Nitrogen-containing heterocyclic compounds are fundamental biochemical components of all life on Earth and,presumably,life elsewhere in our solar system.Detection and characterization of these compounds by traditional...Nitrogen-containing heterocyclic compounds are fundamental biochemical components of all life on Earth and,presumably,life elsewhere in our solar system.Detection and characterization of these compounds by traditional solvent extraction,chromatographic separation,and GC-MS analysis require more sample mass than will be available from samples returned to Earth from Mars.With its small sample mass requirement,Surface Enhanced Raman Spectroscopy could be an appropriate technique for analysis of returned samples.We have developed a SERS method for the detection of maleimide(2,5-pyrroledione),an N-containing heterocycle with a structure that is widespread in biochemicals.This semi-quantitative methodology accurately determines maleimide concentration in the range from 60 mg/mL to 120 mg/mL.We present a maleimide SERS standard spectrum which will be useful as a reference for future works.The present work demonstrates an easy,accurate,and effective method for the non-destructive qualitative and semi-quantitative study of maleimide as a first step toward developing a method for analysis of related compounds.展开更多
The oil-in-water microemulsion containing N-butyl maleimide(NBMI. M_1) and styrene(St, M_2) was prepared. The complexation properties of NBMI and St in microemulsion were investigated by means of 1H-NMR. With the part...The oil-in-water microemulsion containing N-butyl maleimide(NBMI. M_1) and styrene(St, M_2) was prepared. The complexation properties of NBMI and St in microemulsion were investigated by means of 1H-NMR. With the participation of charge-transfer complex(CTC). four reactivity ratios and the relative reactivity of free monomers and CTC were obtained. The result was compared with that measured by Mayo-Lewis method.展开更多
The authors have studied the Diels-Alder reactions between furan derivatives and maleimide derivatives in an ionic liquid and have found that higher reactivity can be obtained in a protic ionic liquid [Mim]Tf2N than i...The authors have studied the Diels-Alder reactions between furan derivatives and maleimide derivatives in an ionic liquid and have found that higher reactivity can be obtained in a protic ionic liquid [Mim]Tf2N than in the conventional organic solvent. Furthermore, in the Diels-Alder reactions of 2- and 2,5-alkylfurans with N-alkylma- leimide, the reactivity increases by extending the alkyl chain length of N-alkylmaleimide. In addition, it was demon- strated that endo-selectivity increases when 2,5-disubstituted furans are used. These results will be explained by comparing the stability of the Diels-Alder adduct with that of the products obtained from the reactions of 2-substituted furans and 2,5-disubstituted furans.展开更多
The self-condensing vinyl polymerization(SCVP) of a novel maleimide inimer(initiator-monomer) 1, N-(4-α-bromobutyryloxy phenyl) maleimide with the complex of CuBr/Bipy(2, 2′-bipyridine) as the catalyst was studied. ...The self-condensing vinyl polymerization(SCVP) of a novel maleimide inimer(initiator-monomer) 1, N-(4-α-bromobutyryloxy phenyl) maleimide with the complex of CuBr/Bipy(2, 2′-bipyridine) as the catalyst was studied. GPC was used to determine the molecular weight and the results show that the molecular weight increases exponentially with polymerization time during the first hour, and then the rate of increase molecular weight slows down. The molecular weight also increases with increasing dosage of the catalyst. The coincidence of the molecular weights determined by 1H NMR and GPC proves that the polymer obtained from the SCVP of inimer 1 has a linear structure, which is further verified by 13C NMR spectrum. A hyperbranched polymer was obtained by the copolymerization of inimer 1 and styrene.展开更多
The methylated β-cyclodextrins derived optically active polymers are firs synthesized through asymmetric polymerization of N-diphenylmethyl maleimide with lithium salt of heptakis(2,6-O-dimethyl) β-cyclodextrin (DM-...The methylated β-cyclodextrins derived optically active polymers are firs synthesized through asymmetric polymerization of N-diphenylmethyl maleimide with lithium salt of heptakis(2,6-O-dimethyl) β-cyclodextrin (DM-β-CD) as an initiator. The resulting polymers show negative specific rotation which is opposite in sign to that of DM-β-CD. The asymmetric induction is further confirmed by circular dichroism. The structure is characterized by IR and NMR spectroscopies展开更多
The copolymer of N-4-dibenzoylmethane maleimide (p-DBMI) with styrene (St) was prepared and characterized by gel permeation chromatography, thermal analysis and spectroscopy.
