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2020 Volume 78 Issue 8
2020, 78(8): 713-718
doi: 10.6023/A20050164
Abstract:
Monomolecular layer polymeric nanocapsules can be easily prepared by the covalent self-assembly of the horizontal cross-linking of rigid building blocks and flexible cross-linker under certain conditions. Compared with the traditional noncovalent supramolecular vesicles, this new type of covalently self-assembled polymeric nanocapsules possess many advantages such as stable structure, controllable size, and excellent dispersibility. Therefore, it is of great significance to fabricate new covalent nanocapsules by means of chemical synthesis to realize their structural control and application exploration. Focusing on these problems, we have developed functionalized pillar[5]arene, tetraphenyl ethylene, porphyrin, triazine, phenylboronic anhydride, etc. to serve as basic building blocks, which were polymerized by flexible alkyl linkers to finally obtain the covalently cross-linked polymeric nanocapsules. Through the structural modification and regulation, we found the functionalized polymeric nanocapsules showed potential application in the field of light harvesting, artificial enzyme, antimicrobial and drug delivery. In the future, more application fields of the covalent polymeric nanocapsules are expected to be further explored.
Monomolecular layer polymeric nanocapsules can be easily prepared by the covalent self-assembly of the horizontal cross-linking of rigid building blocks and flexible cross-linker under certain conditions. Compared with the traditional noncovalent supramolecular vesicles, this new type of covalently self-assembled polymeric nanocapsules possess many advantages such as stable structure, controllable size, and excellent dispersibility. Therefore, it is of great significance to fabricate new covalent nanocapsules by means of chemical synthesis to realize their structural control and application exploration. Focusing on these problems, we have developed functionalized pillar[5]arene, tetraphenyl ethylene, porphyrin, triazine, phenylboronic anhydride, etc. to serve as basic building blocks, which were polymerized by flexible alkyl linkers to finally obtain the covalently cross-linked polymeric nanocapsules. Through the structural modification and regulation, we found the functionalized polymeric nanocapsules showed potential application in the field of light harvesting, artificial enzyme, antimicrobial and drug delivery. In the future, more application fields of the covalent polymeric nanocapsules are expected to be further explored.
2020, 78(8): 719-724
doi: 10.6023/A20050162
Abstract:
Polymerization-induced self-assembly (PISA) is one of the most cutting-edge strategies towards the preparation of nanoparticles with a range of morphologies (spheres, worms, vesicles, etc.) as it combines polymerization and self-assembly and thus can afford high solid contents in various media. Additionally, nanoparticle morphology can be accurately targeted by adjusting the degree of polymerization of the soluble stabilizer block and the insoluble core-forming block, as well as solid contents in PISA formula. Unfortunately, this highly efficient approach is limited to specific polymerization methods, and hence specific monomer types. Currently, PISA based on reversible addition-fragmentation chain-transfer polymerization (RAFT) has been well-established for the in situ preparation of a range of nanoparticle morphologies. This method is relatively mature especially in the mechanism exploration, morphological control, and characterization, which has important impact to other fields of polymer chemistry. However, methacrylates, acrylates, and styrene monomers are often essential for reversible addition-fragmentation chain-transfer polymerization-induced self-assembly (RAFT-PISA), leading to the carbon-carbon backbone, which normally produces nonbiodegradable structures. These drawbacks are detrimental in terms of biomedical applications. Fortunately, new PISA strategies based on ring-opening polymerizations, including ring-opening metathesis polymerization-induced self-assembly (ROMPISA), ring-opening polymerization of N-carboxy- anhydride-induced self-assembly (NCA-PISA) and radical ring-opening polymerization-induced self-assembly (rROPISA), have been developed to overcome these problems. ROMPISA has proven to be an efficient approach for fabricating multifunctional nanoparticles due to its great tolerance for many functional groups. Biodegradable nanoparticles, including spheres and vesicles, have been successfully prepared by rROPISA and NCA-PISA. Therefore, ring-opening PISA (ROPISA) provides not only new polymerization methods but also new strategies for fabricating biodegradable nanoparticles with a range of monomer species. In this perspective, we briefly summarize the current progress and analyze the challenges of ROPISA. Finally, we provide a perspective for the further development of ROPISA addressed on the mechanism, monomers and applications, which provides an insight into ROPISA as well as some suggestions and directions for its future research.
Polymerization-induced self-assembly (PISA) is one of the most cutting-edge strategies towards the preparation of nanoparticles with a range of morphologies (spheres, worms, vesicles, etc.) as it combines polymerization and self-assembly and thus can afford high solid contents in various media. Additionally, nanoparticle morphology can be accurately targeted by adjusting the degree of polymerization of the soluble stabilizer block and the insoluble core-forming block, as well as solid contents in PISA formula. Unfortunately, this highly efficient approach is limited to specific polymerization methods, and hence specific monomer types. Currently, PISA based on reversible addition-fragmentation chain-transfer polymerization (RAFT) has been well-established for the in situ preparation of a range of nanoparticle morphologies. This method is relatively mature especially in the mechanism exploration, morphological control, and characterization, which has important impact to other fields of polymer chemistry. However, methacrylates, acrylates, and styrene monomers are often essential for reversible addition-fragmentation chain-transfer polymerization-induced self-assembly (RAFT-PISA), leading to the carbon-carbon backbone, which normally produces nonbiodegradable structures. These drawbacks are detrimental in terms of biomedical applications. Fortunately, new PISA strategies based on ring-opening polymerizations, including ring-opening metathesis polymerization-induced self-assembly (ROMPISA), ring-opening polymerization of N-carboxy- anhydride-induced self-assembly (NCA-PISA) and radical ring-opening polymerization-induced self-assembly (rROPISA), have been developed to overcome these problems. ROMPISA has proven to be an efficient approach for fabricating multifunctional nanoparticles due to its great tolerance for many functional groups. Biodegradable nanoparticles, including spheres and vesicles, have been successfully prepared by rROPISA and NCA-PISA. Therefore, ring-opening PISA (ROPISA) provides not only new polymerization methods but also new strategies for fabricating biodegradable nanoparticles with a range of monomer species. In this perspective, we briefly summarize the current progress and analyze the challenges of ROPISA. Finally, we provide a perspective for the further development of ROPISA addressed on the mechanism, monomers and applications, which provides an insight into ROPISA as well as some suggestions and directions for its future research.
