The review provides an overview of the approaches, applications, and methods for ester prodrugs. Ester prodrugs are pharmacologically inactive compounds in their original form but become active drugs on biotransformat...The review provides an overview of the approaches, applications, and methods for ester prodrugs. Ester prodrugs are pharmacologically inactive compounds in their original form but become active drugs on biotransformation within the body, which offers advantages concerning the solubility, stability, and targeted delivery of the active drug. Several approaches of ester prodrugs have been reviewed in this review, including simple ester prodrugs, amino acid ester prodrugs, sugar ester prodrugs, lipid ester prodrugs, and polymeric ester prodrugs. This review incorporates in vitro and in vivo methods as well as the characterization of physical and chemical properties for ester prodrugs, cell culture systems, enzymatic assays, and animal models—all of these having a very important bearing on the evaluation of stability, bioavailability, and efficacy for ester prodrugs. While the benefits of using ester prodrugs are significant, there are also disadvantages like instability, poor or variable enzymatic hydrolysis, and toxicity from released promoieties or by-products. This review discusses solutions to the various limitations that include enhancing stability with ionizable promoieties and using physiologically-based pharmacokinetic modeling. The review also highlights the application of ester prodrugs in neurological disorders, such as Parkinson’s disease, and the ongoing efforts to address the critical limitations in treatment efficacy. Future prodrug strategies are poised to advance significantly by harnessing diverse transport mechanisms across the blood-brain barrier and integrating nanotechnology.展开更多
The efficient hydrogenolysis of esters to alkanes is the key protocol for producing advanced biofuels from renewable plant oils or fats.Due to the low reactivity of the carbonyl group in esters,a high reaction tempera...The efficient hydrogenolysis of esters to alkanes is the key protocol for producing advanced biofuels from renewable plant oils or fats.Due to the low reactivity of the carbonyl group in esters,a high reaction temperature(>250℃)is the prerequisite to ensure high conversion of esters.Here,we report a highly dispersed MoO_(x)-Ru/C bimetallic catalyst for the efficient hydrogenolysis of esters to alkanes under 150°C.The optimal catalyst exhibits>99%conversion of methyl stearate and 99%selectivity to diesel-range alkanes,reaching a high rate of up to 2.0 mmol gcat^(–1)h^(–1),5 times higher than that of Ru/C catalyst(MoO_(x)/C is inert).Integrated experimental and theoretical investigations attribute the high performance to the abundant MoO_(x)-Ru interfacial sites on the catalyst surface,which offers high activity for the C–O cleavage of esters.Furthermore,the dispersed MoO_(x)species significantly weaken the hydrocracking activity of the metallic Ru for C–C bonds,thus yielding alkane products without carbon loss.This study provides a facile and novel strategy for the design of high-performance heterogeneous catalysts for the hydrodeoxygenation of biomass-derived esters to alkane products.展开更多
Fifty agricultural soil samples collected from Fuzhou,southeast China,were first investigated for the occurrence,distribution,and potential risks of twelve organophosphate esters(OPEs).The total concentration of OPEs(...Fifty agricultural soil samples collected from Fuzhou,southeast China,were first investigated for the occurrence,distribution,and potential risks of twelve organophosphate esters(OPEs).The total concentration of OPEs(ΣOPEs)in soil ranged from 1.33 to 96.5 ng/g dry weight(dw),with an average value of 17.1 ng/g dw.Especially,halogenated-OPEs were the predominant group with amean level of 9.75 ng/g dw,and tris(1-chloro-2-propyl)phosphate(TCIPP)was the most abundant OPEs,accounting for 51.1%ofΣOPEs.The concentrations of TCIPP andΣOPEs were found to be significantly higher(P<0.05)in soils of urban areas than those in suburban areas.In addition,the use of agricultural plastic films and total organic carbon had a positive effect on the occurrence of OPE in this study.The positive matrix factorization model suggested complex sources of OPEs in agricultural soils from Fuzhou.The ecological risk assessment demonstrated that tricresyl phosphate presented a medium risk to land-based organisms(0.1≤risk quotient<1.0).Nevertheless,the carcinogenic and noncarcinogenic risks for human exposure to OPEs through soil ingestion and dermal absorption were negligible.These findings would facilitate further investigations into the pollution management and risk control of OPEs.展开更多
Phthalic acid esters(PAEs)are a group of compounds widespread in the environment.To investigate the occurrence and accumulation characteristics of PAEs,surface water samples were collected from the Three Gorges Reserv...Phthalic acid esters(PAEs)are a group of compounds widespread in the environment.To investigate the occurrence and accumulation characteristics of PAEs,surface water samples were collected from the Three Gorges Reservoir area,China.The total concentrations of∑_(11)analyzed PAEs(11PAEs)in the collected water samples ranging from 197.7 to 1,409.3 ng/L(mean±IQR:583.1±308.4 ng/L).While DEHP was the most frequently detected PAE,DnBP and DnNP were the most predominant PAEs in the analyzed water samples with a mean contribution of 63.3%of the∑_(11)PAEs.The concentrations of the∑_(11)PAEs in the water samples from the upper reaches of the Yangtze River were significantly higher than those from themiddle reaches.To better understand the transport and fate of the PAEs,seven detected PAEs were modeled by Quantitative Water Air Sediment Interaction(QWASI).The simulated and measured values were close for most PAEs,and differences are within one order of magnitude even for the worst one.For all simulated PAEs,water and particle inflow were main sources in the reservoir,whereas water outflow and degradation in water were important removal pathways.The contribution ratios of different sources/losses varied fromPAEs,depending on their properties.The calculated risk quotients of DnNP in the Three Gorges Reservoir area whether based onmonitoring or simulating results were all far exceeded the safety threshold value,implying the occurrence of this PAE compound may cause potential adverse effects for the aquatic ecology of the Three Gorges Reservoir area.展开更多
The structure-performance relationship of Cu/Al_(2)O_(3) catalysts in the hydrogenation of diethyl oxalate(DEO)for the synthesis of alcohol ether esters has been investigated by various characterization techniques inc...The structure-performance relationship of Cu/Al_(2)O_(3) catalysts in the hydrogenation of diethyl oxalate(DEO)for the synthesis of alcohol ether esters has been investigated by various characterization techniques including XRD,XPS,N2O titration,and 27Al MAS-NMR.The results showed that when the crystal configurations of Al_(2)O_(3) were the same,increasing the specific surface area could effectively refine the size of copper nanoparticles(Cu NPs),and ultimately improve the conversion of DEO.Meanwhile,the smaller size ofγ-Al_(2)O_(3)(HSAl and SBAl)loaded Cu NPs promotes the reaction towards the deep hydrogenation to produce ethanol(EtOH)and ethylene glycol(EG).Besides,the larger size of Cu NPs on the surface of amorphous Al_(2)O_(3)(HTAl and SolAl)resulted in a lower conversion rate,where ethyl glycolate(Egly)is the main product.Despite there are differences in Al^(3+)ionic coordination in Al_(2)O_(3) with different crystal structures,the experimental data showed that the differences in Al^(3+)ionic coordination did not significantly affect the catalytic performance in the hydrogenation reaction.The formation of alcohol-ether ester chemicals is critically dependent on the interactions between Cu sites and acidic sites.Among them,EG and EtOH were dehydrated to form 2-ethoxyethanol via the SN2 mechanism,while Egly and EtOH were reacted to form ethyl ethoxyacetate(EEA)via the SN2 mechanism.This study provides a theoretical basis for the optimization of the coal-based glycol processes to achieve a diversified product portfolio.展开更多
