzinc. After a thorough screening of reaction conditions , we found that with 1 mol % of Ir(dfppy)2(ppy) as photocatalyst, 10 mol % of Cu(OTf)2 as catalyst and 20 mol % of dtbbpy  as ligand, the NHPI ester of 1‐benzoylpiperidine‐4‐carboxylic acid (a1) was coupled with b1 to give the desired product c1 in excellent yield  (DME=dimethoxyethane) were not effective metal catalysts  outweighed the coupling product c1  with 4CzIPN, an easily accessible and inexpensive organic photocatalyst,We started our exploration using (diglyme)Zn(C6F5)2 b as the s6F5)2 b as the s6F5)2 b as the s6F5)2 b as the s6F5)2 b as the s6F5)2 b as the s6F5)2 b as the s6F5)2 b as the sc1–c7) and acyclic (c8–c10) alkyl groups, including those with considerable steric hindrance  were coupled to polyfluoroaryls in good yields. Sulfonamide (c2), ether (c3), ketone (c5), and electron‐rich arene (c9) were compatible with the reaction conditions. Several pharmaceuticals, such as Ibuprofen, Ketoprofen and Naproxen, could be modified via this method into polyfluoroaryl compounds (c11–c13) in excellent yields. A substrate with an α‐oxyalkyl group was not suitable for the reaction, with a GC yield of less than 5 %, possibly due to facile direct oxidation of the α‐oxyalkyl radicalBased on the optimized conditions , alkylbromide (d2) and alkyliodide (d3) groups, which serve as electrophiles in many cross‐coupling reactions,d6) and primary benzyls  were also suitable for this transformation. Despite their high molecular weights, some polyfluoro products were volatile  and suffered from substantial loss of yields during separation . Double polyfluoroarylation on the same substrate was demonstrated (d9). Reactions of NHPI esters derived from natural products and pharmaceuticals (d10–d14) also led to high coupling yields (d10–d13). The reaction of the NHPI ester of the structurally complicated dehydrocholic acid had a modest yield of 42 % (d14). For the coupling of tertiary alkyl NHPI esters, the reaction was generally not productive . Some specific substrates, e.g., those with a cyclopropyl ring, were coupled in modest to good yields .A wide range of primary alkyl NHPI esters were also suitable substrates for this reaction , alkynyl were all tolerated in the reaction, leading to the corresponding products  in good yields. Then, the coupling to a set of aryls with varied F‐content and F‐substitution patterns was probed. All three isomers of tetrafluorophenyl could be coupled to a primary alkyl (f8–f10) or a secondary alkyl (g8–g10) group in good yields. Trifluorophenyl zinc reagents were successfully applied to the reaction as well , so was the 2,6‐difluorophenyl zinc reagent . The coupling of 2,4‐difluorophenyl zinc was inefficient (30 % for g15 and <5 % for f15). Likewise, the coupling of 2‐fluorophenyl or 4‐fluorophenyl zinc reagent was not successful . In these cases, the relatively electron rich aryl zinc reagents were prone to homocoupling to give biaryls. The electron‐deficient tetrafluoropyridyl zinc reagent was not suited to this reaction as well (29 % for g18 and 0 % for f18). Notably, 1 equivalent of diglyme could generally enhance the yields by 5–10 % , possibly because diglyme acted as a ligand to promote the aryl transfer process.We next explored the scope of polyfluoroaryl zinc reagents Figure . Diaryl a2) was used as a substrate to couple with b1 under the standard conditions  was synthesized and was found to be a competent catalyst as well  with a1 under photochemical conditions didn't give any coupling product  and 100 mol % of b1  could enter the catalytic cycle and transfer the ‐C6F5 group on the copper into the product. However, it cannot directly transfer the ‐C6F5 group without a further transformation.Several experiments were conducted to shed light on the mechanism of the coupling. When the NHPI ester derived from 6‐heptenoic acid a was usedb1 was added to a solution containing [(bpy)Cu(C6F5)], an instant color change from orange to light yellow was observed. With UV/Vis spectroscopy, we observed that increasing the ratio of b1 to [(bpy)Cu(C6F5)] in dichloromethane led to a significant decrease of absorbance of [(bpy)Cu(C6F5)] , which could indicate a transmetallation process. Likewise, in the 19F‐NMR spectra of the mixture of b1 and [(bpy)Cu(C6F5)], a new peak A was generated and the peak B in the original spectrum of [(bpy)Cu(C6F5)] disappeared ] to a new M‐C6F5 species with the addition of b1. In the cyclic voltammograms  when b1 was added to [(bpy)Cu(C6F5)], which was 0.60 V