Quantitative correlation of several theoretical electrophilicity measures over different families of organic compounds are examined relative to the experimental values of Mayr et al.Notably,the ability to predict thes...Quantitative correlation of several theoretical electrophilicity measures over different families of organic compounds are examined relative to the experimental values of Mayr et al.Notably,the ability to predict these values accurately will help to elucidate the reactivity and selectivity trends observed in charge-transfer reactions.A crucial advantage of this theoretical approach is that itprovides this information without the need of experiments,which are often demanding and time-consuming.Here,two different types of electrophilicity measures were analyzed.First,models derived from conceptual density functional theory(c-DFT),including Parr's original proposal and further generalizations of this index,are investigated.For instance,the approaches of Gázquez et al.and Chamorro et al.are considered,whereby it is possible to distinguish between processes in which a molecule gains or loses electrons.Further,we also explored two novel electrophilicity definitions.On one hand,the potential of environmental perturbations to affect electron incorporation into a system is analyzed in terms of recent developments in c-DFT.These studies highlight the importance of considering the molecular surroundings when a consistent description of chemical reactivity is needed.On the other hand,we test a new definition of electrophilicity that is free from inconsistencies(so-called thermodynamic electrophilicity).This approach is based on Parr's pioneering insights,though it corrects issues present in the standard working expression for the calculation of electrophilicity.Additionally,we use machine-learning tools(i.e.,symbolic regression)to identify the models that best fit the experimental values.In this way,the best possible description of the electrophilicity values in terms of different electronic structure quantities is obtained.Overall,this straightforward approach enables one to obtain good correlations between the theoretical and experimental quantities by using the simple,yet powerful,interpretative advantage of c-DFT methods.In general,we observed that the correlations found at the HF/6-31 G(d)level of theory are of semi-quantitative value.To obtain more accurate results,we showed that working with families of compounds with similar functional groups is indispensable.展开更多
In recent years, many studies have been done on the structure of fullerene as medicine nano carrier compounds. On this basis, Quantum mechanical calculations have been done and the effect of the nicotine compound in s...In recent years, many studies have been done on the structure of fullerene as medicine nano carrier compounds. On this basis, Quantum mechanical calculations have been done and the effect of the nicotine compound in structure of Nanofullerene C<sub>12</sub> was studied. Density Functional Theory (DFT) can be used to calculate an accurate electronic structure, HOMO and LUMO energies, Mulliken charge of atoms, energetic orbital levels, global hardness, chemical potential and electrophilicity of systems, and finally chemical, physical properties of fullerene and fullerene derivatives. Theoretical calculations such as Natural Bond Orbital (NBO) are very important to understand the pathways of electron transfer in assemblies. Consequently, the obtained results showed that energy orbital levels decreased considerably by linking structure of Nanofullerene to the structure of Nicotine. The intramolecular interaction is formed by the orbital overlap between C-C, C-N, C-H anti bonding orbital which results an intermolecular charge transfer (ICT) from a Lewis valence orbital (donor), with a decreasing of its occupancy, to a non-Lewis orbital (acceptor). The interacting effect is also discussed in terms of the change in the C-C bond lengths, net atomic charge distribution, total dipole moment. The obtained results indicate that the C-C distances are enlarged interaction. Furthermore, there is a complete change in the net atomic charge distribution, as well as a corresponding increase in the value of the total dipole moment. On the basis of fully optimized ground-state structure, TDDFT//B3LYP/3-21G* calculations have been performed to determine the low-lying excited states of nanofullerene interacting with nicotine (NFN).展开更多
For 25 simple reactions, the changes of the hardness （△η）, polarizability （△α） and electrophilicity index （△ω） and their cube-roots （△η^1/3, △α^1/3, △ω^1/3） were calculated. It is shown that althou...For 25 simple reactions, the changes of the hardness （△η）, polarizability （△α） and electrophilicity index （△ω） and their cube-roots （△η^1/3, △α^1/3, △ω^1/3） were calculated. It is shown that although the Maximum Hardness and Minimum Polarizability Principles are not valid for all reactions, but in most cases △ω^1/3〈0, whereas we always find △ω〈0. Our observation implies to this fact that for those chemical reactions in which the number of moles decreases or at least remains constant, the most stable species （reactants or products） have the lowest sum of electrophilicities. In other words ＂the natural direction of a chemical reaction is toward a state of minimum electrophilicity＂. This fact may be called Minimum Electrophilicity Principle （MEP）.展开更多
The catalytic enantioselective electrophilic amination reaction has emerged as a highly efficient method for synthesizing diverse nitrogen-containing chiral molecules,with the development of various asymmetric catalys...The catalytic enantioselective electrophilic amination reaction has emerged as a highly efficient method for synthesizing diverse nitrogen-containing chiral molecules,with the development of various asymmetric catalysis systems.Chiral phosphoric acids(CPA)have been widely acknowledged as versatile chiral organocatalysts since it was first discovered in 2004,finding application in catalyzing diverse asymmetric reactions.A comprehensive overview of recent advances in CPA-catalyzed asymmetric electrophilic amination reactions using different N-electrophilic reagents,including azo reagents,aryldiazonium salts,and imine derivatives,is presented.Furthermore,insights into future developments in this field are offered.展开更多