2020, 78(8): 725-732
doi: 10.6023/A20050187
Abstract:
Anderson type heteropoly acids, also known as Anderson type polyoxometalates, are a kind of important structures in polyoxometalates. Their general structural formula can be expressed as [XM6O24]n－, in which the core heteroatom X can almost be replaced by almost any metal or nonmetal element in the periodic table. Due to unique structure easy to be modified with organic ligands and designability, as well as their potential applications in materials, catalysis and medicines, Anderson type heteropoly acids have been widely concerned by researchers. In recent years, the application of Anderson type heteropoly acids in organic synthesis has gradually shown great significance for the study of green catalytic process. In this paper, the catalytic application of Anderson type heteropoly acids in organic synthesis has been reviewed and summarized according to the structure classification of Anderson type polyoxometalates. This will be helpful for the researchers to further study the catalytic application of Anderson heteropoly acids and provides new ideas for the research of green catalysis.
Anderson type heteropoly acids, also known as Anderson type polyoxometalates, are a kind of important structures in polyoxometalates. Their general structural formula can be expressed as [XM6O24]n－, in which the core heteroatom X can almost be replaced by almost any metal or nonmetal element in the periodic table. Due to unique structure easy to be modified with organic ligands and designability, as well as their potential applications in materials, catalysis and medicines, Anderson type heteropoly acids have been widely concerned by researchers. In recent years, the application of Anderson type heteropoly acids in organic synthesis has gradually shown great significance for the study of green catalytic process. In this paper, the catalytic application of Anderson type heteropoly acids in organic synthesis has been reviewed and summarized according to the structure classification of Anderson type polyoxometalates. This will be helpful for the researchers to further study the catalytic application of Anderson heteropoly acids and provides new ideas for the research of green catalysis.
2020, 78(8): 733-745
doi: 10.6023/A20040115
Abstract:
Group transfer polymerization (GTP) is a living polymerization method for acrylic-derived monomers developed by DuPont after living anionic polymerization in the 1980s. The acrylic-derived monomers mainly include acrylate, methacrylate, acrylamide and acrylonitrile. The elementary initiation and propagation reactions in GTP are all rooted in the Mukaiyama-Michael addition reaction. Therefore, in principle both base and acid can sever as the catalyst for GTP. Before the small molecular organocatalyst is applied to the polymerization method, the normally used base has been a soluble ionic compound containing a sterically hindered cation, in which the nucleophilic anion acts as the true catalyst. The normally used acid has been a metal or transition metal compound having Lewis acidity. Since 2007, small organic bases and acids have been gradually used to catalyze GTP, and this type of polymerization has been named as organocatalyzed GTP. Compared with the conventional one, organocatalyzed GTP has made a great improvement in the aspects of molecular weight and molecular weight distribution control of acrylic polymers, scope of polymerizable monomers, topological design of polymer, etc. This review mainly focuses on the author's recent work and will be discussed from four aspects: GTP using organic strong base, GTP using organic strong acid, a novel hydrosilane-based GTP, and polymerization mechanism.
Group transfer polymerization (GTP) is a living polymerization method for acrylic-derived monomers developed by DuPont after living anionic polymerization in the 1980s. The acrylic-derived monomers mainly include acrylate, methacrylate, acrylamide and acrylonitrile. The elementary initiation and propagation reactions in GTP are all rooted in the Mukaiyama-Michael addition reaction. Therefore, in principle both base and acid can sever as the catalyst for GTP. Before the small molecular organocatalyst is applied to the polymerization method, the normally used base has been a soluble ionic compound containing a sterically hindered cation, in which the nucleophilic anion acts as the true catalyst. The normally used acid has been a metal or transition metal compound having Lewis acidity. Since 2007, small organic bases and acids have been gradually used to catalyze GTP, and this type of polymerization has been named as organocatalyzed GTP. Compared with the conventional one, organocatalyzed GTP has made a great improvement in the aspects of molecular weight and molecular weight distribution control of acrylic polymers, scope of polymerizable monomers, topological design of polymer, etc. This review mainly focuses on the author's recent work and will be discussed from four aspects: GTP using organic strong base, GTP using organic strong acid, a novel hydrosilane-based GTP, and polymerization mechanism.
2020, 78(8): 746-757
doi: 10.6023/A20050147
Abstract:
The reticular frameworks have crystalline and extended porous structures, which can not only orderly organize a variety of building blocks to form mesoscopic materials in a programmable way, but also perform an excellent platform for basic scientific research because of the regulatable and precise structures. The representative systems of reticular frameworks are metal organic frameworks (MOFs) and covalent organic frameworks (COFs). Mechanically interlocked structures are molecular aggregations interacted through mechanical bond to realize complex functions. The combination of reticular frameworks and mechanically interlocked structures can promote the basic research of the microscopic interlocked behaviors in solid states; and also organize the interlocked structures in a regular way to achieve more complex functions. The mechanically interlocked structures can be introduced into reticular frameworks in two strategies, using mechanically interlocked structures as building blocks participating in the construction of reticular frameworks; and forming woven or interlocked frameworks with whole interlocked skeleton from unlocked precursors. This review summarizes the important progresses in the emerging research field combining the reticular frameworks and mechanically interlocked structures. In the first section, after the brief introduction of reticular frameworks and mechanically interlocked structures respectively, the significances and strategies of the combination of the above two fields is described. In the second section, we reveal the systematic and representative research of mechanically interlocked structure as a part of building blocks participating in the construction of reticular frameworks, including rotaxane, shuttle and catenate. The mechanical motions of rotaxanes and shuttle within MOFs are intensively studied. The representative methods and structures of introducing rotaxane or catenate into reticular frameworks are presented. In the third section, we exhibit the reticular frameworks constructed through mechanical bond as the main interaction within the whole skeleton from unlocked precursors, including resilient woven frameworks and mechanically interlocked frameworks. The typical woven or interlocked frameworks are mostly templated from special metal complexes and showing reversible transition between crystal and non-crystal maintaining the whole interlocked skeleton. Finally, we summarize the whole paper and discuss the future development in this crossing field, such as the applications of these combined systems should be expanded and the mechanically interlocked frameworks constructed through interlocking discrete molecular rings are expected due to the potential excellent elastic properties.
