Rational Engineering of Secondary Metabolic Pathways in a Heterologous Host to Enable the Biosynthesis of Hibarimicin Derivatives with Enhanced Anti-Melanomic Activity

A 61-kb biosynthetic gene cluster(BGC),which is accountable for the biosynthesis of hibarimicin(HBM)B from Microbispora rosea subsp.hibaria TP-A0121,was heterologously expressed in Streptomyces coelicolor M1154,which generated a trace of the target products but accumulated a large amount of shunt products.Based on rational analysis of the relevant secondary metabolism,directed engineering of the biosynthetic pathways resulted in the high production of HBM B,as well as new HBM derivates with improved antitumor activity.These results not only establish a biosynthetic system to effectively synthesize HBMs-a class of the largest and most complex Type-Ⅱpolyketides,with a unique pseudo-dimeric structure-but also set the stage for further engineering and deep investigation of this complex biosynthetic pathway toward potent anticancer drugs.

Generalized Mechanism for the Solid Phase Transition of M_(2)O_(3)(M=Al,Ga)Featuring Single Cation Migration and Martensitic Lattice Transformation

Al_(2)O_(3)and Ga_(2)O_(3)exhibit numerous crystal phases with distinct stabilities and materialproperties.However,the phase transitions among thosematerialsare typicallyundesirable in industrial applications,making it imperative to elucidate the transition mechanisms between these phases.The configurational similarities between Al_(2)O_(3)and Ga_(2)O_(3)allow for the replication of phase transition pathways between these materials.In this study,we investigate the potential phase transition pathway of alumina from the 0-phase to the α-phase using stochastic surface walking global optimization based on global neural network potentials,while extending an existing Ga_(2)O_(3)phase transition path.Through this exploration,we identify a novel single-atom migration pseudomartensitic mechanism,which combines martensitic transformation with single-atom diffusion.This discovery offers valuable insights for experimental endeavors aimed at stabilizing alumina in transitional phases.

Immobilization of metal-organic molecular cage on g-C3N4 semiconductor for enhancement of photocatalytic H2 generation

A new compound based on immobilizing of Pd6(RuL3)8(BF4)28 (L=2-(pyridin-3-yl)-1H-imidazo [4,5-f][1,10]-phenanthroline) cage (MOC-16) on g-C3N4 was synthesized. Infrared spectrum and powder X-ray diffraction were used to characterize structure of hybrid MOC-16/g-C3N4, as well as UV-vis absorption spectrum and X-ray photoelectron spectroscopy were carried out to unveil photocatalytic mechanism. With the introduction of MOC-16, the absorption edge of MOC-16/g-C3N4 in UV-vis spectrum extended apparently to long-wavelength region compared with pristine g-C3N4. H2 evolution yielded with MOC-16/g-C3N4 in aqueous solution containing TEOA was much higher than that with RuL3/g-C3N4, Pd/RuL3/g-C3N4 and mixture of MOC-16 and g-C3N4, showing that the octahedral cage structure with high-efficient electron transfer and the interface interaction between MOC-16 and g-C3N4 were significant for improvement of H2 evolution.

Recovery of Li_(2)CO_(3)and FePO_(4)from spent LiFePO_(4)by coupling technics of isomorphic substitution leaching and solvent extraction

Efficient and low-cost recycling of spent lithium iron phosphate(LiFePO_(4),LFP)batteries has become an inevitable trend.In this study,an integrated closed-loop recycling strategy including isomorphic substitution leaching and solvent extraction process for spent LFP was proposed.An inexpensive FeCl_(3)was used as leaching agent to directly substitute Fe^(2+)from LFP.99%of Li can be rapidly leached in just 30 min,accompanied by 98%of FePO_(4)precipitated in lixivium.The tri-n-butyl phosphate(TBP)-sulfonated kerosene(SK)system was applied to extract Li from lixivium through a twelve-stage countercurrent process containing synchronous extraction and stepwise stripping of Li^(+)and Fe^(3+).80.81%of Li can be selectively enriched in stripping liquor containing 3.059 mol·L^(-1)of Li^(+)under optimal conditions.And the Fe stripping liquor was recovered for LFP re-leaching,of which,Fe^(2+)was oxidized to Fe^(3+)by appropriate H_(2)O_(2).Raffinate and lixivium were concentrated and entered into extraction process to accomplished closeloop recycling process.Overall,the results suggest that more than 99%of Li was recovered.FeCl_(3)holding in solution was directly regenerated without any pollutant emission.The sustainable mothed would be an alternative candidate for total element recycling of spent LFP batteries with industrial potential.

