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2018 Volume 76 Issue 5
2018, 76(5): 329-346
doi: 10.6023/A18020076
Abstract:
In biological system, metalloenzymes utilize dioxygen for metabolically oxidative transformations, in which organic compounds can be oxidized efficiently. Therefore, it is of great interest to unravel the enzymatic mechanism in the development of clean and efficient catalytic oxidation reactions. In the dioxygen activation by metalloenzymes, a series of metal-oxygen adducts, such as metal-superoxo, -peroxo, -hydroperoxo, -oxo and -hydroxo species, are formed as the active intermediates. In general, these intermeditates are difficult to capture for further characterizations and investigations because of their unstability and the complicated enzymatic systems. Alternatively, the enzyme models, designed and synthesized by mimicking the active center and coordination environment of metalloenzymes, can be easily acquired and manipulated for further structure and reactivity studies. In this review, we briefly illustrate the active sites of metalloenzymes in biology and focus on the recent achievements in mononuclear iron-oxygen and manganese-oxygen adducts in biomimetic studies.
In biological system, metalloenzymes utilize dioxygen for metabolically oxidative transformations, in which organic compounds can be oxidized efficiently. Therefore, it is of great interest to unravel the enzymatic mechanism in the development of clean and efficient catalytic oxidation reactions. In the dioxygen activation by metalloenzymes, a series of metal-oxygen adducts, such as metal-superoxo, -peroxo, -hydroperoxo, -oxo and -hydroxo species, are formed as the active intermediates. In general, these intermeditates are difficult to capture for further characterizations and investigations because of their unstability and the complicated enzymatic systems. Alternatively, the enzyme models, designed and synthesized by mimicking the active center and coordination environment of metalloenzymes, can be easily acquired and manipulated for further structure and reactivity studies. In this review, we briefly illustrate the active sites of metalloenzymes in biology and focus on the recent achievements in mononuclear iron-oxygen and manganese-oxygen adducts in biomimetic studies.
2018, 76(5): 347-356
doi: 10.6023/A18010023
Abstract:
Isocyanide is an important reactive reactant containing stable divalent carbon atoms, which has been widely used in the construction of nitrogen compounds, new drugs and natural products. During the past decades, exhaustive efforts have been devoted to the discovery of highly efficient reactions involving isocyanide on the basis of the development of the Passerini and Ugi reactions. Several types of reactions involving isocyanides have been reported, such as nucleophilic attack, electrophilic addition, imidoylation reactions, and oxidation, etc. Recently, isocyanides have found a new application as versatile C1 building blocks in transition metal catalysis. The transition metal catalyzed reactions involving isocyanide insertion offer a vast potential to construct C—C or C-N bonds for the synthesis of nitrogen-containing fine chemicals. As we know, the catalysts used in isocyanide insertion reactions are mainly concentrated in some valuable transition metals compounds, such as Pd, Rh, Ag and other metals. Therefore, the development of catalysts based on the naturally more abundant, cost efficient transition metal complexes, represents an attractive alternative. In this context, rather environmentally benign cobalt complexes bear great potential for applications in the coupling reactions. The reduced electronegativity of cobalt as compared to the homologous group 9 elements translates into more nucleophilic organometallic cobalt intermediates which allow for unprecedented reaction pathways in transition-metal catalyzed C—H activations as well as significantly improved positional and chemo-selectivities. And in the recent years, notable success has been achieved with the development of cobalt catalyzed C—H functionalizations with either in situ generated or single-component cobalt-complexes under mild reaction conditions. How to find and use the cost efficient cobalt-complexes to catalyze the isocyanide coupling reaction is of great significance. Our group has been devoted to explore the isocyanide chemistry, and in recent years, we have achieved several progresses in the reaction of cobalt-catalyzed isocyanides. In this review we summarize the recent advances in the cobalt-catalyzed isocyanide coupling reactions.