Pyrrolidine-2,5-dione and maleimide are important scaffolds of many organic substances, and their derivatives are now attracting more and more interests from researchers in organic synthesis, medicinal chemistry, and ...Pyrrolidine-2,5-dione and maleimide are important scaffolds of many organic substances, and their derivatives are now attracting more and more interests from researchers in organic synthesis, medicinal chemistry, and drug development. Tosyloxy (-OTs) group is an important functional group widely used in organic synthesis, because it can be readily prepared from alcohols and is an excellent leaving group. However, surprisingly, substances bearing tosyloxy groups on pyrrolidine-2,5-dione or maleimide scaffolds are very rare. In this study, we discovered that, when treated with TsCl/Et3N,?trans-3,4-dihydroxypyrrolidine-2,5- dione will eliminate a TsOH molecule to form monotosyloxymaleimide. Thermodynamic and kinetic factors affecting this reaction were investigated by theoretical computation using density functional theory (DFT), and the possible reaction mechanism was proposed based on the computation results. Our results showed that tosylates of trans -3,4-dihydroxypyrrolidine- 2,5-dione, either monotosylate or ditosylate, are thermodynamically instable and may spontaneously convert to maleimides. This knowledge could be useful in understanding the properties of pyrrolidine-2,5-diones and maleimides, as well as the related organic synthesis.展开更多
A commercial albumin-bound paclitaxel nano-formulation has been considered a gold standard against breast cancer.However,its application still restricted unfavorable pharmacokinetics and the immunogenicity of exogenou...A commercial albumin-bound paclitaxel nano-formulation has been considered a gold standard against breast cancer.However,its application still restricted unfavorable pharmacokinetics and the immunogenicity of exogenous albumin carrier.Herein,we report an albumin-bound tumor redoxresponsive paclitaxel prodrugs nano-delivery strategy.Using diverse linkages(thioether bond and disulfide bond),paclitaxel(PTX)was conjugated with an albumin-binding maleimide(MAL)functional group.These pure PTX prodrugs could self-assemble to form uniform and spherical nanoparticles(NPs)in aqueous solution without any excipients.By immediately binding to blood circulating albumin after intravenous administration,NPs are rapidly disintegrated into small prodrug/albumin nanoaggregates in vivo,facilitating PTX prodrugs accumulation in the tumor region via albumin receptormediated active targeting.The tumor redox dual-responsive drug release property of prodrugs improves the selectivity of cytotoxicity between normal and cancer cells.Moreover,disulfide bond-containing prodrug/albumin nanoaggregates exhibit long circulation time and superior antitumor efficacy in vivo.This simple and facile strategy integrates the biomimetic characteristic of albumin,tumor redox-responsive on-demand drug release,and provides new opportunities for the development of the high-efficiency antitumor nanomedicines.展开更多
Thermo-responsive butyl acrylate/furfuryl methacrylate copolymer-based (PBF backbone) graft (co)polymers with dynamic covalent linkages between their backbones and side chains via the Diels-Alder reaction of furar...Thermo-responsive butyl acrylate/furfuryl methacrylate copolymer-based (PBF backbone) graft (co)polymers with dynamic covalent linkages between their backbones and side chains via the Diels-Alder reaction of furardmaleimide were synthesized. Atom transfer radical polymerization (ATRP) was used to synthesize graft copolymers with thermo-responsive transformation from graft copolymers to linear polymers with bimodal or wide MWD. The NMR measurements indicated that the Diels-Alder reaction and retro- Diels-Alder reaction occurred, depending on the change of the temperature, meaning that the side chains could be cleaved and reformed according to the variation of the temperature. GPC measurements demonstrated that the molecular weights of the polymers were thermo- responsive. Furthermore, three graft copolymers with various branching chains (PBF-g-PBA, PBF-g-P(BMA-co-MA) and PBF-g-PBMA) were compared to study the influence of compatibility between the backbone and the branching chain on the efficiency of Diels-Alder reaction after the cleavage of the DA linkage. The results showed that the ability of the side chains to come back to the main chain was strongly affected by the compatibility between the backbone and the side chains and the flexibility of the polymer chains.展开更多
Three basic conditions for preparation of alternating copolymer with narrow molecular weight distribution were derived from the element kinetic equations of binary radical copolymerization. Using maleimide (MI) and ...Three basic conditions for preparation of alternating copolymer with narrow molecular weight distribution were derived from the element kinetic equations of binary radical copolymerization. Using maleimide (MI) and atropie acid (ATA) as model monomer pairs and dioxane as the solvent the alternating copolymer with molecular weight distribution in the range of 1.09--1.20 was prepared successfully by charger transfer complex (CTC) mechanism in the presence of benzoyl peroxide at 85℃. The monomer reactivity ratioes r<sub>1</sub>(MI)=0.05±0.01 and r<sub>2</sub>(ATA)=0.03±0.02 were measured. The alternating eopolymerization was carried out through formation of a contact-type CTG and then alternating addition of MI and ATA monomers. The molecular weight of the copolymers is nearly independent of the feed ratio in a large range and the polymerization rate dropped with an increase in ATA in feed ratio.展开更多
