Integrating photodynamic therapy(PDT)with immunosuppression reversal represents a promising synergistic approach to boost cancer immunotherapy.However,the complicated components and cumbersome preparation procedures o...Integrating photodynamic therapy(PDT)with immunosuppression reversal represents a promising synergistic approach to boost cancer immunotherapy.However,the complicated components and cumbersome preparation procedures of the currently developed nano drug delivery systems heavily hinder their further clinical translation.Herein,a reactive oxygen species(ROS)/photo dual-responsive amphipathic prodrug(denoted as PPTN)was designed and synthesized by linking NLG919,an indoleamine-2,3-dioxygenase(IDO)inhibitor,with the photosensitizer protoporphyrin IX(PpIX)by a thioketal moiety,and further modifying with mPEG2k.PPTN could self-assemble into nanoscale unimolecular micelles in aqueous solution without additional excipients,increasing tumor accumulation while effectively addressing the pronounced hydrophobicity challenge of PpIX.Upon light exposure,PPTN generated ROS,not only directly damaging cancer cells,but also trigger the breakage of thioketal bond to accelerate simultaneous release of NLG919.Therefore,PPTN potentially act as a promising ROS/photo dual-responsive carrier-free prodrug delivery system for controllable drug release and specific tumor therapy.Moreover,PPTN induced simultaneous PDT-triggered immunogenic cell death(ICD)effect and specific IDO blockade to boost immune response,exhibiting potent suppression efficacy against primary and distant tumors.Overall,with the superiorities of easily controllable preparation procedures,synchronous drug delivery and ROS/photo dual-responsiveness,such a prodrug unimolecular micelle may represent a promising nanoplatform for photoactivated-immunotherapy.展开更多
Chirality is pervasive and plays a crucial role in biological processes.Although amino acids possess inherent chirality,the stereochemical influence of this property on the regulation of immune cells remains insuffici...Chirality is pervasive and plays a crucial role in biological processes.Although amino acids possess inherent chirality,the stereochemical influence of this property on the regulation of immune cells remains insufficiently explored.To address this,the unimolecular chiral poly(amino acid)s were synthesized to evaluate their immunostimulatory effects and anti-cancer potential.Among the candidates,G0-P_(D)-Lys_(50)emerged as the most effective adjuvant through in vitro screening.When complexed with antigen ovalbumin(OVA)to form chiral nanovaccines,G0-P_(L)-Lys_(50)-OVA and G0-P_(D)-Lys_(50)-OVA exhibited similar morphology,particle size,and zeta potential.Despite these comparable physicochemical properties,G0-P_(D)Lys_(50)-OVA induced significantly stronger activation of dendritic cells(DCs).Specifically,it resulted in 1.38-and 1.34-fold increases in CD11c^(+)CD80^(+)DCs and CD11c^(+)SIINFEKL-H-2Kb^(+)DCs in lymph nodes,respectively.In the LLC-OVA cancer model,G0-P_(D)-Lys_(50)-OVA reduced tumor volume by 50%compared to its enantiomer.These results establish a unique approach to designing chiral nanovaccines and provide a foundational strategy for developing broadly applicable immunotherapies.展开更多
The low energy collisioninduced dissociation, linked scan techniques and isotopic labeling experiment were used to investigate the unimolecular fragmentation of protonated N-hydroxyphthalimide under electron impact a...The low energy collisioninduced dissociation, linked scan techniques and isotopic labeling experiment were used to investigate the unimolecular fragmentation of protonated N-hydroxyphthalimide under electron impact and chemical ionization conditions. It was found that this compound shows an unusual reactivity towards protonation. Two possible sites of protonation have been proposed to explain the corresponding fragmentation processes, one is that the protonation takes place on the oxygen atom of hydroxyl group, resulting in the loss of water and the other is the formation of an intermediary protonbound complex in the fragmentation process, giving rise to the fragment ions of m/z 133 and m/z 135. The results show both cases are coexistence in the fragmentations of protonated N-hydroxyphthalimide, and the unimolecular fragmentation pathways are available.展开更多
Quantum mechanical and Rice-Ramsperger-Kassel-Marcus （RRKM） calculations are carried out to study the thermal unimolecular decomposition of 2,5-dihydrofuran （1）,2,5dihydrothiophene （2）,and 3-pyrroline （3） at t...Quantum mechanical and Rice-Ramsperger-Kassel-Marcus （RRKM） calculations are carried out to study the thermal unimolecular decomposition of 2,5-dihydrofuran （1）,2,5dihydrothiophene （2）,and 3-pyrroline （3） at the MPW1PW91/6-31＋＋G level of theory,and the results are in good agreement with the experimental values.The predicted high pressure limit rate constants （k（T）） in various states of activation energy and pre-exponential （S1：（A（calc.）,E a（calc.））,S2：（A （calc.）,E a（exp.））,and S3：（A （exp.）,E a（calc.））） for the thermal decomposition processes 1-3 were evaluated.Also,the fall-off pressures （P1/2） for compounds 1-3 in the states 1-3 are found to be （1.24×10-2,1.09×10-3,and 4.19×10-2mmHg）,（1.24×10-2,1.63×10-3,and 2.79×10-2mmHg）,and （1.24×10-2,1.63×10-3,and 4.19×10-2 mmHg）,respectively.As the fall-off pressure of thermal decomposition process of compounds 1-3 is in the following order：P1/2（3）〉 P1/2（1）〉 P1/2 （2）,the decomposition rates are as below：rate（3） 〈rate（1）〈rate（2）.展开更多