Isocyanide is an important reactive reactant containing stable divalent carbon atoms, which has been widely used in the construction of nitrogen compounds, new drugs and natural products. During the past decades, exhaustive efforts have been devoted to the discovery of highly efficient reactions involving isocyanide on the basis of the development of the Passerini and Ugi reactions. Several types of reactions involving isocyanides have been reported, such as nucleophilic attack, electrophilic addition, imidoylation reactions, and oxidation, etc. Recently, isocyanides have found a new application as versatile C1 building blocks in transition metal catalysis. The transition metal catalyzed reactions involving isocyanide insertion offer a vast potential to construct C—C or C-N bonds for the synthesis of nitrogen-containing fine chemicals. As we know, the catalysts used in isocyanide insertion reactions are mainly concentrated in some valuable transition metals compounds, such as Pd, Rh, Ag and other metals. Therefore, the development of catalysts based on the naturally more abundant, cost efficient transition metal complexes, represents an attractive alternative. In this context, rather environmentally benign cobalt complexes bear great potential for applications in the coupling reactions. The reduced electronegativity of cobalt as compared to the homologous group 9 elements translates into more nucleophilic organometallic cobalt intermediates which allow for unprecedented reaction pathways in transition-metal catalyzed C—H activations as well as significantly improved positional and chemo-selectivities. And in the recent years, notable success has been achieved with the development of cobalt catalyzed C—H functionalizations with either in situ generated or single-component cobalt-complexes under mild reaction conditions. How to find and use the cost efficient cobalt-complexes to catalyze the isocyanide coupling reaction is of great significance. Our group has been devoted to explore the isocyanide chemistry, and in recent years, we have achieved several progresses in the reaction of cobalt-catalyzed isocyanides. In this review we summarize the recent advances in the cobalt-catalyzed isocyanide coupling reactions.
2018, 76(5): 357-365
doi: 10.6023/A18020054
Abstract:
Amides are a class of easily available compounds, and widely serve as versatile intermediates in organic synthesis and medicinal chemistry. Amide-based transformations could lead to many useful compounds and intermediates including various amines, ketones and enaminones. Though direct transformation of amides is of high demand, many current chemoselective transformations are only achieved in multistep approaches. In recent years, direct transformation of amides is emerging as an exciting area. A number of recent progresses on nucleophilic addition to amide carbonyl group that led to new C—C bond formation are highlighted in this review, including (1) in situ amide activation with trifluoromethanesulfonic anhydride (Tf2O) followed by addition of π- and σ-nucleophiles or reactive organometallic reagents; (2) direct transformation of N-alkoxyamides; (3) direct transformation of amides using Schwartz reagent; and (4) catalytic reductive C—C bond forming reactions of amides, and metal catalyzed coupling of amides.
Amides are a class of easily available compounds, and widely serve as versatile intermediates in organic synthesis and medicinal chemistry. Amide-based transformations could lead to many useful compounds and intermediates including various amines, ketones and enaminones. Though direct transformation of amides is of high demand, many current chemoselective transformations are only achieved in multistep approaches. In recent years, direct transformation of amides is emerging as an exciting area. A number of recent progresses on nucleophilic addition to amide carbonyl group that led to new C—C bond formation are highlighted in this review, including (1) in situ amide activation with trifluoromethanesulfonic anhydride (Tf2O) followed by addition of π- and σ-nucleophiles or reactive organometallic reagents; (2) direct transformation of N-alkoxyamides; (3) direct transformation of amides using Schwartz reagent; and (4) catalytic reductive C—C bond forming reactions of amides, and metal catalyzed coupling of amides.
2018, 76(5): 366-376
doi: 10.6023/A18020050
Abstract:
It is an effective way to solve the problems of environmental pollution and energy shortage by exploring and utilizing clean, renewable energy. Porous carbons which prepared by carbonized porous organic materials with high carbon content, have high specific surface area, good physical and chemical stability, and excellent mechanical performance, generally higher conductivity, therefore can be widely used in many fields, such as clean energy storage, different gases separation, and energy storage and conversion, etc. The common methods for preparing porous carbon from porous organic materials are divided into non-activated carbonization and activation carbonization. The morphology and pore structure of porous carbons which prepared by different preparation methods are different. The structure properties of porous carbon materials can affect their application. Reasonable design and utilization of the "pore" of porous carbon, displaying "sieving effect" of pore size can effectively store and separate the gas molecules. In the field of energy storage and conversion, such as lithium battery, the "confinement effect" is an important factor that affects the electrical performance of lithium battery. The smaller pores in the porous carbon materials can limited the active components, while the larger pores are in favor of rapidly diffusion, the synergistic effect of the two different type pores can greatly improve the electrical performance of lithium battery. This review systematically summarize the preparation methods of porous carbons derived from porous organic materials, and a brief comparison of different methods for preparing porous carbon is presented which proved that carbonized porous organic materials is a simple, efficient, environmentally friendly, and controllable pore structure method for the preparation of porous carbon with excellent performance. Then, the review describes in detail about the application of porous carbons in gas adsorption, storage, separation, energy storage and conversion. At the last, combination with the research status of porous carbons, the review points out the challenges for porous carbons, and also prospects the application of porous carbons.