A visible-light-promoted[1+2]cycloaddition of gem-difluoroalkenes with aryl diazo esters provides an efficient and important route to 1,1-difluorocyclopropanes.The reaction conditions are mild,and the operation is ver...A visible-light-promoted[1+2]cycloaddition of gem-difluoroalkenes with aryl diazo esters provides an efficient and important route to 1,1-difluorocyclopropanes.The reaction conditions are mild,and the operation is very simple.A number of diazo esters and gem-difluoroalkenes are suitable for this reaction(36 examples),providing the desired products in good yields with excellent diastereoselectivity(>20∶1).展开更多
As one of the most essential components in photocuring system,photoinitiators(PIs)exert a crucial influence on the properties of the cured product.However,commercially available PIs encounter challenges in simultaneou...As one of the most essential components in photocuring system,photoinitiators(PIs)exert a crucial influence on the properties of the cured product.However,commercially available PIs encounter challenges in simultaneously achieving efficient photoinitiation performance and excellent light absorption properties,significantly limiting their applications in various fields.Here,two bis-chalcones and four corresponding oxime esters(OXEs)were designed and synthesized as highly efficient PIs.Featuring a structure comprising bis-chalcone and two diphenyl sulfides,the conjugated systems in these compounds enhance their light-absorption properties in near-ultraviolet and visible region,effectively.Both the frontier molecular orbital simulations and excited state calculations suggest the contribution of sulfur atoms to electron delocalization and the formation of conjugated structure.Due to the high reactivity of the N–O bond in OXE moiety,the four OXEs exhibit exceptional free radical photoinitiating ability in commercial acrylic monomers/oligomers with LED@365nm as light source.Notably,one of them demonstrates superior performance in the photoinitiation of multifunctional crosslinker,achieving more than 70%conversion within 3 s,coupled with outstanding absorption at 365 nm.These chalcone-based OXEs are considered to exert significant potential in the realm of free radical photocuring.展开更多
An enantioselective catalytic method for the direct [4 + 1] annulation of yne–allylic acetates with pyrazolones has been realized by a copper-catalyzed remote strategy. A variety of enantioenriched spiropyrazolones a...An enantioselective catalytic method for the direct [4 + 1] annulation of yne–allylic acetates with pyrazolones has been realized by a copper-catalyzed remote strategy. A variety of enantioenriched spiropyrazolones are rapidly accessed in high yields with moderate to good enantiocontrol. The facile follow-up transformations highlight its potential utility in the synthesis of diverse spiropyrazolones building blocks.展开更多
It is important to understand the evolution of the matter on the polymer membrane surface.The in situ and real-time monitoring of the membrane surface will not only favor the investigation of selective layer formation...It is important to understand the evolution of the matter on the polymer membrane surface.The in situ and real-time monitoring of the membrane surface will not only favor the investigation of selective layer formation but can also track the fouling process during operation.Herein,an aggregation-induced emission(AIE)-active polymer membrane was prepared by the interfacial polymerization of a cyclodextrin-based glycocluster(CD@Glucose)and a tetraphenylethylene derivative modified with boronic acid groups(TPEDB)on the surface of a polyacrylonitrile(PAN)ultrafiltration membrane.This interfacial polymerization method can be stacked layer-by-layer to regulate the hydrophilicity and pore structure of the membrane.With the increase in the number of polymer layers,the separation and antifouling properties of the membrane gradually improved.Owing to the AIE property of the crosslinking agent TPEDB,the occurrence of interfacial polymerization and the degree of fouling during membrane operation can be monitored by the fluorescence distribution and intensity.With the aggravation of membrane fouling,the fluorescence decreased gradually,but recovered after cleaning.Therefore,this AIE effect can be used for real-time monitoring of interfacial polymerization as well as membrane fouling.展开更多
To develop new environmentally friendly fungicides,we designed and synthesized a novel series of D/Lconfigured camphor oxime ester derivatives based on the natural product camphor as a lead compound.We investigated th...To develop new environmentally friendly fungicides,we designed and synthesized a novel series of D/Lconfigured camphor oxime ester derivatives based on the natural product camphor as a lead compound.We investigated the in vitro antifungal activity of these compounds against six common plant pathogenic fungi.Among them,compounds B1-6,B1-17 and B2-6 displayed great in vitro activity against Rhizoctonia solani with EC50 values of 7.28,4.64,and 7.62μg/mL.The HOMO and LUMO calculations indicated that strong electronwithdrawing halogen elements exhibit better activity compared to electron-donating alkyl groups.Preliminary mechanistic studies,using SEM and TEM,indicated that compound B1-17 induced disordered entanglement of hyphae,shrinkage of hyphal surfaces,and vacuole swelling and rupture,which disrupted normal hyphal growth.Additionally,compound B1-17 induced the production and accumulation of ROS,disrupted MMP,and effectively inhibited the germination and formation of sclerotia in Rhizoctonia solani.These compounds hold potential as new antifungal agents for further research.展开更多
Phthalic acid esters(PAEs)are widely released into the environment due to industrial and agricultural activities.This poses significant risks,not only to crops grown on contaminated soil but also to humans.PAEs enter ...Phthalic acid esters(PAEs)are widely released into the environment due to industrial and agricultural activities.This poses significant risks,not only to crops grown on contaminated soil but also to humans.PAEs enter the human body through the food chain,causing potential health hazards.Endophytic bacteria have demonstrated a significant potential as effective bioremediation agents,with specialized mechanisms of PAEs degradation.Endophytic bacteria such as Rhodococcus,Pseudomonas and Sphingomona recognize root exudates,adhere to and penetrate root surfaces,and ultimately colonize crops.They form symbiotic relationships with crops,obtaining nutrients and habitats from crops,meanwhile,promoting plant growth and health through hormone production,nutrient regulation,and the suppression of pathogenic microorganisms.Furthermore,endophytic bacteria efficiently degrade PAEs in soil-crop systems through synergistic interactions with indigenous rhizosphere microflora and regulatory effects on enzyme activity in crops.Here,we review the role of endophytic bacteria in the bioremediation of PAEs-contaminated crops and soils.In addition,we discuss the scarcity of endophytic bacterial strains with a confirmed ability to degrade PAEs,and underscore the lack of the research on the mechanisms of PAEs degradation by these bacteria.This review also points out that future study should investigate the molecular mechanisms underlying the interaction between endophytic bacteria and PAEs to offer novel insights and solutions for environmental protection and sustainable agricultural development.展开更多