The reticular frameworks have crystalline and extended porous structures, which can not only orderly organize a variety of building blocks to form mesoscopic materials in a programmable way, but also perform an excellent platform for basic scientific research because of the regulatable and precise structures. The representative systems of reticular frameworks are metal organic frameworks (MOFs) and covalent organic frameworks (COFs). Mechanically interlocked structures are molecular aggregations interacted through mechanical bond to realize complex functions. The combination of reticular frameworks and mechanically interlocked structures can promote the basic research of the microscopic interlocked behaviors in solid states; and also organize the interlocked structures in a regular way to achieve more complex functions. The mechanically interlocked structures can be introduced into reticular frameworks in two strategies, using mechanically interlocked structures as building blocks participating in the construction of reticular frameworks; and forming woven or interlocked frameworks with whole interlocked skeleton from unlocked precursors. This review summarizes the important progresses in the emerging research field combining the reticular frameworks and mechanically interlocked structures. In the first section, after the brief introduction of reticular frameworks and mechanically interlocked structures respectively, the significances and strategies of the combination of the above two fields is described. In the second section, we reveal the systematic and representative research of mechanically interlocked structure as a part of building blocks participating in the construction of reticular frameworks, including rotaxane, shuttle and catenate. The mechanical motions of rotaxanes and shuttle within MOFs are intensively studied. The representative methods and structures of introducing rotaxane or catenate into reticular frameworks are presented. In the third section, we exhibit the reticular frameworks constructed through mechanical bond as the main interaction within the whole skeleton from unlocked precursors, including resilient woven frameworks and mechanically interlocked frameworks. The typical woven or interlocked frameworks are mostly templated from special metal complexes and showing reversible transition between crystal and non-crystal maintaining the whole interlocked skeleton. Finally, we summarize the whole paper and discuss the future development in this crossing field, such as the applications of these combined systems should be expanded and the mechanically interlocked frameworks constructed through interlocking discrete molecular rings are expected due to the potential excellent elastic properties.
2020, 78(8): 758-762
doi: 10.6023/A20050191
Abstract:
Hydroxylamines have a wide range of biological properties and have been used as a useful synthon in organic synthesis. In the past decades, many transformations of hydroxylamines have been developed and widely applied. In contrast, one of the interesting reactions of hydroxylamines through C—C bond cleavage, named Stieglitz rearrangement, was less developed. Due to the poor leaving ability of the hydroxyl groups, the reported Stieglitz rearrangement reactions suffered from the harsh conditions and the very limited substrate scope with triarylmethyl hydroxylamine substrates. Since an interesting C—C bond cleavage is involved which will extend the synthetic application of hydroxylamine, the practical method under mild conditions with broad substrate scope for Stieglitz rearrangement is very desired. However, there are three potential problems which need to be addressed. First, the activator must selectively react with the hydroxyl group but not the N-nucleophile of the hydroxylamine substrates. Secondary, a suitable leaving group must be generated to weaken the N—O bond. In addition, the employed activator must be inactive to the formed imine intermediates and the subsequent amine products. Herein, we developed an efficient Stieglitz rearrangement reaction of hydroxylamines under mild conditions for the preparation of corresponding primary aryl amines. This chemistry using simple trifluoroacetic anhydride (TFAA) as an activator resolves the issues mentioned above and therefore provides a practical protocol for the further transformation and application of hydroxylamines. Mechanistic studies demonstrate that the in situ generation of an active trifluoroacetate leaving group derived the aryl migration process via both of the C—C and N—O bond cleavage. A general procedure for the TFAA assisted stieglitz rearrangement is as follows: BF3·Et2O (28.4 mg, 0.2 mmol), TFAA (46.2 mg, 0.22 mmol) were added to the solution of hydroxylamine (0.2 mmol) in 2 mL hexafluoroisopropanol (HFIP). The reaction mixture was stirred at room temperature for 1 h. After that, the reaction was quenched by 4 mL 2 mol/L NaOH (aq.) and extracted by the mixture of petroleum ether and ethyl acetate (1:1, V:V). The combined organic phase was concentrated, and purified by flash chromatography on a short silica gel to afford the desired product (eluent: petroleum ether/ethyl acetate).
Hydroxylamines have a wide range of biological properties and have been used as a useful synthon in organic synthesis. In the past decades, many transformations of hydroxylamines have been developed and widely applied. In contrast, one of the interesting reactions of hydroxylamines through C—C bond cleavage, named Stieglitz rearrangement, was less developed. Due to the poor leaving ability of the hydroxyl groups, the reported Stieglitz rearrangement reactions suffered from the harsh conditions and the very limited substrate scope with triarylmethyl hydroxylamine substrates. Since an interesting C—C bond cleavage is involved which will extend the synthetic application of hydroxylamine, the practical method under mild conditions with broad substrate scope for Stieglitz rearrangement is very desired. However, there are three potential problems which need to be addressed. First, the activator must selectively react with the hydroxyl group but not the N-nucleophile of the hydroxylamine substrates. Secondary, a suitable leaving group must be generated to weaken the N—O bond. In addition, the employed activator must be inactive to the formed imine intermediates and the subsequent amine products. Herein, we developed an efficient Stieglitz rearrangement reaction of hydroxylamines under mild conditions for the preparation of corresponding primary aryl amines. This chemistry using simple trifluoroacetic anhydride (TFAA) as an activator resolves the issues mentioned above and therefore provides a practical protocol for the further transformation and application of hydroxylamines. Mechanistic studies demonstrate that the in situ generation of an active trifluoroacetate leaving group derived the aryl migration process via both of the C—C and N—O bond cleavage. A general procedure for the TFAA assisted stieglitz rearrangement is as follows: BF3·Et2O (28.4 mg, 0.2 mmol), TFAA (46.2 mg, 0.22 mmol) were added to the solution of hydroxylamine (0.2 mmol) in 2 mL hexafluoroisopropanol (HFIP). The reaction mixture was stirred at room temperature for 1 h. After that, the reaction was quenched by 4 mL 2 mol/L NaOH (aq.) and extracted by the mixture of petroleum ether and ethyl acetate (1:1, V:V). The combined organic phase was concentrated, and purified by flash chromatography on a short silica gel to afford the desired product (eluent: petroleum ether/ethyl acetate).