This study focuses on the synthesis of new liquid aromatic bismaleimide monomers in order to improve self-curing on demand(SCOD)systems previously based on aliphatic bismaleimides.These SCOD systems are based on Diels...This study focuses on the synthesis of new liquid aromatic bismaleimide monomers in order to improve self-curing on demand(SCOD)systems previously based on aliphatic bismaleimides.These SCOD systems are based on Diels-Alder(DA)/retro-DA reactions.The syntheses of new different aromatic bismaleimides with ester and amide bonds are presented.These maleimides have been protected using DA reaction and characterized by 1H NMR analysis to determine protection rate and diastereomer ratios.The retro-DA reactions of both aromatic and aliphatic DA adducts in presence of thiol molecules were studied.Kinetic analysis was monitored by 1H NMR and compared to model study.Finally,both aromatic and aliphatic bismaleimides-based polymers were synthesized with 2-mercaptoethyl ether and thermal properties of polymers were compared.The glass transition temperature values ranged from–20°C to 14°C and very good thermal stabilities were observed(up to 300°C).展开更多
Herein is presented a compilation of the main characteristics of maleimide chemistry in developing the precisely controlled polymers,including the design of sequence-controlled polymers,topological polymers,and polyme...Herein is presented a compilation of the main characteristics of maleimide chemistry in developing the precisely controlled polymers,including the design of sequence-controlled polymers,topological polymers,and polymeric single-chain nanoparticles.The synthetic methods,relied on the versatilities of the maleimide moieties as a latent monomer which leads to an efficient alternative in various innovative applications,especially in self-healing material,self-reporting materials for real-time monitoring,and also in data storage and anticounterfeiting technologies.The core of the content in this review is focused on the up-to-data advances and publications on the major of maleimide chemistry in our research group.展开更多
A new optically active polymer, (+)poly(N_diphenylmethyl maleimide), was coated on macroporous silica gel and used as a chiral stationary phase for high performance liquid chromatographic resolution of enantiomers. Th...A new optically active polymer, (+)poly(N_diphenylmethyl maleimide), was coated on macroporous silica gel and used as a chiral stationary phase for high performance liquid chromatographic resolution of enantiomers. The chiral polymer showed efficient resolution ability to some polar racemates, and eleven pairs of racemates are resolved effectively.展开更多
The geometric structures,electronic absorption spectrum,and thermodynamic pro-perties of 3-(4-N-maleimido)-phenyl-2,4-dihydro-2H-1,3-benzoxazine molecule were studied at the B3LYP/6-311+G* level by density functio...The geometric structures,electronic absorption spectrum,and thermodynamic pro-perties of 3-(4-N-maleimido)-phenyl-2,4-dihydro-2H-1,3-benzoxazine molecule were studied at the B3LYP/6-311+G* level by density functional theory.The results show that three rings of this molecule are in different planes.In gas,absorption wavelength of the lowest energy excitation was obtained at 503 nm,and solvents made it blue-shifted by 3-7 nm,both corresponding to the electron transition of HOMO → LUMO.At 298.15 K,the standard molar formed enthalpy and free energy of the title compound molecule were-549.43 and-273.37 kJ·mol-1,respectively.展开更多
Localized prostate cancer is curable via annihilation of the entire cancer neighborhood by surgery or local radiation.Unfortunately,once metastatic,no available therapy is curative.The vast majority will die despite a...Localized prostate cancer is curable via annihilation of the entire cancer neighborhood by surgery or local radiation.Unfortunately,once metastatic,no available therapy is curative.The vast majority will die despite aggressive systemic combinational androgenablation therapies.Thus,there is an urgent need for effective systemic therapeutics that sterilize the entire microenvironment in metastatic castration-resistant prostate cancer(mCRPC).To accomplish this goal,advantage can be taken of the unique biology of mCRPC cells.Like their normal cell of origin,mCRPCs retain expression of the prostate-specific differentiation protein,prostate-specific antigen(PSA),which they abundantly secrete into their extracellular fluid(ECF).This unique,and essentially universal,secretion of enzymatically active PSA into the ECF by mCRPCs creates an exploitable therapeutic index for activation of systemically delivered highly lipophilic toxins as“molecular grenades”covalently linked to cysteine-34 of human serum albumin(HSA)via a stable maleimide containing PSA cleavable peptide such that PSA-dependent hydrolysis(i.e.,“detonation”)releases the grenades restrictively within the ECF of mCRPC.This approach decreases dose-limiting host toxicity while enhancing plasma half-life from minutes to days(i.e.,pharmacokinetic effect)and increasing the tissue concentration of the maleimide coupled albumin delivery(MAD)in the ECF at sites of cancer due to the enhanced permeability of albumin at these sites(i.e.,enhanced permeability and retention effect).This allows the MAD-PSA detonated grenades to circulate throughout the body in a non-toxic form.Only within sites of mCRPC is there a sufficiently high level of enzymatically active PSA to efficiently“pull the pin”on the grenades releasing their lipophilic cellpenetrant toxins from HSA.Thus,if a sufficient level of“detonation”occurs,this will kill mCRPC cells,and sterilize the entire PSA-rich metastatic sites via a bystander effect.In this review,two examples of such MAD-PSA detonated molecular grenades are presenteddone based upon thapsigagin and the other on niclosamide.展开更多