It is an effective way to solve the problems of environmental pollution and energy shortage by exploring and utilizing clean, renewable energy. Porous carbons which prepared by carbonized porous organic materials with high carbon content, have high specific surface area, good physical and chemical stability, and excellent mechanical performance, generally higher conductivity, therefore can be widely used in many fields, such as clean energy storage, different gases separation, and energy storage and conversion, etc. The common methods for preparing porous carbon from porous organic materials are divided into non-activated carbonization and activation carbonization. The morphology and pore structure of porous carbons which prepared by different preparation methods are different. The structure properties of porous carbon materials can affect their application. Reasonable design and utilization of the "pore" of porous carbon, displaying "sieving effect" of pore size can effectively store and separate the gas molecules. In the field of energy storage and conversion, such as lithium battery, the "confinement effect" is an important factor that affects the electrical performance of lithium battery. The smaller pores in the porous carbon materials can limited the active components, while the larger pores are in favor of rapidly diffusion, the synergistic effect of the two different type pores can greatly improve the electrical performance of lithium battery. This review systematically summarize the preparation methods of porous carbons derived from porous organic materials, and a brief comparison of different methods for preparing porous carbon is presented which proved that carbonized porous organic materials is a simple, efficient, environmentally friendly, and controllable pore structure method for the preparation of porous carbon with excellent performance. Then, the review describes in detail about the application of porous carbons in gas adsorption, storage, separation, energy storage and conversion. At the last, combination with the research status of porous carbons, the review points out the challenges for porous carbons, and also prospects the application of porous carbons.
2018, 76(5): 377-381
doi: 10.6023/A18020073
Abstract:
Fluoren-9-ones derivatives have attracted much attention due to their extensively applications in pharmaceuticals, natural products and photoelectric materials. In recent decades, C—H bond functionalization is the most powerful method to access fluorenone skeleton. Although these interesting studies exploited highly efficient routes to the fluoren-9-one, in many examples, it is easy to produce two isomers in the meta-substituted substrates because of the existence of two different C—H bonds in the ortho-position. It is still indispensable to develop efficient methods for fluoren-9-ones construction. Diaryliodonium salt as a stable and easily prepared reagent reported by Hartmann and Meyer since 1894, which has been one of the most efficient arylation reagents in organic synthesis. Generally, diaryliodonium salt was employed as a single arylation reagent. In the past few years, the both aryl employments of diaryliodonium salt were explored due to the improvement of atom economy. Recently, we developed the atom exchange reactions of intramolecular and intermolecular diaryliodonium salts for sulfide, selenide, sulfone, acridine and carbazole constructions, which could employ both aryl groups of diaryliodonium salt. Continuous with our research of using such atom exchange method for significant molecular construction, herein, a CO/I exchange method of diaryliodonium salts with carbon monoxide was developed for construction of functional fluoren-9-ones. Both aryl groups in diaryliodonium salt were fully exerted in this transformation, which proceeded smoothly in a CO balloon atmosphere to afford the desired products in moderate to excellent yields with good functional-group compatibility. Note that this protocol avoided the emerging of isomers, which were easy to be formed in C—H bond functionalization method. A representative procedure for this reaction is as following:Under a CO atmosphere, Pd(OAc)2 (0.01 mmol), dppf (0.012 mmol), K3PO4 (0.2 mmol), diaryliodonium salts 1 and toluene (1 mL) were added to a flame-dried Schlenk tube. The resulting mixture was stirred at 80℃ for 24 h. Water (5 mL) was added and the solution was extracted with ethyl acetate, organic layers were combined, dried over sodium sulfate. After evaporation of solvent, the residue was purified by column chromatography to give the corresponding products.