2020, 78(8): 763-766
doi: 10.6023/A20050163
Abstract:
Silylenes, isoelectronic with carbenes, are a kind of key intermediates in organosilicon chemistry. They possess a lone pair and an empty orbital on the silicon center, and thus could be used as donors and acceptors. Consequently, they could form complexes with various metals to support new structures and chemistry similar to both carbenes and phosphines. Iron complexes played important roles in the development of catalysts because of the inexpensive, nontoxic and sustainable characteristics.Catalytic hydroboration of alkynes presents the most atom-economic and straightforward protocol for the synthesis of vinylboranes which are indispensable intermediates for C—C coupling reactions. For the catalytic hydroboration of alkynes with iron catalysts, Enthaler's group developed the first iron catalytic system for hydroboration of alkynes by using Fe2(CO)9 (A, Chart 1) as the catalyst. Almost at the same time, Thomas's group reported the bis(imino)pyridine derived iron complexes (B) in combination with an activator for catalytic hydroboration of alkynes and alkenes. In 2017, Nishibayashi and co-workers employed an iron(Ⅱ) hydride complex (C) supported by a PNP pincer ligand for catalytic E-selective hydroboration of alkynes. In 2020, Findlater et al. reported the regioselective hydroboration of alkynes and alkenes with iron complexes supported by bis(2, 6-diisopropylaniline)acenaphthene ligands. However, these catalysts still suffered from limited substrate scope or harsh conditions. The development of highly selective catalysts for a wide substrate scope is still desirable. On the basis of our design on silylene ligands for iron chemistry, we are interested in the silylene-iron complexes for catalytic hydroboration reactions. In this paper, hydroborylation of terminal alkynes catalyzed by a neutral silylene-imine iron(0) dinitrogen complex D was studied. The reaction is highly regio- and stereoselective and almost exclusively gave E-hydroboration products. The optimized reaction conditions are as following: To a dried Schlenk tube were added complex D (0.006 g, 0.01 mmol), toluene (1.0 mL), alkyne (0.20 mmol), and catechol borane (0.02 g, 0.20 mmol). After the mixture was stirred at 80 ℃ for 24 h, it was cooled down to room temperature. The solvents were removed under vacuum and the residue was purified by flash chromatography on silica gel to afford the desired products.
Silylenes, isoelectronic with carbenes, are a kind of key intermediates in organosilicon chemistry. They possess a lone pair and an empty orbital on the silicon center, and thus could be used as donors and acceptors. Consequently, they could form complexes with various metals to support new structures and chemistry similar to both carbenes and phosphines. Iron complexes played important roles in the development of catalysts because of the inexpensive, nontoxic and sustainable characteristics.Catalytic hydroboration of alkynes presents the most atom-economic and straightforward protocol for the synthesis of vinylboranes which are indispensable intermediates for C—C coupling reactions. For the catalytic hydroboration of alkynes with iron catalysts, Enthaler's group developed the first iron catalytic system for hydroboration of alkynes by using Fe2(CO)9 (A, Chart 1) as the catalyst. Almost at the same time, Thomas's group reported the bis(imino)pyridine derived iron complexes (B) in combination with an activator for catalytic hydroboration of alkynes and alkenes. In 2017, Nishibayashi and co-workers employed an iron(Ⅱ) hydride complex (C) supported by a PNP pincer ligand for catalytic E-selective hydroboration of alkynes. In 2020, Findlater et al. reported the regioselective hydroboration of alkynes and alkenes with iron complexes supported by bis(2, 6-diisopropylaniline)acenaphthene ligands. However, these catalysts still suffered from limited substrate scope or harsh conditions. The development of highly selective catalysts for a wide substrate scope is still desirable. On the basis of our design on silylene ligands for iron chemistry, we are interested in the silylene-iron complexes for catalytic hydroboration reactions. In this paper, hydroborylation of terminal alkynes catalyzed by a neutral silylene-imine iron(0) dinitrogen complex D was studied. The reaction is highly regio- and stereoselective and almost exclusively gave E-hydroboration products. The optimized reaction conditions are as following: To a dried Schlenk tube were added complex D (0.006 g, 0.01 mmol), toluene (1.0 mL), alkyne (0.20 mmol), and catechol borane (0.02 g, 0.20 mmol). After the mixture was stirred at 80 ℃ for 24 h, it was cooled down to room temperature. The solvents were removed under vacuum and the residue was purified by flash chromatography on silica gel to afford the desired products.
Synthesis of Oligosaccharides Relevant to the Substrates of Heparanase via Dehydrative Glycosylation
2020, 78(8): 767-777
doi: 10.6023/A20060201
Abstract:
Heparanase, an endo-b-D-glucuronidase responsible for specific cleavage of heparin and heparan sulfates, is relevant to a number of biological processes, such as inflammation, tumor angiogenesis and metastasis. Heparin and heparan sulfate(HS), ubiquitously distributed on the cell surface and in the extracellular matrix, play significant roles in a diverse set of biological processes, including cell growth, virus infection, and tumor metastasis. The substrate specificity of the purified recombinant human heparinase has been investigated, and an optimal tetrasaccharide substrate of heparinase was found to be DHexUA(2S)-GlcN(NS, 6S)-GlcUA-GlcN(NS, 6S). Here we report an efficient alternative to the chemical synthesis of oligosaccharides relevant to the substrates of heparanase, including the stereoselective construction of a-GlcN-(1→4)-GlcA glycoside bonds and the effective post-assembly manipulations on the fully elaborated oligosaccharides. The dehydrative glycosylation protocol, capitalizing on direct activation of C1-hemiacetals as glycosyl donors, was employed to construct the challenging a-GlcN-(1→4)-GlcA linkages, using diphenyl sulfoxide(Ph2SO)/triflic anhydride(Tf2O) as promoters, 2, 4, 6-tri-tert- butylpyrimidine(TTBP) as base, toluene as a solvent, and －60 ℃ to room temperature as the working temperature. Under these optimized conditions, mono- and disaccharide donors(9 and 10) and disaccharide acceptors(11 and 12) were condensed to provide the coupled tri- and tetrasaccharides 5~8 in good yields and satisfactory stereoselectivity(>65% yield and a/b>5.4/1.0). The fully elaborated oligosaccharides 5~8 have then been successfully transformed into the target heparin oligosaccharides 1~4 via an effective sequence of manipulation of the protecting groups(>52% yield for 5 steps). The post-assembly manipulations include saponification under Zemplén conditions(for removal of benzyl ester and benzoyl group), O-sulfonation with sulfur trioxide pyridine complex(for hydroxyl groups), reduction and N-sulfonation(for azido group), and high pressure hydrogenation(for removal of benzyl groups). The availability of these heparin oligosaccharides would facilitate in-depth elucidation of the substrate selectivity of heparanase and the development of an effective assay for measuring the heparanase activities.
