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2016 Volume 74 Issue 3
2016, 74(3): 219-233
doi: 10.6023/A16020078
Abstract:
Palladium-catalyzed allylic substitution is one of the most important methodologies for the construction of C—C and C—X bonds, and has been widely applied in the synthesis of bioactive natural and pharmaceutical products. Tremendous progress has been made towards the development of increasingly elaborate nucleophiles and catalysts to facilitate the aforementioned reaction. Despite significant advances, Pd-catalyzed allylic substitution reactions remain limited to substrates possessing a good leaving group such as a carboxylate, carbonate, phosphate, or other related derivatives on the allylic moiety. Allylic alcohols and amines have also gained attention for use as substrates for Pd-catalyzed allylic substitutions, because of their use in aiding waste minimization and sustainability. Allyl groups containing allylic C—H bond(s) widely are present in numerous commercially available organic compounds and various kinds of intermediates for chemical synthesis. There is no doubt that the transformation of allylic C—H bonds into new C—C and C—X bonds is an ideal method to introduce new functional groups into molecules to construct more complex structures. However, allylic C—H functionalizations catalyzed by transition-metals are more challenging than allylic alcohols and other related allyl substrates, due to the difficult cleavage of the C—H bond and the need for a suitable oxidant. Recently, some significant advances have been reported by chemists and so Pd-catalyzed allylic C—H activations for the construction of C—C and C—X bonds have become a hot topic in the chemical community. A series of novel reactions based on new catalytic systems have been developed to produce useful molecules and complex natural products. The control of branch/linear selectivity and enantioselectivity has also been realized in the latest reports. Related work in this field is reviewed in this paper from the viewpoint of alkene substrates and nucleophiles. Pd(Ⅱ)-catalyzed asymmetric allylic C—H functionalizations are also introduced. The advantages and disadvantages of different kinds of catalytic systems (including DMSO, bissulfoxide, PPh3 and phosphoramidate as ligands) are discussed. Finally, pathways for future developments have been proposed.
Palladium-catalyzed allylic substitution is one of the most important methodologies for the construction of C—C and C—X bonds, and has been widely applied in the synthesis of bioactive natural and pharmaceutical products. Tremendous progress has been made towards the development of increasingly elaborate nucleophiles and catalysts to facilitate the aforementioned reaction. Despite significant advances, Pd-catalyzed allylic substitution reactions remain limited to substrates possessing a good leaving group such as a carboxylate, carbonate, phosphate, or other related derivatives on the allylic moiety. Allylic alcohols and amines have also gained attention for use as substrates for Pd-catalyzed allylic substitutions, because of their use in aiding waste minimization and sustainability. Allyl groups containing allylic C—H bond(s) widely are present in numerous commercially available organic compounds and various kinds of intermediates for chemical synthesis. There is no doubt that the transformation of allylic C—H bonds into new C—C and C—X bonds is an ideal method to introduce new functional groups into molecules to construct more complex structures. However, allylic C—H functionalizations catalyzed by transition-metals are more challenging than allylic alcohols and other related allyl substrates, due to the difficult cleavage of the C—H bond and the need for a suitable oxidant. Recently, some significant advances have been reported by chemists and so Pd-catalyzed allylic C—H activations for the construction of C—C and C—X bonds have become a hot topic in the chemical community. A series of novel reactions based on new catalytic systems have been developed to produce useful molecules and complex natural products. The control of branch/linear selectivity and enantioselectivity has also been realized in the latest reports. Related work in this field is reviewed in this paper from the viewpoint of alkene substrates and nucleophiles. Pd(Ⅱ)-catalyzed asymmetric allylic C—H functionalizations are also introduced. The advantages and disadvantages of different kinds of catalytic systems (including DMSO, bissulfoxide, PPh3 and phosphoramidate as ligands) are discussed. Finally, pathways for future developments have been proposed.