（2-acrylamido） ethyl tetradecyl dimethylammonium bromide （AMC14AB） was polymerized in aqueous solu- tion to form the homopolymer P（AMC14AB）. The physicochemical properties of P（AMC14AB） in aqueous solution wer...（2-acrylamido） ethyl tetradecyl dimethylammonium bromide （AMC14AB） was polymerized in aqueous solu- tion to form the homopolymer P（AMC14AB）. The physicochemical properties of P（AMC14AB） in aqueous solution were mainly studied with fluorescent probe method, surface tension measurement and conductom- etry. The experimental results show that the aggregation morphology of P（AMC14AB） in aqueous solution is unimolecular micelle as expected. Being different from conventional multimolecular micelle systems, the unimolecular micelle system of P（AMC14AB） not only shows critical micellar concentration （CMC=0）, （i.e. once added to pure water, the surface tension decreases immediately in spite how small the density is）, but also the surface tension stays almost the same with the concentration increasing. That is to say, there is no mutational point on the relationship curve between surface tension and concentration. Furthermore, the unimolecular micelle system of P（AMC14AB） has no Krafft temperature, i.e. at any temperature, so long as it is dissolved in water, the unimolecular micelles will form. Besides this, for the solubilization of hydrophobic organic substances, the unimolecular micelle system of P（AMC14AB） is obviously different from the common multimolecular micelle system, having no turning point on the relationship curve between toluene solubi- lizaion amount and P（AMC14AB） concentration, and the solubilizing ability of the unimolecular-micelle system of P（AMC14AB） for hydrophobic organic substances is much higher than that of the conventional multimolecular micelle solutions of common surfactants, such as centyl trimethyl ammonium bromide.展开更多
The unimolecular dissociation of methylformate free radical cation(CH_3OCHO^+) was studied by ab initio theoretical calculations, Molecular orbital and state correlation diagrams have been examined in the ground and l...The unimolecular dissociation of methylformate free radical cation(CH_3OCHO^+) was studied by ab initio theoretical calculations, Molecular orbital and state correlation diagrams have been examined in the ground and lower excited states. The dissociation mechanism has been explained along the reaction paths. For two possible dissociation pathways in the ground and lower excited states, the activation barriers and reaction heats have been calculated by MCSCF method respectively.展开更多
Polymer systems can be designed into different structures and morphologies according to their physical and chemical performance requirements,and are considered as one of the most promising controlled delivery systems ...Polymer systems can be designed into different structures and morphologies according to their physical and chemical performance requirements,and are considered as one of the most promising controlled delivery systems that can effectively improve the cancer therapeutic index.However,the majority of the polymer delivery systems are designed to be simple spherical nanostructures.To explore morphology/size-oriented delivery performance optimization,here,we synthesized three novel cylindrical polymer brushes(CPBs)by atom transfer radical polymerization(ATRP),which were cellulose-g-(CPT-b-OEGMA)(CCO)with different lengths(~86,~40,and~21 nm).The CPBs are composed of bio-degradable cellulose as the carrier,poly(ethylene glycol)methyl ether methacrylate(OEGMA)as hydrophily block,and glutathione(GSH)-responsive hydrophobic camptothecin(CPT)monomer as loaded anticancer drug.By controlling the chain length of the initiator,three kinds of polymeric prodrugs with different lengths(CCO-1,CCO-2,and CCO-3)could be self-organized into unimolecular micelles in water.We carried out comparative studies of three polymers,whose results verified that the shorter CPBs exhibited higher drug release efficiency,more cellular uptake,and enhanced tumor permeability,accompanied by shortened blood circulation time and lower tumor accumulation.As evidenced by in vivo experiments,the shorter CPBs exhibited higher anti-tumor efficiency,revealing that the size advantage has a higher priority than the anisotropic structure advantage.This provided vital information as to design an anisotropic polymer-based drug delivery system for cancer therapy.展开更多
A novel type of bioreducible amphiphilic multiarm hyperbranched copolymer(H40-star-PLA-SS-PEG)based on BoltornH40 core,poly(L-lactide)(PLA)inner-shell,and poly(ethylene glycol)(PEG)outer-shell with disulfide-linkages ...A novel type of bioreducible amphiphilic multiarm hyperbranched copolymer(H40-star-PLA-SS-PEG)based on BoltornH40 core,poly(L-lactide)(PLA)inner-shell,and poly(ethylene glycol)(PEG)outer-shell with disulfide-linkages between the hydrophobic and hydrophilic moieties was developed as unimolecular micelles for controlled drug release triggered by reduction.The obtained H40-star-PLA-SS-PEG was characterized in detail by nuclear magnetic resonance(NMR),Fourier transform infrared(FTIR),gel permeation chromatography(GPC),differential scanning calorimeter(DSC),and thermal gravimetric analysis(TGA).Transmission electron microscopy(TEM)and dynamic light scattering(DLS)analyses suggested that H40-star-PLA-SS-PEG formed stable unimolecular micelles in aqueous solution with an average diameter of 19 nm.Interestingly,these micelles aggregated into large particles rapidly in response to 10 mM dithiothreitol(DTT),most likely due to shedding of the hydrophilic PEG outer-shell through reductive cleavage of the disulfide bonds.As a hydrophobic anticancer model drug,doxorubicin(DOX)was encapsulated into these reductive unimolecular micelles.In vitro release studies revealed that under the reduction-stimulus,the detachment of PEG outer-shell in DOX-loaded micelles resulted in a rapid drug release.Flow cytometry and confocal laser scanning microscopy(CLSM)measurements indicated that these DOX-loaded micelles were easily internalized by living cells.Methyl tetrazolium(MTT)assay demonstrated a markedly enhanced drug efficacy of DOX-loaded H40-star-PLA-SS-PEG micelles as compared to free DOX.All of these results show that these bioreducible unimolecular micelles are promising carriers for the triggered intracellular delivery of hydrophobic anticancer drugs.展开更多