Chiral N-substituted amino amides and esters are ubiquitous scaffolds in pesticides and pharmaceutical chemicals,but their asymmetric synthesis remains challenging especially for those with multiple chiral centers.In ...Chiral N-substituted amino amides and esters are ubiquitous scaffolds in pesticides and pharmaceutical chemicals,but their asymmetric synthesis remains challenging especially for those with multiple chiral centers.In this study,IR104 from Streptomyces aureocirculatus was identified from 157 wild-type imine reductases for the synthesis of(S)-2-((R)-2-oxo-4-propylpyrrolidin-1-yl)butanamide(antiepileptic drug Brivaracetam)via dynamic kinetic resolution reductive amination from ethyl 3-formylhexanoate and(S)-2-aminobutylamide with high diastereoselectivity.To further improve the catalytic efficiency of IR104,its mutant D191E/L195I/E253S/M258A(M3)was identified by saturation mutagenesis and iterative combinatorial mutagenesis,which exhibited a 102-fold increase in the catalytic efficiency relative to that of wild-type enzyme and high diastereoselectivity(98:2 d.r.).Crystal structural analysis and molecular dynamics simulations provided some insights into the molecular basis for the improved activity of the mutant enzyme.The imine reductase identified in this study could accept chiral amino amides/esters as amino donors for the dynamic kinetic resolution reductive amination of racemicα-substituted aldehydo-esters,expanding the substrate scope of imine reductases in the dynamic kinetic resolution-reductive amination.Finally,IR104-M3 was successfully used for the preparation of Brivaracetam at gram scale.Using this mutant,various N-substituted amino amides/esters with two chiral centers were also synthesized with up to 99:1 d.r.and 96%yields and subsequently converted intoγ-andδ-lactams,providing an efficient protocol for the synthesis of these important compounds via enzymatic dynamic kinetic resolution-reductive amination from simple building blocks.展开更多
Most commercial plastics cannot easily degrade,which raises a number of sustainability issues.To address the current problem of plastic pollution,the research and development of easily degradable and recyclable polyme...Most commercial plastics cannot easily degrade,which raises a number of sustainability issues.To address the current problem of plastic pollution,the research and development of easily degradable and recyclable polymers has become an attractive subject.Herein,a new monomer of thiosalicylic methyl glycolide(TSMG)was synthesized using one-pot method and high molecular weight poly(thiosalicylic methyl glycolide)(PTSMG,M_(n) up to 300 kDa)can be obtained via the ring-opening polymerization(ROP)of TSMG.PTSMG exhibits good closed-loop recyclability and hydrolytic degradability,where PTSMG can generate pristine monomers through sublimation thermal depolymerization conditions due to the presence of thiophenol ester bond in the polymer chains,and can be degraded rapidly in aqueous solution,which provides a potential solution to the current plastic pollution problem.展开更多
Different reactive flame retardants have been extensively developed for vinyl ester resins(VERs),but very few of them can yield a flame-retardant resin that meets defined standards(e.g.UL-94 V-0 rating).In this work,p...Different reactive flame retardants have been extensively developed for vinyl ester resins(VERs),but very few of them can yield a flame-retardant resin that meets defined standards(e.g.UL-94 V-0 rating).In this work,phosphorous-containing 1-vinylimidazole salts(called VIDHP and VIDPP)were synthesized through the facile neutralization of the acid and 1-vinylimidazole.VIDHP and VIDPP were then applied as flame-retardant crosslinking agents of VERs,by which phosphorus-containing groups could be incorporated into the resin chain via ionic bonds.VIDHP/VER and VIDPP/VER showed a high curing activity and can be well cured in moderate temperatures.With 20 wt.%additions of VIDHP and VIDPP,VIDHP20/VER,and VIDPP20/VER presented a limiting oxygen index value of 29.7%and 28.4%,respectively,with the latter achieving a UL 94 V0 rating.In the cone calorimetric test,compared to the unmodified VERs,VIDPP20/VER exhibited large reductions in the peak heat release rate,total heat release rate,and total smoke release rate while VIDHP20/VER demonstrated comparatively inferior performance in terms of the heat release.VIDHP20/VER and VIDPP20/VER showed good thermal stability and presented a little lower glass transition temperature than the control sample.VIDPP with a low phosphorus oxidation state(+1)demonstrated high flame-retardant activities in the gaseous phase,whereas VIDHP with a high phosphorus oxidation state(+5)primarily exhibited efficacy in the condensed phase.展开更多
Ethanol synthesis via dimethyl oxalate hydrogenation has garnered increasing attention in the fields of syngas utilization.Althoughε-Fe_(2)C has been identified as a promising active species for DMO hydrogenation to ...Ethanol synthesis via dimethyl oxalate hydrogenation has garnered increasing attention in the fields of syngas utilization.Althoughε-Fe_(2)C has been identified as a promising active species for DMO hydrogenation to ethanol,its formation is kinetically challenging during carbonization.In this work,a Fe_(4)N phase was first synthesized by pretreating a 30Fe/SiO_(2)catalyst in an ammonia environment,followed by carbonization in a methanol-H_(2) flow to obtain ε-Fe_(2)C as the active phase.Fe_(4)N,rather than Fe-O-Si,facilitates the transformation into iron carbide during the carbonization process.The transformation pathway of iron nitride(Fe_(x)N)is mediated by intermediate iron carbonyl species(Fe-CO),ultimately leading to the formation of iron carbide as the active phase.The resulting catalyst exhibited 40 times higher catalytic activity than the untreated catalyst in DMO hydrogenation.Combined structure properties and DFT calculation revealed that the lower energy barrier ofε-Fe_(2)C for ester hydrogenation underpins/strengthens its superior performance,while the STY of ε-Fe_(2)C is 2.8 times that ofε'-Fe_(2.2)C and 58 times that ofχ-Fe_(5)C_(2).This study provides a novel strategy for designing highly efficient iron carbide catalysts for the esters hydrogenation system.展开更多