A couple of novel sulfobetaine copolymer is developed via Michael-type addition reaction. The comonomers, diamines and maleimide react via Michael reaction through UV irradiation using AIBN as photoinitiator producing...A couple of novel sulfobetaine copolymer is developed via Michael-type addition reaction. The comonomers, diamines and maleimide react via Michael reaction through UV irradiation using AIBN as photoinitiator producing polyamine chain. Further, sulfobetaine copolymers were obtained on treatment of the polyamine with sulfopropylating agent, 1,3-propane sultone. These novel sulfobetaine polymers were grafted on silica surface to produce responsive biocompatible surface. This easy straightforward, catalyst free facile protocol for synthesis of polymer grafted surface is useful for developing biomedical devices. Additionally, both the copolymers show fluorescence characteristics.展开更多
Novel compounds, (3,6-dichloro-2-nitrophenyl)(3-nitrophenyl)methanone(2), (2-amino-3,6-dichloro- phenyl)(3-aminophenyl)methanone(3) and 1-[3-(2-amino-3,6-dichlorobenzoyl)phenyl]-1H-pyrrole-2,5-dione(4)...Novel compounds, (3,6-dichloro-2-nitrophenyl)(3-nitrophenyl)methanone(2), (2-amino-3,6-dichloro- phenyl)(3-aminophenyl)methanone(3) and 1-[3-(2-amino-3,6-dichlorobenzoyl)phenyl]-1H-pyrrole-2,5-dione(4), were synthesized from the initial compound 2,5-dichlorobenzophenone(1) and characterized by 1H NMR, 13C NMR, IR, mass spectrum and element analysis, respectively. The single crystal of compound 2 was obtained and determined by X-ray diffraction analysis. The single crystal data illustrates that it belongs to the monoclinic system, space group P21/c with a=0.7587(4) nm, b=2.4724(4) nm, c=0.8081(3) nm, α=90°, β=112.85(2)°, γ=90o, V=1.3970(9) nm3, Z=4, Dc=1.622 g/cm3, Mr(C13H6Cl2N2O5)=341.10, μ(Mo Kα)=0.49 mm?1, F(000)=688, the final R=0.048 and wR=0.144 for 1665 observed reflections with I2σ(I). The title molecule forms a "T" type crystal structure and the dihedral angel of the two phenyl rings is 65.0(1)°.展开更多
Transition-metal-catalyzed cross-coupling reactions as very efficient and atom-economical approaches have been widely used to build up complex heterocyclic compounds.However,modification of 2-oxyl benzimidazole skelet...Transition-metal-catalyzed cross-coupling reactions as very efficient and atom-economical approaches have been widely used to build up complex heterocyclic compounds.However,modification of 2-oxyl benzimidazole skeleton using maleimide compounds via C–H activation has remained unprecedented.Herein,we developed a rhodium(III)-catalyzed[5+1]cascade spiroannulation to construct diversified novel benzimidazole-incorporated spirosuccinimide derivatives from 2-oxyl benzimidazoles and maleimides.展开更多
The controlled and efficient synthesis of polymers with tailored topologies is challenging but important for exploring structure/property research. Herein, we proposed a concept of macro-latent monomer to achieve the ...The controlled and efficient synthesis of polymers with tailored topologies is challenging but important for exploring structure/property research. Herein, we proposed a concept of macro-latent monomer to achieve the controlled growth of polymer topologies.The macro-latent monomer was installed by a dynamic furan/maleimide covalent bond at the chain terminal. One-shot reversible additionfragmentation chain transfer(RAFT) polymerization of styrene and the macro-latent monomer created controlled growth of polymer topologies.Low temperature such as 40 ℃ could not activate the macro-latent monomer and thus the polymerization created the homo-polystyrene. By contrast, high temperature of ~110 ℃ activated the macro-latent monomer, and a maleimide-terminated macro-monomer was released via the retro-Diels Alder reaction. This macro-monomer immediately joined the cross polymerization with styrene and thus produced the side chains. By delicately manipulating the polymerization temperature, the predetermined placement of the macro-latent monomer-derived polymeric sidechains created controllably growing topologies, including star-, π-shaped, and density-variable grafting copolymers. This work paved a new way for creating on-demand topologies and would greatly enrich the topology synthesis.展开更多
The on-demand building copolymer structures,from sequence to architecture,is crucial in understanding the relation between pol-ymer structure and property,meanwhile motivating the innovation of polymer hierarchy.Howev...The on-demand building copolymer structures,from sequence to architecture,is crucial in understanding the relation between pol-ymer structure and property,meanwhile motivating the innovation of polymer hierarchy.However,the challenge is conspicuous for,complicated polymer structures from inherently intricate polymerization.In this work,copolymers with tailored grafting density and distributions were achieved using successive latent monomer and grafting-from strategies.The hydroxyl group functionalized fu-ran/maleimide adduct(FMOH)was selected as the latent monomer for RAFT polymerization of an array of copolymers with tailored localization of hydroxyl group along the main chain.The hydroxyI group further initiated the ring opening polymerization(ROP)of L-lactide or ε-caprolactone,resulting in a library of multicomponent copolymers via grafting-from strategy.The initiating efficiency reached to-100% with variable molecular weight(21300-58600 Da)and narrow distributions(Ð_(M)<1.25),indicating that such graft copolymers possessed controlled density and distribution of side chains as its linear template.The investigation on thermal properties of the well-defined graft copolymers implied that the precise tailoring over copolymer structures at the molecule level could lead to tunable chemical/physical properties.This work bridged polymer from sequence to architecture,unveiled a new meth-od in creating graft copolymers with programmable structures and provided the insight into the structure/property relationship.展开更多
基金supported through the“Terrestrial and Planetary Alteration Processes”strategic project(ref.PES 18/57)funded by the University of the Basque Country(UPV/EHU).