The carbon-carbon bond is the one of the most fundamental and abundant bonds that exist in organic molecules,and the challenge of functionalization of carbon-carbon bond has always been a critical pursuit in organic s...The carbon-carbon bond is the one of the most fundamental and abundant bonds that exist in organic molecules,and the challenge of functionalization of carbon-carbon bond has always been a critical pursuit in organic synthesis.In recent years,there have been a growing number of studies on the C-C bond activation.Nevertheless,the metal-catalyzed cleavage of the C-C(O)bond in unstrained ketones has remained relatively underexplored due to the strong affinity of carbonyl groups for metals.In this study,we report a nickel-catalyzed strategy for the reductive alkynylation of ketoimines viaβ-carbon elimination.This method involves the conversion of aryl ketones into aryl ketoimines,thus expanding the toolbox of aryl electrophiles.The use of a N-heterocyclic carbene(NHC)ligand is crucial for this catalytic transformation.This discovery leads to a cross electrophile coupling reaction characterized by its operational simplicity,unique chemo-selectivity and excellent functional group tolerance.In addition,the approach has been effectively applied to the late-stage alkynylation of diverse pharmaceuticals.Ultimately,a series of comprehensive experiments and theoretical studies were conducted to provide insights into the reaction pathway,which supports the proposedβ-carbon elimination process.展开更多
Chemotherapy and chemoprevention have been two of the most important means to control cancer incidence and mortality, and the cellular defensive machinery against oxidative/electrophilic stresses plays significant rol...Chemotherapy and chemoprevention have been two of the most important means to control cancer incidence and mortality, and the cellular defensive machinery against oxidative/electrophilic stresses plays significant roles in both means. This defensive system is composed of cytoprotective enzymes that metabolize and eliminate oxidative/electrophitic species. The transcription factor nuclear factor erythroid 2-related factor 2 （Nrf2） controls the basal and inducible expression of many cytoprotective genes, and plays a pivotal role in coordinating cellular defensive responses. Under basal conditions, the activity of Nrf2 is inhibited by binding to Kelch-like ECH-associated protein 1 （Keap 1）, which is capable of sensing oxidative/electrophilic signals. Upon oxidative/electrophilic stresses, the binding of Nrf2 to Keapl is disrupted, leading to activation of Nrf2 and induction of cytoprotective enzymes. Thus, Nrf2 has emerged as an important target of chemopreventive drugs. However, activation of Nrf2 could lead to very different outcomes depending on the cellular context. The indiscriminative protective effects of Nrf2 lead to its undesired functions in carcinogenesis and chemoresistance of cancer cells. Activation of Nrf2 provides neoplastic cells with growth advantages and protects cancer cells from chemotherapeutic drugs, resulting in poor clinical outcomes. In this means, inhibitors of Nrf2 signaling can enhance the efficacy of chemotherapeutic drugs and deserve further development. A better understanding of the regulation and functions of Nrf2 would be helpful for researches in both chemoprevention and chemotherapy of cancer.展开更多
Charge density distribution in ampicillin trihydrate was investigated experimentally. Results were compared with the quantum calculations using density functional theory. The charge derived properties including Mullik...Charge density distribution in ampicillin trihydrate was investigated experimentally. Results were compared with the quantum calculations using density functional theory. The charge derived properties including Mulliken atomic charges, dipole moment, and molecular electrostatic potential were calculated. The multipole analysis was done for the refinement of experimental population parameters. The structure factors obtained from multipole treat- ment were used for the construction of Fourier maps. Topological properties of the charge distribution were discussed and the characteristics of （3, -1） critical points were analyzed.展开更多
Excessive consumption of alcoholic beverages is a serious cause of liver disease worldwide.The metabolism of ethanol generates reactive oxygen species,which play a significant role in the deterio-ration of alcoholic l...Excessive consumption of alcoholic beverages is a serious cause of liver disease worldwide.The metabolism of ethanol generates reactive oxygen species,which play a significant role in the deterio-ration of alcoholic liver disease(ALD).Antioxidant phytochemicals,such as polyphenols,regulate the expression of ALD-associated proteins and peptides,namely,catalase,superoxide dismutase,glutathione,glutathione peroxidase,and glutathione reductase.These plant antioxidants have electrophilic activity and may induce antioxidant enzymes via the Kelch-like ECH-associated protein 1--NF--E2--related factor--2 pathway and antioxidant responsive elements.Furthermore,these antioxidants are reported to alleviate cell injury caused by oxidants or inflammatory cytokines.These phenomena are likely induced via the regulation of mitogen--activating protein kinase(MAPK)pathways by plant antioxidants,similar to preconditioning in ischemia-reperfusion models.Although the relationship between plant antioxidants and ALD has not been adequately investigated,plant antioxidants may be preventive for ALD because of their electrophilic and regulatory activities in the MAPK pathway.展开更多