Background:In today’s context,vegetable oils,commonly used in culinary practices such as frying and baking,are integral to numerous daily dietary choices.Palm oil,a frequently employed vegetable oil,raises concerns s...Background:In today’s context,vegetable oils,commonly used in culinary practices such as frying and baking,are integral to numerous daily dietary choices.Palm oil,a frequently employed vegetable oil,raises concerns surrounding food safety,thus presenting a significant challenge.Methods:This research aims to enhance consumer awareness regarding the potential health risks associated with 3-monochloropropane-1,2-diol(3-MCPD)and glycidyl fatty acid esters(GEs)commonly found in food and edible oil products.The study endeavours to apprise consumers of these health risks through a comprehensive survey.The survey enlisted the participation of 120 respondents within the age bracket of 18 years to those above 36 years(capped at 50 years).Results:Strikingly,a significant proportion,ranging from 88%to 89%,demonstrated a lack of awareness concerning the potential risks associated with 3-MCPD and GEs in food products.Conclusion:This study underscores the urgency of augmenting consumer's awareness levels regarding 3-MCPD and GEs.Furthermore,it promotes a more detailed examination of Malaysian edible oils and food products available in the market to establish an appropriate Tolerable Daily Intake for the Malaysian population.This research contributes to the broader discourse on food safety and public health by highlighting these crucial facets.展开更多
It is well known that cationic polymers have excellent antimicrobial capacity accompanied with high biotoxicity,to reduce biotoxicity needs to decrease the number of cationic groups on polymers,which will influence an...It is well known that cationic polymers have excellent antimicrobial capacity accompanied with high biotoxicity,to reduce biotoxicity needs to decrease the number of cationic groups on polymers,which will influence antimicrobial activity.It is necessary to design a cationic polymer mimic natural antimicrobial peptide with excellent antibacterial activity and low toxicity to solve the above dilemma.Here,we designed and prepared a series of cationic poly(β-amino ester)s(PBAEs)with different cationic contents,and introducing hydrophobic alkyl chain to adjust the balance between antimicrobial activity and biotoxicity to obtain an ideal antimicrobial polymer.The optimum one of synthesized PBAE(hydrophilic cationic monomer:hydrophobic monomer=5:5)was screened by testing cytotoxicity and minimum inhibitory concentration(MIC),which can effectively kill S.aureus and E.coli with PBAE concentration of15μg/m L by a spread plate bacteriostatic method and dead and alive staining test.The way of PBAE killing bacterial was destroying the membrane like natural antimicrobial peptide observed by scanning electron microscopy(SEM).In addition,PBAE did not exhibit hemolysis and cytotoxicity.In particular,from the result of animal tests,the PBAE was able to promote healing of infected wounds from removing mature S.aureus and E.coli on the surface of infected wound.As a result,our work offers a viable approach for designing antimicrobial materials,highlighting the significant potential of PBAE polymers in the field of biomedical materials.展开更多
Cholesteryl esters(CEs) have been increasingly implicated in neurodegenerative disorders such as Alzheimer's disease(AD).Alois Alzheimer noted three prominent neuropathologic features in his original analysis of t...Cholesteryl esters(CEs) have been increasingly implicated in neurodegenerative disorders such as Alzheimer's disease(AD).Alois Alzheimer noted three prominent neuropathologic features in his original analysis of the AD brain:senile plaques,neurofibrillary tangles,and lipid granule accumulation.Senile plaques,which are aggregates of amyloid-beta(Aβ),and neurofibrillary tangles,which are aggregates of phosphorylated tau,have been regarded as more consistent characteristics of the AD brain compared with lipid granule accumulation and thus have been studied more intensively(Foley,2010).展开更多
As primary degradation products of phthalate esters,phthalate monoesters(MPEs)have been widely detected in various aquatic environments and drawn growing toxicological concerns.Hydrolysis kinetics that is of importanc...As primary degradation products of phthalate esters,phthalate monoesters(MPEs)have been widely detected in various aquatic environments and drawn growing toxicological concerns.Hydrolysis kinetics that is of importance for assessing environmental persistence of chemicals remain elusive for MPEs.Herein,kinetics of base-catalyzed and neutral hydrolysis for 18 MPEs with different leaving groups was investigated by density functional theory calculation.Results indicate that MPEs with leaving groups having p Kaof<10 prefer dissociative transition states.MPEs are more persistent than their parents,and their hydrolysis half-lives were calculated to vary from 3.4 min to 79.2 years(p H=7–9).A quantitative structure-activity relationship model was developed for predicting the hydrolysis kinetics parameters.It was found that p Kaof the leaving groups and electronegativity of the MPEs are key factors determining the hydrolysis kinetics.This work may lay a theoretical foundation for better understanding the chemical process that governs MPE persistence in aquatic environments.展开更多
Cholesterol is a sterol with a four-membered ring structure and a single hydroxyl group attached to one of the rings. It is the active, raw form of cholesterol. Cholesteryl Ester is the inactive form in which choleste...Cholesterol is a sterol with a four-membered ring structure and a single hydroxyl group attached to one of the rings. It is the active, raw form of cholesterol. Cholesteryl Ester is the inactive form in which cholesterol is esterified to be transported to target organs. The newly developed process of making bulky esters from unprecedented tertiary alcohols is applied to synthesize cholesterol esters successfully. Although cholesterol is a secondary alcohol, it is a very bulky and interesting compound due to its immense application. Usually, specific enzymes catalyze cholesterol to cholesterol ester. This project aims to develop a cross-coupling chemistry process to synthesize cholesterol esters and see the broader application of those new cholesterol esters in chemical biology. The mixture of cholesterol, sodium tert-butoxide, aroyl chloride, the catalyst PdCl2 (dtbpf) complex, and the solvent 1,4-dioxane, when microwaved at 100˚C for 2 hours, works well for the formation of cross-coupling cholesterol ester products in good to high yields.展开更多
文摘The review provides an overview of the approaches, applications, and methods for ester prodrugs. Ester prodrugs are pharmacologically inactive compounds in their original form but become active drugs on biotransformation within the body, which offers advantages concerning the solubility, stability, and targeted delivery of the active drug. Several approaches of ester prodrugs have been reviewed in this review, including simple ester prodrugs, amino acid ester prodrugs, sugar ester prodrugs, lipid ester prodrugs, and polymeric ester prodrugs. This review incorporates in vitro and in vivo methods as well as the characterization of physical and chemical properties for ester prodrugs, cell culture systems, enzymatic assays, and animal models—all of these having a very important bearing on the evaluation of stability, bioavailability, and efficacy for ester prodrugs. While the benefits of using ester prodrugs are significant, there are also disadvantages like instability, poor or variable enzymatic hydrolysis, and toxicity from released promoieties or by-products. This review discusses solutions to the various limitations that include enhancing stability with ionizable promoieties and using physiologically-based pharmacokinetic modeling. The review also highlights the application of ester prodrugs in neurological disorders, such as Parkinson’s disease, and the ongoing efforts to address the critical limitations in treatment efficacy. Future prodrug strategies are poised to advance significantly by harnessing diverse transport mechanisms across the blood-brain barrier and integrating nanotechnology.