文摘Nitrogen-containing heterocyclic compounds are fundamental biochemical components of all life on Earth and,presumably,life elsewhere in our solar system.Detection and characterization of these compounds by traditional solvent extraction,chromatographic separation,and GC-MS analysis require more sample mass than will be available from samples returned to Earth from Mars.With its small sample mass requirement,Surface Enhanced Raman Spectroscopy could be an appropriate technique for analysis of returned samples.We have developed a SERS method for the detection of maleimide(2,5-pyrroledione),an N-containing heterocycle with a structure that is widespread in biochemicals.This semi-quantitative methodology accurately determines maleimide concentration in the range from 60 mg/mL to 120 mg/mL.We present a maleimide SERS standard spectrum which will be useful as a reference for future works.The present work demonstrates an easy,accurate,and effective method for the non-destructive qualitative and semi-quantitative study of maleimide as a first step toward developing a method for analysis of related compounds.
文摘The oil-in-water microemulsion containing N-butyl maleimide(NBMI. M_1) and styrene(St, M_2) was prepared. The complexation properties of NBMI and St in microemulsion were investigated by means of 1H-NMR. With the participation of charge-transfer complex(CTC). four reactivity ratios and the relative reactivity of free monomers and CTC were obtained. The result was compared with that measured by Mayo-Lewis method.
文摘The authors have studied the Diels-Alder reactions between furan derivatives and maleimide derivatives in an ionic liquid and have found that higher reactivity can be obtained in a protic ionic liquid [Mim]Tf2N than in the conventional organic solvent. Furthermore, in the Diels-Alder reactions of 2- and 2,5-alkylfurans with N-alkylma- leimide, the reactivity increases by extending the alkyl chain length of N-alkylmaleimide. In addition, it was demon- strated that endo-selectivity increases when 2,5-disubstituted furans are used. These results will be explained by comparing the stability of the Diels-Alder adduct with that of the products obtained from the reactions of 2-substituted furans and 2,5-disubstituted furans.
文摘The self-condensing vinyl polymerization(SCVP) of a novel maleimide inimer(initiator-monomer) 1, N-(4-α-bromobutyryloxy phenyl) maleimide with the complex of CuBr/Bipy(2, 2′-bipyridine) as the catalyst was studied. GPC was used to determine the molecular weight and the results show that the molecular weight increases exponentially with polymerization time during the first hour, and then the rate of increase molecular weight slows down. The molecular weight also increases with increasing dosage of the catalyst. The coincidence of the molecular weights determined by 1H NMR and GPC proves that the polymer obtained from the SCVP of inimer 1 has a linear structure, which is further verified by 13C NMR spectrum. A hyperbranched polymer was obtained by the copolymerization of inimer 1 and styrene.
文摘The methylated β-cyclodextrins derived optically active polymers are firs synthesized through asymmetric polymerization of N-diphenylmethyl maleimide with lithium salt of heptakis(2,6-O-dimethyl) β-cyclodextrin (DM-β-CD) as an initiator. The resulting polymers show negative specific rotation which is opposite in sign to that of DM-β-CD. The asymmetric induction is further confirmed by circular dichroism. The structure is characterized by IR and NMR spectroscopies
文摘The copolymer of N-4-dibenzoylmethane maleimide (p-DBMI) with styrene (St) was prepared and characterized by gel permeation chromatography, thermal analysis and spectroscopy.
文摘Pyrrolidine-2,5-dione and maleimide are important scaffolds of many organic substances, and their derivatives are now attracting more and more interests from researchers in organic synthesis, medicinal chemistry, and drug development. Tosyloxy (-OTs) group is an important functional group widely used in organic synthesis, because it can be readily prepared from alcohols and is an excellent leaving group. However, surprisingly, substances bearing tosyloxy groups on pyrrolidine-2,5-dione or maleimide scaffolds are very rare. In this study, we discovered that, when treated with TsCl/Et3N,?trans-3,4-dihydroxypyrrolidine-2,5- dione will eliminate a TsOH molecule to form monotosyloxymaleimide. Thermodynamic and kinetic factors affecting this reaction were investigated by theoretical computation using density functional theory (DFT), and the possible reaction mechanism was proposed based on the computation results. Our results showed that tosylates of trans -3,4-dihydroxypyrrolidine- 2,5-dione, either monotosylate or ditosylate, are thermodynamically instable and may spontaneously convert to maleimides. This knowledge could be useful in understanding the properties of pyrrolidine-2,5-diones and maleimides, as well as the related organic synthesis.