Heparanase, an endo-b-D-glucuronidase responsible for specific cleavage of heparin and heparan sulfates, is relevant to a number of biological processes, such as inflammation, tumor angiogenesis and metastasis. Heparin and heparan sulfate(HS), ubiquitously distributed on the cell surface and in the extracellular matrix, play significant roles in a diverse set of biological processes, including cell growth, virus infection, and tumor metastasis. The substrate specificity of the purified recombinant human heparinase has been investigated, and an optimal tetrasaccharide substrate of heparinase was found to be DHexUA(2S)-GlcN(NS, 6S)-GlcUA-GlcN(NS, 6S). Here we report an efficient alternative to the chemical synthesis of oligosaccharides relevant to the substrates of heparanase, including the stereoselective construction of a-GlcN-(1→4)-GlcA glycoside bonds and the effective post-assembly manipulations on the fully elaborated oligosaccharides. The dehydrative glycosylation protocol, capitalizing on direct activation of C1-hemiacetals as glycosyl donors, was employed to construct the challenging a-GlcN-(1→4)-GlcA linkages, using diphenyl sulfoxide(Ph2SO)/triflic anhydride(Tf2O) as promoters, 2, 4, 6-tri-tert- butylpyrimidine(TTBP) as base, toluene as a solvent, and －60 ℃ to room temperature as the working temperature. Under these optimized conditions, mono- and disaccharide donors(9 and 10) and disaccharide acceptors(11 and 12) were condensed to provide the coupled tri- and tetrasaccharides 5~8 in good yields and satisfactory stereoselectivity(>65% yield and a/b>5.4/1.0). The fully elaborated oligosaccharides 5~8 have then been successfully transformed into the target heparin oligosaccharides 1~4 via an effective sequence of manipulation of the protecting groups(>52% yield for 5 steps). The post-assembly manipulations include saponification under Zemplén conditions(for removal of benzyl ester and benzoyl group), O-sulfonation with sulfur trioxide pyridine complex(for hydroxyl groups), reduction and N-sulfonation(for azido group), and high pressure hydrogenation(for removal of benzyl groups). The availability of these heparin oligosaccharides would facilitate in-depth elucidation of the substrate selectivity of heparanase and the development of an effective assay for measuring the heparanase activities.
2020, 78(8): 778-787
doi: 10.6023/A20030092
Abstract:
In metallocene-mediated propylene polymerization, β-methyl elimination (β-Me elimination) is considered as the key chain-release step for obtaining allyl-terminated products, which are highly preferred as macro(co)monomers or building blocks for preparing novel polymers. However, for most metallocene catalysts the transfer of a β-methyl is instinctively less favored due to its steric and electronic disadvantages. Up to date, very few cases have been found to be efficient for triggering selective β-methyl elimination. In this work, a series of novel ansa-metallocene complexes, ansa-C2H4-{2-Me-3-Bn- 5, 6-[1, 3-(CH2)3]Ind}(Flu)ZrCl2 (C1), ansa-C2H4-{2-Me-3-Bn-5, 6-[1, 3-(CH2)3]Ind}(2, 7-tBu2-Flu)ZrCl2 (C2), ansa-C2H4-{2-Me-3-Bn-5, 6-[1, 3-(CH2)3]Ind}(3, 6-tBu2-Flu)ZrCl2 (C3) and ansa-C2H4-{2-Me-3-Bn-5, 6-[1, 3-(CH2)3]Ind}(Flu)HfCl2 (C4), were synthesized via the reaction of the dilithium salts of the corresponding proligand with 1 equiv. of ZrCl4 or HfCl4 in Et2O. All complexes were characterized by 1H NMR, 13C NMR and elemental analysis. The molecular structures of complexes C1, C2, and C3 were further determined via X-ray diffraction method. In the solid state, these complexes adopted an indenyl-backward orientation with rotation angles (RA: the orientation of the indenyl ring with respect to the fluorenyl ring) ranging from －11.30° to －17.07°. Upon activation with modified methylaluminoxane (MMAO) or AliBu3/ [Ph3C][B(C6F5)4] (TIBA/TrB), all these complexes exhibited moderate to high activities for propylene oligomerization at 40~100 ℃, affording propylene oligomers with both allyl and vinylidene chain-ends, which arised from β-Me elimination and β-H eliminations respectively. The methyl group at the 2-position of the indenyl ring turned out to have negative effects on both catalytic activity and β-Me elimination selectivity. Zirconocene complex C1 polymerized propylene to give oligomers with 40%~52% allyl chain-ends. However, further modification of the fluorenyl moiety allowed a great improvement in β-Me elimination selectivity. At 40~100 ℃, zirconocene complexes C2 and C3 bearing a 2, 7- or 3, 6-di-tert-butyl- substituted fluorenyl moiety showed significantly higher β-Me elimination selectivities (C2, 81%~86%; C3, 68%~77%), affording propylene oligomers (Mn 400~4500 g·mol－1) with allyl-dominant chain-ends. Moreover the substitution pattern of the fluorenyl moiety also substantially influenced the catalytic activities. The incorporation of an electron-donating 2, 7-di-tert-butyl groups on the fluorenyl moiety led to notably increased catalytic activities of complex C2 at higher temper-atures above 60 ℃, while complex C3 bearing a 3, 6-di-tert-butyl-substituted fluorenyl moiety showed lowest activities among the zirconocene series due to its overcrowded coordination sites. Compared with its zirconocene analogue, the hafnocene complex C4 activated with TIBA/TrB proved to be even more selective toward β-Me elimination, and meanwhile gave products with much lower molecular weights. At 100 ℃, the hafnocene system mainly oligomerized propylene to dimers and trimers. Studies on the dependence of the product molecular weight and the chain-release selectivity on monomer concentration suggested that both β-Me and β-H elimination involved in these systems mainly operate in a bimolecular pathway.