2016, 74(3): 234-240
doi: 10.6023/A15120787
Abstract:
The Michael addition reaction, which is a mild reaction between activated olefins and nucleophiles, has been widely used in synthesis of tailored macromolecular architectures. We designed a copolymer nanoparticle to obtain the ROS and pH dual responsive capability. We synthesized the amphiphilic poly(β-thioester)s copolymers (D-D-P) composed of di(ethylene glycol) diacrylate (DEDA), DL-dithiothreitol (DTT), acryloyl chloride (AC) and hydrophilic PEG-SH with average Mn=2000 g·mol-1 via Michael addition reaction. The reactions are facile and controllable, and the structures of acquired copolymers are well characterized. The structures of the polymers were confirmed by 1H NMR, and the number molecular weight and distribution of the copolymer D-D-P was measured by GPC (Mn=50400). D-D-P could self-assemble into nanoparticles with core-shell structures by dialysis method due to the composition of hydrophilic side chains and hydrophobic polymer backbones. After the preparation of ROS and pH dual responsive D-D-P nanoparticles in phosphate buffer solution, the morphology and size of D-D-P nanoparticles were observed by transmission electron microscopy (TEM) and dynamic light scattering (DLS) showed that the number size distribution of nanoparticles was around 280 nm. Nile Red (NR) is a unique neutral hydrophobic molecule, which shows very weak fluorescence in aqueous solution and can emit strong fluorescence in the hydrophobic environment. NR absorption and emission spectra are strongly dependent on environment polarity, which make it as a probe molecule that is widely used in the evaluation of microenvironment polarity. The disassembly behaviors of D-D-P nanoparticles were investigated by the change of the nanoparticle size and NR fluorescence spectra. The diameter of nanoparticle decreased under pH 5 and ROS environment conditions, and the NR fluorescence also became weak under pH 5 and ROS environment conditions, which could be attributed to the gradual dissociation of nanoparticles, proving the ROS and pH dual responsive properties of the poly(β-thioester)s. The release behaviors of the DOX encapsulated D-D-P nanoparticles in acidic and oxidative condition were studied by the UV absorption and were further proved in MCF-7 cells.
The Michael addition reaction, which is a mild reaction between activated olefins and nucleophiles, has been widely used in synthesis of tailored macromolecular architectures. We designed a copolymer nanoparticle to obtain the ROS and pH dual responsive capability. We synthesized the amphiphilic poly(β-thioester)s copolymers (D-D-P) composed of di(ethylene glycol) diacrylate (DEDA), DL-dithiothreitol (DTT), acryloyl chloride (AC) and hydrophilic PEG-SH with average Mn=2000 g·mol-1 via Michael addition reaction. The reactions are facile and controllable, and the structures of acquired copolymers are well characterized. The structures of the polymers were confirmed by 1H NMR, and the number molecular weight and distribution of the copolymer D-D-P was measured by GPC (Mn=50400). D-D-P could self-assemble into nanoparticles with core-shell structures by dialysis method due to the composition of hydrophilic side chains and hydrophobic polymer backbones. After the preparation of ROS and pH dual responsive D-D-P nanoparticles in phosphate buffer solution, the morphology and size of D-D-P nanoparticles were observed by transmission electron microscopy (TEM) and dynamic light scattering (DLS) showed that the number size distribution of nanoparticles was around 280 nm. Nile Red (NR) is a unique neutral hydrophobic molecule, which shows very weak fluorescence in aqueous solution and can emit strong fluorescence in the hydrophobic environment. NR absorption and emission spectra are strongly dependent on environment polarity, which make it as a probe molecule that is widely used in the evaluation of microenvironment polarity. The disassembly behaviors of D-D-P nanoparticles were investigated by the change of the nanoparticle size and NR fluorescence spectra. The diameter of nanoparticle decreased under pH 5 and ROS environment conditions, and the NR fluorescence also became weak under pH 5 and ROS environment conditions, which could be attributed to the gradual dissociation of nanoparticles, proving the ROS and pH dual responsive properties of the poly(β-thioester)s. The release behaviors of the DOX encapsulated D-D-P nanoparticles in acidic and oxidative condition were studied by the UV absorption and were further proved in MCF-7 cells.