Fluoren-9-ones derivatives have attracted much attention due to their extensively applications in pharmaceuticals, natural products and photoelectric materials. In recent decades, C—H bond functionalization is the most powerful method to access fluorenone skeleton. Although these interesting studies exploited highly efficient routes to the fluoren-9-one, in many examples, it is easy to produce two isomers in the meta-substituted substrates because of the existence of two different C—H bonds in the ortho-position. It is still indispensable to develop efficient methods for fluoren-9-ones construction. Diaryliodonium salt as a stable and easily prepared reagent reported by Hartmann and Meyer since 1894, which has been one of the most efficient arylation reagents in organic synthesis. Generally, diaryliodonium salt was employed as a single arylation reagent. In the past few years, the both aryl employments of diaryliodonium salt were explored due to the improvement of atom economy. Recently, we developed the atom exchange reactions of intramolecular and intermolecular diaryliodonium salts for sulfide, selenide, sulfone, acridine and carbazole constructions, which could employ both aryl groups of diaryliodonium salt. Continuous with our research of using such atom exchange method for significant molecular construction, herein, a CO/I exchange method of diaryliodonium salts with carbon monoxide was developed for construction of functional fluoren-9-ones. Both aryl groups in diaryliodonium salt were fully exerted in this transformation, which proceeded smoothly in a CO balloon atmosphere to afford the desired products in moderate to excellent yields with good functional-group compatibility. Note that this protocol avoided the emerging of isomers, which were easy to be formed in C—H bond functionalization method. A representative procedure for this reaction is as following:Under a CO atmosphere, Pd(OAc)2 (0.01 mmol), dppf (0.012 mmol), K3PO4 (0.2 mmol), diaryliodonium salts 1 and toluene (1 mL) were added to a flame-dried Schlenk tube. The resulting mixture was stirred at 80℃ for 24 h. Water (5 mL) was added and the solution was extracted with ethyl acetate, organic layers were combined, dried over sodium sulfate. After evaporation of solvent, the residue was purified by column chromatography to give the corresponding products.
2018, 76(5): 382-386
doi: 10.6023/A18040131
Abstract:
The bicyclic lactones possess multiple reactive sites, and are usually employed as the key intermediates in the synthesis of natural products and bioactive substances. Among the methods for the construction of these chiral skeletons, the asymmetric Diels-Alder (DA) reaction with 2-pyrone substrates represents one of the most straightforward protocols, generally with high stereocontrol. However, in regard to the electron-deficient 2-pyrone substrates, the corresponding asymmetric DA reactions usually rely on LUMO-activation by chiral Lewis acids, suffering from relatively narrow substitutions and functional group limitations. As a result, the development of new activation modes for this type of DA reactions is in high demand. Here we report an asymmetric inverse-electron-demand Diels-Alder (IEDDA) reaction of 3-methoxycarbonyl-2-pyrone and cyclic 2, 5-dienones in the presence of a primary amine derived from cinchona alkaloid, through the in situ generation of extended trienamine species. In this case, the remote δ, e-C=C bond of 2, 5-dienone substrates is activated via a HOMO-raising strategy. A variety of bicyclic lactones with contiguous stereogenic centers were produced in moderate to good yields (46%~82%) with excellent diastereo-and enantioselectivity (>19:1 dr, 93%~99% ee). In addition, the cycloadduct underwent the ring-opening reaction with methanol, affording a cyclohexenol derivative with dense substitutions in an excellent yield with a retained ee value. Therefore, the current method supplies an efficient tool to construct chiral bicyclic lactones with high molecular complexity under mild aminocatalytic conditions, which might have potential application in organic synthesis and medicinal chemistry. A representative procedure for the asymmetric IEDDA reaction is as follows:3-Methoxycarbonyl-2-pyrone 1 (0.1 mmol), cyclic 2, 5-dienone 2 (0.2 mmol), amine catalyst C2 (0.02 mmol) and acid A4 (0.04 mmol) were added into an oven-dried vial equipped with a magnetic stirbar. p-Xylene (1.0 mL) was added and the mixture was stirred at 60℃ and monitored by TLC. After completion, the residue was purified by flash chromatography on silica gel eluting with petroleum ether/ethyl acetate (8:1 to 4:1) to afford the product 3.
The bicyclic lactones possess multiple reactive sites, and are usually employed as the key intermediates in the synthesis of natural products and bioactive substances. Among the methods for the construction of these chiral skeletons, the asymmetric Diels-Alder (DA) reaction with 2-pyrone substrates represents one of the most straightforward protocols, generally with high stereocontrol. However, in regard to the electron-deficient 2-pyrone substrates, the corresponding asymmetric DA reactions usually rely on LUMO-activation by chiral Lewis acids, suffering from relatively narrow substitutions and functional group limitations. As a result, the development of new activation modes for this type of DA reactions is in high demand. Here we report an asymmetric inverse-electron-demand Diels-Alder (IEDDA) reaction of 3-methoxycarbonyl-2-pyrone and cyclic 2, 5-dienones in the presence of a primary amine derived from cinchona alkaloid, through the in situ generation of extended trienamine species. In this case, the remote δ, e-C=C bond of 2, 5-dienone substrates is activated via a HOMO-raising strategy. A variety of bicyclic lactones with contiguous stereogenic centers were produced in moderate to good yields (46%~82%) with excellent diastereo-and enantioselectivity (>19:1 dr, 93%~99% ee). In addition, the cycloadduct underwent the ring-opening reaction with methanol, affording a cyclohexenol derivative with dense substitutions in an excellent yield with a retained ee value. Therefore, the current method supplies an efficient tool to construct chiral bicyclic lactones with high molecular complexity under mild aminocatalytic conditions, which might have potential application in organic synthesis and medicinal chemistry. A representative procedure for the asymmetric IEDDA reaction is as follows:3-Methoxycarbonyl-2-pyrone 1 (0.1 mmol), cyclic 2, 5-dienone 2 (0.2 mmol), amine catalyst C2 (0.02 mmol) and acid A4 (0.04 mmol) were added into an oven-dried vial equipped with a magnetic stirbar. p-Xylene (1.0 mL) was added and the mixture was stirred at 60℃ and monitored by TLC. After completion, the residue was purified by flash chromatography on silica gel eluting with petroleum ether/ethyl acetate (8:1 to 4:1) to afford the product 3.