In metallocene-mediated propylene polymerization, β-methyl elimination (β-Me elimination) is considered as the key chain-release step for obtaining allyl-terminated products, which are highly preferred as macro(co)monomers or building blocks for preparing novel polymers. However, for most metallocene catalysts the transfer of a β-methyl is instinctively less favored due to its steric and electronic disadvantages. Up to date, very few cases have been found to be efficient for triggering selective β-methyl elimination. In this work, a series of novel ansa-metallocene complexes, ansa-C2H4-{2-Me-3-Bn- 5, 6-[1, 3-(CH2)3]Ind}(Flu)ZrCl2 (C1), ansa-C2H4-{2-Me-3-Bn-5, 6-[1, 3-(CH2)3]Ind}(2, 7-tBu2-Flu)ZrCl2 (C2), ansa-C2H4-{2-Me-3-Bn-5, 6-[1, 3-(CH2)3]Ind}(3, 6-tBu2-Flu)ZrCl2 (C3) and ansa-C2H4-{2-Me-3-Bn-5, 6-[1, 3-(CH2)3]Ind}(Flu)HfCl2 (C4), were synthesized via the reaction of the dilithium salts of the corresponding proligand with 1 equiv. of ZrCl4 or HfCl4 in Et2O. All complexes were characterized by 1H NMR, 13C NMR and elemental analysis. The molecular structures of complexes C1, C2, and C3 were further determined via X-ray diffraction method. In the solid state, these complexes adopted an indenyl-backward orientation with rotation angles (RA: the orientation of the indenyl ring with respect to the fluorenyl ring) ranging from －11.30° to －17.07°. Upon activation with modified methylaluminoxane (MMAO) or AliBu3/ [Ph3C][B(C6F5)4] (TIBA/TrB), all these complexes exhibited moderate to high activities for propylene oligomerization at 40~100 ℃, affording propylene oligomers with both allyl and vinylidene chain-ends, which arised from β-Me elimination and β-H eliminations respectively. The methyl group at the 2-position of the indenyl ring turned out to have negative effects on both catalytic activity and β-Me elimination selectivity. Zirconocene complex C1 polymerized propylene to give oligomers with 40%~52% allyl chain-ends. However, further modification of the fluorenyl moiety allowed a great improvement in β-Me elimination selectivity. At 40~100 ℃, zirconocene complexes C2 and C3 bearing a 2, 7- or 3, 6-di-tert-butyl- substituted fluorenyl moiety showed significantly higher β-Me elimination selectivities (C2, 81%~86%; C3, 68%~77%), affording propylene oligomers (Mn 400~4500 g·mol－1) with allyl-dominant chain-ends. Moreover the substitution pattern of the fluorenyl moiety also substantially influenced the catalytic activities. The incorporation of an electron-donating 2, 7-di-tert-butyl groups on the fluorenyl moiety led to notably increased catalytic activities of complex C2 at higher temper-atures above 60 ℃, while complex C3 bearing a 3, 6-di-tert-butyl-substituted fluorenyl moiety showed lowest activities among the zirconocene series due to its overcrowded coordination sites. Compared with its zirconocene analogue, the hafnocene complex C4 activated with TIBA/TrB proved to be even more selective toward β-Me elimination, and meanwhile gave products with much lower molecular weights. At 100 ℃, the hafnocene system mainly oligomerized propylene to dimers and trimers. Studies on the dependence of the product molecular weight and the chain-release selectivity on monomer concentration suggested that both β-Me and β-H elimination involved in these systems mainly operate in a bimolecular pathway.
2020, 78(8): 788-796
doi: 10.6023/A20050161
Abstract:
Azulene, a bicyclic nonbenzenoid aromatic hydrocarbon, shows completely different physicochemical properties compared with its isomeric naphthalene. Herein, we made use of the diverse reactivity of each position on azulene to design a new synthetic strategy for azulene-based diimides bridged by phenyl or thieno[3, 2-b]thiophenyl group, 2-(azulen-2'-yl)-5-(azulen-2''-yl)benzene-1, 1':4, 1''-tetracarboxylic diimides (AzAzBDI-1/2) and 2-(azulen-2'-yl)-5- (azulen-2''-yl)thieno[3, 2-b]thiophene-3, 1':6, 1''-tetracarboxylic diimide (AzAzTTDI). The key step was double trifluoroacetylation at 1-position of two azulene moieties of the molecule followed by hydrolysis, anhydridization and imidization to obtain the target compounds. The single crystal structure analysis demonstrates that AzAzBDI-2 has twisted molecular backbone. The adjacent two molecules form a dimer through the intermolecular π-π stacking (0.365 nm) between the five-membered ring and the seven-membered ring of two different azulene units. Strong π-π intermolecular interactions (0.355 nm) exist among the dimers to form a slipped one-dimensional (1D) packing motif in the crystal. For three compounds, the optoelectronic properties were investigated by UV-vis absorption spectra and cyclic voltammetry, and their energy levels of highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) and the energy gaps were calculated. The HOMO/LUMO energy levels of AzAzBDI-1, AzAzBDI-2 and AzAzTTDI are －5.56/－3.28 eV, －5.56/ －3.30 eV and －5.57/－3.42 eV, respectively. The end absorptions of AzAzBDI-1, AzAzBDI-2 and AzAzTTDI in thin films show obvious red-shift (13, 13 and 25 nm) relative to those in CHCl3 solution, indicating strong intermolecular interactions in solid state. The charge carrier transport properties of three compounds were studied through organic field-effect transistors (OFETs). Bottom-gate and top-contact OFET devices of AzAzBDI-1, AzAzBDI-2 and AzAzTTDI were fabricated by spin-coated their respective solution on octadecyltrimethoxysilane (OTMS)-treated SiO2/Si substrates. Under nitrogen atmosphere, all of these three compounds displayed electron-dominated ambipolar organic semiconductor characteristics. The electron mobilities of AzAzBDI-1 and AzAzBDI-2 were 0.068 cm2·V－1·s－1 and 0.086 cm2·V－1·s－1 and the hole mobility were 3.1×10－4 cm2·V－1·s－1 and 1.5×10－3 cm2·V－1·s－1, respectively. OFETs based on AzAzTTDI showed the highest electron mobility and hole mobilities of 0.087 cm2·V－1·s－1 and 8.8×10－3 cm2·V－1·s－1, respectively. The X-ray diffraction (XRD) and atomic force microscopy (AFM) studies demonstrate thin films of AzAzBDI-1, AzAzBDI-2 and AzAzTTDI show better crystallinity and form larger size of microstructures by annealing, which is consistent with the enhanced device performance after thermal annealing.