This mini-review presents the authors＇ vision on the current status and future trends in the development of neuroprotective agents working via activation of nuclear factor erythroid 2-related factor 2 （Nrf2）, and i...This mini-review presents the authors＇ vision on the current status and future trends in the development of neuroprotective agents working via activation of nuclear factor erythroid 2-related factor 2 （Nrf2）, and in particular, via disruption of Nrf2-Keap 1 interaction. There are two opposite ＂chemical＂ mechanisms underlying such activation： the first one is a non-specific covalent modification of Keapl thiols, resulting in side effects of varied severity, and the second one is the shift of the Nrf2-Kelch-like ECH associated protein-1 （Keapl） binding equilibrium in the presence of a competitive and chemically benign displacement agent. At this point, no displacement activators exhibit sufficient biological activity in comparison with common Nrf2 activators working via Keapl thiol modification. Hence, the hope in therapeutics is now linked to the FDA approved dimethylfumarate, whose derivative, monomethylfumarate, as we demonstrated recently, is much less toxic but equally biologically potent and an ideal candidate for clinical trials right now. A newly emerging player is a nuclear inhibitor of Nrf2, BTB domain and CNC homolog 1 （Bach1）. The commercially developed Bachl inhibitors are currently under investigation in our laboratory showing promising results. In our viewpoint, the perfect future drug will present the combination of a displacement activator and Bach 1 inhibitor to insure safety and efficiency of Nrf2 activation.展开更多
Two electrophilic pentafluoroethylating reagents of pentafluoroethyl(p-methylphenyl)sulfonium bis(carbometh-oxy)methylide(4a)and pentafluoroethyl(4-nitrophenyl)sulfonium bis(carbomethoxy)methylide(4b),and their reacti...Two electrophilic pentafluoroethylating reagents of pentafluoroethyl(p-methylphenyl)sulfonium bis(carbometh-oxy)methylide(4a)and pentafluoroethyl(4-nitrophenyl)sulfonium bis(carbomethoxy)methylide(4b),and their reactions under mild conditions withβ-ketoesters,aryl iodides and heteroaromatics are described.展开更多
The reaction of nitrosonium (NO+) with Schiff bases produced diazonium salts and aldehydes in good yield. The reaction is assumed to be an electrophilic reaction of nitrosonium with imines via a four-member ring inter...The reaction of nitrosonium (NO+) with Schiff bases produced diazonium salts and aldehydes in good yield. The reaction is assumed to be an electrophilic reaction of nitrosonium with imines via a four-member ring intermediate.展开更多
Two new compounds, isoquinoline-1, 3-dicarboxyaldehyde and (IDA) were synthesized via 6 or 7 steps starting from benzaldehyde, or prepared via 4 steps starting from allylbenzene.
A new approach for isolation and identification of elecrtophilic mutagens from complex matrix was developed. Thiosulforfic anion was immobilized onto polystyrene beads and used as separation media. Potassium polystyry...A new approach for isolation and identification of elecrtophilic mutagens from complex matrix was developed. Thiosulforfic anion was immobilized onto polystyrene beads and used as separation media. Potassium polystyryl-thiosulfonate, prepared from polystyryl- sulfonyl chloride and KHS, was observed to selectively react with model electrophilic mutagens such as alkyl halides, ct-chloroketones and α-chloroesters to produce polystyryl-thiosulfonlc esters. After separation from other nonreactive organic compounds, the beads then reacted with ethanethiol to produce unsymmetrical ethyl disulfides which are easily detected by GC/MS. For one mutagenic compound, only one unsymmetrical disulfide was found to contain its structure part. Thus, the structure of the parent mutagens could be deduced from that of the unsymmetrical disulfides. The degree of functionalization of the potassium polystyryl-thiosulfonate resin was 1.11 mmol/g. Its reactivity was discussed and its recycling method was reported here.展开更多
A novel trifunctional initiator with one alkyne and two trifluoromethanesulfonate moieties was synthesized from a protected alcohol 5-hydroxyl-2-phenyl-1, 3-dioxane. The alkyne func- tionalized intermediate with two p...A novel trifunctional initiator with one alkyne and two trifluoromethanesulfonate moieties was synthesized from a protected alcohol 5-hydroxyl-2-phenyl-1, 3-dioxane. The alkyne func- tionalized intermediate with two protected alcohol groups was synthesized by reacting with propargyl bromide. The alcohol groups were cleaved using a mixture of tetrahydrofuran and hydrochloric acid aqueous solution. In the last step the initiator was synthesized us- ing triflic anhydride in carbon tetrachloride. The initiator was characterized by 1H NMR and used for the polymerization of 2-ethyl-2-oxazoline which gives polymers with narrow distribution. For comparison a similar initiator with two tosylates was prepared and used for the polymerization of the monomer 2-ethyl-2-oxazoline, the resulting product has a wide molecular weight distribution and most of the initiator remains unreacted after 24 h which may be due to the steric hindrance between the two tosylate groups. To further explore the steric hindrance phenomenon, a linear tosylate initiator was synthesized, but still some of the initiator remains unreacted, illustrating that both steric hindrance and electrophilic balance affect the efficiency of the cationic ring-opening polymerization. All of the polymers were characterized in detail by using IH NMR, matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy, and size exclusion chromatography to confirm the purity and distribution of the polymers.展开更多