lower than the oxidation peak of [(bpy)Cu(C6F5)]. These results could be attributed to the formation of a [(bpy)Cu(C6F5)2] species upon the addition of b1 to [(bpy)Cu(C6F5)]  and the 1:1 mixture of b1 with (bpy)CuC6F5 were effective quenchers. These data suggest that the reaction possibly starts by a reductive quenching of the excited 4CzIPN by the CuI species. Considering the large excess of b1 to copper catalyst under the coupling conditions, the neutral [LCu(ArF)] are expected to have a very low concentration and [LCu(ArF)2]− is more likely to be the quencher of the excited 4CzIPN.Stern–Volmer quenching was used to probe the interaction of the excited photocatalyst with different reagents . NHPI ester I(ArF)2] species i to form the reduced 4CzIPN and a LCuII(ArF)2 species (j). The radical anion of 4CzIPN then reduces the NHPI ester a to give an alkyl radical after decarboxylation. The alkyl radical is captured by j to form a formal CuIII intermediate k, which undergoes reductive elimination to give the coupling product and a LCuI(ArF) species l. Although there is no precedent for a polyfluoroaryl alkyl reductive elimination from such a CuIII complex, reductive elimination from an analogous [(bpy)Cu(CF3)2(CH3)] was reported to form CF3CH3 and [(bpy)Cu(CF3)].F transfer process (in dash square) could not be ruled out. [LCuI(ArF)] undergoes transmetallation with the Zn‐ArF reagent to regenerate i and closes the catalytic cycle.Based on these results, we propose a plausible mechanism Scheme . The reaF reagents with alkyl radicals generated by other methods, leading to new methods in polyfluoroarylation.In summary, we have developed a dual photo‐ and Cu‐catalyzed method for the decarboxylative coupling of aliphatic acids with polyfluoroaryl zinc reagents. This method allows the installation of polyfluoroaryls with variable F‐content and F‐substitution patterns on a primary or secondary alkyl group, with good compatibility of functional groups. Our strategy might be extended to the coupling of Zn‐ArThe authors declare no conflict of interest.As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re‐organized for online delivery, but are not copy‐edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors.Supporting InformationClick here for additional data file.


Cluster randomization design is increasingly used for the evaluation of health-care, screeening or educational interventions. At the planning stage, sample size calculations usually consider an average cluster size without taking into account any potential imbalance in cluster size. However, there may exist high discrepancies in cluster sizes.We performed simulations to study the impact of an imbalance in cluster size on power. We determined by simulations to which extent four methods proposed to adapt the sample size calculations to a pre-specified imbalance in cluster size could lead to adequately powered trials.We showed that an imbalance in cluster size can be of high influence on the power in the case of severe imbalance, particularly if the number of clusters is low and/or the intraclass correlation coefficient is high. In the case of a severe imbalance, our simulations confirmed that the minimum variance weights correction of the variation inflaction factor (VIF) used in the sample size calculations has the best properties.γ) of clusters actually recruit a proportion (τ) of subjects to be included (γ ≤ τ)".Publication of cluster sizes is important to assess the real power of the trial which was conducted and to help designing future trials. We derived an adaptation of the VIF from the minimum variance weights correction to be used in case the imbalance can be a priori formulated such as "a proportion ( This clustering effect is used during the planning of cluster randomized trials as an inflation factor to increase the sample size required by an individual randomization trial. However, such an approach does not take into account variations in cluster size, which might differ greatly. Indeed, as illustrated by Kerry et al With a Pareto imbalance, the equation can be written as:withwhich leads to Distribution-based correction (denoted d) [noted d) So we have:withthat is to say:One then recognizes the results obtained using the cluster size weights correction.Characteristics of the Pareto-like imbalanceg refers to the number of clusters within each arm and Minimum variance weighs VIFSo we obtain:mi - mj| can be written as:Given the characteristics of the Pareto-like imbalance presented in appendix B, considering that clusters are ordered hierarchically by increasing size, the matrix of the difference |γg,γg) (and 0γ)g,(1-γ)g) ((1-are squared matrices of size γg and (1-γ)g respectively and 1γg,(1-γ)g) (and 1γ)g,γg) ((1-are matices of size γg × (1-γ)g and (1-γ)g × γg respectively, containing only 1 s.Where 0Thus:The pre-publication history for this paper can be accessed here:


Semiconductor photocatalysts have attracted increased attention due to their great potential for solving energy and environmental problems. The formation of Z‐scheme photocatalytic systems that mimic natural photosynthesis is a promising strategy to improve photocatalytic activity that is superior to single component photocatalysts. The connection between photosystem I (PS I) and photosystem II (PS II) are crucial for constructing efficient Z‐scheme photocatalytic systems using two photocatalysts (PS I and PS II). The present review concisely summarizes and highlights recent state‐of‐the‐art accomplishments of Z‐scheme photocatalytic systems with diverse connection modes, including i) with shuttle redox mediators, ii) without electron mediators, and iii) with solid‐state electron mediators, which effectively increase visible‐light absorption, promote the separation and transportation of photoinduced charge carriers, and thus enhance the photocatalytic efficiency. The challenges and prospects for future development of Z‐scheme photocatalytic systems are also presented. These methods use solar energy as the source of photons to promote reactions.2 and WO3) and non‐oxides  are widely used as photocatalysts, their performance of the photocatalytic reaction is still very low.Energy and environmental issues are important topics on a global level. To tackle the issue of the depletion of fossil fuels and their environmental misdeeds, the exploration of renewable and clean energy resources and the development of eco‐friendly practical systems for environmental remediation have been drawing increasing attention Figure1. Semi2O and CO2 are converted into O2 and carbohydrate through natural photosynthesis (NPS) in green plants, as shown in Figure+ into NADP that is used to fix CO2 into carbohydrate in the dark reaction, and the water oxidation occurs at a manganese calcium oxide cluster in PS II.FigureIn nature, H3+/Fe2+, IO3–/I–, NO3–/NO2–) are usually served as electron transport chain in Z‐scheme water splitting.– by holes in the O2 evolution photocatalyst when using IO3–/I– as redox mediator. Therefore, the reaction efficiency of reversible redox mediator Z‐scheme photocatalytic system could be destroyed. In addition, the redox mediators also strongly absorb the visible light, reducing the light absorption of semiconductor photocatalysts. Thus, the Z‐scheme photocatalytic systems without reversible redox pair mediators or with solid state electron mediators are necessary to be developed for water splitting.2 photoreduction.Z‐scheme water splitting was first reported by Bard et al. in 1979.Based on the discussion above, we know that the connection between two photocatalysts is crucial for constructing efficient Z‐scheme photocatalytic systems. Many works studied different connection modes of Z‐scheme photocatalytic systems.22 evolution (PS I) photocatalyst occur as follows: As shown in Figure 2 evolution (PS II) photocatalyst should occur as follows: The forward reactions on an O2 and O2 is extremely difficult in a Z‐scheme system because the backward reactions also easily proceed over each photocatalyst,However, the demonstration of the simultaneous evolution of H2/TaON and Pt‐loaded WO3 as the H2‐ and O2‐evolution photocatalysts, respectively, in the presence of an IO3–/I– redox mediator.– ions on the Pt‐loaded WO3 and the reduction of IO3– on the Pt‐loaded ZrO2/TaON, were significantly minimized. As a result, the highest apparent quantum efficiency (AQE) of 6.3% at 420 nm was achieved. This high selectivity for the forward reactions in the Z‐scheme system was also demonstrated by using Pt‐SrTiO3:Cr/Ta, Pt‐WO3, and the IO3–/I– redox mediator.x, RuO2), that was loaded onto the photocatalyst surface to produce active sites and reduce the activation energy for the surface chemical reactions.2O3, and RuO2) loaded on SrTiO3:Rh/WO3 visible‐light‐driven Z‐scheme photocatalysis systems for H2 and O2 evolution with Fe3+/Fe2+ as the electron mediator were investigated, and the water splitting was obviously enhanced in comparison with the non‐loaded system.2 and O2 were increased. However, such