2018, 76(5): 387-392
doi: 10.6023/A18020067
Abstract:
With the development of nanoscience and nanotechnology, nanomaterials have been applied in many areas including environments. Silver nanoparticles (AgNPs) are being widely used in drinking water disinfection due to their excellent bactericidal performance. As the bactericide, AgNPs could minimize or eliminate bacteria exceeding standards and water treatment membrane fouling. Arsenic contamination, especially in the underground water, has gained great attention from the environmental science community, demanding effective methods to eliminate or remove more acutely toxic inorganic species[i.e., As(Ⅲ) and As(Ⅴ)]. Given the good photocatalytic activity, AgNPs could have an impact on the transformaiton of As(Ⅲ) and As(Ⅴ). In this study, high performance liquid chromatography (HPLC) coupled with inductively coupled plasma mass spectrometer (HPLC-ICP/MS) were used to investigate the effects of some environmental relative factors like pH, natural organic matter, cation ions (e.g., Ca2+), and the intrinsic properties of AgNPs like size and coatings, on the conversion of the two main inorganic arsenic[As(Ⅲ) and As(Ⅴ)] in the aqueous solution in the presence of AgNPs. It was found that AgNPs showed no physical adsorption for As(Ⅲ), while resulted in significant catalytic oxidation of As(Ⅲ) into As(Ⅴ). Moreover, environmental factors including pH, sunlight, NOM, Ca2+, and properties of AgNPs (e.g., size, coating) showed significant effects on the catalytic oxidation of As(Ⅲ). The catalytic oxidation was also confirmed in the real environmental waters. Finally, the catalytic ability of AuNPs and AgNPs were compared to unveil the mechanism of catalytic oxidation of As(Ⅲ) by AgNPs. In addition to oxidation of superoxo or peroxo species formed due to activation of molecular oxygen by the electron transfer from negatively charged AgNPs, the redox potential of silver (φΘAg+/Ag0=0.80 V) mostly contributed to the transformation of As(Ⅲ) into As(Ⅴ). Therefore, given the coexisting of As(Ⅲ) and AgNPs in the water treatment system, AgNPs could play dual function in both sterilization and detoxification of As(Ⅲ), which paved the novel way to effectively treat As contamination.
With the development of nanoscience and nanotechnology, nanomaterials have been applied in many areas including environments. Silver nanoparticles (AgNPs) are being widely used in drinking water disinfection due to their excellent bactericidal performance. As the bactericide, AgNPs could minimize or eliminate bacteria exceeding standards and water treatment membrane fouling. Arsenic contamination, especially in the underground water, has gained great attention from the environmental science community, demanding effective methods to eliminate or remove more acutely toxic inorganic species[i.e., As(Ⅲ) and As(Ⅴ)]. Given the good photocatalytic activity, AgNPs could have an impact on the transformaiton of As(Ⅲ) and As(Ⅴ). In this study, high performance liquid chromatography (HPLC) coupled with inductively coupled plasma mass spectrometer (HPLC-ICP/MS) were used to investigate the effects of some environmental relative factors like pH, natural organic matter, cation ions (e.g., Ca2+), and the intrinsic properties of AgNPs like size and coatings, on the conversion of the two main inorganic arsenic[As(Ⅲ) and As(Ⅴ)] in the aqueous solution in the presence of AgNPs. It was found that AgNPs showed no physical adsorption for As(Ⅲ), while resulted in significant catalytic oxidation of As(Ⅲ) into As(Ⅴ). Moreover, environmental factors including pH, sunlight, NOM, Ca2+, and properties of AgNPs (e.g., size, coating) showed significant effects on the catalytic oxidation of As(Ⅲ). The catalytic oxidation was also confirmed in the real environmental waters. Finally, the catalytic ability of AuNPs and AgNPs were compared to unveil the mechanism of catalytic oxidation of As(Ⅲ) by AgNPs. In addition to oxidation of superoxo or peroxo species formed due to activation of molecular oxygen by the electron transfer from negatively charged AgNPs, the redox potential of silver (φΘAg+/Ag0=0.80 V) mostly contributed to the transformation of As(Ⅲ) into As(Ⅴ). Therefore, given the coexisting of As(Ⅲ) and AgNPs in the water treatment system, AgNPs could play dual function in both sterilization and detoxification of As(Ⅲ), which paved the novel way to effectively treat As contamination.