文摘The efficient hydrogenolysis of esters to alkanes is the key protocol for producing advanced biofuels from renewable plant oils or fats.Due to the low reactivity of the carbonyl group in esters,a high reaction temperature(>250℃)is the prerequisite to ensure high conversion of esters.Here,we report a highly dispersed MoO_(x)-Ru/C bimetallic catalyst for the efficient hydrogenolysis of esters to alkanes under 150°C.The optimal catalyst exhibits>99%conversion of methyl stearate and 99%selectivity to diesel-range alkanes,reaching a high rate of up to 2.0 mmol gcat^(–1)h^(–1),5 times higher than that of Ru/C catalyst(MoO_(x)/C is inert).Integrated experimental and theoretical investigations attribute the high performance to the abundant MoO_(x)-Ru interfacial sites on the catalyst surface,which offers high activity for the C–O cleavage of esters.Furthermore,the dispersed MoO_(x)species significantly weaken the hydrocracking activity of the metallic Ru for C–C bonds,thus yielding alkane products without carbon loss.This study provides a facile and novel strategy for the design of high-performance heterogeneous catalysts for the hydrodeoxygenation of biomass-derived esters to alkane products.
基金supported by the Open Fund of the Laboratory for Earth Surface Processes,Ministry of Education,Peking University,Beijing,China,and the Cultivation Fund Program for Excellent Dissertation in Fujian Normal University,China(No.LWPYS202315)the Research Start-up Fund of Fujian Normal University,China(No.Y0720304X13).
文摘Fifty agricultural soil samples collected from Fuzhou,southeast China,were first investigated for the occurrence,distribution,and potential risks of twelve organophosphate esters(OPEs).The total concentration of OPEs(ΣOPEs)in soil ranged from 1.33 to 96.5 ng/g dry weight(dw),with an average value of 17.1 ng/g dw.Especially,halogenated-OPEs were the predominant group with amean level of 9.75 ng/g dw,and tris(1-chloro-2-propyl)phosphate(TCIPP)was the most abundant OPEs,accounting for 51.1%ofΣOPEs.The concentrations of TCIPP andΣOPEs were found to be significantly higher(P<0.05)in soils of urban areas than those in suburban areas.In addition,the use of agricultural plastic films and total organic carbon had a positive effect on the occurrence of OPE in this study.The positive matrix factorization model suggested complex sources of OPEs in agricultural soils from Fuzhou.The ecological risk assessment demonstrated that tricresyl phosphate presented a medium risk to land-based organisms(0.1≤risk quotient<1.0).Nevertheless,the carcinogenic and noncarcinogenic risks for human exposure to OPEs through soil ingestion and dermal absorption were negligible.These findings would facilitate further investigations into the pollution management and risk control of OPEs.
基金supported by the Innovation Fund of Nanjing Institute of Environmental Science,Ministry of Ecology and Environment,China(No.ZX2023QT003)the National Natural Science Foundation of China(No.22306130)+1 种基金Jiangsu Funding Program for Excellent Postdoctoral Talent(No.2022ZB789)the Ecological Environment Research Project of Jiangsu Province,China(No.2022014).
文摘Phthalic acid esters(PAEs)are a group of compounds widespread in the environment.To investigate the occurrence and accumulation characteristics of PAEs,surface water samples were collected from the Three Gorges Reservoir area,China.The total concentrations of∑_(11)analyzed PAEs(11PAEs)in the collected water samples ranging from 197.7 to 1,409.3 ng/L(mean±IQR:583.1±308.4 ng/L).While DEHP was the most frequently detected PAE,DnBP and DnNP were the most predominant PAEs in the analyzed water samples with a mean contribution of 63.3%of the∑_(11)PAEs.The concentrations of the∑_(11)PAEs in the water samples from the upper reaches of the Yangtze River were significantly higher than those from themiddle reaches.To better understand the transport and fate of the PAEs,seven detected PAEs were modeled by Quantitative Water Air Sediment Interaction(QWASI).The simulated and measured values were close for most PAEs,and differences are within one order of magnitude even for the worst one.For all simulated PAEs,water and particle inflow were main sources in the reservoir,whereas water outflow and degradation in water were important removal pathways.The contribution ratios of different sources/losses varied fromPAEs,depending on their properties.The calculated risk quotients of DnNP in the Three Gorges Reservoir area whether based onmonitoring or simulating results were all far exceeded the safety threshold value,implying the occurrence of this PAE compound may cause potential adverse effects for the aquatic ecology of the Three Gorges Reservoir area.