The unimolecular dissociation of HCO ground state was investigated with the time-dependent full-quantum symplectic propagation based on the newest potential energy surface of the system. Calculated energy and widths o...The unimolecular dissociation of HCO ground state was investigated with the time-dependent full-quantum symplectic propagation based on the newest potential energy surface of the system. Calculated energy and widths of HCO resonance states agree well with those in the literature. CO product distribution was systematically investigated. A simple model was presented to interpret the rovibrational distributions in HCO dissociation.展开更多
To understand the relationships between channel size and ion selectivity,we have developed a new type of artificial ion channel based on pore-forming helical polymers consisting of phenanthrolineoxadiazole units with ...To understand the relationships between channel size and ion selectivity,we have developed a new type of artificial ion channel based on pore-forming helical polymers consisting of phenanthrolineoxadiazole units with a pore aperture 2.3A close to the diameter of the Na^(+)ion(2.04A).Successful preparation of high molecular weight helical polymers(HP1)gives rise to a 4.6 nm long artificial unimolecular transmembrane channel.The transport property of artificial channel HP1 was elaborately investigated by means of vesicle-based kinetic assay and symmetry/asymmetry bilayer membrane(BLM)experiments as well.These results unambiguously demonstrate that HP1 is a Na^(+)-selective channel with extremely high transport activity(EC_(50)=0.017 mol% relative to lipid).Moreover,the Na^(+)/K^(+)selectivity ratio of HP1 reaches 1.9,as determined by asymmetry BLM experiments.Owing to the narrowest 2.3A size constraint so far,HP1 transport naked Na^(+)ion across the membrane,which represents a different Na^(+)transport mode from that of natural Na^(+)channels,which transports partially hydrated Na^(+)ions during transmembrane conduction.This study provides crucial insights on the chemical basis of ion selectivity in the field of ion channels.展开更多
The use of linear amphiphilic block copolymers as templates is an important method for the preparation of mesoporous materials.However,the obtained assemblies are usually sensitive to synthetic conditions,which impede...The use of linear amphiphilic block copolymers as templates is an important method for the preparation of mesoporous materials.However,the obtained assemblies are usually sensitive to synthetic conditions,which impedes the preparation of such mesoporous materials in certain environments.Herein,we report a universal strategy applying an amphiphilic multiarm triblock copolymer in the preparation of mesoporous metal oxide nanofibers(NFs)using one metal oxide(TiO_(2),ZrO_(2),WO_(3),CeO_(2)),or two(TiO_(2)/WO 3,TiO_(2)/ZrO_(2),TiO_(2)/CeO_(2))and three(TiO_(2)/WO_(3)/CuO)metal oxides as composites.The template consists of modified β-cyclodextrin as the center of the macromolecule which is attached sequentially to a block of polystyrene,poly(acrylic acid),and poly(ethylene oxide).Under electrospinning conditions,stable unimolecular micelles are formed and effectively co-assemble with metal ions to form fibrous nanostructures.As indicated by various characterization methods,the synthesized TiO_(2) and its derived composite NFs maintain a straight and continuous fibrous structure after calcination,and TiO_(2) NFs exhibit uniform mesopores of 10.8 nm in diameter and a large Brunauer-Emmett-Teller surface area of 143.3 m^(2)g^(−1).Benefiting from the characteristic structure,still present after modification,Pt-decorated mesoporous TiO_(2) NFs display excellent ability in the visible-light photocatalytic degradation of tetracycline,which is superior to the commercial P25 catalyst.This study reveals a promising strategy for the preparation of fibrous mesoporous metal oxides.展开更多
With the support by the National Natural Science Foundation of China and partially by the National Key Research and Development Program of China,the research team led by Prof.Zhu LiangLiang(朱亮亮)at the State Key Lab...With the support by the National Natural Science Foundation of China and partially by the National Key Research and Development Program of China,the research team led by Prof.Zhu LiangLiang(朱亮亮)at the State Key Laboratory of Molecular Engineering of Polymers,Department of Macromolecular Science,Fudan University,cooperated with the research team led by Prof.展开更多
Microcanonical rate constants k(E) and canonical rate constants k(T) for unimolecular reactions have been obtained through the calculations of cumulative reaction probabilities N(E) with the unsymmetrical Eckart poten...Microcanonical rate constants k(E) and canonical rate constants k(T) for unimolecular reactions have been obtained through the calculations of cumulative reaction probabilities N(E) with the unsymmetrical Eckart potential tunneling correction. By way of example, the reactions HCN→CNH (I) and FNC→NCF (II) have been employed. For reaction (I), the calculated rate constants are in agreement with the experimental data; for reaction (II), the results are in accordance with the rate constants kCVT/MEPSAG(T) calculated by the common program POLYRATE.展开更多
This paper reports calculations of the rate of isomerization of HCN - HCN based on the theory of Gary and Rice as extended by Zhao and Rice. The major task is to determine the effect of intramolecular energy transfer ...This paper reports calculations of the rate of isomerization of HCN - HCN based on the theory of Gary and Rice as extended by Zhao and Rice. The major task is to determine the effect of intramolecular energy transfer on the prediction of the rate of isomerization. Both the full three-dimensional (3D) system and the reduced two-dimensional (2D) system obtained from freezing CN bond at 1.159 A are analyzed to check the validity of the freezing bond approximation. Meanwhile, RRKM rates are calculated to test RRKM choice of the transition state by comparing to Gary-Rice three-state model. The comparison shows that the rates from 2D model and 3D model are differing up to 20% with 2D rates consistently larger. The intramolecular energy transfer modifies the isomerization rate for HCN system up to 30% that is modestly small by the expectation. The isomerization rate predicted from RRKM theory is greater than those of Gary-Rice three-state model theory up to 65%, and it overstimates the rates under all considerations, including the contribution from intramolecular energy transfer, for the studied system by about a factor of 2.展开更多