deactivation was not observed for the system using the Ru cocatalyst due to the significant suppression of the backward reactions. Moreover, the selective catalysis is achieved via the introduction of a proper cocatalyst on the photocatalyst surface. Mn3O4, RuO2, IrO2, and CoOx nanoparticles were found to function as O2 evolution cocatalysts.2‐loaded TaON is an effective photocatalyst for O2 evolution to achieve water splitting in combination with Pt‐loaded TaON as a H2 evolution photocatalyst with an IO3–/I– redox mediator.2 evolution due to the efficiently competitive oxidation of I–. However, loading RuO2 on the TaON surface enables water oxidation even in the presence of I–.2‐loaded Ta3N5 or Pt‐BaTaO2N is another interesting example that allows water oxidation in the presence of IO3–/I–, respectively.2 and rutile TiO2 as a H2 and O2 evolution photocatalyst, respectively, achieved much higher evolution rates of H2 and O2 at pH > 9.The electron acceptor (A) and donor (D) react with the photogenerated electrons in the CB of PS I and holes in the VB of PS II, respectively, resulting in the obviously decrease in the effective number of photogenerated electrons and holes. Thus, it is critical to suppress the backward reactions involving redox mediators that are thermodynamically more favorable than water splitting. In 2010, Domen et al. succeeded in water splitting using a Z‐scheme system consisting of Pt‐loaded ZrOTableAll primary semiconductor‐based Z‐scheme systems with shuttle redox mediators are summarized in 3FigureA direct Z‐scheme system without redox mediators was schematically illustrated in 0.91O2 nanosheets (≈0.75 nm) and CdS nanoparticles (≈5–6 nm) via an exquisite layer‐by‐layer self‐assembly to realize a redox mediator‐free direct Z‐scheme system for the photocatalytic reduction of CO2 into CH4 2 precipitate, resulting in a Z‐scheme ZnO/CdS photocatalytic system.2 evolution under simulated solar light irradiation, due to the strong phase interaction by the binding energy shift of Zn 2p3/2, Cd 3d5/2, O 1s, and S 2p in the ZnO/CdS heterostructure in contrast to the pure ZnO and CdS. Z‐scheme BiVO4/g‐C3N4 composites that the facet coupling occurred between the g‐C3N4 (002) and BiVO4 (121) were obtained by calcination of a mixture of appropriate amounts of BiVO4 and g‐C3N4 at 400°C for 4 h.3/g‐C3N4, ZnO/g‐C3N4, and WO3/g‐C3N4, have also been synthesized through calcination process.2 composites were fabricated via a facile hydrothermal reaction with tetrabutyltitanate and as‐prepared Si nanospheres.The chemical contact is the other contact mode to form intimate interface between PS I and PS II for effective carriers transfer, due to the surface conjugation via chemical bond. Wet chemistry is widely used to synthesize direct Z‐scheme systems.2, and decompose various organic contaminations , which consists of only carbon and nitrogen, is a sustainable, cost‐effective and environmental‐friendly semiconductor that has attracted extensive interest.3N4 with other appropriate semiconductors for construction of a direct Z‐scheme system can effectively improve the photocatalytic performance.3N4/AgBr photocatalyst was prepared by loading AgBr nanoparticles on a protonated g‐C3N4 matrix.3N4. As a result, the photodegradation rate of methyl orange (MO) over the g‐C3N4/AgBr photocatalyst was 33.8 and 2.1 times higher than that over pure g‐C3N4 and AgBr samples, respectively.The direct Z‐scheme system can work in both liquid‐phase and gas‐phase environments, which are widely used to split water, photoreduce COsee Table2. SolaAlthough direct Z‐scheme systems effectively improve photocatalytic activities due to the recombination of photoexcited electrons from the CB of PS II and holes from the VB of PS I at the interface, the photoexcited carrier transport process at the interface between PS II and PS I is often poor due to surface relaxation and the recombination of charge carriers within each component. Therefore, the design of a new structural system with pathways for quick transport of charge carriers at the interface is highly desired.4FigureTableAs shown in 2 system, which was fabricated using a simple photochemical technique, is the first example of an all‐solid‐state Z‐scheme system.2 transferred to Au and then to the VB of CdS, subsequently recombined with the holes photogenerated in CdS. Simultaneously, the photogenerated electrons in the CB of CdS and the holes in the VB of TiO2 exhibited a strong reduction power and oxidation power, respectively, leading to a high photocatalytic reduction of methylviologen (MV2+). Moreover, the photoexcited holes in the VB of CdS were recombined with electrons from TiO2, resulting in improvement in the photostability of CdS. Similarly, the photocatalytic activities of CdS/Au/ZnO and CdS/Au/TiO1.96C0.04 were also improved due to the solid‐state Z‐scheme mechanism.The CdS/Au/TiO3PO4/Ag/SiC, the band gap energies of Ag3PO4 and SiC were approximately 2.41 and 2.58 eV, respectively.