基金supported by National Natural Science Foundation of China(No.81773656 and U1608283)Liaoning Revitalization Talents Program(No XLYC1808017,China)+2 种基金Key projects of Technology bureau in Shenyang(No.18400408,China)Key projects of Liaoning Province Department of Education(No.2017LZD03,China)111 Project(D20029,China)
文摘A commercial albumin-bound paclitaxel nano-formulation has been considered a gold standard against breast cancer.However,its application still restricted unfavorable pharmacokinetics and the immunogenicity of exogenous albumin carrier.Herein,we report an albumin-bound tumor redoxresponsive paclitaxel prodrugs nano-delivery strategy.Using diverse linkages(thioether bond and disulfide bond),paclitaxel(PTX)was conjugated with an albumin-binding maleimide(MAL)functional group.These pure PTX prodrugs could self-assemble to form uniform and spherical nanoparticles(NPs)in aqueous solution without any excipients.By immediately binding to blood circulating albumin after intravenous administration,NPs are rapidly disintegrated into small prodrug/albumin nanoaggregates in vivo,facilitating PTX prodrugs accumulation in the tumor region via albumin receptormediated active targeting.The tumor redox dual-responsive drug release property of prodrugs improves the selectivity of cytotoxicity between normal and cancer cells.Moreover,disulfide bond-containing prodrug/albumin nanoaggregates exhibit long circulation time and superior antitumor efficacy in vivo.This simple and facile strategy integrates the biomimetic characteristic of albumin,tumor redox-responsive on-demand drug release,and provides new opportunities for the development of the high-efficiency antitumor nanomedicines.
基金financially supported by the National Natural Science Foundation of China(Nos.51233005,21374114,and21274152)
文摘Thermo-responsive butyl acrylate/furfuryl methacrylate copolymer-based (PBF backbone) graft (co)polymers with dynamic covalent linkages between their backbones and side chains via the Diels-Alder reaction of furardmaleimide were synthesized. Atom transfer radical polymerization (ATRP) was used to synthesize graft copolymers with thermo-responsive transformation from graft copolymers to linear polymers with bimodal or wide MWD. The NMR measurements indicated that the Diels-Alder reaction and retro- Diels-Alder reaction occurred, depending on the change of the temperature, meaning that the side chains could be cleaved and reformed according to the variation of the temperature. GPC measurements demonstrated that the molecular weights of the polymers were thermo- responsive. Furthermore, three graft copolymers with various branching chains (PBF-g-PBA, PBF-g-P(BMA-co-MA) and PBF-g-PBMA) were compared to study the influence of compatibility between the backbone and the branching chain on the efficiency of Diels-Alder reaction after the cleavage of the DA linkage. The results showed that the ability of the side chains to come back to the main chain was strongly affected by the compatibility between the backbone and the side chains and the flexibility of the polymer chains.
基金Project supported by the National Natural Science Foundation of China (Grant No. 29634010-3)Doctor Training Foundation of State Education Ministry of China.
文摘Three basic conditions for preparation of alternating copolymer with narrow molecular weight distribution were derived from the element kinetic equations of binary radical copolymerization. Using maleimide (MI) and atropie acid (ATA) as model monomer pairs and dioxane as the solvent the alternating copolymer with molecular weight distribution in the range of 1.09--1.20 was prepared successfully by charger transfer complex (CTC) mechanism in the presence of benzoyl peroxide at 85℃. The monomer reactivity ratioes r<sub>1</sub>(MI)=0.05±0.01 and r<sub>2</sub>(ATA)=0.03±0.02 were measured. The alternating eopolymerization was carried out through formation of a contact-type CTG and then alternating addition of MI and ATA monomers. The molecular weight of the copolymers is nearly independent of the feed ratio in a large range and the polymerization rate dropped with an increase in ATA in feed ratio.
基金The authors thank the Hutchinson Company for its financial support,Biobased Polymer Company for reactants supply.
文摘This study focuses on the synthesis of new liquid aromatic bismaleimide monomers in order to improve self-curing on demand(SCOD)systems previously based on aliphatic bismaleimides.These SCOD systems are based on Diels-Alder(DA)/retro-DA reactions.The syntheses of new different aromatic bismaleimides with ester and amide bonds are presented.These maleimides have been protected using DA reaction and characterized by 1H NMR analysis to determine protection rate and diastereomer ratios.The retro-DA reactions of both aromatic and aliphatic DA adducts in presence of thiol molecules were studied.Kinetic analysis was monitored by 1H NMR and compared to model study.Finally,both aromatic and aliphatic bismaleimides-based polymers were synthesized with 2-mercaptoethyl ether and thermal properties of polymers were compared.The glass transition temperature values ranged from–20°C to 14°C and very good thermal stabilities were observed(up to 300°C).