2016, 74(3): 241-250
doi: 10.6023/A15120780
Abstract:
A folated-functionalized nano-carrier system based on carbon dots was successfully synthesized for cancer cell-targeted drug delivery. In this report, using microwave-assisted assay the fluorescent CDots could be obtained via microwave-assisted pyrolysis of glycerol in the presence of 4,7,10-trioxa-1,13-tridecanediamine. The particle size of the CDots was confirmed by AFM and HR-TEM. The finding showed that the average diameter of CDots is about 4 nm. Incorporating (via a cleavable bond) an anticancer drug, which was Doxorubicin (DOX) in this study, and a targeting ligand (folic acid) onto carbon dot produces a more specific anticancer prodrug DOX-CDots-FA. The structure of the DOX-CDots-FA was characterized by 1H NMR and UV-vis analysis. The loading content of DOX was determined by UV-vis analysis to be 13.5 wt%, and the content of the targeting ligand FA was calculated as 3.13 wt% based on 1H NMR measurement. Particle size parameter of DOX-CDots-FA was determined by HR-TEM. The results showed that the average diameter of DOX-CDots-FA is about 6 nm. In addition, DOX-CDots-FA showed pH-dependent release, that is, the drug releases faster in pH=5.2 buffer solution than in pH=7.4 one. The cytotoxicity of DOX-CDots-FA, DOX-CDots nanoparticles and free DOX were evaluated and compared using HeLa and L929 cell lines. For the FR-positive HeLa cells, DOX-CDots-FA nanoparticles exhibit superior cytotoxicity as compared to DOX-CDots nanoparticles. These results showed that the FA moieties in DOX-CDots-FA nanoparticles play an important role in enhancing the cytotoxic effect as they increase the binding to FR-expressing cells. This high affinity binding subsequently increases their intracellular uptake as a result of receptor-mediated endocytosis. The FA molecules present on the surface of the nanoparticle prodrug do not have a remarkable effect on cellular uptake and/or cytotoxicity for FR-negative L929 cell lines. The confocal microscope studies revealed that FA-conjugated prodrug DOX-CDots-FA exhibited higher cellular uptake than FA-free nanosystem DOX-CDots which also led to higher cytotoxicity. Thus, multifunctional nano-carrier system could be a promising nanosize anticancer drug carrier with excellent targeting property.
A folated-functionalized nano-carrier system based on carbon dots was successfully synthesized for cancer cell-targeted drug delivery. In this report, using microwave-assisted assay the fluorescent CDots could be obtained via microwave-assisted pyrolysis of glycerol in the presence of 4,7,10-trioxa-1,13-tridecanediamine. The particle size of the CDots was confirmed by AFM and HR-TEM. The finding showed that the average diameter of CDots is about 4 nm. Incorporating (via a cleavable bond) an anticancer drug, which was Doxorubicin (DOX) in this study, and a targeting ligand (folic acid) onto carbon dot produces a more specific anticancer prodrug DOX-CDots-FA. The structure of the DOX-CDots-FA was characterized by 1H NMR and UV-vis analysis. The loading content of DOX was determined by UV-vis analysis to be 13.5 wt%, and the content of the targeting ligand FA was calculated as 3.13 wt% based on 1H NMR measurement. Particle size parameter of DOX-CDots-FA was determined by HR-TEM. The results showed that the average diameter of DOX-CDots-FA is about 6 nm. In addition, DOX-CDots-FA showed pH-dependent release, that is, the drug releases faster in pH=5.2 buffer solution than in pH=7.4 one. The cytotoxicity of DOX-CDots-FA, DOX-CDots nanoparticles and free DOX were evaluated and compared using HeLa and L929 cell lines. For the FR-positive HeLa cells, DOX-CDots-FA nanoparticles exhibit superior cytotoxicity as compared to DOX-CDots nanoparticles. These results showed that the FA moieties in DOX-CDots-FA nanoparticles play an important role in enhancing the cytotoxic effect as they increase the binding to FR-expressing cells. This high affinity binding subsequently increases their intracellular uptake as a result of receptor-mediated endocytosis. The FA molecules present on the surface of the nanoparticle prodrug do not have a remarkable effect on cellular uptake and/or cytotoxicity for FR-negative L929 cell lines. The confocal microscope studies revealed that FA-conjugated prodrug DOX-CDots-FA exhibited higher cellular uptake than FA-free nanosystem DOX-CDots which also led to higher cytotoxicity. Thus, multifunctional nano-carrier system could be a promising nanosize anticancer drug carrier with excellent targeting property.