Atmospheric CO_(2)concentrations are soaring due to the continued use of fossil fuels in energy production,an anthropogenic activity that is playing a leading role in global warming.Thus,research aimed at the capture ...Atmospheric CO_(2)concentrations are soaring due to the continued use of fossil fuels in energy production,an anthropogenic activity that is playing a leading role in global warming.Thus,research aimed at the capture and conversion of CO_(2)into value-added products,such as cyclic carbonates,is booming.While CO_(2)is an abundant,cheap,non-toxic,and readily accessible Cl feedstock,its thermodynamic stability necessitates the development of highly efficient catalysts that are able to promote chemical reactions under mild conditions.In this work,a novel mesoporous poly(ionic liquid)with dual active sites was synthesized through a facile method that involves co-polymerization,post-synthetic metalation,and supercritical CO_(2)drying.Due to a high density of nucleophilic and electrophilic sites,the as-prepared poly(ionic liquid),denoted as P2D-4BrBQA-Zn,offers excellent performance in a CO_(2)cycloaddition reaction using epichlorohydrin as the substrate(98.9%conversion and 96.9%selectivity).Moreover the reaction is carried out under mild,solvent-free,and additive-free conditions.Notably,P2D-4BrBQA-Zn also efficiently promotes the conversion of various other epoxide substrates into cyclic carbonates.Overall,the catalyst is found to have excellent substrate compatibility,stability,and recyclability.展开更多
Different reaction conditions may cause different reaction paths for cleavage of the Se-Se bonds.Further reactions of(PhSe)2 with methylenecyclopropanes(MCPs)under different conditions lead to the construction of tota...Different reaction conditions may cause different reaction paths for cleavage of the Se-Se bonds.Further reactions of(PhSe)2 with methylenecyclopropanes(MCPs)under different conditions lead to the construction of totally different organic skeletons.Example described herein is typical for students to understand the cleavages of chemical bonds as well as the differences between free radical additions and electrophilic additions.展开更多
The valorization of Chinese medicine residues(CMRs)into high-value-added products,such as microcrystalline cellulose(MCC),has garnered significant interest in the current post-pandemic era,particularly in regions wher...The valorization of Chinese medicine residues(CMRs)into high-value-added products,such as microcrystalline cellulose(MCC),has garnered significant interest in the current post-pandemic era,particularly in regions where Chinese medicine(CM)is widely utilized(i.e.,southeast Asia).In this study,we propose a facile and economical protocol for selectively extracting MCC from CMRs via one-step direct peroxymonosulfate(PMS)oxidation without the need for intricate steps.Importantly,our proposed protocol has been verified to be versatile and can be applied to various solid waste sources rich in cellulose,with an average extraction rate of 75%.Analysis using the Fukui index revealed that theβ-O-4 bond,the aromatic ring in lignin,specific O sites in hemicellulose,and the amorphous region of cellulose are more susceptible to electrophilic attack by PMS than to reactions involving HO^(·),SO_(4)^(·-),or^(1)O_(2).Leveraging this distinct mechanism,the extracted MCC demonstrated ultrahigh purity(~95%)and crystallinity(~85.36%).Overall,our work involves transforming solid waste into high-value products through the provision of a technical solution,with the potential for onsite application.This represents a significant advancement to the valorization of CMRs,particularly in providing theoretical guidance for accelerating the recycling of waste materials.展开更多
Haloacetamides（HAMs） are cytotoxic, genotoxic, and mutagenic byproducts of drinking water disinfection. They are soft electrophilic compounds that form covalent bonds with the free thiol/thiolate in cysteine residue...Haloacetamides（HAMs） are cytotoxic, genotoxic, and mutagenic byproducts of drinking water disinfection. They are soft electrophilic compounds that form covalent bonds with the free thiol/thiolate in cysteine residues through an S_N2 reaction mechanism.Toxicity of the monohalogenated HAMs（iodoacetamide, IAM; bromoacetamide, BAM;or chloroacetamide, CAM） varied depending on the halogen substituent. The aim of this research was to investigate how the halogen atom affects the reactivity and toxicological properties of HAMs, measured as induction of oxidative/electrophilic stress response and genotoxicity. Additionally, we wanted to determine how well in silico estimates of electrophilic softness matched thiol/thiolate reactivity and in vitro toxicological endpoints.Each of the HAMs significantly induced nuclear Rad51 accumulation and ARE signaling activity compared to a negative control. The rank order of effect was IAM 〉 BAM 〉 CAM for Rad51, and BAM ≈ IAM 〉 CAM for ARE. In general, electrophilic softness and in chemico thiol/thiolate reactivity provided a qualitative indicator of toxicity, as the softer electrophiles IAM and BAM were more thiol/thiolate reactive and were more toxic than CAM.展开更多
A new,stable and scalable reagent for deuteriodifluoromethylthiolation(deuterated N-difluoromethylthiophthalimide,PhthSCF_(2)D)has been developed.This reagent can be applied for the photocatalytic radical deuteriodifl...A new,stable and scalable reagent for deuteriodifluoromethylthiolation(deuterated N-difluoromethylthiophthalimide,PhthSCF_(2)D)has been developed.This reagent can be applied for the photocatalytic radical deuteriodifluoromethylthiolation of various olefins and aldehydes(30 examples).Meanwhile,it can achieve the electrophilic deuteriodifluoromethylthiolation of a series of electrophilic substrates including electron-rich arenes,aryl/vinylboronicacids,alkynes,amines,thiols andβ-ketoesters(22 examples).Some complex molecules can also be applied in both radical and electrophilic deuteriodifluoromethylthiolation using PhthSCF_(2)D as the reagent.展开更多