文摘The structure-performance relationship of Cu/Al_(2)O_(3) catalysts in the hydrogenation of diethyl oxalate(DEO)for the synthesis of alcohol ether esters has been investigated by various characterization techniques including XRD,XPS,N2O titration,and 27Al MAS-NMR.The results showed that when the crystal configurations of Al_(2)O_(3) were the same,increasing the specific surface area could effectively refine the size of copper nanoparticles(Cu NPs),and ultimately improve the conversion of DEO.Meanwhile,the smaller size ofγ-Al_(2)O_(3)(HSAl and SBAl)loaded Cu NPs promotes the reaction towards the deep hydrogenation to produce ethanol(EtOH)and ethylene glycol(EG).Besides,the larger size of Cu NPs on the surface of amorphous Al_(2)O_(3)(HTAl and SolAl)resulted in a lower conversion rate,where ethyl glycolate(Egly)is the main product.Despite there are differences in Al^(3+)ionic coordination in Al_(2)O_(3) with different crystal structures,the experimental data showed that the differences in Al^(3+)ionic coordination did not significantly affect the catalytic performance in the hydrogenation reaction.The formation of alcohol-ether ester chemicals is critically dependent on the interactions between Cu sites and acidic sites.Among them,EG and EtOH were dehydrated to form 2-ethoxyethanol via the SN2 mechanism,while Egly and EtOH were reacted to form ethyl ethoxyacetate(EEA)via the SN2 mechanism.This study provides a theoretical basis for the optimization of the coal-based glycol processes to achieve a diversified product portfolio.
文摘A visible-light-promoted[1+2]cycloaddition of gem-difluoroalkenes with aryl diazo esters provides an efficient and important route to 1,1-difluorocyclopropanes.The reaction conditions are mild,and the operation is very simple.A number of diazo esters and gem-difluoroalkenes are suitable for this reaction(36 examples),providing the desired products in good yields with excellent diastereoselectivity(>20∶1).
基金National Nature Science Foundation of China(Nos.52025032,52103144 and 523B2026)for their financial supportsupported by the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation(No.GZC20231544)。
文摘As one of the most essential components in photocuring system,photoinitiators(PIs)exert a crucial influence on the properties of the cured product.However,commercially available PIs encounter challenges in simultaneously achieving efficient photoinitiation performance and excellent light absorption properties,significantly limiting their applications in various fields.Here,two bis-chalcones and four corresponding oxime esters(OXEs)were designed and synthesized as highly efficient PIs.Featuring a structure comprising bis-chalcone and two diphenyl sulfides,the conjugated systems in these compounds enhance their light-absorption properties in near-ultraviolet and visible region,effectively.Both the frontier molecular orbital simulations and excited state calculations suggest the contribution of sulfur atoms to electron delocalization and the formation of conjugated structure.Due to the high reactivity of the N–O bond in OXE moiety,the four OXEs exhibit exceptional free radical photoinitiating ability in commercial acrylic monomers/oligomers with LED@365nm as light source.Notably,one of them demonstrates superior performance in the photoinitiation of multifunctional crosslinker,achieving more than 70%conversion within 3 s,coupled with outstanding absorption at 365 nm.These chalcone-based OXEs are considered to exert significant potential in the realm of free radical photocuring.
基金financial support from the National Natural Science Foundation of China (Nos. 21801087 and 22201089)。
文摘An enantioselective catalytic method for the direct [4 + 1] annulation of yne–allylic acetates with pyrazolones has been realized by a copper-catalyzed remote strategy. A variety of enantioenriched spiropyrazolones are rapidly accessed in high yields with moderate to good enantiocontrol. The facile follow-up transformations highlight its potential utility in the synthesis of diverse spiropyrazolones building blocks.
基金supported by the Fundamental Research Funds for Central Universities(No.30922010811).
文摘It is important to understand the evolution of the matter on the polymer membrane surface.The in situ and real-time monitoring of the membrane surface will not only favor the investigation of selective layer formation but can also track the fouling process during operation.Herein,an aggregation-induced emission(AIE)-active polymer membrane was prepared by the interfacial polymerization of a cyclodextrin-based glycocluster(CD@Glucose)and a tetraphenylethylene derivative modified with boronic acid groups(TPEDB)on the surface of a polyacrylonitrile(PAN)ultrafiltration membrane.This interfacial polymerization method can be stacked layer-by-layer to regulate the hydrophilicity and pore structure of the membrane.With the increase in the number of polymer layers,the separation and antifouling properties of the membrane gradually improved.Owing to the AIE property of the crosslinking agent TPEDB,the occurrence of interfacial polymerization and the degree of fouling during membrane operation can be monitored by the fluorescence distribution and intensity.With the aggravation of membrane fouling,the fluorescence decreased gradually,but recovered after cleaning.Therefore,this AIE effect can be used for real-time monitoring of interfacial polymerization as well as membrane fouling.
基金the Fundamental Research Funds for the Central Universities(KYCYXT2022011,KJYQ2024014)the National Key Research and Development Program of China(2021YFD1700102)for the generous financial support for our programs.
文摘To develop new environmentally friendly fungicides,we designed and synthesized a novel series of D/Lconfigured camphor oxime ester derivatives based on the natural product camphor as a lead compound.We investigated the in vitro antifungal activity of these compounds against six common plant pathogenic fungi.Among them,compounds B1-6,B1-17 and B2-6 displayed great in vitro activity against Rhizoctonia solani with EC50 values of 7.28,4.64,and 7.62μg/mL.The HOMO and LUMO calculations indicated that strong electronwithdrawing halogen elements exhibit better activity compared to electron-donating alkyl groups.Preliminary mechanistic studies,using SEM and TEM,indicated that compound B1-17 induced disordered entanglement of hyphae,shrinkage of hyphal surfaces,and vacuole swelling and rupture,which disrupted normal hyphal growth.Additionally,compound B1-17 induced the production and accumulation of ROS,disrupted MMP,and effectively inhibited the germination and formation of sclerotia in Rhizoctonia solani.These compounds hold potential as new antifungal agents for further research.
基金supported by the National Natural Science Foundation of China(No.22161132011)Jiangsu Provincial Special Fund for S&T Innovation in Carbon Emission Peak and Neutrality(No.20220013)+1 种基金the National Key Research and Development Program of China(Nos.2023YFE0110800 and 2023YFC3708100)the Fundamental Research Funds for the Central Universities(No.QTPY2024001).