λ ≥ 420 nm), the photogenerated electrons and holes appeared in both Ag3PO4 and SiC. The photoinduced electron in the CB of Ag3PO4 easily shifted to the Ag nanoparticles and recombined with the photogenerated holes in the VB of SiC, resulting in a high efficiency of the electron‐hole separation and an enhancement in the photocatalytic activities. The solid‐state Z‐scheme system of ZnRh2O4/Ag/Ag1–xSbO3–y was developed to split pure water under visible light irradiation.1–xSbO3–y to the valence band of ZnRh2O4. As a result, the water‐splitting activity of ZnRh2O4/Ag/Ag1–xSbO3–y was higher than that of ZnRh2O4, Ag1–xSbO3–y, and ZnRh2O4/Ag1–xSbO3–y. With Ag nanoparticles as the solid electron mediator, other Z‐scheme systems, such as Ag2CO3/Ag/AgBr, Ag3PO4/Ag/SiC, and α/β‐Bi2O3/Ag/AgCl, have also been reported enhancement in their photocatalytic activities.Recently, Ag nanoparticles have been extensively investigated as solid electron mediator for the design of a high‐efficiency Z‐scheme system. For the visible‐light‐driven Z‐scheme of Ag2WO4/Ag/AgCl reported by Yu et al.,g = 3.25 eV) was not photoexcited under visible‐light irradiation (λ ≥ 420 nm); however, H2WO4 (Eg = 2.48 eV) absorbed visible‐light photons to produce photogenerated electrons and holes. Meanwhile, photoinduced electrons and holes appeared in the Ag nanoparticles because of the SPR effects. The photogenerated electrons of H2WO4 transferred to the Ag nanoparticles to recombine with the plasmon‐induced holes. Simultaneously, the holes of H2WO4 oxidized organic substances. However, the plasmon‐induced electrons of the Ag nanoparticles were injected into the CB of AgCl to reduce oxygen. Other visible‐light‐driven plasmonic Z‐scheme systems, including Ag/AgCl/Bi20TiO32, α‐β‐Bi2O3/Ag/AgCl, Ag/AgCl/ZnO, and Ag/AgCl/BiOCl, have also been investigated.Notably, noble‐metal nanoparticles  used as photosensitizers can strongly absorb visible light due to their localized SPR effects.4)/RGO/(Ru/SrTiO3:Rh) for water splitting.4 and the holes in Ru/SrTiO3:Rh to recombine, leaving holes in BiVO4 and electrons in Ru/SrTiO3:Rh to split the water. This “Z” mechanism of electron flow enhanced the charge separation efficiency, resulting in enhancement of the photocatalytic activities. Recently, Kudo et al. also demonstrated that RGO was used to construct Z‐scheme systems that consist of various metal sulphides.2 and RGO‐TiO2 continuously splits water into H2 and O2 for 12 h, producing a 1.3% apparent quantum yield under 380 nm of monochromatic light irradiation. Our group fabricated a Fe2V4O13/RGO/CdS Z‐scheme system that perpendicularly grew on a stainless‐steel mesh for the photocatalytic reduction of CO2 into methane.2O4/ITO/WO3, WO3/W/PbBi2Nb1.9Ti0.1O9, and ZnO/Cd/CdS Z‐scheme systems, respectively. The enhanced the photocatalytic activity of these systems is attributed to the fast recombination of photogenerated holes in PS I and electrons in PS II within the conductive support.In addition to the noble metals discussed above, some low‐cost nonmetal materials and metal oxides with excellent conductivities can also be used as electron mediators in solid state Z‐scheme systems. RGO was employed as a solid‐state electron mediator to promote electron transfer between the photocatalyst particles in the Z‐scheme system.5Photocatalysis is a promising avenue for solving environmental and energy issues in the future, which is attracting an ever‐growing number of scientists to this field. Thus far, the development of photocatalysts with high efficiency, long‐term stability, and at a low cost is the main challenge for their practical application, and it is difficult for a single‐component photocatalyst to simultaneously possess all of these features. The formation of Z‐scheme photocatalytic systems effectively expands the utilization of visible light, improves the separation/transportation of the charge carriers, and substantially enhances the efficiency of the photocatalytic activities.4 photocatalyst.Z‐scheme systems with shuttle redox mediators are primarily used for