2018, 76(5): 393-399
doi: 10.6023/A18010039
Abstract:
Ag2S quantum dot with excellent NIR-Ⅱ fluorescence can provide deeper tissue penetration (>1.1 cm) and higher spatiotemporal resolution (25 μm, 50 ms) in comparison to the conventional fluorophore. In this study, we designed a NIR-Ⅱ probe based Ag2S quantum dot for imaging of brain tumor. Angiopep-2 was used to modify Ag2S quantum dot, which is a 19-mer peptide exhibiting high binding efficiency with low-density lipoprotein receptor-related protein-1 (LRP-1) of blood brain barrier and glioma. Due to the surface of Ag2S quantum dots with carboxyl groups and angiopep-2 peptide with amino groups, Ag2S was conjugated with Angiopep-2 (Ag2S-ANG) through the condensation reaction of amino and carboxyl groups mediated by EDC and NHS. The structure, size and spectral properties of Ag2S-ANG were characterized by agarose electrophoresis, dynamic light scattering transmission, electron microscope (TEM), UV-vis spectrometer and NIR fluorescence spectrometer, respectively. Results showed that Ag2S-ANG had a short migration distance compared with Ag2S in the agarose gel electrophoresis. The hydrate particle size of Ag2S was approximately 6 nm, Ag2S-ANG was approximately 8 nm and its zeta potential exhibited electropositive reinforcement, zeta potential of Ag2S is -11.47±1.56 mV and Ag2S-ANG is +28.7±1.35 mV. Ag2S-ANG exhibited similar absorbance and fluorescence spectra to Ag2S, except a slight enhancement of emission peak. These results indicated that Ag2S-ANG was synthesized successfully. We further observed its cell cytotoxicity, distribution and uptake in Uppsala 87 Malignant Glioma cells(U87MG), and in vivo distribution in the solid tumor-bearing mouse. Ag2S-ANG had no obvious cytotoxicity when the concentration is inferior to 100 μg/mL and had more uptake in U87MG cells than that of Ag2S. In animal experiments, glioma tumor-bearing mice were used to investigate the distribution and tumor targeting of Ag2S-ANG. Results showed that Ag2S-ANG can distribute and accumulate in subcutaneous tumor site, indicating that Ag2S-ANG had the potential of targeting the glioma cells.
Ag2S quantum dot with excellent NIR-Ⅱ fluorescence can provide deeper tissue penetration (>1.1 cm) and higher spatiotemporal resolution (25 μm, 50 ms) in comparison to the conventional fluorophore. In this study, we designed a NIR-Ⅱ probe based Ag2S quantum dot for imaging of brain tumor. Angiopep-2 was used to modify Ag2S quantum dot, which is a 19-mer peptide exhibiting high binding efficiency with low-density lipoprotein receptor-related protein-1 (LRP-1) of blood brain barrier and glioma. Due to the surface of Ag2S quantum dots with carboxyl groups and angiopep-2 peptide with amino groups, Ag2S was conjugated with Angiopep-2 (Ag2S-ANG) through the condensation reaction of amino and carboxyl groups mediated by EDC and NHS. The structure, size and spectral properties of Ag2S-ANG were characterized by agarose electrophoresis, dynamic light scattering transmission, electron microscope (TEM), UV-vis spectrometer and NIR fluorescence spectrometer, respectively. Results showed that Ag2S-ANG had a short migration distance compared with Ag2S in the agarose gel electrophoresis. The hydrate particle size of Ag2S was approximately 6 nm, Ag2S-ANG was approximately 8 nm and its zeta potential exhibited electropositive reinforcement, zeta potential of Ag2S is -11.47±1.56 mV and Ag2S-ANG is +28.7±1.35 mV. Ag2S-ANG exhibited similar absorbance and fluorescence spectra to Ag2S, except a slight enhancement of emission peak. These results indicated that Ag2S-ANG was synthesized successfully. We further observed its cell cytotoxicity, distribution and uptake in Uppsala 87 Malignant Glioma cells(U87MG), and in vivo distribution in the solid tumor-bearing mouse. Ag2S-ANG had no obvious cytotoxicity when the concentration is inferior to 100 μg/mL and had more uptake in U87MG cells than that of Ag2S. In animal experiments, glioma tumor-bearing mice were used to investigate the distribution and tumor targeting of Ag2S-ANG. Results showed that Ag2S-ANG can distribute and accumulate in subcutaneous tumor site, indicating that Ag2S-ANG had the potential of targeting the glioma cells.