A new formulation of the Lindemann mechanism of unimolecular reactions in gaseous phase is presented,without the use of steady state hypothesis. It is hereby shown that the nature of applicability of steady state hypo...A new formulation of the Lindemann mechanism of unimolecular reactions in gaseous phase is presented,without the use of steady state hypothesis. It is hereby shown that the nature of applicability of steady state hypothesis in the regime of high reactant gas pressure is different from that in the regime of low gas pressure. In the former case it is an equilibrium approximation,while in the latter case it is a highly reactive intermediate approximation in no connection with a steady state. Furthermore for the latter case it is shown that in the classical formulation of Lindemann mechanism the use of steady state hypothesis is an ad hoc assumption. A highly reactive intermediate in the sense that its concentration is very small during the whole course of reaction is a necessary condition for the applicability of very reactive intermediate approximation. When the two distinctive nature of the applicability of steady state hypothesis is mixed-up,wrong or useless conclusion may be arrived at. The only possible case of realizing a true steady state in a complex reaction is pointed out.展开更多
Developing“green”catalytic systems with desirable performance such as good water solubility,recyclability,and switchability is a great challenge.Here,to address this challenge,we extend the concept of polymeric unim...Developing“green”catalytic systems with desirable performance such as good water solubility,recyclability,and switchability is a great challenge.Here,to address this challenge,we extend the concept of polymeric unimolecular micelles(a typical selfassembled structure)to the construction of a stimuli-responsive and recoverable molecular catalyst with single-metal atoms that exhibits switchable photocatalytic activity for water splitting.展开更多
The unimolecular reactions of silathione:(a)dehydrogenation,(b)trans-isomerization, (c)cis-isomerization,are investigated by ab initio MO calculations using RHF/4-31G basis set.The geometries and energies of the react...The unimolecular reactions of silathione:(a)dehydrogenation,(b)trans-isomerization, (c)cis-isomerization,are investigated by ab initio MO calculations using RHF/4-31G basis set.The geometries and energies of the reactant,transition states and products have been determined on the singlet potential energy surface of the ground state.The reaction ergodography along the intrinsic reaction coordinate(IRC)for the three reactions has also been performed.展开更多
The unimolccular reactions of ammonia oxide H_3NO,isomerization and dehydrogenation, are investigated by ab initio MO calculations with the 4-31G basis set.The geometries and energies of the reactant,transition states...The unimolccular reactions of ammonia oxide H_3NO,isomerization and dehydrogenation, are investigated by ab initio MO calculations with the 4-31G basis set.The geometries and energies of the reactant,transition states and products have been determined on the singlet potential energy sur- face.The reaction ergodography along the intrinsic reaction coordinate(IRC)for the two reactions have been performed.The vibrational frequency correlation diagram of the two reactions are analyzed along the IRC.展开更多
Auranofin(AF)is the most used gold(I)-containing drug,whose mechanism of action involves targeting sulfur and selenium-containing amino acids,including cysteine(Cys)and selenocysteine(Sec).These residues are present i...Auranofin(AF)is the most used gold(I)-containing drug,whose mechanism of action involves targeting sulfur and selenium-containing amino acids,including cysteine(Cys)and selenocysteine(Sec).These residues are present in the active sites of crucial proteins including thioredoxin reductase.Despite extensive exploration of AF-protein interactions over the years,experimental data at the molecular level are still limited.In this work,we studied the vibrational and structural features of solvent-free complexes obtained by the reaction of AF with Cys and Sec,[(Et_(3)P)AuCys]^(+) and[(Et_(3)P)AuSec]^(+) ions,respectively.Using tandem mass spectrometry and IR ion spectroscopy supported by density functional theory(DFT)calculations,we unveiled markedly different behaviors for the Cys and Sec bound complexes.In particular,our results indicate that,whereas the[(Et_(3)P)AuSec]^(+) ions are mainly Se-bound,in agreement with the well-known affinity of Se for gold(I),the sampled[(Et_(3)P)AuCys]^(+) ionic population is composed of both N-and S-bound isomers,with their ratio depending on the dielectric constant of the solvent used in the starting solution.Additionally,we found that the deamination process occurring in the gas-phase during collision-induced dissociation experiments significantly differ between the two complexes.This work's findings contribute to a deeper understanding of AF's reactivity with Cys and Sec-containing protein targets and highlight how the chemical environment may influence target selectivity of gold-containing drugs,which is crucial for their pharmacological activities.展开更多
基金supported by the National Natural Science Foundation of China(82373811,82574333,82504683)Natural Science Foundation of Guangdong Province(2024A1515012132).