3-Acetamidotropolone 1 reacted with p-substitutedbenzenediazonium chloride in pyridine to afford 3-acetamido-5-(4-substitutedphenylazo)tropolones 2a~f. Hydrolysis of compounds 2a~f gave 3-amino-5-(4-substitutedphenyla...3-Acetamidotropolone 1 reacted with p-substitutedbenzenediazonium chloride in pyridine to afford 3-acetamido-5-(4-substitutedphenylazo)tropolones 2a~f. Hydrolysis of compounds 2a~f gave 3-amino-5-(4-substitutedphenylazo)tropolones 3a~f which could not be obtained directly from reactions of 3-aminotropolone with p-substitutedbenzenediazonium chloride. The structures of these new compounds 2a, 2c~f, 3a, 3c~f were confirmed from the elemental analysis and spectral data.展开更多
基金support by FONDECYT(1140313)Financiamiento Basal para Centros Cientificos y Tecnoldgicos de Excelencia-FB0807project RC-130006 CILLIS,Chile
文摘Quantitative correlation of several theoretical electrophilicity measures over different families of organic compounds are examined relative to the experimental values of Mayr et al.Notably,the ability to predict these values accurately will help to elucidate the reactivity and selectivity trends observed in charge-transfer reactions.A crucial advantage of this theoretical approach is that itprovides this information without the need of experiments,which are often demanding and time-consuming.Here,two different types of electrophilicity measures were analyzed.First,models derived from conceptual density functional theory(c-DFT),including Parr's original proposal and further generalizations of this index,are investigated.For instance,the approaches of Gázquez et al.and Chamorro et al.are considered,whereby it is possible to distinguish between processes in which a molecule gains or loses electrons.Further,we also explored two novel electrophilicity definitions.On one hand,the potential of environmental perturbations to affect electron incorporation into a system is analyzed in terms of recent developments in c-DFT.These studies highlight the importance of considering the molecular surroundings when a consistent description of chemical reactivity is needed.On the other hand,we test a new definition of electrophilicity that is free from inconsistencies(so-called thermodynamic electrophilicity).This approach is based on Parr's pioneering insights,though it corrects issues present in the standard working expression for the calculation of electrophilicity.Additionally,we use machine-learning tools(i.e.,symbolic regression)to identify the models that best fit the experimental values.In this way,the best possible description of the electrophilicity values in terms of different electronic structure quantities is obtained.Overall,this straightforward approach enables one to obtain good correlations between the theoretical and experimental quantities by using the simple,yet powerful,interpretative advantage of c-DFT methods.In general,we observed that the correlations found at the HF/6-31 G(d)level of theory are of semi-quantitative value.To obtain more accurate results,we showed that working with families of compounds with similar functional groups is indispensable.
文摘In recent years, many studies have been done on the structure of fullerene as medicine nano carrier compounds. On this basis, Quantum mechanical calculations have been done and the effect of the nicotine compound in structure of Nanofullerene C<sub>12</sub> was studied. Density Functional Theory (DFT) can be used to calculate an accurate electronic structure, HOMO and LUMO energies, Mulliken charge of atoms, energetic orbital levels, global hardness, chemical potential and electrophilicity of systems, and finally chemical, physical properties of fullerene and fullerene derivatives. Theoretical calculations such as Natural Bond Orbital (NBO) are very important to understand the pathways of electron transfer in assemblies. Consequently, the obtained results showed that energy orbital levels decreased considerably by linking structure of Nanofullerene to the structure of Nicotine. The intramolecular interaction is formed by the orbital overlap between C-C, C-N, C-H anti bonding orbital which results an intermolecular charge transfer (ICT) from a Lewis valence orbital (donor), with a decreasing of its occupancy, to a non-Lewis orbital (acceptor). The interacting effect is also discussed in terms of the change in the C-C bond lengths, net atomic charge distribution, total dipole moment. The obtained results indicate that the C-C distances are enlarged interaction. Furthermore, there is a complete change in the net atomic charge distribution, as well as a corresponding increase in the value of the total dipole moment. On the basis of fully optimized ground-state structure, TDDFT//B3LYP/3-21G* calculations have been performed to determine the low-lying excited states of nanofullerene interacting with nicotine (NFN).
文摘For 25 simple reactions, the changes of the hardness （△η）, polarizability （△α） and electrophilicity index （△ω） and their cube-roots （△η^1/3, △α^1/3, △ω^1/3） were calculated. It is shown that although the Maximum Hardness and Minimum Polarizability Principles are not valid for all reactions, but in most cases △ω^1/3〈0, whereas we always find △ω〈0. Our observation implies to this fact that for those chemical reactions in which the number of moles decreases or at least remains constant, the most stable species （reactants or products） have the lowest sum of electrophilicities. In other words ＂the natural direction of a chemical reaction is toward a state of minimum electrophilicity＂. This fact may be called Minimum Electrophilicity Principle （MEP）.
文摘The catalytic enantioselective electrophilic amination reaction has emerged as a highly efficient method for synthesizing diverse nitrogen-containing chiral molecules,with the development of various asymmetric catalysis systems.Chiral phosphoric acids(CPA)have been widely acknowledged as versatile chiral organocatalysts since it was first discovered in 2004,finding application in catalyzing diverse asymmetric reactions.A comprehensive overview of recent advances in CPA-catalyzed asymmetric electrophilic amination reactions using different N-electrophilic reagents,including azo reagents,aryldiazonium salts,and imine derivatives,is presented.Furthermore,insights into future developments in this field are offered.
