The electrophilic addition to an alkene with an electrophile has been widely studied and applied in organic synthesis.The organic chemistry textbook describes the classical reaction between an alkene and an iodine ele...The electrophilic addition to an alkene with an electrophile has been widely studied and applied in organic synthesis.The organic chemistry textbook describes the classical reaction between an alkene and an iodine electrophile(such as elemental iodine and N-iodosuccinimide(NIS))as a typical ionic reaction,in which an iodonium ion is formed and then attacked by a nucleophile.However,in this article,we report a new and unusual reaction mode between an alkene and NIS;that is,a single electron transfer(SET)process occurs between these two reactants by forming an electron-donor acceptor complex.Not only does this unusual single electron transfer reaction between an alkene and NIS add fundamentally important knowledge to organic chemistry,it also provides a valuable synthetic method as the new SET reaction mode with opposite regioselectivity as compared with the traditional ionic mode.展开更多
Transition metal-catalyzed carbonylation reactions represent a direct and atom-economical approach to synthesize carbonyl compounds or their derivatives by using CO as a cheap and readily available C1 feedstock.While ...Transition metal-catalyzed carbonylation reactions represent a direct and atom-economical approach to synthesize carbonyl compounds or their derivatives by using CO as a cheap and readily available C1 feedstock.While carbonylation of C(sp^(2))-hybridized electrophiles (e.g.,aryl halides) is well developed,carbonylation of less reactive unactivated alkyl electrophiles remains challenging.Recently,the use of earth-abundant base metals including Cu,Co,Mn,Fe,Ni as catalysts has enabled advances in carbonylative coupling of alkyl electrophiles for approaching diverse carbonyl compounds or their derivatives,notably,some of which are of synthetic importance but difficult to be synthesized through previous reported methods.Herein,we have summarized and discussed these recent achievements in base-metal-catalyzed carbonylative C—C,C—N,C—O,C—X coupling and other carbonylation reactions of unactivated alkyl electrophiles using CO as C1 source.展开更多
We analysed the photooxidation reaction in the electro-(1O2) and nucleophilic (O2•−) reaction of 2-pyridone azo derivatives. First, we calculated the energy (enthalpies) of tautomers formation, which is a measure of d...We analysed the photooxidation reaction in the electro-(1O2) and nucleophilic (O2•−) reaction of 2-pyridone azo derivatives. First, we calculated the energy (enthalpies) of tautomers formation, which is a measure of durability and the probability of their formation. We performed the light fastness calculations of the monoazopyridone dyes. Using the semi-empirical methods of quantum chemistry AM1 and PM3, the reactivity indicators of superdelocalisability (SrE(N)) and the electron density distribution in ground state on the highest occupied HOMO orbital and the lowest unoccupied excited state LUMO in 2-pyridone phenylazo derivatives were calculated. Superdelocalisability coefficients enable the stability to oxidising agents of various chemical molecules depending on the tautomeric forms in which they may occur. The results of the electron density calculations at the HOMO and LUMO boundary orbitals allow to determine the tendency to electrophilic attack with singlet oxygen 1O2 or nucleophilic attack of the superoxide anion O2•−on a specific atom in the molecule. The structure of the dyes was optimised with MM+, MD and AM1 or PM3 until a constant energy value was achieved with a convergence criterion of 0.01 kcal/mol.展开更多
Regiodivergent catalysis provides an efficient strategic approach for the construction of architecturally different molecules from the same starting materials. In this field, the intermolecular regiodivergent 1,2-difu...Regiodivergent catalysis provides an efficient strategic approach for the construction of architecturally different molecules from the same starting materials. In this field, the intermolecular regiodivergent 1,2-difunctionalization of alkenes with two electrophiles is still a challenging task. A ligand-controlled, nickel-catalyzed regiodivergent dicarbofunctionalization of alkenes using both aryl/vinyl halides and acetals as electrophiles under mild reductive reaction conditions has been accomplished. This study provides a general approach to accessing both β-methoxyl esters and γ-methoxyl esters from readily available acrylates,aryl halides and acetals. Experimental mechanistic evidence supports that the difference in regioselective outcomes is attributed to the ligand tuning the reactivity of the nickel catalyst, which results in different catalytic cycles operating for these two reaction conditions.展开更多
The reaction of thiourea with p-methyl-β-p-chlorophenyl acrylophenone(1)is,in princi- ple,an attractive[3+ 3]-fragment approach to the synthesis of dihydropyrimidine bearing aryl groups.