文摘Integrating photodynamic therapy(PDT)with immunosuppression reversal represents a promising synergistic approach to boost cancer immunotherapy.However,the complicated components and cumbersome preparation procedures of the currently developed nano drug delivery systems heavily hinder their further clinical translation.Herein,a reactive oxygen species(ROS)/photo dual-responsive amphipathic prodrug(denoted as PPTN)was designed and synthesized by linking NLG919,an indoleamine-2,3-dioxygenase(IDO)inhibitor,with the photosensitizer protoporphyrin IX(PpIX)by a thioketal moiety,and further modifying with mPEG2k.PPTN could self-assemble into nanoscale unimolecular micelles in aqueous solution without additional excipients,increasing tumor accumulation while effectively addressing the pronounced hydrophobicity challenge of PpIX.Upon light exposure,PPTN generated ROS,not only directly damaging cancer cells,but also trigger the breakage of thioketal bond to accelerate simultaneous release of NLG919.Therefore,PPTN potentially act as a promising ROS/photo dual-responsive carrier-free prodrug delivery system for controllable drug release and specific tumor therapy.Moreover,PPTN induced simultaneous PDT-triggered immunogenic cell death(ICD)effect and specific IDO blockade to boost immune response,exhibiting potent suppression efficacy against primary and distant tumors.Overall,with the superiorities of easily controllable preparation procedures,synchronous drug delivery and ROS/photo dual-responsiveness,such a prodrug unimolecular micelle may represent a promising nanoplatform for photoactivated-immunotherapy.
基金financially supported by the National Natural Science Foundation of China(Nos.U23A20591,82472144,52273158,52273159,and W2421115)the Science and Technology Department Project of Jilin Province(No.20220204018YY)+3 种基金the Industrial Technology Research and Development Project of Jilin Province(No.2023C040-8)the Health Research Talent Special Project of Jilin Province(Nos.2023SCZ70 and 2024SCZ46)the Youth Innovation Promotion Association of Chinese Academy of Sciences(No.Y2023066)the Bethune Project of Jilin University(No.2023B01)。
文摘Chirality is pervasive and plays a crucial role in biological processes.Although amino acids possess inherent chirality,the stereochemical influence of this property on the regulation of immune cells remains insufficiently explored.To address this,the unimolecular chiral poly(amino acid)s were synthesized to evaluate their immunostimulatory effects and anti-cancer potential.Among the candidates,G0-P_(D)-Lys_(50)emerged as the most effective adjuvant through in vitro screening.When complexed with antigen ovalbumin(OVA)to form chiral nanovaccines,G0-P_(L)-Lys_(50)-OVA and G0-P_(D)-Lys_(50)-OVA exhibited similar morphology,particle size,and zeta potential.Despite these comparable physicochemical properties,G0-P_(D)Lys_(50)-OVA induced significantly stronger activation of dendritic cells(DCs).Specifically,it resulted in 1.38-and 1.34-fold increases in CD11c^(+)CD80^(+)DCs and CD11c^(+)SIINFEKL-H-2Kb^(+)DCs in lymph nodes,respectively.In the LLC-OVA cancer model,G0-P_(D)-Lys_(50)-OVA reduced tumor volume by 50%compared to its enantiomer.These results establish a unique approach to designing chiral nanovaccines and provide a foundational strategy for developing broadly applicable immunotherapies.
文摘The low energy collisioninduced dissociation, linked scan techniques and isotopic labeling experiment were used to investigate the unimolecular fragmentation of protonated N-hydroxyphthalimide under electron impact and chemical ionization conditions. It was found that this compound shows an unusual reactivity towards protonation. Two possible sites of protonation have been proposed to explain the corresponding fragmentation processes, one is that the protonation takes place on the oxygen atom of hydroxyl group, resulting in the loss of water and the other is the formation of an intermediary protonbound complex in the fragmentation process, giving rise to the fragment ions of m/z 133 and m/z 135. The results show both cases are coexistence in the fragmentations of protonated N-hydroxyphthalimide, and the unimolecular fragmentation pathways are available.
文摘Quantum mechanical and Rice-Ramsperger-Kassel-Marcus （RRKM） calculations are carried out to study the thermal unimolecular decomposition of 2,5-dihydrofuran （1）,2,5dihydrothiophene （2）,and 3-pyrroline （3） at the MPW1PW91/6-31＋＋G level of theory,and the results are in good agreement with the experimental values.The predicted high pressure limit rate constants （k（T）） in various states of activation energy and pre-exponential （S1：（A（calc.）,E a（calc.））,S2：（A （calc.）,E a（exp.））,and S3：（A （exp.）,E a（calc.））） for the thermal decomposition processes 1-3 were evaluated.Also,the fall-off pressures （P1/2） for compounds 1-3 in the states 1-3 are found to be （1.24×10-2,1.09×10-3,and 4.19×10-2mmHg）,（1.24×10-2,1.63×10-3,and 2.79×10-2mmHg）,and （1.24×10-2,1.63×10-3,and 4.19×10-2 mmHg）,respectively.As the fall-off pressure of thermal decomposition process of compounds 1-3 is in the following order：P1/2（3）〉 P1/2（1）〉 P1/2 （2）,the decomposition rates are as below：rate（3） 〈rate（1）〈rate（2）.