基金financial support from the National Natural Science Foundation of China(Nos.22001147,22371171)Taishan Scholars Project of Shandong Province(No.tsqn202103027)+1 种基金Distinguished Young Scholars of Shandong Province(Overseas)(No.2022HWYQ-001)Qilu Youth Scholar Funding of Shandong University。
文摘The carbon-carbon bond is the one of the most fundamental and abundant bonds that exist in organic molecules,and the challenge of functionalization of carbon-carbon bond has always been a critical pursuit in organic synthesis.In recent years,there have been a growing number of studies on the C-C bond activation.Nevertheless,the metal-catalyzed cleavage of the C-C(O)bond in unstrained ketones has remained relatively underexplored due to the strong affinity of carbonyl groups for metals.In this study,we report a nickel-catalyzed strategy for the reductive alkynylation of ketoimines viaβ-carbon elimination.This method involves the conversion of aryl ketones into aryl ketoimines,thus expanding the toolbox of aryl electrophiles.The use of a N-heterocyclic carbene(NHC)ligand is crucial for this catalytic transformation.This discovery leads to a cross electrophile coupling reaction characterized by its operational simplicity,unique chemo-selectivity and excellent functional group tolerance.In addition,the approach has been effectively applied to the late-stage alkynylation of diverse pharmaceuticals.Ultimately,a series of comprehensive experiments and theoretical studies were conducted to provide insights into the reaction pathway,which supports the proposedβ-carbon elimination process.
基金Ministry of Science and Technology of China (The National Basic research Program of China, Grant No. 2009CB526509)supported by Peking University Health Science Center (bmu2009138-121)
文摘Chemotherapy and chemoprevention have been two of the most important means to control cancer incidence and mortality, and the cellular defensive machinery against oxidative/electrophilic stresses plays significant roles in both means. This defensive system is composed of cytoprotective enzymes that metabolize and eliminate oxidative/electrophitic species. The transcription factor nuclear factor erythroid 2-related factor 2 （Nrf2） controls the basal and inducible expression of many cytoprotective genes, and plays a pivotal role in coordinating cellular defensive responses. Under basal conditions, the activity of Nrf2 is inhibited by binding to Kelch-like ECH-associated protein 1 （Keap 1）, which is capable of sensing oxidative/electrophilic signals. Upon oxidative/electrophilic stresses, the binding of Nrf2 to Keapl is disrupted, leading to activation of Nrf2 and induction of cytoprotective enzymes. Thus, Nrf2 has emerged as an important target of chemopreventive drugs. However, activation of Nrf2 could lead to very different outcomes depending on the cellular context. The indiscriminative protective effects of Nrf2 lead to its undesired functions in carcinogenesis and chemoresistance of cancer cells. Activation of Nrf2 provides neoplastic cells with growth advantages and protects cancer cells from chemotherapeutic drugs, resulting in poor clinical outcomes. In this means, inhibitors of Nrf2 signaling can enhance the efficacy of chemotherapeutic drugs and deserve further development. A better understanding of the regulation and functions of Nrf2 would be helpful for researches in both chemoprevention and chemotherapy of cancer.
文摘Charge density distribution in ampicillin trihydrate was investigated experimentally. Results were compared with the quantum calculations using density functional theory. The charge derived properties including Mulliken atomic charges, dipole moment, and molecular electrostatic potential were calculated. The multipole analysis was done for the refinement of experimental population parameters. The structure factors obtained from multipole treat- ment were used for the construction of Fourier maps. Topological properties of the charge distribution were discussed and the characteristics of （3, -1） critical points were analyzed.
基金Supported by JSPS KAKENHI Grant Number 25450196grants-in-aid from The Ministry of Agriculture,Forestry and Fisheries of Japan
文摘Excessive consumption of alcoholic beverages is a serious cause of liver disease worldwide.The metabolism of ethanol generates reactive oxygen species,which play a significant role in the deterio-ration of alcoholic liver disease(ALD).Antioxidant phytochemicals,such as polyphenols,regulate the expression of ALD-associated proteins and peptides,namely,catalase,superoxide dismutase,glutathione,glutathione peroxidase,and glutathione reductase.These plant antioxidants have electrophilic activity and may induce antioxidant enzymes via the Kelch-like ECH-associated protein 1--NF--E2--related factor--2 pathway and antioxidant responsive elements.Furthermore,these antioxidants are reported to alleviate cell injury caused by oxidants or inflammatory cytokines.These phenomena are likely induced via the regulation of mitogen--activating protein kinase(MAPK)pathways by plant antioxidants,similar to preconditioning in ischemia-reperfusion models.Although the relationship between plant antioxidants and ALD has not been adequately investigated,plant antioxidants may be preventive for ALD because of their electrophilic and regulatory activities in the MAPK pathway.