Azulene, a bicyclic nonbenzenoid aromatic hydrocarbon, shows completely different physicochemical properties compared with its isomeric naphthalene. Herein, we made use of the diverse reactivity of each position on azulene to design a new synthetic strategy for azulene-based diimides bridged by phenyl or thieno[3, 2-b]thiophenyl group, 2-(azulen-2'-yl)-5-(azulen-2''-yl)benzene-1, 1':4, 1''-tetracarboxylic diimides (AzAzBDI-1/2) and 2-(azulen-2'-yl)-5- (azulen-2''-yl)thieno[3, 2-b]thiophene-3, 1':6, 1''-tetracarboxylic diimide (AzAzTTDI). The key step was double trifluoroacetylation at 1-position of two azulene moieties of the molecule followed by hydrolysis, anhydridization and imidization to obtain the target compounds. The single crystal structure analysis demonstrates that AzAzBDI-2 has twisted molecular backbone. The adjacent two molecules form a dimer through the intermolecular π-π stacking (0.365 nm) between the five-membered ring and the seven-membered ring of two different azulene units. Strong π-π intermolecular interactions (0.355 nm) exist among the dimers to form a slipped one-dimensional (1D) packing motif in the crystal. For three compounds, the optoelectronic properties were investigated by UV-vis absorption spectra and cyclic voltammetry, and their energy levels of highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) and the energy gaps were calculated. The HOMO/LUMO energy levels of AzAzBDI-1, AzAzBDI-2 and AzAzTTDI are －5.56/－3.28 eV, －5.56/ －3.30 eV and －5.57/－3.42 eV, respectively. The end absorptions of AzAzBDI-1, AzAzBDI-2 and AzAzTTDI in thin films show obvious red-shift (13, 13 and 25 nm) relative to those in CHCl3 solution, indicating strong intermolecular interactions in solid state. The charge carrier transport properties of three compounds were studied through organic field-effect transistors (OFETs). Bottom-gate and top-contact OFET devices of AzAzBDI-1, AzAzBDI-2 and AzAzTTDI were fabricated by spin-coated their respective solution on octadecyltrimethoxysilane (OTMS)-treated SiO2/Si substrates. Under nitrogen atmosphere, all of these three compounds displayed electron-dominated ambipolar organic semiconductor characteristics. The electron mobilities of AzAzBDI-1 and AzAzBDI-2 were 0.068 cm2·V－1·s－1 and 0.086 cm2·V－1·s－1 and the hole mobility were 3.1×10－4 cm2·V－1·s－1 and 1.5×10－3 cm2·V－1·s－1, respectively. OFETs based on AzAzTTDI showed the highest electron mobility and hole mobilities of 0.087 cm2·V－1·s－1 and 8.8×10－3 cm2·V－1·s－1, respectively. The X-ray diffraction (XRD) and atomic force microscopy (AFM) studies demonstrate thin films of AzAzBDI-1, AzAzBDI-2 and AzAzTTDI show better crystallinity and form larger size of microstructures by annealing, which is consistent with the enhanced device performance after thermal annealing.
2020, 78(8): 797-804
doi: 10.6023/A20050146
Abstract:
Nitroxyl (HNO), produced by nitric oxide (NO) with one-electron reduction and protonation, has recently received substantial interest due to its important roles in various biological functions and pharmacological activities. Research indicates that HNO also has many potential pharmacological applications for different diseases. Therefore, the development of a reliable method for HNO assay in biosystems is highly desired. Ratiometric fluorescent probes show significant advantages over traditional "turn-on" ones, because simultaneous measurement of two emission signals can provide a built-in correction and thus minimize the inaccurate fluorescence signal readouts. As far as we know, there is no ratiometric fluorescent probe for HNO detection based on upconversion nanoparticles (UCNPs). Herein, a ratiometric nanoprobe for HNO assay was constructed based on the luminescence resonance energy transfer (LRET) principle by using UCNPs with a core-shell structure (NaYbF4:30%Gd@NaYF4:2%Yb:1%Tm) as the energy donor and an organic dye Fl-TP as the potential energy acceptor. The oleate-coated UCNPs (OA-UCNPs) and Fl-TP were assembled through hydrophobic interaction to construct the upconversion nanoprobe (termed as Fl-TP-UCNPs). Because of the ring-closed form, Fl-TP displayed weak absorption and was non-fluorescent, which blocked the LRET process. After reaction with HNO, the triphenylphosphine moiety left and released Fl-HNO with the fluorescent ring-open form. Fl-HNO showed strong absorption in the range of 400~500 nm, which completely overlapped with the blue luminescence of UCNPs and triggered the LRET process between UCNPs and Fl-HNO. Thus, the luminescence from UCNPs around 480 nm decreased and the emission from Fl-HNO around 525 nm increased with a [HNO]-dependent manner. The ratiometric luminescence intensity F525 nm/F480 nm showed a good linear relationship (R2＝0.9914) to the logarithm of AS (Angeli's salt, a generally used HNO donor) concentration in the range of 3~100 μmol·L－1 and the limit of detection was 23.4 nmol·L－1. The excellent sensitivity, stability, selectivity and low cytotoxicity endow Fl-TP-UCNPs with the superior capability for HNO assay in vitro and in vivo. We found that Fl-TP-UCNPs probe is appropriate for monitoring HNO in living cells as well as imaging HNO in liver tissues. This probe may be a powerful tool for HNO assay in various physiological processes.