文摘（2-acrylamido） ethyl tetradecyl dimethylammonium bromide （AMC14AB） was polymerized in aqueous solu- tion to form the homopolymer P（AMC14AB）. The physicochemical properties of P（AMC14AB） in aqueous solution were mainly studied with fluorescent probe method, surface tension measurement and conductom- etry. The experimental results show that the aggregation morphology of P（AMC14AB） in aqueous solution is unimolecular micelle as expected. Being different from conventional multimolecular micelle systems, the unimolecular micelle system of P（AMC14AB） not only shows critical micellar concentration （CMC=0）, （i.e. once added to pure water, the surface tension decreases immediately in spite how small the density is）, but also the surface tension stays almost the same with the concentration increasing. That is to say, there is no mutational point on the relationship curve between surface tension and concentration. Furthermore, the unimolecular micelle system of P（AMC14AB） has no Krafft temperature, i.e. at any temperature, so long as it is dissolved in water, the unimolecular micelles will form. Besides this, for the solubilization of hydrophobic organic substances, the unimolecular micelle system of P（AMC14AB） is obviously different from the common multimolecular micelle system, having no turning point on the relationship curve between toluene solubi- lizaion amount and P（AMC14AB） concentration, and the solubilizing ability of the unimolecular-micelle system of P（AMC14AB） for hydrophobic organic substances is much higher than that of the conventional multimolecular micelle solutions of common surfactants, such as centyl trimethyl ammonium bromide.
文摘The unimolecular dissociation of methylformate free radical cation(CH_3OCHO^+) was studied by ab initio theoretical calculations, Molecular orbital and state correlation diagrams have been examined in the ground and lower excited states. The dissociation mechanism has been explained along the reaction paths. For two possible dissociation pathways in the ground and lower excited states, the activation barriers and reaction heats have been calculated by MCSCF method respectively.
基金This work was financially supported by National Natural Science Foundation of China(51703187,31671037)the Basic and Frontier Research Project of Chongqing(cstc2018jcyjAX0104).
文摘Polymer systems can be designed into different structures and morphologies according to their physical and chemical performance requirements,and are considered as one of the most promising controlled delivery systems that can effectively improve the cancer therapeutic index.However,the majority of the polymer delivery systems are designed to be simple spherical nanostructures.To explore morphology/size-oriented delivery performance optimization,here,we synthesized three novel cylindrical polymer brushes(CPBs)by atom transfer radical polymerization(ATRP),which were cellulose-g-(CPT-b-OEGMA)(CCO)with different lengths(~86,~40,and~21 nm).The CPBs are composed of bio-degradable cellulose as the carrier,poly(ethylene glycol)methyl ether methacrylate(OEGMA)as hydrophily block,and glutathione(GSH)-responsive hydrophobic camptothecin(CPT)monomer as loaded anticancer drug.By controlling the chain length of the initiator,three kinds of polymeric prodrugs with different lengths(CCO-1,CCO-2,and CCO-3)could be self-organized into unimolecular micelles in water.We carried out comparative studies of three polymers,whose results verified that the shorter CPBs exhibited higher drug release efficiency,more cellular uptake,and enhanced tumor permeability,accompanied by shortened blood circulation time and lower tumor accumulation.As evidenced by in vivo experiments,the shorter CPBs exhibited higher anti-tumor efficiency,revealing that the size advantage has a higher priority than the anisotropic structure advantage.This provided vital information as to design an anisotropic polymer-based drug delivery system for cancer therapy.
基金sponsored by the National Natural Science Foundation of China(21025417,20974062,50773037&50633010)National Basic Research Program 2007CB808000+2 种基金the Fok Ying Tung Education Foundation(111048)Shuguang Program(08SG14)Shanghai Leading Academic Discipline Project(Project Number:B202)
文摘A novel type of bioreducible amphiphilic multiarm hyperbranched copolymer(H40-star-PLA-SS-PEG)based on BoltornH40 core,poly(L-lactide)(PLA)inner-shell,and poly(ethylene glycol)(PEG)outer-shell with disulfide-linkages between the hydrophobic and hydrophilic moieties was developed as unimolecular micelles for controlled drug release triggered by reduction.The obtained H40-star-PLA-SS-PEG was characterized in detail by nuclear magnetic resonance(NMR),Fourier transform infrared(FTIR),gel permeation chromatography(GPC),differential scanning calorimeter(DSC),and thermal gravimetric analysis(TGA).Transmission electron microscopy(TEM)and dynamic light scattering(DLS)analyses suggested that H40-star-PLA-SS-PEG formed stable unimolecular micelles in aqueous solution with an average diameter of 19 nm.Interestingly,these micelles aggregated into large particles rapidly in response to 10 mM dithiothreitol(DTT),most likely due to shedding of the hydrophilic PEG outer-shell through reductive cleavage of the disulfide bonds.As a hydrophobic anticancer model drug,doxorubicin(DOX)was encapsulated into these reductive unimolecular micelles.In vitro release studies revealed that under the reduction-stimulus,the detachment of PEG outer-shell in DOX-loaded micelles resulted in a rapid drug release.Flow cytometry and confocal laser scanning microscopy(CLSM)measurements indicated that these DOX-loaded micelles were easily internalized by living cells.Methyl tetrazolium(MTT)assay demonstrated a markedly enhanced drug efficacy of DOX-loaded H40-star-PLA-SS-PEG micelles as compared to free DOX.All of these results show that these bioreducible unimolecular micelles are promising carriers for the triggered intracellular delivery of hydrophobic anticancer drugs.
