Search

Isoniazid (INH) is a first-line anti-tuberculosis drug used for nearly 70 years. However, the mechanism underlying the side effects of INH has remained elusive. Here, we report that INH and its metabolites induce a post-translational modification (PTM) of histones, lysine isonicotinylation (Kinic), also called 4-picolinylation, in cells and mice. INH promotes the biosynthesis of isonicotinyl-CoA (Inic-CoA), a co-factor of intracellular isonicotinylation. Mass spectrometry reveals 26 Kinic sites in histones in HepG2 cells. Acetyltransferases CREB-binding protein (CBP) and P300 catalyse histone Kinic, while histone deacetylase HDAC3 functions as a deisonicotinylase. Notably, MNase sensitivity assay and RNA-seq analysis show that histone Kinic relaxes chromatin structure and promotes gene transcription. INH-mediated histone Kinic upregulates PIK3R1 gene expression and activates the PI3K/Akt/mTOR signalling pathway in liver cancer cells, linking INH to tumourigenicity in the liver. We demonstrate that Kinic is a histone acylation mark with a pyridine ring, which may have broad biological effects. Therefore, INH-induced isonicotinylation potentially accounts for the side effects in patients taking INH long-term for anti-tuberculosis therapy, and this modification may increase the risk of cancer in humans., Isoniazid (INH) is an anti-tuberculosis drug; however the underlying cause of its various side effects are not understood. Here the authors identified lysine isonicotinylation as a histone modification on chromatin that is metabolically regulated by INH and its metabolites.

Although chirality is an ever-present characteristic in biology and some artificial molecules, controlling the chirality and demystifying the chirality origin of complex assemblies remain challenging. Herein, we report two homochiral Ag14 nanoclusters with inherent chirality originated from identical rotation of six square faces on a Ag8 cube driven by intra-cluster π···π stacking interaction between pntp− (Hpntp = p-nitrothiophenol) ligands. The spontaneous resolution of the racemic (SD/rac-Ag14a) to homochiral nanoclusters (SD/L-Ag14 and SD/R-Ag14) can be realized by re-crystallizing SD/rac-Ag14a in acetonitrile, which promotes the homochiral crystallization in solid state by forming C–H···O/N hydrogen bonds with nitro oxygen atoms in pntp− or aromatic hydrogen atoms in dpph (dpph = 1,6-bis(diphenylphosphino)hexane) on Ag14 nanocluster. This work not only provides strategic guidance for the syntheses of chiral silver nanoclusters in an all-achiral environment, but also deciphers the origin of chirality at molecular level by identifying the special effects of intra- and inter-cluster supramolecular interactions., The preparation of chiral monolayer-protected metal clusters is interesting for their potential applications in a variety of fields, including catalysis. Here, the authors synthesize chiral Ag14 nanoclusters in an all-achiral environment, and decipher the origin of chirality at the molecular level; the solvent choice is key to achieve homochiral crystallization.

Histone acetylation is a ubiquitous hallmark of transcription, but whether the link between histone acetylation and transcription is causal or consequential has not been addressed. Using immunoblot and chromatin immunoprecipitation-sequencing in S. cerevisiae, here we show that the majority of histone acetylation is dependent on transcription. This dependency is partially explained by the requirement of RNA polymerase II (RNAPII) for the interaction of H4 histone acetyltransferases (HATs) with gene bodies. Our data also confirms the targeting of HATs by transcription activators, but interestingly, promoter-bound HATs are unable to acetylate histones in the absence of transcription. Indeed, HAT occupancy alone poorly predicts histone acetylation genome-wide, suggesting that HAT activity is regulated post-recruitment. Consistent with this, we show that histone acetylation increases at nucleosomes predicted to stall RNAPII, supporting the hypothesis that this modification is dependent on nucleosome disruption during transcription. Collectively, these data show that histone acetylation is a consequence of RNAPII promoting both the recruitment and activity of histone acetyltransferases., Histone acetylation is a ubiquitous hallmark of transcription. Here the authors provide evidence that the majority of histone acetylation is dependent on transcription, specifically due to the requirement of RNAPII for the recruitment and activity of histone acetyltransferases.