Nitroxyl (HNO), produced by nitric oxide (NO) with one-electron reduction and protonation, has recently received substantial interest due to its important roles in various biological functions and pharmacological activities. Research indicates that HNO also has many potential pharmacological applications for different diseases. Therefore, the development of a reliable method for HNO assay in biosystems is highly desired. Ratiometric fluorescent probes show significant advantages over traditional "turn-on" ones, because simultaneous measurement of two emission signals can provide a built-in correction and thus minimize the inaccurate fluorescence signal readouts. As far as we know, there is no ratiometric fluorescent probe for HNO detection based on upconversion nanoparticles (UCNPs). Herein, a ratiometric nanoprobe for HNO assay was constructed based on the luminescence resonance energy transfer (LRET) principle by using UCNPs with a core-shell structure (NaYbF4:30%Gd@NaYF4:2%Yb:1%Tm) as the energy donor and an organic dye Fl-TP as the potential energy acceptor. The oleate-coated UCNPs (OA-UCNPs) and Fl-TP were assembled through hydrophobic interaction to construct the upconversion nanoprobe (termed as Fl-TP-UCNPs). Because of the ring-closed form, Fl-TP displayed weak absorption and was non-fluorescent, which blocked the LRET process. After reaction with HNO, the triphenylphosphine moiety left and released Fl-HNO with the fluorescent ring-open form. Fl-HNO showed strong absorption in the range of 400~500 nm, which completely overlapped with the blue luminescence of UCNPs and triggered the LRET process between UCNPs and Fl-HNO. Thus, the luminescence from UCNPs around 480 nm decreased and the emission from Fl-HNO around 525 nm increased with a [HNO]-dependent manner. The ratiometric luminescence intensity F525 nm/F480 nm showed a good linear relationship (R2＝0.9914) to the logarithm of AS (Angeli's salt, a generally used HNO donor) concentration in the range of 3~100 μmol·L－1 and the limit of detection was 23.4 nmol·L－1. The excellent sensitivity, stability, selectivity and low cytotoxicity endow Fl-TP-UCNPs with the superior capability for HNO assay in vitro and in vivo. We found that Fl-TP-UCNPs probe is appropriate for monitoring HNO in living cells as well as imaging HNO in liver tissues. This probe may be a powerful tool for HNO assay in various physiological processes.
2020, 78(8): 805-814
doi: 10.6023/A20040128
Abstract:
Herein, we employ 2, 5-dimethoxyterephthalaldehyde (DMTA) containing ether oxygen group in the structure as the construction unit to react with tetra-(4-anilyl)-methane (TAM) through Schiff-based condensation reaction in a Teflon-lined autoclave to synthesize a novel three-dimensional covalent organic framework named DMTA-COF. Furthermore, the condensation reaction was confirmed by Fourier transform infrared spectroscopy (FT-IR). The crystal structure of DMTA-COF was analyzed by the powder X-ray diffraction (PXRD) measurement in conjunction with structural simulation. The morphology, thermal stability, porosity and pore distribution of DMTA-COF were measured by scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and N2 adsorption-desorption at 77 K. The high affinity for CO2 adsorption was also confirmed by low pressure CO2 sorption. Considering the relatively small pore size and the strong CO2 adsorption interaction of DMTA-COF due to an abundant of ether oxygen group and imine linkage, we synthesized one continuous supported DMTA-COF membrane for H2/CO2 separation. In our study, the porous Al2O3 support surface was first coated with polyaniline (PANI) and was then further functionalized with aldehyde groups by reaction with DMTA at 150 ℃ for 1 h. Finally, in situ growth of the COF membrane utilizing the covalent linkage yielded a novel continuous DMTA-COF membrane. X-ray diffraction (XRD) result indicated that the DMTA-COF membrane was pure phase and had high crystallinity. From SEM characterization, we could see that the DMTA-COF membrane was compact and well intergrowth and adhered to the support tightly. Gas separation performance results shown that DMTA-COF membrane had a high H2 permeance and selectivity of H2/CO2. For DMTA-COF membrane, the 1:1 binary mixture gas separation factors of H2/CO2 calculated as the gas molar ratios in permeate and retentate side was 8.3 at room temperature and atmospheric pressure. And H2/CO2 separation factor of DMTA-COF membrane exceeded the corresponding Knudsen coefficient (4.7), with H2 permeance of up to 6.3×10－7 mol·m－2·s－1·Pa－1. Because of its outstanding characteristics, the novel DMTA-COF membrane is expected to be widely used in the field of H2 purification and separation.
Herein, we employ 2, 5-dimethoxyterephthalaldehyde (DMTA) containing ether oxygen group in the structure as the construction unit to react with tetra-(4-anilyl)-methane (TAM) through Schiff-based condensation reaction in a Teflon-lined autoclave to synthesize a novel three-dimensional covalent organic framework named DMTA-COF. Furthermore, the condensation reaction was confirmed by Fourier transform infrared spectroscopy (FT-IR). The crystal structure of DMTA-COF was analyzed by the powder X-ray diffraction (PXRD) measurement in conjunction with structural simulation. The morphology, thermal stability, porosity and pore distribution of DMTA-COF were measured by scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and N2 adsorption-desorption at 77 K. The high affinity for CO2 adsorption was also confirmed by low pressure CO2 sorption. Considering the relatively small pore size and the strong CO2 adsorption interaction of DMTA-COF due to an abundant of ether oxygen group and imine linkage, we synthesized one continuous supported DMTA-COF membrane for H2/CO2 separation. In our study, the porous Al2O3 support surface was first coated with polyaniline (PANI) and was then further functionalized with aldehyde groups by reaction with DMTA at 150 ℃ for 1 h. Finally, in situ growth of the COF membrane utilizing the covalent linkage yielded a novel continuous DMTA-COF membrane. X-ray diffraction (XRD) result indicated that the DMTA-COF membrane was pure phase and had high crystallinity. From SEM characterization, we could see that the DMTA-COF membrane was compact and well intergrowth and adhered to the support tightly. Gas separation performance results shown that DMTA-COF membrane had a high H2 permeance and selectivity of H2/CO2. For DMTA-COF membrane, the 1:1 binary mixture gas separation factors of H2/CO2 calculated as the gas molar ratios in permeate and retentate side was 8.3 at room temperature and atmospheric pressure. And H2/CO2 separation factor of DMTA-COF membrane exceeded the corresponding Knudsen coefficient (4.7), with H2 permeance of up to 6.3×10－7 mol·m－2·s－1·Pa－1. Because of its outstanding characteristics, the novel DMTA-COF membrane is expected to be widely used in the field of H2 purification and separation.