文摘The unimolecular dissociation of HCO ground state was investigated with the time-dependent full-quantum symplectic propagation based on the newest potential energy surface of the system. Calculated energy and widths of HCO resonance states agree well with those in the literature. CO product distribution was systematically investigated. A simple model was presented to interpret the rovibrational distributions in HCO dissociation.
基金supported by the National Science Foundation of China(nos.22071078 and 21722403)the Program for JLU Science and Technology Innovative Research Team(JLUSTIRT)(no.2019TD-36).
文摘To understand the relationships between channel size and ion selectivity,we have developed a new type of artificial ion channel based on pore-forming helical polymers consisting of phenanthrolineoxadiazole units with a pore aperture 2.3A close to the diameter of the Na^(+)ion(2.04A).Successful preparation of high molecular weight helical polymers(HP1)gives rise to a 4.6 nm long artificial unimolecular transmembrane channel.The transport property of artificial channel HP1 was elaborately investigated by means of vesicle-based kinetic assay and symmetry/asymmetry bilayer membrane(BLM)experiments as well.These results unambiguously demonstrate that HP1 is a Na^(+)-selective channel with extremely high transport activity(EC_(50)=0.017 mol% relative to lipid).Moreover,the Na^(+)/K^(+)selectivity ratio of HP1 reaches 1.9,as determined by asymmetry BLM experiments.Owing to the narrowest 2.3A size constraint so far,HP1 transport naked Na^(+)ion across the membrane,which represents a different Na^(+)transport mode from that of natural Na^(+)channels,which transports partially hydrated Na^(+)ions during transmembrane conduction.This study provides crucial insights on the chemical basis of ion selectivity in the field of ion channels.
基金funded by the National Natural Science Foundation of China(Grants No.51822202,52173233 and 51772050)Innovation Program of Shanghai Municipal Education Commission(Grant No.2021-01-07-00-03-E00109)+8 种基金Science and Technology Commission of Shanghai Municipality(Grant No.19520713200)Shanghai Scientific and Technological Innovation Project(Grant No.19JC1410400)“Shuguang Program”supported by Shanghai Education Development Foundation and Shanghai Municipal Education Commission(Grant No.20SG33)Key Basic Research Program of Science and Technology Com-mission of Shanghai Municipality(Grant No.20JC1415300)DHU Distinguished Young Professor Program and Fundamental Research Funds for the Central Universitiesthe Fundamental Research Funds for the Central Universities(Grant No.2232020D-02)Shanghai Sailing program(Grant No.20YF1400500)Shanghai Natural Science Foundation(Grant No.20ZR1401500)the Opening Project of Key Laboratory of Inorganic Functional Materials and Devices,Chinese Academy of Sciences(KLIFMD202104).
文摘The use of linear amphiphilic block copolymers as templates is an important method for the preparation of mesoporous materials.However,the obtained assemblies are usually sensitive to synthetic conditions,which impedes the preparation of such mesoporous materials in certain environments.Herein,we report a universal strategy applying an amphiphilic multiarm triblock copolymer in the preparation of mesoporous metal oxide nanofibers(NFs)using one metal oxide(TiO_(2),ZrO_(2),WO_(3),CeO_(2)),or two(TiO_(2)/WO 3,TiO_(2)/ZrO_(2),TiO_(2)/CeO_(2))and three(TiO_(2)/WO_(3)/CuO)metal oxides as composites.The template consists of modified β-cyclodextrin as the center of the macromolecule which is attached sequentially to a block of polystyrene,poly(acrylic acid),and poly(ethylene oxide).Under electrospinning conditions,stable unimolecular micelles are formed and effectively co-assemble with metal ions to form fibrous nanostructures.As indicated by various characterization methods,the synthesized TiO_(2) and its derived composite NFs maintain a straight and continuous fibrous structure after calcination,and TiO_(2) NFs exhibit uniform mesopores of 10.8 nm in diameter and a large Brunauer-Emmett-Teller surface area of 143.3 m^(2)g^(−1).Benefiting from the characteristic structure,still present after modification,Pt-decorated mesoporous TiO_(2) NFs display excellent ability in the visible-light photocatalytic degradation of tetracycline,which is superior to the commercial P25 catalyst.This study reveals a promising strategy for the preparation of fibrous mesoporous metal oxides.
文摘With the support by the National Natural Science Foundation of China and partially by the National Key Research and Development Program of China,the research team led by Prof.Zhu LiangLiang(朱亮亮)at the State Key Laboratory of Molecular Engineering of Polymers,Department of Macromolecular Science,Fudan University,cooperated with the research team led by Prof.
基金Project supported by the National Natural Science Foundation of China
文摘Microcanonical rate constants k(E) and canonical rate constants k(T) for unimolecular reactions have been obtained through the calculations of cumulative reaction probabilities N(E) with the unsymmetrical Eckart potential tunneling correction. By way of example, the reactions HCN→CNH (I) and FNC→NCF (II) have been employed. For reaction (I), the calculated rate constants are in agreement with the experimental data; for reaction (II), the results are in accordance with the rate constants kCVT/MEPSAG(T) calculated by the common program POLYRATE.
文摘This paper reports calculations of the rate of isomerization of HCN - HCN based on the theory of Gary and Rice as extended by Zhao and Rice. The major task is to determine the effect of intramolecular energy transfer on the prediction of the rate of isomerization. Both the full three-dimensional (3D) system and the reduced two-dimensional (2D) system obtained from freezing CN bond at 1.159 A are analyzed to check the validity of the freezing bond approximation. Meanwhile, RRKM rates are calculated to test RRKM choice of the transition state by comparing to Gary-Rice three-state model. The comparison shows that the rates from 2D model and 3D model are differing up to 20% with 2D rates consistently larger. The intramolecular energy transfer modifies the isomerization rate for HCN system up to 30% that is modestly small by the expectation. The isomerization rate predicted from RRKM theory is greater than those of Gary-Rice three-state model theory up to 65%, and it overstimates the rates under all considerations, including the contribution from intramolecular energy transfer, for the studied system by about a factor of 2.