2018, 76(5): 400-407
doi: 10.6023/A18010030
Abstract:
Ion channels in cell membranes play crucial roles in many biological activities. Many artificial nanochannels have been constructed to mimic the organism functions and sensitive to external stimuli. The artificial nanochannels have drawn enormous research attention due to their potential applications and simplicity. In this work, the hourglass shaped alumina nanochannels were fabricated using a double-sided anodization method with an in situ pore opening process. We constructed organic-inorganic heterogeneous nanochannels based on anodic alumina oxide (AAO) and transparent tape by the method of heat treatment. The surface morphology and component of nanoporous heterogeneous membrane were characterized by scanning electron microscope (SEM) and ATR-FTIR spectrum. These two kinds of nanochannels have differential diameters and amphoteric characteristics. Heterogeneous nanochannels are composed of organic nanochannels and AAO pores containing carboxyl and hydroxyl groups, respectively. Ion transport through the heterogeneous nanochannels can be modulated, because of the protonation state of the nanochannels under different pH conditions. Because of the heterogeneity of structure and charge, heterojunction is formed in the junction of anodic alumina oxide nanochannels and organic nanochannels. Such an abrupt junction yields a more efficient control of ion accumulation and depletion in the heterogeneous nanochannel. The ionic transport properties of heterogeneous nanochannels can be studied by measuring the current-voltage (I-V) curves. The heterogeneous nanochannels exhibit pH sensitivity. Changing the pH value from acidic to alkaline values, a significant decrease in positive charges and the deprotonated carboxyl group with negative charges can be observed. Due to the synergistic effect of the nanoporous AAO and organic nanochannels, heterogeneous nanochannels exhibit high and controllable rectification with single rectification direction over a wide pH range. The diode-like behavior is quantified by measuring the current rectification ratios. The novel strategy introduced here is a low-cost, scalable, and robust alternative for the fabrication of heterogeneous nanochannels system for nanofluidic applications. This porous heterogeneous membrane have potential applications in the fields of ion transport, separation of biomolecules and energy conversion system.
Ion channels in cell membranes play crucial roles in many biological activities. Many artificial nanochannels have been constructed to mimic the organism functions and sensitive to external stimuli. The artificial nanochannels have drawn enormous research attention due to their potential applications and simplicity. In this work, the hourglass shaped alumina nanochannels were fabricated using a double-sided anodization method with an in situ pore opening process. We constructed organic-inorganic heterogeneous nanochannels based on anodic alumina oxide (AAO) and transparent tape by the method of heat treatment. The surface morphology and component of nanoporous heterogeneous membrane were characterized by scanning electron microscope (SEM) and ATR-FTIR spectrum. These two kinds of nanochannels have differential diameters and amphoteric characteristics. Heterogeneous nanochannels are composed of organic nanochannels and AAO pores containing carboxyl and hydroxyl groups, respectively. Ion transport through the heterogeneous nanochannels can be modulated, because of the protonation state of the nanochannels under different pH conditions. Because of the heterogeneity of structure and charge, heterojunction is formed in the junction of anodic alumina oxide nanochannels and organic nanochannels. Such an abrupt junction yields a more efficient control of ion accumulation and depletion in the heterogeneous nanochannel. The ionic transport properties of heterogeneous nanochannels can be studied by measuring the current-voltage (I-V) curves. The heterogeneous nanochannels exhibit pH sensitivity. Changing the pH value from acidic to alkaline values, a significant decrease in positive charges and the deprotonated carboxyl group with negative charges can be observed. Due to the synergistic effect of the nanoporous AAO and organic nanochannels, heterogeneous nanochannels exhibit high and controllable rectification with single rectification direction over a wide pH range. The diode-like behavior is quantified by measuring the current rectification ratios. The novel strategy introduced here is a low-cost, scalable, and robust alternative for the fabrication of heterogeneous nanochannels system for nanofluidic applications. This porous heterogeneous membrane have potential applications in the fields of ion transport, separation of biomolecules and energy conversion system.