Adsorption structure of macrocyclic energetic molecule DOATF on Au(111)

Furazan macrocyclic compound 3,4:7,8:11,12:15,16-tetrafurazan-1,9-dioxazo-5,13-diazocyclohexadecane(DOATF)is an ideal energetic material with high heat of formation.Here,using scanning tunneling microscopy(STM)and noncontact atomic force microscopy(nc-AFM),we investigated the adsorption structure of DOATF molecules on Au(111)surface,which shows the four furanzan rings in the STM images and a bright protrusion off the center of the molecule in the nc-AFM images.Combined with density functional theory(DFT)calculations,we confirmed that the bright feature in the nc-AFM images is an N-O coordinate bond pointing upwards in one of the two azoxy groups;while the other N-O bond pointing towards the Au(111)surface.Our work contributes for a deeper understanding of the adsorption structure of macrocyclic compounds,which would promote the designing of DOATF-metal frameworks.

Machine Learning for Chemistry:Basics and Applications

The past decade has seen a sharp increase in machine learning(ML)applications in scientific research.This review introduces the basic constituents of ML,including databases,features,and algorithms,and highlights a few important achievements in chemistry that have been aided by ML techniques.The described databases include some of the most popular chemical databases for molecules and materials obtained from either experiments or computational calculations.Important two-dimensional(2D)and three-dimensional(3D)features representing the chemical environment of molecules and solids are briefly introduced.Decision tree and deep learning neural network algorithms are overviewed to emphasize their frameworks and typical application scenarios.Three important fields of ML in chemistry are discussed:(1)retrosynthesis,in which ML predicts the likely routes of organic synthesis;(2)atomic simulations,which utilize the ML potential to accelerate potential energy surface sampling;and(3)heterogeneous catalysis,in which ML assists in various aspects of catalytic design,ranging from synthetic condition optimization to reaction mechanism exploration.Finally,a prospect on future ML applications is provided.

The role of SLC12A family of cation-chloride cotransporters and drug discovery methodologies

The solute carrier family 12(SLC12)of cation-chloride cotransporters(CCCs)comprises potassium chloride cotransporters(KCCs,e.g.KCC1,KCC2,KCC3,and KCC4)-mediated Cl^(-)extrusion,and sodium potassium chloride cotransporters(N[K]CCs,NKCC1,NKCC2,and NCC)-mediated Cl^(-)loading.The CCCs play vital roles in cell volume regulation and ion homeostasis.Gain-of-function or loss-of-function of these ion transporters can cause diseases in many tissues.In recent years,there have been considerable advances in our understanding of CCCs'control mechanisms in cell volume regulations,with many techniques developed in studying the functions and activities of CCCs.Classic approaches to directly measure CCC activity involve assays that measure the transport of potassium substitutes through the CCCs.These techniques include the ammonium pulse technique,radioactive or nonradioactive rubidium ion uptakeassay,and thallium ion-uptake assay.CCCs'activity can also be indirectly observed by measuring gaminobutyric acid(GABA)activity with patch-clamp electrophysiology and intracellular chloride concentration with sensitive microelectrodes,radiotracer^(36)Cl^(-),and fluorescent dyes.Other techniques include directly looking at kinase regulatory sites phosphorylation,flame photometry,22Nat uptake assay,structural biology,molecular modeling,and high-throughput drug screening.This review summarizes the role of CCCs in genetic disorders and cell volume regulation,current methods applied in studying CCCs biology,and compounds developed that directly or indirectly target the CCCs for disease treatments.

Asymmetric side-chain engineering of organic semiconductor for ultrasensitive gas sensing

Molecular structure of organic semiconductor plays a critical role in determining the performance and functionality of organic electronic devices,by optimizing the electrical,optical and physicochemical properties.Substituted alkyl chains are fundamental units in tailering the solubility and assemblability,among which the asymmetric properties have been reported as key element for controlling the packing motifs and intrinsic charge transport.Here,we expanded the scope of molecular asymmetry dependent sensing features based on a new series of naphthalene diimides(NDI)-based derivatives substituted with a same branching alkyl chain but various linear-shaped alkyl chains(Cn-).A clear molecular stacking change,from head-to-head bilayer to head-to-tail monolayer packing model,is observed based on the features of anisotropic molecular interactions with the change in the chain length.Most importantly,a unique LUMO level shift of 0.17 eV is validated for NDI-PhC4,providing a record sensitivity up to 150%to 0.01 ppb ammonia,due to the desired molecular reactivity and device amplification properties.These results indicate that asymmetric side-chain engineering opens a route for breath healthcare.