文摘Phthalic acid esters(PAEs)are widely released into the environment due to industrial and agricultural activities.This poses significant risks,not only to crops grown on contaminated soil but also to humans.PAEs enter the human body through the food chain,causing potential health hazards.Endophytic bacteria have demonstrated a significant potential as effective bioremediation agents,with specialized mechanisms of PAEs degradation.Endophytic bacteria such as Rhodococcus,Pseudomonas and Sphingomona recognize root exudates,adhere to and penetrate root surfaces,and ultimately colonize crops.They form symbiotic relationships with crops,obtaining nutrients and habitats from crops,meanwhile,promoting plant growth and health through hormone production,nutrient regulation,and the suppression of pathogenic microorganisms.Furthermore,endophytic bacteria efficiently degrade PAEs in soil-crop systems through synergistic interactions with indigenous rhizosphere microflora and regulatory effects on enzyme activity in crops.Here,we review the role of endophytic bacteria in the bioremediation of PAEs-contaminated crops and soils.In addition,we discuss the scarcity of endophytic bacterial strains with a confirmed ability to degrade PAEs,and underscore the lack of the research on the mechanisms of PAEs degradation by these bacteria.This review also points out that future study should investigate the molecular mechanisms underlying the interaction between endophytic bacteria and PAEs to offer novel insights and solutions for environmental protection and sustainable agricultural development.
文摘Chiral N-substituted amino amides and esters are ubiquitous scaffolds in pesticides and pharmaceutical chemicals,but their asymmetric synthesis remains challenging especially for those with multiple chiral centers.In this study,IR104 from Streptomyces aureocirculatus was identified from 157 wild-type imine reductases for the synthesis of(S)-2-((R)-2-oxo-4-propylpyrrolidin-1-yl)butanamide(antiepileptic drug Brivaracetam)via dynamic kinetic resolution reductive amination from ethyl 3-formylhexanoate and(S)-2-aminobutylamide with high diastereoselectivity.To further improve the catalytic efficiency of IR104,its mutant D191E/L195I/E253S/M258A(M3)was identified by saturation mutagenesis and iterative combinatorial mutagenesis,which exhibited a 102-fold increase in the catalytic efficiency relative to that of wild-type enzyme and high diastereoselectivity(98:2 d.r.).Crystal structural analysis and molecular dynamics simulations provided some insights into the molecular basis for the improved activity of the mutant enzyme.The imine reductase identified in this study could accept chiral amino amides/esters as amino donors for the dynamic kinetic resolution reductive amination of racemicα-substituted aldehydo-esters,expanding the substrate scope of imine reductases in the dynamic kinetic resolution-reductive amination.Finally,IR104-M3 was successfully used for the preparation of Brivaracetam at gram scale.Using this mutant,various N-substituted amino amides/esters with two chiral centers were also synthesized with up to 99:1 d.r.and 96%yields and subsequently converted intoγ-andδ-lactams,providing an efficient protocol for the synthesis of these important compounds via enzymatic dynamic kinetic resolution-reductive amination from simple building blocks.
基金supported by the National Key R&D Program of China(No.2023YFA1506804)the National Natural Science Foundation of China(Nos.22471110,22171111,22131007 and 22071093)+1 种基金the Science Foundation of Gansu Province of China(No.22JR5RA406)the Fundamental Research Funds for the Central Universities(No.lzujbky-2023-15)。
文摘Most commercial plastics cannot easily degrade,which raises a number of sustainability issues.To address the current problem of plastic pollution,the research and development of easily degradable and recyclable polymers has become an attractive subject.Herein,a new monomer of thiosalicylic methyl glycolide(TSMG)was synthesized using one-pot method and high molecular weight poly(thiosalicylic methyl glycolide)(PTSMG,M_(n) up to 300 kDa)can be obtained via the ring-opening polymerization(ROP)of TSMG.PTSMG exhibits good closed-loop recyclability and hydrolytic degradability,where PTSMG can generate pristine monomers through sublimation thermal depolymerization conditions due to the presence of thiophenol ester bond in the polymer chains,and can be degraded rapidly in aqueous solution,which provides a potential solution to the current plastic pollution problem.
基金supported by the National Natural Science Foundation of China(Grant Nos.51991351 and51903132)the Young Elite Scientist Sponsorship Program by CAST(No.2022QNRC001).
文摘Different reactive flame retardants have been extensively developed for vinyl ester resins(VERs),but very few of them can yield a flame-retardant resin that meets defined standards(e.g.UL-94 V-0 rating).In this work,phosphorous-containing 1-vinylimidazole salts(called VIDHP and VIDPP)were synthesized through the facile neutralization of the acid and 1-vinylimidazole.VIDHP and VIDPP were then applied as flame-retardant crosslinking agents of VERs,by which phosphorus-containing groups could be incorporated into the resin chain via ionic bonds.VIDHP/VER and VIDPP/VER showed a high curing activity and can be well cured in moderate temperatures.With 20 wt.%additions of VIDHP and VIDPP,VIDHP20/VER,and VIDPP20/VER presented a limiting oxygen index value of 29.7%and 28.4%,respectively,with the latter achieving a UL 94 V0 rating.In the cone calorimetric test,compared to the unmodified VERs,VIDPP20/VER exhibited large reductions in the peak heat release rate,total heat release rate,and total smoke release rate while VIDHP20/VER demonstrated comparatively inferior performance in terms of the heat release.VIDHP20/VER and VIDPP20/VER showed good thermal stability and presented a little lower glass transition temperature than the control sample.VIDPP with a low phosphorus oxidation state(+1)demonstrated high flame-retardant activities in the gaseous phase,whereas VIDHP with a high phosphorus oxidation state(+5)primarily exhibited efficacy in the condensed phase.