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
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
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
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
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
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
Pyridinium ylids 4 were generated as reaction intermediates from the decarboxylation of pyridinium betaines 3, which were prepared from the reactions of a-amino acid ester hydrochlorides with 2, 4, 6-triphenylpyrylium...Pyridinium ylids 4 were generated as reaction intermediates from the decarboxylation of pyridinium betaines 3, which were prepared from the reactions of a-amino acid ester hydrochlorides with 2, 4, 6-triphenylpyrylium tetrafluoroborate. Protonation, addition and substitution reactions of 4 with electrophiles were studied in this paper.展开更多
The Lewis acid mediated polystyrene supported selenium cyclization of chalcones and oxidative cleavage of selenium resins flavonoids in good yields and purities have been reported. induced intramolecular gave the cor...The Lewis acid mediated polystyrene supported selenium cyclization of chalcones and oxidative cleavage of selenium resins flavonoids in good yields and purities have been reported. induced intramolecular gave the corresponding展开更多
Serotonin is one of the significant signaling molecules used by several neural systems in the gut and brain. This study aimed to develop a novel and potent tracer for targeting, detecting, and imaging serotonin recept...Serotonin is one of the significant signaling molecules used by several neural systems in the gut and brain. This study aimed to develop a novel and potent tracer for targeting, detecting, and imaging serotonin receptors(5-HTRs), which is a promising tool in the determination of the receptor’s function and relationship with the diseases related to serotonin and its receptor dysfunction. Serotonin was effectively labeled via a direct electrophilic substitutional reaction using an oxidizing agent such as iodogen with 125I in a neutral medium, and 125I-serotonin was achieved with a maximum labeling yield of 91 ± 0.63% with in vitro stability up to 24 h. Molecular modeling was conducted to signify 125I-serotonin structure and confirm that the radiolabeling process did not affect serotonin binding ability to its receptors. Biodistribution studies show that the maximum gastro intestinal tract uptake of 125I-serotonin was 17.8 ± 0.93% ID/organ after 30 min postinjection and the tracer’s ability to pass the blood–brain barrier. Thus, 125I-serotonin is a promising single photon emission computed tomography tracer in the detection of 5 HTRs.展开更多
Treatment of N-t-butylbenzenesulfonamide with an excess of BuLi, followed by the reaction with methyl 2-（4-methylphenyl）propanoate, gave the corresponding 2-carboxybenzenesulfonamide, which underwent a sequence of c...Treatment of N-t-butylbenzenesulfonamide with an excess of BuLi, followed by the reaction with methyl 2-（4-methylphenyl）propanoate, gave the corresponding 2-carboxybenzenesulfonamide, which underwent a sequence of consecutive N-deprotective cyclization process mediated by TMSCI-NaI-MeCN reagent to afford the N-sulfonylimine. Following the bromination and ring expansion, 3-methyl-3-（4-methylphenyl）-2H-benzo[e][1,2]thiazine-l,l,4-trione was obtained. Optical resolution of the racemic benzosultam using （-）-menthoxyacetyl chloride, furnished the optically p.ure （＋）- and （-）-3-methyl-3-（4-methylphenyl）-2H- benzo[e][1,2]thiazine-1,1,4-triones, which were fluorinated with FC103 to produce the corresponding chiral N-F agents.展开更多
DFT and TD-DFT calculations of HOMO and LUMO energies and photovoltaic properties are carried out on four selected pentathiophene donor and one IDIC-4F acceptor molecules using B3LYP and PBE0 functionals for the groun...DFT and TD-DFT calculations of HOMO and LUMO energies and photovoltaic properties are carried out on four selected pentathiophene donor and one IDIC-4F acceptor molecules using B3LYP and PBE0 functionals for the ground state energy calculations and CAM-B3LYP functional for the excited state calculations.The discrepancy between the calculated and experimental energies is reduced by correlating them with a linear fit.The fitted energies of HOMO and LUMO are used to calculate the Voc of an OSC based on these donors and acceptor blend and compared with experimental values.Using the Scharber model the calculated PCE of the donor-acceptor molecules agree with the experiment.It has been found that fluorine substitution can be used to improve charge transport by reducing the electron and hole reorganization energies of the molecules.It is also found that the introduction of fluorine onto the donor pentathiophene unit of the donor molecule results in a change of polarity of the distributed charges in the molecule due to the high electronegativity of the fluorine atom.The quantum chemical potential(μ),chemical hardness(η)and electronegativity(χ),and electrostatic potential maps(EPMs)are also calculated to identify different charge distribution regions in all five molecules.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
基金supported by National Key Research and Development Program of China(2021YFF0701700)the National Natural Science Foundationof China(22271299 and 22261132514).