Separating molecules or ions with sub-Angstrom scale precision is important but technically challenging. Achieving such a precise separation using membranes requires Angstrom scale pores with a high level of pore size uniformity. Herein, we demonstrate that precise solute-solute separation can be achieved using polyamide membranes formed via surfactant-assembly regulated interfacial polymerization (SARIP). The dynamic, self-assembled network of surfactants facilitates faster and more homogeneous diffusion of amine monomers across the water/hexane interface during interfacial polymerization, thereby forming a polyamide active layer with more uniform sub-nanometre pores compared to those formed via conventional interfacial polymerization. The polyamide membrane formed by SARIP exhibits highly size-dependent sieving of solutes, yielding a step-wise transition from low rejection to near-perfect rejection over a solute size range smaller than half Angstrom. SARIP represents an approach for the scalable fabrication of ultra-selective membranes with uniform nanopores for precise separation of ions and small solutes., Separating molecules or ions with sub-Angstrom scale precision is important but technically challenging. Here, the authors demonstrate that precise solute-solute separation can be achieved using polyamide membranes formed via surfactant-assembly regulated interfacial polymerization.

Salt passivation of perovskite often results in formation of 2D perovskite layers, which impaired charge transport behaviour. Here, the authors study the energy barrier of 2D perovskite formation upon passivation by different iodide salt, and provide insight how to manipulate this to maximise device performance., Organic halide salt passivation is considered to be an essential strategy to reduce defects in state-of-the-art perovskite solar cells (PSCs). This strategy, however, suffers from the inevitable formation of in-plane favored two-dimensional (2D) perovskite layers with impaired charge transport, especially under thermal conditions, impeding photovoltaic performance and device scale-up. To overcome this limitation, we studied the energy barrier of 2D perovskite formation from ortho-, meta- and para-isomers of (phenylene)di(ethylammonium) iodide (PDEAI(2)) that were designed for tailored defect passivation. Treatment with the most sterically hindered ortho-isomer not only prevents the formation of surficial 2D perovskite film, even at elevated temperatures, but also maximizes the passivation effect on both shallow- and deep-level defects. The ensuing PSCs achieve an efficiency of 23.9% with long-term operational stability (over 1000 h). Importantly, a record efficiency of 21.4% for the perovskite module with an active area of 26 cm(2) was achieved.

Single-atom catalysts represent a unique catalytic system with high atomic utilization and tunable reaction pathway. Despite current successes in their optimization and tailoring through structural and synthetic innovations, there is a lack of dynamic modulation approach for the single-atom catalysis. Inspired by the electrostatic interaction within specific natural enzymes, here we show the performance of model single-atom catalysts anchored on two-dimensional atomic crystals can be systematically and efficiently tuned by oriented external electric fields. Superior electrocatalytic performance have been achieved in single-atom catalysts under electrostatic modulations. Theoretical investigations suggest a universal “onsite electrostatic polarization” mechanism, in which electrostatic fields significantly polarize charge distributions at the single-atom sites and alter the kinetics of the rate determining steps, leading to boosted reaction performances. Such field-induced on-site polarization offers a unique strategy for simulating the catalytic processes in natural enzyme systems with quantitative, precise and dynamic external electric fields.

Aromatic N-heterocyclic compounds are very important chemicals, which are currently produced mostly from petroleum. Here we report that a pyridazine-based compound 6-(4-hydroxy-3-methoxyphenyl)pyridazin-3(2H)-one (GSPZ) can be efficiently synthesized by the Friedel-Crafts reaction of guaiacol and succinic anhydride, both of which can be derived from biomass. GSPZ is then treated with bio-based epichlorohydrin to prepare the epoxy resin precursor GSPZ-EP. With 4,4'-diaminodiphenylmethane as curing agent, GSPZ-EP possesses higher glass transition temperature (187 oC vs. 173 oC) and shows a 140%, 70 and 93% increase in char yield (in N2), storage modulus (30 oC) and Young’s modulus, respectively when compared with a standard petroleum-based bisphenol A epoxy resin. Moreover, the cured GSPZ-EP shows good intrinsic flame retardancy properties and is very close to the V-0 rating of UL-94 test. This work opens the door for production of aromatic N-heterocyclic compounds, which can be derived from biomass and employed to construct high performance polymers., Aromatic N-heterocyclic compounds are important chemicals, but produced from petroleum. Here the authors show a pyridazine-based compound 6-(4-hydroxy-3-methoxyphenyl)pyridazin-3(2H)-one, used as polymer feedstocks, can be synthesized by a Friedel-Crafts reaction from biomass starting materials.