基金supported by the National Natural Science Foundation of China(21878227,22278309)。
文摘Ethanol synthesis via dimethyl oxalate hydrogenation has garnered increasing attention in the fields of syngas utilization.Althoughε-Fe_(2)C has been identified as a promising active species for DMO hydrogenation to ethanol,its formation is kinetically challenging during carbonization.In this work,a Fe_(4)N phase was first synthesized by pretreating a 30Fe/SiO_(2)catalyst in an ammonia environment,followed by carbonization in a methanol-H_(2) flow to obtain ε-Fe_(2)C as the active phase.Fe_(4)N,rather than Fe-O-Si,facilitates the transformation into iron carbide during the carbonization process.The transformation pathway of iron nitride(Fe_(x)N)is mediated by intermediate iron carbonyl species(Fe-CO),ultimately leading to the formation of iron carbide as the active phase.The resulting catalyst exhibited 40 times higher catalytic activity than the untreated catalyst in DMO hydrogenation.Combined structure properties and DFT calculation revealed that the lower energy barrier ofε-Fe_(2)C for ester hydrogenation underpins/strengthens its superior performance,while the STY of ε-Fe_(2)C is 2.8 times that ofε'-Fe_(2.2)C and 58 times that ofχ-Fe_(5)C_(2).This study provides a novel strategy for designing highly efficient iron carbide catalysts for the esters hydrogenation system.
文摘Background:In today’s context,vegetable oils,commonly used in culinary practices such as frying and baking,are integral to numerous daily dietary choices.Palm oil,a frequently employed vegetable oil,raises concerns surrounding food safety,thus presenting a significant challenge.Methods:This research aims to enhance consumer awareness regarding the potential health risks associated with 3-monochloropropane-1,2-diol(3-MCPD)and glycidyl fatty acid esters(GEs)commonly found in food and edible oil products.The study endeavours to apprise consumers of these health risks through a comprehensive survey.The survey enlisted the participation of 120 respondents within the age bracket of 18 years to those above 36 years(capped at 50 years).Results:Strikingly,a significant proportion,ranging from 88%to 89%,demonstrated a lack of awareness concerning the potential risks associated with 3-MCPD and GEs in food products.Conclusion:This study underscores the urgency of augmenting consumer's awareness levels regarding 3-MCPD and GEs.Furthermore,it promotes a more detailed examination of Malaysian edible oils and food products available in the market to establish an appropriate Tolerable Daily Intake for the Malaysian population.This research contributes to the broader discourse on food safety and public health by highlighting these crucial facets.
基金financially supported by the Natural Science Foundation of Jilin Province Science and Technology Department(No.20230101221JC)the National Natural Science Foundation of China(Nos.52173115,52073278,52203189)the Research Foundation for Advanced Talents of Xiamen University of Technology(Nos.5010423019,YKJ22052R)。
文摘It is well known that cationic polymers have excellent antimicrobial capacity accompanied with high biotoxicity,to reduce biotoxicity needs to decrease the number of cationic groups on polymers,which will influence antimicrobial activity.It is necessary to design a cationic polymer mimic natural antimicrobial peptide with excellent antibacterial activity and low toxicity to solve the above dilemma.Here,we designed and prepared a series of cationic poly(β-amino ester)s(PBAEs)with different cationic contents,and introducing hydrophobic alkyl chain to adjust the balance between antimicrobial activity and biotoxicity to obtain an ideal antimicrobial polymer.The optimum one of synthesized PBAE(hydrophilic cationic monomer:hydrophobic monomer=5:5)was screened by testing cytotoxicity and minimum inhibitory concentration(MIC),which can effectively kill S.aureus and E.coli with PBAE concentration of15μg/m L by a spread plate bacteriostatic method and dead and alive staining test.The way of PBAE killing bacterial was destroying the membrane like natural antimicrobial peptide observed by scanning electron microscopy(SEM).In addition,PBAE did not exhibit hemolysis and cytotoxicity.In particular,from the result of animal tests,the PBAE was able to promote healing of infected wounds from removing mature S.aureus and E.coli on the surface of infected wound.As a result,our work offers a viable approach for designing antimicrobial materials,highlighting the significant potential of PBAE polymers in the field of biomedical materials.
文摘Cholesteryl esters(CEs) have been increasingly implicated in neurodegenerative disorders such as Alzheimer's disease(AD).Alois Alzheimer noted three prominent neuropathologic features in his original analysis of the AD brain:senile plaques,neurofibrillary tangles,and lipid granule accumulation.Senile plaques,which are aggregates of amyloid-beta(Aβ),and neurofibrillary tangles,which are aggregates of phosphorylated tau,have been regarded as more consistent characteristics of the AD brain compared with lipid granule accumulation and thus have been studied more intensively(Foley,2010).
基金supported by the National Natural Science Foundation of China (No.22136001)the National Key R&D Program of China (No.2022YFC3902100)+2 种基金the Key R&D Program of Hebei Province (No.21374001D)the Supercomputing Center of Dalian University of Technologythe National Supercomputer Center in Tianjin。
文摘As primary degradation products of phthalate esters,phthalate monoesters(MPEs)have been widely detected in various aquatic environments and drawn growing toxicological concerns.Hydrolysis kinetics that is of importance for assessing environmental persistence of chemicals remain elusive for MPEs.Herein,kinetics of base-catalyzed and neutral hydrolysis for 18 MPEs with different leaving groups was investigated by density functional theory calculation.Results indicate that MPEs with leaving groups having p Kaof<10 prefer dissociative transition states.MPEs are more persistent than their parents,and their hydrolysis half-lives were calculated to vary from 3.4 min to 79.2 years(p H=7–9).A quantitative structure-activity relationship model was developed for predicting the hydrolysis kinetics parameters.It was found that p Kaof the leaving groups and electronegativity of the MPEs are key factors determining the hydrolysis kinetics.This work may lay a theoretical foundation for better understanding the chemical process that governs MPE persistence in aquatic environments.
文摘Cholesterol is a sterol with a four-membered ring structure and a single hydroxyl group attached to one of the rings. It is the active, raw form of cholesterol. Cholesteryl Ester is the inactive form in which cholesterol is esterified to be transported to target organs. The newly developed process of making bulky esters from unprecedented tertiary alcohols is applied to synthesize cholesterol esters successfully. Although cholesterol is a secondary alcohol, it is a very bulky and interesting compound due to its immense application. Usually, specific enzymes catalyze cholesterol to cholesterol ester. This project aims to develop a cross-coupling chemistry process to synthesize cholesterol esters and see the broader application of those new cholesterol esters in chemical biology. The mixture of cholesterol, sodium tert-butoxide, aroyl chloride, the catalyst PdCl2 (dtbpf) complex, and the solvent 1,4-dioxane, when microwaved at 100˚C for 2 hours, works well for the formation of cross-coupling cholesterol ester products in good to high yields.