文摘The electrophilic addition to an alkene with an electrophile has been widely studied and applied in organic synthesis.The organic chemistry textbook describes the classical reaction between an alkene and an iodine electrophile(such as elemental iodine and N-iodosuccinimide(NIS))as a typical ionic reaction,in which an iodonium ion is formed and then attacked by a nucleophile.However,in this article,we report a new and unusual reaction mode between an alkene and NIS;that is,a single electron transfer(SET)process occurs between these two reactants by forming an electron-donor acceptor complex.Not only does this unusual single electron transfer reaction between an alkene and NIS add fundamentally important knowledge to organic chemistry,it also provides a valuable synthetic method as the new SET reaction mode with opposite regioselectivity as compared with the traditional ionic mode.
基金Fundamental Research Funds for the Central Universities and Natural Science Foundation of Hunan Province(2022JJ30122,2023JJ10003)for financial support.
文摘Transition metal-catalyzed carbonylation reactions represent a direct and atom-economical approach to synthesize carbonyl compounds or their derivatives by using CO as a cheap and readily available C1 feedstock.While carbonylation of C(sp^(2))-hybridized electrophiles (e.g.,aryl halides) is well developed,carbonylation of less reactive unactivated alkyl electrophiles remains challenging.Recently,the use of earth-abundant base metals including Cu,Co,Mn,Fe,Ni as catalysts has enabled advances in carbonylative coupling of alkyl electrophiles for approaching diverse carbonyl compounds or their derivatives,notably,some of which are of synthetic importance but difficult to be synthesized through previous reported methods.Herein,we have summarized and discussed these recent achievements in base-metal-catalyzed carbonylative C—C,C—N,C—O,C—X coupling and other carbonylation reactions of unactivated alkyl electrophiles using CO as C1 source.
文摘We analysed the photooxidation reaction in the electro-(1O2) and nucleophilic (O2•−) reaction of 2-pyridone azo derivatives. First, we calculated the energy (enthalpies) of tautomers formation, which is a measure of durability and the probability of their formation. We performed the light fastness calculations of the monoazopyridone dyes. Using the semi-empirical methods of quantum chemistry AM1 and PM3, the reactivity indicators of superdelocalisability (SrE(N)) and the electron density distribution in ground state on the highest occupied HOMO orbital and the lowest unoccupied excited state LUMO in 2-pyridone phenylazo derivatives were calculated. Superdelocalisability coefficients enable the stability to oxidising agents of various chemical molecules depending on the tautomeric forms in which they may occur. The results of the electron density calculations at the HOMO and LUMO boundary orbitals allow to determine the tendency to electrophilic attack with singlet oxygen 1O2 or nucleophilic attack of the superoxide anion O2•−on a specific atom in the molecule. The structure of the dyes was optimised with MM+, MD and AM1 or PM3 until a constant energy value was achieved with a convergence criterion of 0.01 kcal/mol.
基金supported by the National Natural Science Foundation of China (21871211, 21774029, 22122107)the Fundamental Research Funds for Central Universities (2042019kf0208)。
文摘Regiodivergent catalysis provides an efficient strategic approach for the construction of architecturally different molecules from the same starting materials. In this field, the intermolecular regiodivergent 1,2-difunctionalization of alkenes with two electrophiles is still a challenging task. A ligand-controlled, nickel-catalyzed regiodivergent dicarbofunctionalization of alkenes using both aryl/vinyl halides and acetals as electrophiles under mild reductive reaction conditions has been accomplished. This study provides a general approach to accessing both β-methoxyl esters and γ-methoxyl esters from readily available acrylates,aryl halides and acetals. Experimental mechanistic evidence supports that the difference in regioselective outcomes is attributed to the ligand tuning the reactivity of the nickel catalyst, which results in different catalytic cycles operating for these two reaction conditions.