基金supported in part by grants from NIH NS062165,NS060885,Michael J Fox Foundation for Parkinson’s ResearchParfore Parkinson,National Parkinson Foundation(CSRA chapter) to BT+1 种基金Winifred Masterson Burke FoundationThomas Hartman Foundat ion for Parkinson’s disease to IGG
文摘This mini-review presents the authors＇ vision on the current status and future trends in the development of neuroprotective agents working via activation of nuclear factor erythroid 2-related factor 2 （Nrf2）, and in particular, via disruption of Nrf2-Keap 1 interaction. There are two opposite ＂chemical＂ mechanisms underlying such activation： the first one is a non-specific covalent modification of Keapl thiols, resulting in side effects of varied severity, and the second one is the shift of the Nrf2-Kelch-like ECH associated protein-1 （Keapl） binding equilibrium in the presence of a competitive and chemically benign displacement agent. At this point, no displacement activators exhibit sufficient biological activity in comparison with common Nrf2 activators working via Keapl thiol modification. Hence, the hope in therapeutics is now linked to the FDA approved dimethylfumarate, whose derivative, monomethylfumarate, as we demonstrated recently, is much less toxic but equally biologically potent and an ideal candidate for clinical trials right now. A newly emerging player is a nuclear inhibitor of Nrf2, BTB domain and CNC homolog 1 （Bach1）. The commercially developed Bachl inhibitors are currently under investigation in our laboratory showing promising results. In our viewpoint, the perfect future drug will present the combination of a displacement activator and Bach 1 inhibitor to insure safety and efficiency of Nrf2 activation.
文摘Two electrophilic pentafluoroethylating reagents of pentafluoroethyl(p-methylphenyl)sulfonium bis(carbometh-oxy)methylide(4a)and pentafluoroethyl(4-nitrophenyl)sulfonium bis(carbomethoxy)methylide(4b),and their reactions under mild conditions withβ-ketoesters,aryl iodides and heteroaromatics are described.
文摘The reaction of nitrosonium (NO+) with Schiff bases produced diazonium salts and aldehydes in good yield. The reaction is assumed to be an electrophilic reaction of nitrosonium with imines via a four-member ring intermediate.
文摘Two new compounds, isoquinoline-1, 3-dicarboxyaldehyde and (IDA) were synthesized via 6 or 7 steps starting from benzaldehyde, or prepared via 4 steps starting from allylbenzene.
文摘A new approach for isolation and identification of elecrtophilic mutagens from complex matrix was developed. Thiosulforfic anion was immobilized onto polystyrene beads and used as separation media. Potassium polystyryl-thiosulfonate, prepared from polystyryl- sulfonyl chloride and KHS, was observed to selectively react with model electrophilic mutagens such as alkyl halides, ct-chloroketones and α-chloroesters to produce polystyryl-thiosulfonlc esters. After separation from other nonreactive organic compounds, the beads then reacted with ethanethiol to produce unsymmetrical ethyl disulfides which are easily detected by GC/MS. For one mutagenic compound, only one unsymmetrical disulfide was found to contain its structure part. Thus, the structure of the parent mutagens could be deduced from that of the unsymmetrical disulfides. The degree of functionalization of the potassium polystyryl-thiosulfonate resin was 1.11 mmol/g. Its reactivity was discussed and its recycling method was reported here.
基金supported by the National Natural Scientific Foundation of China(No.21674107)the Fundamental Research Funds for the Central Universities(No.WK2340000066)the financial support from CASTWAS President’s PhD Fellowship Programme 2013
文摘A novel trifunctional initiator with one alkyne and two trifluoromethanesulfonate moieties was synthesized from a protected alcohol 5-hydroxyl-2-phenyl-1, 3-dioxane. The alkyne func- tionalized intermediate with two protected alcohol groups was synthesized by reacting with propargyl bromide. The alcohol groups were cleaved using a mixture of tetrahydrofuran and hydrochloric acid aqueous solution. In the last step the initiator was synthesized us- ing triflic anhydride in carbon tetrachloride. The initiator was characterized by 1H NMR and used for the polymerization of 2-ethyl-2-oxazoline which gives polymers with narrow distribution. For comparison a similar initiator with two tosylates was prepared and used for the polymerization of the monomer 2-ethyl-2-oxazoline, the resulting product has a wide molecular weight distribution and most of the initiator remains unreacted after 24 h which may be due to the steric hindrance between the two tosylate groups. To further explore the steric hindrance phenomenon, a linear tosylate initiator was synthesized, but still some of the initiator remains unreacted, illustrating that both steric hindrance and electrophilic balance affect the efficiency of the cationic ring-opening polymerization. All of the polymers were characterized in detail by using IH NMR, matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy, and size exclusion chromatography to confirm the purity and distribution of the polymers.
基金financial support from the National Natural Science Foundation of China(22078274,21903066)。
文摘Atmospheric CO_(2)concentrations are soaring due to the continued use of fossil fuels in energy production,an anthropogenic activity that is playing a leading role in global warming.Thus,research aimed at the capture and conversion of CO_(2)into value-added products,such as cyclic carbonates,is booming.While CO_(2)is an abundant,cheap,non-toxic,and readily accessible Cl feedstock,its thermodynamic stability necessitates the development of highly efficient catalysts that are able to promote chemical reactions under mild conditions.In this work,a novel mesoporous poly(ionic liquid)with dual active sites was synthesized through a facile method that involves co-polymerization,post-synthetic metalation,and supercritical CO_(2)drying.Due to a high density of nucleophilic and electrophilic sites,the as-prepared poly(ionic liquid),denoted as P2D-4BrBQA-Zn,offers excellent performance in a CO_(2)cycloaddition reaction using epichlorohydrin as the substrate(98.9%conversion and 96.9%selectivity).Moreover the reaction is carried out under mild,solvent-free,and additive-free conditions.Notably,P2D-4BrBQA-Zn also efficiently promotes the conversion of various other epoxide substrates into cyclic carbonates.Overall,the catalyst is found to have excellent substrate compatibility,stability,and recyclability.