2018, 76(5): 408-414
doi: 10.6023/A18020060
Abstract:
In this paper, human serum albumin (HSA) binding to small molecule 2, 2', 4, 4', 5, 6'-hexabromodiphenyl ether (BDE154) is studied by means of inducing protonation or deprotonation at four different pH levels (pH=3.0, 6.0, 7.4, 9.0). Firstly, it has been indicated that the charge distribution on HSA is very uniform even after protonation of HSA at different pH levels. From this, it can be inferred that the uniform charge distribution makes the electrostatic forces between the amino acid residues of the ⅡA region of HSA aspartic acid (Asp), glutamate (Glu) and histidine (His) to gradually reach a relative equilibrium and thus stabilize the HSA conformation. The results from synchronous fluorescence spectroscopy show that BDE154 has been bind to the ⅡA region of HSA, and is more closely to tryptophan (Try), and that causes the fluorescence quenching of HSA. After that, the semi-flexible docking of HSA with BDE 154 reveals that BDE154 has a cationic-π-conjugated effect and strong hydrophobic interaction with the surrounding amino acids, such as tyrosine 150 (Tyr150), lysine 195 (Lys195), lysine 199 (Lys199), etc. Next, the dynamic and thermodynamic properties of HSA under different protonation conditions have been studied by using molecular dynamic simulation. The results of simulation also show that too much positive charge deteriorates the system stability of HSA or HSA-BDE154 complex. Then, the binding free energy of HSA-BDE154 complex under different protonation states has been predicted by MM-PBSA method, and the contribution of amino acid residues to free energy of binding has also been analyzed. In addition, lysine 199 (Lys199), leucine 238 (Leu238), arginine 257 (Arg257), alanine 261 (Ala261), and isoleucine 264 (Ile264) in the HSA, being located in the hydrophobic cavity in subdomain ⅡA, are the most important residues when binding with BDE154. Therefore, the hydrophobic interaction has been identified as the major driving force for the binding between HSA-BDE154 systems, which is consistent with the results of molecular docking and the analysis of binding free energy. Finally, the results of secondary structure analysis of molecular dynamics simulation show that the binding could promote the de-helix process of HSA by increasing the acidity in HSA-BDE154 complex system.
In this paper, human serum albumin (HSA) binding to small molecule 2, 2', 4, 4', 5, 6'-hexabromodiphenyl ether (BDE154) is studied by means of inducing protonation or deprotonation at four different pH levels (pH=3.0, 6.0, 7.4, 9.0). Firstly, it has been indicated that the charge distribution on HSA is very uniform even after protonation of HSA at different pH levels. From this, it can be inferred that the uniform charge distribution makes the electrostatic forces between the amino acid residues of the ⅡA region of HSA aspartic acid (Asp), glutamate (Glu) and histidine (His) to gradually reach a relative equilibrium and thus stabilize the HSA conformation. The results from synchronous fluorescence spectroscopy show that BDE154 has been bind to the ⅡA region of HSA, and is more closely to tryptophan (Try), and that causes the fluorescence quenching of HSA. After that, the semi-flexible docking of HSA with BDE 154 reveals that BDE154 has a cationic-π-conjugated effect and strong hydrophobic interaction with the surrounding amino acids, such as tyrosine 150 (Tyr150), lysine 195 (Lys195), lysine 199 (Lys199), etc. Next, the dynamic and thermodynamic properties of HSA under different protonation conditions have been studied by using molecular dynamic simulation. The results of simulation also show that too much positive charge deteriorates the system stability of HSA or HSA-BDE154 complex. Then, the binding free energy of HSA-BDE154 complex under different protonation states has been predicted by MM-PBSA method, and the contribution of amino acid residues to free energy of binding has also been analyzed. In addition, lysine 199 (Lys199), leucine 238 (Leu238), arginine 257 (Arg257), alanine 261 (Ala261), and isoleucine 264 (Ile264) in the HSA, being located in the hydrophobic cavity in subdomain ⅡA, are the most important residues when binding with BDE154. Therefore, the hydrophobic interaction has been identified as the major driving force for the binding between HSA-BDE154 systems, which is consistent with the results of molecular docking and the analysis of binding free energy. Finally, the results of secondary structure analysis of molecular dynamics simulation show that the binding could promote the de-helix process of HSA by increasing the acidity in HSA-BDE154 complex system.