Prediction of Bond Dissociation Energy for Organic Molecules Based on a Machine-Learning Approach

Bond dissociation energy(BDE),which refers to the enthalpy change for the homolysis of a specific covalent bond,is one of the basic thermodynamic properties of molecules.It is very important for understanding chemical reactivities,chemical properties and chemical transformations.Here,a machine learning-based comprehensive BDE prediction model was established based on the iBonD experimental BDE dataset and the calculated BDE dataset by St.John et al.Differential Structural and PhysicOChemical(D-SPOC)descriptors that reflected changes in molecules'structural and physicochemical features in the process of bond homolysis were designed as input features.

Multi-site Passivation of ZnO Metal Oxides via Biomolecules for Efficient and Highly Stable Organic Solar Cells

ZnO nanoparticles(nps)among metal oxide(MOs)are proven to be essential electron transporting layers(ETLs)applied in organic solar cells(OSCs).However,intrinsic defects,interfacial charge recombination,and catalytic behavior towards the active layer restrict the applications of ZnO nps for efficient and long-term stable OSCs.The commonly available biomolecule cytidine 5'-monophosphate(CMP-OH)with phosphonic acid,its salt cytidine 5'-monophosphate disodium salt(CMP-ONa)with a phosphate group as an anchoring group and conjugated terminal functional in both analogous molecules provide carrier transfer bridge at bottom interface of the active layer.Systematized theoretical investigations and characterizations have discovered the multi-site coordination of CMP-OH towards acceptor molecules and ZnO nps.The dual-side alignment of CMP analogous molecules hinders interfacial charge recombination and enhances charge transfer potential at once.Inevitably,PM6:L8-BO-based OSCs with modified ETL obtain 18.13%efficiency,12%higher than that of unmodified nps.Besides higher efficiency,CMP-OH-based OSC devices illustrate remarkably improved thermal stability for 500 h at 85℃with 72%of initial PCE and operation stability for 2000 h with 90.1%of initial PCE.This work reveals the passivation mechanism of multi-anchoring groups towards MOs and single-functional groups towards the active layer to optimize the interface for efficient and highly stable OSCs.

Combination of methylthio-chemistry with living crystallization-driven self-assembly toward uniformπ-conjugated nanostructures with antibacterial activity,surface tailorability,tunable morphology and dimension

Living crystallization-driven self-assembly(CDSA)provides robust access to uniformπ-conjugated nanostructures(CNSs)from block copolymers(BCPs)containing a crystallineπ-conjugated segment with controlled dimension,morphology and composition,which show appealing applications in biomedicine,photocatalysis and microelectronics.To further expand the application spectrum of these CNSs,the development of facile strategies toward diverse CNSs with varying structures/functionalities is highly desired.Herein,BCPs consisting of oligo(p-phenylene ethynylene)-b-poly(polypropyl-3-methanethiol acrylate)(OPE_(9)-bPMTPA35and OPE_(9)-b-PMTPA_(58);the subscript represents the number of repeat unit of each block)consisting of a crystallineπ-conjugated core-forming OPE_(9)segment and a corona-forming PMTPA block are synthesized.By efficient“click-type”alkylation of methylthio groups,OPE_(9)-b-PMTPA with varying contents of sulfonium unit is obtained.Uniform ribbon-like micelles with different widths and lengths can then be generated in a controlled manner via the self-seeding approach of living CDSA.Additionally,negatively charged polymeric and Ag nanoparticles can be immobilized on sulfonium/methylthio-containing shells by taking advantage of electrostatic attraction and coordination interaction,respectively.Interestingly,the ribbon-like micelles with positively charged shells exhibit antibacterial activity against E.coli.Given the ease of modification of PMTPA-based shell and attractive opto-electronic/photocatalytic properties ofπ-conjugated units,the combination of methylthio-chemistry and living CDSA opens a new avenue to generate multi-functional CNSs for widespread applications from biomedicine to photocatalysis.

The Molecular Link Between Glucose Sensing and Pyroptosis

Researchers led by Dr.XU Daichao from the Interdisciplinary Research Center on Biology and Chemistry,Shanghai Institute of Organic Chemistry(SIOC)of the Chinese Academy of Sciences,have uncovered the molecular link between glucose sensing and non-classical pyroptosis.This work was published in Nature Microbiology on June 6,2024.The nutritional status and pyroptosis play a crucial role in the host’s defense against pathogens.