efficient water splitting. In this system, the effective separation of charge carriers occurs via recyclable redox reactions of the shuttle redox mediators. However, Z‐scheme systems with shuttle redox mediators have various negative effects, such as back reactions, visible light absorption of the redox mediators and short‐term stability. Z‐scheme systems with solid‐state electron mediators typically suppress the above shortcomings because of the absence of redox mediators. Solid‐state electron mediators provide a pathway for the photogenerated electrons in PS II and the holes in PS I to quickly travel and recombine, leaving more electrons in PS I and more holes in PS II to participate in the redox reaction. Additionally, the SPR effect of metal nanoparticles  also plays an important role in Z‐scheme systems. When PS II or PS I is photoexcited, the SPR effect of metal nanoparticles becomes significant for Z‐scheme photocatalytic activities. However, when both PS II and PS I are photoexcited, the metal nanoparticles mainly act as electron mediators. The contact interface of PS I–PS II has a significant impact on the charge transfer in the direct Z‐scheme system without electron mediators. A high‐quality interface of PS I–PS II facilitates the transfer of photogenerated charge carriers across the interface, resulting in an enhancement of the photocatalytic performance. As the increasing amount of literatures presented direct Z‐scheme system, it must be strict and careful for distinguishing the direct Z‐scheme system from traditional heterostructure systems such as type‐II heterostructure. Recently, our group applied transient time‐resolved luminescence decay measurements to analyze the difference between type‐II heterostructure and direct Z‐scheme system.4 and a platinized protein photosystem I (PSI) in an all‐solid‐state was constructed for H2 evolution without redox mediators. This hybrid system provides a new means of using a photosynthetic protein as a practical material in the design of a photocatalytic system.Great progress has been achieved in the investigation of Z‐scheme systems. However, the photocatalytic reaction is a complex process, and there are many important aspects that need further research, including developing new photocatalytic materials, fundamentally understanding the separation and transport of charge carriers on the interface, and understanding photocatalytic reaction pathways. Therefore, a greater knowledge of the Z‐scheme photocatalytic mechanism and the exploration of new materials are indispensable for making substantial breakthroughs for the practical application of photocatalysts. In this regard, several key considerations could be concerned, including: i) a deep understanding of processes, such as the charge carrier transfer processes and the photocatalytic reaction pathways. The research would integrate experimental and computational approaches to evaluate photocatalytic activity, and would advance fundamental understanding of Z‐scheme photocatalytic mechanism. The transient time‐resolved luminescence decay measurements are well applied to analyze the behavior of photogenerated charge carriers, due to the high time resolution. Surface photovoltaic technique is another advanced technology for probing into the charge carrier transfer processes. ii) The shuttle redox mediators or solid‐state electron mediators of Z‐scheme system plays an important role in charge carrier transportation. It is urgent to develop new shuttle redox mediators or solid‐state electron mediators for solving unfortunate problem, such as backward reactions and light absorption of mediators. iii) Exploitation of new Z‐scheme photocatalytic system is also desired to avoid the mentioned problems in the inorganic Z‐scheme photocatalytic system. A hybrid Z‐scheme by integrating BiVOAlthough the conversion efficiency is still low at the present stage, the Z‐scheme photocatalytic system that mimics the natural photosynthesis in green plants may be the most promising photocatalytic system in photocatalytic field. It is sincerely expected that multiple collaboration for this rapidly evolving field can lead to a breakthrough in the efficiency for the commercialization and industrialization.


In Fig 2, the y-axis for the graphs Runx2 and RANKL are incorrectly labeled. The axis should be labeled “Rative RNA abundance” Please see the corrected In S1 File, the data for Runx2 and RANKL is incorrect. Please see the corrected S1 File(XLSX)Click here for additional data file.