基金This work was supported by the National Outstanding Youth Foundation of China(No.21925107)The Collaborative Innovation Center of Suzhou Nano Science and Technology,the China Post-doctoral Science Foundation(No.2020M671571)+1 种基金the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)the Program of Innovative Research Team of Soochow University.
文摘Herein is presented a compilation of the main characteristics of maleimide chemistry in developing the precisely controlled polymers,including the design of sequence-controlled polymers,topological polymers,and polymeric single-chain nanoparticles.The synthetic methods,relied on the versatilities of the maleimide moieties as a latent monomer which leads to an efficient alternative in various innovative applications,especially in self-healing material,self-reporting materials for real-time monitoring,and also in data storage and anticounterfeiting technologies.The core of the content in this review is focused on the up-to-data advances and publications on the major of maleimide chemistry in our research group.
文摘A new optically active polymer, (+)poly(N_diphenylmethyl maleimide), was coated on macroporous silica gel and used as a chiral stationary phase for high performance liquid chromatographic resolution of enantiomers. The chiral polymer showed efficient resolution ability to some polar racemates, and eleven pairs of racemates are resolved effectively.
基金Sponsored by the Supporting Project of Sichuan Province Key Technology Support Program (2011ZG0247)Sichuan Province Education Office Natural Science Foundation (10ZC080)
文摘The geometric structures,electronic absorption spectrum,and thermodynamic pro-perties of 3-(4-N-maleimido)-phenyl-2,4-dihydro-2H-1,3-benzoxazine molecule were studied at the B3LYP/6-311+G* level by density functional theory.The results show that three rings of this molecule are in different planes.In gas,absorption wavelength of the lowest energy excitation was obtained at 503 nm,and solvents made it blue-shifted by 3-7 nm,both corresponding to the electron transition of HOMO → LUMO.At 298.15 K,the standard molar formed enthalpy and free energy of the title compound molecule were-549.43 and-273.37 kJ·mol-1,respectively.
基金We would like to acknowledge the Prostate Cancer Foundation,Department of Defense Prostate Cancer Research Program(W81XWH-16-1-0410)NIH Prostate SPORE(P50 CA058236)Patrick C.Walsh Prostate Cancer Research Fund,and the Hopkins-Allegheny Health Network Cancer Research Fund。
文摘Localized prostate cancer is curable via annihilation of the entire cancer neighborhood by surgery or local radiation.Unfortunately,once metastatic,no available therapy is curative.The vast majority will die despite aggressive systemic combinational androgenablation therapies.Thus,there is an urgent need for effective systemic therapeutics that sterilize the entire microenvironment in metastatic castration-resistant prostate cancer(mCRPC).To accomplish this goal,advantage can be taken of the unique biology of mCRPC cells.Like their normal cell of origin,mCRPCs retain expression of the prostate-specific differentiation protein,prostate-specific antigen(PSA),which they abundantly secrete into their extracellular fluid(ECF).This unique,and essentially universal,secretion of enzymatically active PSA into the ECF by mCRPCs creates an exploitable therapeutic index for activation of systemically delivered highly lipophilic toxins as“molecular grenades”covalently linked to cysteine-34 of human serum albumin(HSA)via a stable maleimide containing PSA cleavable peptide such that PSA-dependent hydrolysis(i.e.,“detonation”)releases the grenades restrictively within the ECF of mCRPC.This approach decreases dose-limiting host toxicity while enhancing plasma half-life from minutes to days(i.e.,pharmacokinetic effect)and increasing the tissue concentration of the maleimide coupled albumin delivery(MAD)in the ECF at sites of cancer due to the enhanced permeability of albumin at these sites(i.e.,enhanced permeability and retention effect).This allows the MAD-PSA detonated grenades to circulate throughout the body in a non-toxic form.Only within sites of mCRPC is there a sufficiently high level of enzymatically active PSA to efficiently“pull the pin”on the grenades releasing their lipophilic cellpenetrant toxins from HSA.Thus,if a sufficient level of“detonation”occurs,this will kill mCRPC cells,and sterilize the entire PSA-rich metastatic sites via a bystander effect.In this review,two examples of such MAD-PSA detonated molecular grenades are presenteddone based upon thapsigagin and the other on niclosamide.
文摘A couple of novel sulfobetaine copolymer is developed via Michael-type addition reaction. The comonomers, diamines and maleimide react via Michael reaction through UV irradiation using AIBN as photoinitiator producing polyamine chain. Further, sulfobetaine copolymers were obtained on treatment of the polyamine with sulfopropylating agent, 1,3-propane sultone. These novel sulfobetaine polymers were grafted on silica surface to produce responsive biocompatible surface. This easy straightforward, catalyst free facile protocol for synthesis of polymer grafted surface is useful for developing biomedical devices. Additionally, both the copolymers show fluorescence characteristics.