文摘The reaction of thiourea with p-methyl-β-p-chlorophenyl acrylophenone(1)is,in princi- ple,an attractive[3+ 3]-fragment approach to the synthesis of dihydropyrimidine bearing aryl groups.
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.
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.
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.
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CC acknowledges support by FONDECYT (1140313), Financiamiento Basal para Centros Cientificos y Tecnoldgicos de Excelencia-FB0807, and project RC-130006 CIL[S Chile. PWA acknowledges support from NSERC, the Canada Research Chairs, and Compute Canada： Cana
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.
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.
基金We want to express our sincere appreciation to Professor Joe Wilson of University of Kentucky and Professor Xiulin Ye of Peking University for their favorable suggestions and assistance for the work.
文摘Pyridinium ylids 4 were generated as reaction intermediates from the decarboxylation of pyridinium betaines 3, which were prepared from the reactions of a-amino acid ester hydrochlorides with 2, 4, 6-triphenylpyrylium tetrafluoroborate. Protonation, addition and substitution reactions of 4 with electrophiles were studied in this paper.
基金the National Natural Science Foundation of China （No. 20332050）
文摘The Lewis acid mediated polystyrene supported selenium cyclization of chalcones and oxidative cleavage of selenium resins flavonoids in good yields and purities have been reported. induced intramolecular gave the corresponding
文摘Serotonin is one of the significant signaling molecules used by several neural systems in the gut and brain. This study aimed to develop a novel and potent tracer for targeting, detecting, and imaging serotonin receptors(5-HTRs), which is a promising tool in the determination of the receptor’s function and relationship with the diseases related to serotonin and its receptor dysfunction. Serotonin was effectively labeled via a direct electrophilic substitutional reaction using an oxidizing agent such as iodogen with 125I in a neutral medium, and 125I-serotonin was achieved with a maximum labeling yield of 91 ± 0.63% with in vitro stability up to 24 h. Molecular modeling was conducted to signify 125I-serotonin structure and confirm that the radiolabeling process did not affect serotonin binding ability to its receptors. Biodistribution studies show that the maximum gastro intestinal tract uptake of 125I-serotonin was 17.8 ± 0.93% ID/organ after 30 min postinjection and the tracer’s ability to pass the blood–brain barrier. Thus, 125I-serotonin is a promising single photon emission computed tomography tracer in the detection of 5 HTRs.
基金the Scientific Research Foundation for the Returned Oversea Chinese Scholars of Shandong University.
文摘Treatment of N-t-butylbenzenesulfonamide with an excess of BuLi, followed by the reaction with methyl 2-（4-methylphenyl）propanoate, gave the corresponding 2-carboxybenzenesulfonamide, which underwent a sequence of consecutive N-deprotective cyclization process mediated by TMSCI-NaI-MeCN reagent to afford the N-sulfonylimine. Following the bromination and ring expansion, 3-methyl-3-（4-methylphenyl）-2H-benzo[e][1,2]thiazine-l,l,4-trione was obtained. Optical resolution of the racemic benzosultam using （-）-menthoxyacetyl chloride, furnished the optically p.ure （＋）- and （-）-3-methyl-3-（4-methylphenyl）-2H- benzo[e][1,2]thiazine-1,1,4-triones, which were fluorinated with FC103 to produce the corresponding chiral N-F agents.
文摘DFT and TD-DFT calculations of HOMO and LUMO energies and photovoltaic properties are carried out on four selected pentathiophene donor and one IDIC-4F acceptor molecules using B3LYP and PBE0 functionals for the ground state energy calculations and CAM-B3LYP functional for the excited state calculations.The discrepancy between the calculated and experimental energies is reduced by correlating them with a linear fit.The fitted energies of HOMO and LUMO are used to calculate the Voc of an OSC based on these donors and acceptor blend and compared with experimental values.Using the Scharber model the calculated PCE of the donor-acceptor molecules agree with the experiment.It has been found that fluorine substitution can be used to improve charge transport by reducing the electron and hole reorganization energies of the molecules.It is also found that the introduction of fluorine onto the donor pentathiophene unit of the donor molecule results in a change of polarity of the distributed charges in the molecule due to the high electronegativity of the fluorine atom.The quantum chemical potential(μ),chemical hardness(η)and electronegativity(χ),and electrostatic potential maps(EPMs)are also calculated to identify different charge distribution regions in all five molecules.
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.