Synthesis and Crystal Structure of 3,4-Bis(azidoacetamino)furazan

Bis(azidoacetamino)furazan (DAZAF) was synthesized and characterized by elemental analysis, IR, 1H NMR and MS as an energetic compound. The crystal structure of the title compound was determined by single-crystal X-ray diffraction with the following data: C6H6N10O3, monoclinic, P21/n, Z = 4, a = 8.402(3), b = 15.146(3), c = 9.247(3) ? ?= 111.09(2)? V = 1098.0(6) 3, Mr = 266.18, Dc = 1.610 g/cm3, F(000) = 544, ?=1.34 cm-1, R = 0.037 and wR = 0.044 for 2136 observed reflections (I > 2(I)). Intra- and inter-molecular hydrogen bonds were identified between the O and H atoms of two intramolecular acetylamino groups and two intermolecular acetylamino groups, respectively.

Superior performance of iridium supported on rutile titania for the catalytic decomposition of N_2O propellants

N2O is a promising green propellant and exhibits great potential for satellite propulsion systems. It is difficult for catalytic decomposition, which is an important way to initiate the propulsion process, to occur at temperatures below 600 °C due to the high activation energy of N2O. In this work, we report an Ir supported on rutile TiO2（Ir/r-TiO2） catalyst which exhibits a fairly high activity for high-concentration N2O decomposition. HAADF-STEM, H2-TPR, and XPS results indicate that highly dispersed Ir particles and improved oxygen mobility on the Ir/r-TiO2 could facilitate the decompo-sition of N2O and desorption of the adsorbed oxygen. Bridge-bonded peroxide intermediates were observed with in-situ DRIFT and herein, a detailed decomposition route is proposed.

Electron paramagnetic resonance study of amphiphiles partitioning behavior in desiccation-tolerant moss during dehydration

Desiccation tolerance is a crucial characteristic for desert moss surviving in arid regions. Desiccation procedure always induces amphiphiles transferring from the polar cytoplasm into lipid bodies. The behavior of amphiphiles transferring can contribute to the enhancement of desiccation tolerance and the reduction of plasma membrane integrity simultaneously. The effects of amphiphiles partitioning into the lipid phase during water loss has been studied for pollen and seeds using electron paramagnetic resonance （EPR） spectroscopy. However, desiccation-tolerant high plants occur among mosses, several angiosperms and higher plants seeds or pollens. They have different strategies for survival in dehydration and rehydration. A desiccation-tolerant moss Tortula desertorurn was used to investigate the behaviors of amphiphilic molecules during drying by spin label technology. There are small amount of amphiphilic probes partitioning into membrane during moss leaves dehydration, comparing with that in higher plants. Cytoplasm viscosity changed from 1.14 into glass state only dehydration less than 60 min. Moss leaves lost plasma membrane integrity slightly,from 0.115 to 0.237, occurred simultaneously with amphiphiles partition. The results showed the more advantages of mosses than higher plants in adapting fast dehydration. We propose that EPR spin label is feasible for studying the amphiphiles partitioning mechanisms in membrane protection and damage for desiccation-tolerant mosses.

Synthesis of Enamines via the Cross-coupling of Thioamides and Diarylketones Promoted by the Sm/SmI_(2)Mixed Reagent

Enamines, promoted by the samarium/samarium diiodide mixed reagent, were synthesized via the cross-coupling of thioamides and diarylketones in good yields.

Fabrication of a novel poly(dimethylsiloxane) microchips with two sharpened stretching tips

An integrated poly(dimethylsiloxane) (PDMS) microchip with two sharpened stretching has been presented. The sample was directly introduced into the separation channel through the stretching inlet tip without complicated power switching supplies and without injection cross-channel. Operations of running buffer refreshing or channel cleaning also becomes simple by vacuumed in one end and placed another tip into solution vial. The fabrication method can be easily applied in most analytical laboratories at low cost in the absence of soft lithography and plasma bonding equipments. Characteristics of the chips were tested and it can be used to separate fluorescence labeled molecules.

HOW DO THE RATES OF HALOPHILIC ATTACKS COMPARE WITH THE RATES OF PROTOPHILIC ATTACKS?

The measured relative rates of halophilic and protophilic attacks (k_X/k_H) indicate that the rates of halophilic attacks are comparable in magnitude to those of protophilic attacks (deprotonations).

ISOLATION AND STRUCTURES OF FOUR CYCLODIPEPTIDES

Three novel interesting polychlorinated cyclodipeptides,designated dyssmide A(1),B(2),C(3)and a known compound,2,3-dihydrodyeamide C(4)were isolated from the sponge Dysidea sp.Their structures were elucidated by spectroscopic methods.