文摘Novel compounds, (3,6-dichloro-2-nitrophenyl)(3-nitrophenyl)methanone(2), (2-amino-3,6-dichloro- phenyl)(3-aminophenyl)methanone(3) and 1-[3-(2-amino-3,6-dichlorobenzoyl)phenyl]-1H-pyrrole-2,5-dione(4), were synthesized from the initial compound 2,5-dichlorobenzophenone(1) and characterized by 1H NMR, 13C NMR, IR, mass spectrum and element analysis, respectively. The single crystal of compound 2 was obtained and determined by X-ray diffraction analysis. The single crystal data illustrates that it belongs to the monoclinic system, space group P21/c with a=0.7587(4) nm, b=2.4724(4) nm, c=0.8081(3) nm, α=90°, β=112.85(2)°, γ=90o, V=1.3970(9) nm3, Z=4, Dc=1.622 g/cm3, Mr(C13H6Cl2N2O5)=341.10, μ(Mo Kα)=0.49 mm?1, F(000)=688, the final R=0.048 and wR=0.144 for 1665 observed reflections with I2σ(I). The title molecule forms a "T" type crystal structure and the dihedral angel of the two phenyl rings is 65.0(1)°.
基金We are grateful for the financial support from 111 Project(No.B18035)and“the Fundamental Research Funds for the Central Universities”.
文摘Transition-metal-catalyzed cross-coupling reactions as very efficient and atom-economical approaches have been widely used to build up complex heterocyclic compounds.However,modification of 2-oxyl benzimidazole skeleton using maleimide compounds via C–H activation has remained unprecedented.Herein,we developed a rhodium(III)-catalyzed[5+1]cascade spiroannulation to construct diversified novel benzimidazole-incorporated spirosuccinimide derivatives from 2-oxyl benzimidazoles and maleimides.
基金financially supported by the National Natural Science Foundation of China(Nos.21925107 and 21674072)the Collaborative Innovation Center of Suzhou Nano Science and Technology+1 种基金the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)the Program of Innovative Research Team of Soochow University。
文摘The controlled and efficient synthesis of polymers with tailored topologies is challenging but important for exploring structure/property research. Herein, we proposed a concept of macro-latent monomer to achieve the controlled growth of polymer topologies.The macro-latent monomer was installed by a dynamic furan/maleimide covalent bond at the chain terminal. One-shot reversible additionfragmentation chain transfer(RAFT) polymerization of styrene and the macro-latent monomer created controlled growth of polymer topologies.Low temperature such as 40 ℃ could not activate the macro-latent monomer and thus the polymerization created the homo-polystyrene. By contrast, high temperature of ~110 ℃ activated the macro-latent monomer, and a maleimide-terminated macro-monomer was released via the retro-Diels Alder reaction. This macro-monomer immediately joined the cross polymerization with styrene and thus produced the side chains. By delicately manipulating the polymerization temperature, the predetermined placement of the macro-latent monomer-derived polymeric sidechains created controllably growing topologies, including star-, π-shaped, and density-variable grafting copolymers. This work paved a new way for creating on-demand topologies and would greatly enrich the topology synthesis.
基金the National Natural Science Foundation of China(21925107 and 21674072)the Collaborative Innovation Center of Suzhou Nano Science and Technology,the China Post-doctoral Science Foundation(2020M671571)the Priority Academic Program Development of Jiangsu Higher Edu-caction Institutions(PAPD)and the Program of Innovative Research Team of Soochow University.
文摘The on-demand building copolymer structures,from sequence to architecture,is crucial in understanding the relation between pol-ymer structure and property,meanwhile motivating the innovation of polymer hierarchy.However,the challenge is conspicuous for,complicated polymer structures from inherently intricate polymerization.In this work,copolymers with tailored grafting density and distributions were achieved using successive latent monomer and grafting-from strategies.The hydroxyl group functionalized fu-ran/maleimide adduct(FMOH)was selected as the latent monomer for RAFT polymerization of an array of copolymers with tailored localization of hydroxyl group along the main chain.The hydroxyI group further initiated the ring opening polymerization(ROP)of L-lactide or ε-caprolactone,resulting in a library of multicomponent copolymers via grafting-from strategy.The initiating efficiency reached to-100% with variable molecular weight(21300-58600 Da)and narrow distributions(Ð_(M)<1.25),indicating that such graft copolymers possessed controlled density and distribution of side chains as its linear template.The investigation on thermal properties of the well-defined graft copolymers implied that the precise tailoring over copolymer structures at the molecule level could lead to tunable chemical/physical properties.This work bridged polymer from sequence to architecture,unveiled a new meth-od in creating graft copolymers with programmable structures and provided the insight into the structure/property relationship.