It is highly profitable to transform glycerol – the main by-product from biodiesel production to high value-added chemicals. In this work, we develop a photoelectrochemical system based on nanoporous BiVO4 for selective oxidation of glycerol to 1,3-dihydroxyacetone – one of the most valuable derivatives of glycerol. Under AM 1.5G front illumination (100 mW cm−2) in an acidic medium (pH = 2) without adscititious oxidant, the nanoporous BiVO4 photoanode achieves a glycerol oxidation photocurrent density of 3.7 mA cm−2 at a potential of 1.2 V versus RHE with 51% 1,3-dihydroxyacetone selectivity, equivalent to a production rate of 200 mmol of 1,3-dihydroxyacetone per m2 of illumination area in one hour., The selective conversion of inexpensive precursors to high-value chemicals presents valuable academic and industrial consequences. Here, the authors show bismuth vanadate photoanodes to utilize light and photoelectrochemically oxidize glycerol selectively to valuable industrial products.

Surface-supported isolated atoms in single-atom catalysts (SACs) are usually stabilized by diverse defects. The fabrication of high-metal-loading and thermally stable SACs remains a formidable challenge due to the difficulty of creating high densities of underpinning stable defects. Here we report that isolated Pt atoms can be stabilized through a strong covalent metal-support interaction (CMSI) that is not associated with support defects, yielding a high-loading and thermally stable SAC by trapping either the already deposited Pt atoms or the PtO2 units vaporized from nanoparticles during high-temperature calcination. Experimental and computational modeling studies reveal that iron oxide reducibility is crucial to anchor isolated Pt atoms. The resulting high concentrations of single atoms enable specific activities far exceeding those of conventional nanoparticle catalysts. This non defect-stabilization strategy can be extended to non-reducible supports by simply doping with iron oxide, thus paving a new way for constructing high-loading SACs for diverse industrially important catalytic reactions.

The Zr-based metal–organic frameworks are generally prepared by solvothermal procedure. To overcome the slow kinetics of nucleation and crystallization of Zr-based metal–organic frameworks is of great interest and challenging. Here, we find that an ionic liquid as solvent can significantly accelerate the formation of Zr-based metal–organic frameworks at room temperature. For example, the reaction time is shortened to 0.5 h in 1-hexyl-3-methylimidazolium chloride for Zr-based metal–organic framework formation, while that in the conventional solvent N,N-dimethylformamide needs at least 120 h. The reaction mechanism was investigated in situ by 1H nuclear magnetic resonance, spectroscopy synchrotron small angle X-ray scattering and X-ray absorption fine structure. This rapid, low-energy, and facile route produces Zr-based metal–organic framework nanoparticles with small particle size, missing-linker defects and large surface area, which can be used as heterogeneous catalysts for Meerwein–Ponndorf–Verley reaction., Crystallization kinetics of metal-organic frameworks in conventional organic solvents are usually very slow. Here, the authors show that an ionic liquid medium accelerates considerably the formation of Zr-based metal-organic frameworks that are active catalysts in the Meerwein-Ponndorf-Verley reaction.

The mesoporous metal–organic frameworks are a family of materials that have pore sizes ranging from 2 to 50 nm, which have shown promising applications in catalysis, adsorption, chemical sensing and so on. The preparation of mesoporous metal–organic frameworks usually needs the supramolecular or cooperative template strategy. Here we report the template-free assembly of mesoporous metal–organic frameworks by using CO2-expanded liquids as switchable solvents. The mesocellular metal–organic frameworks with large mesopores (13–23 nm) are formed, and their porosity properties can be easily adjusted by controlling CO2 pressure. Moreover, the use of CO2 can accelerate the reaction for metal–organic framework formation from metal salt and organic linker due to the viscosity-lowering effect of CO2, and the product can be recovered through CO2 extraction. The as-synthesized mesocellular metal–organic frameworks are highly active in catalysing the aerobic oxidation of benzylic alcohols under mild temperature at atmospheric pressure., Large pore metal–organic frameworks may have improved catalytic or molecular sieving properties. Here, the authors demonstrate that carbon dioxide expanded liquids can be used to synthesize these materials and that pore size may, to an extent, be tuned by varying gas pressure.