文摘A new formulation of the Lindemann mechanism of unimolecular reactions in gaseous phase is presented,without the use of steady state hypothesis. It is hereby shown that the nature of applicability of steady state hypothesis in the regime of high reactant gas pressure is different from that in the regime of low gas pressure. In the former case it is an equilibrium approximation,while in the latter case it is a highly reactive intermediate approximation in no connection with a steady state. Furthermore for the latter case it is shown that in the classical formulation of Lindemann mechanism the use of steady state hypothesis is an ad hoc assumption. A highly reactive intermediate in the sense that its concentration is very small during the whole course of reaction is a necessary condition for the applicability of very reactive intermediate approximation. When the two distinctive nature of the applicability of steady state hypothesis is mixed-up,wrong or useless conclusion may be arrived at. The only possible case of realizing a true steady state in a complex reaction is pointed out.
基金supported by the National Natural Science Foundation of China(21774076,21890730,21890733,and 51773115)the Program for Basic Research of Shanghai Science and Technology Commission(17JC1403200,19JC1410400,and 19JC1410404)+1 种基金the Program of Shanghai Academic Research Leader(19XD1421700)the Shanghai Eastern Scholar Program.The authors appreciate Shanghai Synchrotron Radiation Facility(SSRF)(Beamline BL14W1 and BL11B)for the synchrotron beam time.
文摘Developing“green”catalytic systems with desirable performance such as good water solubility,recyclability,and switchability is a great challenge.Here,to address this challenge,we extend the concept of polymeric unimolecular micelles(a typical selfassembled structure)to the construction of a stimuli-responsive and recoverable molecular catalyst with single-metal atoms that exhibits switchable photocatalytic activity for water splitting.
基金This work was supported by the National Natural Science Foundation of China.
文摘The unimolecular reactions of silathione:(a)dehydrogenation,(b)trans-isomerization, (c)cis-isomerization,are investigated by ab initio MO calculations using RHF/4-31G basis set.The geometries and energies of the reactant,transition states and products have been determined on the singlet potential energy surface of the ground state.The reaction ergodography along the intrinsic reaction coordinate(IRC)for the three reactions has also been performed.
基金This work was supported by the National Natural Science Foundation of China.
文摘The unimolccular reactions of ammonia oxide H_3NO,isomerization and dehydrogenation, are investigated by ab initio MO calculations with the 4-31G basis set.The geometries and energies of the reactant,transition states and products have been determined on the singlet potential energy sur- face.The reaction ergodography along the intrinsic reaction coordinate(IRC)for the two reactions have been performed.The vibrational frequency correlation diagram of the two reactions are analyzed along the IRC.
基金funded by Sapienza Universitàdi RomaProgetti medi di Ateneo 2023,grant number RM123188F7509A0Bfrom LASERLAB-EUROPE(grant agreement No.871124,European Union’s Horizon 2020 research and innovation programme)+2 种基金the Nederlandse Organisatie voor Wetenschappelijk Onderzoek(NWO)for the support of the FELIX Laboratorythe CINECA award,under the ISCRA initiative,for the availability of high-performance computing resources and support(project IsCb5_G4MeFMO)support funded by the European Union NextGenerationEU,under the National Recovery and Resilience Plan(NRRP),Mission 4 Component 2 M4C2,Investment 1.5 Call for tender No.3277 of 30.12.2021,Italian Ministry of University,Award Number:ECS00000041,Project Title:“Innovation,digitalization and sustainability for the diffused economy in Central Italy”,Concession Degree No.1057 of 23.06.2022 adopted by the Italian Ministry of University.CUP:D73C22000840006.
文摘Auranofin(AF)is the most used gold(I)-containing drug,whose mechanism of action involves targeting sulfur and selenium-containing amino acids,including cysteine(Cys)and selenocysteine(Sec).These residues are present in the active sites of crucial proteins including thioredoxin reductase.Despite extensive exploration of AF-protein interactions over the years,experimental data at the molecular level are still limited.In this work,we studied the vibrational and structural features of solvent-free complexes obtained by the reaction of AF with Cys and Sec,[(Et_(3)P)AuCys]^(+) and[(Et_(3)P)AuSec]^(+) ions,respectively.Using tandem mass spectrometry and IR ion spectroscopy supported by density functional theory(DFT)calculations,we unveiled markedly different behaviors for the Cys and Sec bound complexes.In particular,our results indicate that,whereas the[(Et_(3)P)AuSec]^(+) ions are mainly Se-bound,in agreement with the well-known affinity of Se for gold(I),the sampled[(Et_(3)P)AuCys]^(+) ionic population is composed of both N-and S-bound isomers,with their ratio depending on the dielectric constant of the solvent used in the starting solution.Additionally,we found that the deamination process occurring in the gas-phase during collision-induced dissociation experiments significantly differ between the two complexes.This work's findings contribute to a deeper understanding of AF's reactivity with Cys and Sec-containing protein targets and highlight how the chemical environment may influence target selectivity of gold-containing drugs,which is crucial for their pharmacological activities.