文摘Different reaction conditions may cause different reaction paths for cleavage of the Se-Se bonds.Further reactions of(PhSe)2 with methylenecyclopropanes(MCPs)under different conditions lead to the construction of totally different organic skeletons.Example described herein is typical for students to understand the cleavages of chemical bonds as well as the differences between free radical additions and electrophilic additions.
基金financially supported by the National Key Research and Development Program of China(2022YFC3205300)。
文摘The valorization of Chinese medicine residues(CMRs)into high-value-added products,such as microcrystalline cellulose(MCC),has garnered significant interest in the current post-pandemic era,particularly in regions where Chinese medicine(CM)is widely utilized(i.e.,southeast Asia).In this study,we propose a facile and economical protocol for selectively extracting MCC from CMRs via one-step direct peroxymonosulfate(PMS)oxidation without the need for intricate steps.Importantly,our proposed protocol has been verified to be versatile and can be applied to various solid waste sources rich in cellulose,with an average extraction rate of 75%.Analysis using the Fukui index revealed that theβ-O-4 bond,the aromatic ring in lignin,specific O sites in hemicellulose,and the amorphous region of cellulose are more susceptible to electrophilic attack by PMS than to reactions involving HO^(·),SO_(4)^(·-),or^(1)O_(2).Leveraging this distinct mechanism,the extracted MCC demonstrated ultrahigh purity(~95%)and crystallinity(~85.36%).Overall,our work involves transforming solid waste into high-value products through the provision of a technical solution,with the potential for onsite application.This represents a significant advancement to the valorization of CMRs,particularly in providing theoretical guidance for accelerating the recycling of waste materials.
基金partial support from the U.S.Army Engineer Research and Development Center and the Army Environmental Quality Technology program, CESU W9132T-16-2-0005 (MJP)partly supported by the interagency agreement IAG #NTR 12003 from the National Institute of Environmental Health Sciences/Division of the National Toxicology Program to the National Center for Advancing Translational Sciences, National Institutes of Health
文摘Haloacetamides（HAMs） are cytotoxic, genotoxic, and mutagenic byproducts of drinking water disinfection. They are soft electrophilic compounds that form covalent bonds with the free thiol/thiolate in cysteine residues through an S_N2 reaction mechanism.Toxicity of the monohalogenated HAMs（iodoacetamide, IAM; bromoacetamide, BAM;or chloroacetamide, CAM） varied depending on the halogen substituent. The aim of this research was to investigate how the halogen atom affects the reactivity and toxicological properties of HAMs, measured as induction of oxidative/electrophilic stress response and genotoxicity. Additionally, we wanted to determine how well in silico estimates of electrophilic softness matched thiol/thiolate reactivity and in vitro toxicological endpoints.Each of the HAMs significantly induced nuclear Rad51 accumulation and ARE signaling activity compared to a negative control. The rank order of effect was IAM 〉 BAM 〉 CAM for Rad51, and BAM ≈ IAM 〉 CAM for ARE. In general, electrophilic softness and in chemico thiol/thiolate reactivity provided a qualitative indicator of toxicity, as the softer electrophiles IAM and BAM were more thiol/thiolate reactive and were more toxic than CAM.
基金the National Natural Science Foundation of China (Nos. 21776138, 22078161)the Fundamental Research Funds for the Central Universities (Nos. 30920021124, 30918011314)+3 种基金the Natural Science Foundation of Jiangsu Province (No. BK20180476)the Postdoctoral Science Foundation Funded Project (No. 2019M661848)the Priority Academic Program Development of Jiangsu Higher Education Institutionsthe Center for Advanced Materials and Technology in Nanjing University of Science and Technology for their financial support
文摘A new,stable and scalable reagent for deuteriodifluoromethylthiolation(deuterated N-difluoromethylthiophthalimide,PhthSCF_(2)D)has been developed.This reagent can be applied for the photocatalytic radical deuteriodifluoromethylthiolation of various olefins and aldehydes(30 examples).Meanwhile,it can achieve the electrophilic deuteriodifluoromethylthiolation of a series of electrophilic substrates including electron-rich arenes,aryl/vinylboronicacids,alkynes,amines,thiols andβ-ketoesters(22 examples).Some complex molecules can also be applied in both radical and electrophilic deuteriodifluoromethylthiolation using PhthSCF_(2)D as the reagent.
基金The National Natural Science Foundation of China (29933050) and Natural Science Foundation of Liaoning Province (972004).
文摘3-Acetamidotropolone 1 reacted with p-substitutedbenzenediazonium chloride in pyridine to afford 3-acetamido-5-(4-substitutedphenylazo)tropolones 2a~f. Hydrolysis of compounds 2a~f gave 3-amino-5-(4-substitutedphenylazo)tropolones 3a~f which could not be obtained directly from reactions of 3-aminotropolone with p-substitutedbenzenediazonium chloride. The structures of these new compounds 2a, 2c~f, 3a, 3c~f were confirmed from the elemental analysis and spectral data.