2016, 74(3): 265-270
doi: 10.6023/A15120761
Abstract:
With the development of biotechnology and life science, both recombinant protein drug productions and proteomics research depend largely on fast and efficient protein separation technology. Analysis of complex samples has put forward higher and higher requirements to separation science. Therefore, developing new separation material, separation mode and more sensitive detection method should be one of the effective ways to solve these problems. Based on a novel strong cation exchange/hydrophobic interaction chromatography (SCX/HIC) dual-function column, which displays HIC character in a high salt concentration, and IEC character in a low salt concentration in mobile phase employed and can be employed to separate proteins with SCX and HIC modes, respectively, a new on-line two-dimensional liquid chromatography technology with a single column (2DLC-1C) was developed. An equipment with automatic control system called as “ChromatoExpert” for processing fast protein separation online 2DLC-1C was constructed, which has multiple functions, such as on-line fraction collection from the first separation mode and quantitatively sample re-injection into the second separation mode, on-line buffer exchange, etc. Eight kinds of protein standards were separated using SCX/HIC 2DLC-1C. The unretained and uncompletely separated proteins in SCX mode were collected online and could be separated completely with each other by online re-injection and second dimensional separation of HIC mode. As a result, these eight kinds of proteins can be separated within 2 h. It also was applied to purify three kinds of active intact proteins from egg white successfully. The results indicated that lysozyme, ovotransferrin and ovalbumin from egg white could be purified just within 70 min by online 2DLC-1C. The purity of these proteins obtained was 95%, 93% and 97%, respectively. The new online 2DLC-1C technology can simplify the purification process and lower the separation cost. It is easy to realize automation and scale-up to preparative scale. Therefore, this new technology has a broad application prospect in the fast separation and preparation of active protein.
With the development of biotechnology and life science, both recombinant protein drug productions and proteomics research depend largely on fast and efficient protein separation technology. Analysis of complex samples has put forward higher and higher requirements to separation science. Therefore, developing new separation material, separation mode and more sensitive detection method should be one of the effective ways to solve these problems. Based on a novel strong cation exchange/hydrophobic interaction chromatography (SCX/HIC) dual-function column, which displays HIC character in a high salt concentration, and IEC character in a low salt concentration in mobile phase employed and can be employed to separate proteins with SCX and HIC modes, respectively, a new on-line two-dimensional liquid chromatography technology with a single column (2DLC-1C) was developed. An equipment with automatic control system called as “ChromatoExpert” for processing fast protein separation online 2DLC-1C was constructed, which has multiple functions, such as on-line fraction collection from the first separation mode and quantitatively sample re-injection into the second separation mode, on-line buffer exchange, etc. Eight kinds of protein standards were separated using SCX/HIC 2DLC-1C. The unretained and uncompletely separated proteins in SCX mode were collected online and could be separated completely with each other by online re-injection and second dimensional separation of HIC mode. As a result, these eight kinds of proteins can be separated within 2 h. It also was applied to purify three kinds of active intact proteins from egg white successfully. The results indicated that lysozyme, ovotransferrin and ovalbumin from egg white could be purified just within 70 min by online 2DLC-1C. The purity of these proteins obtained was 95%, 93% and 97%, respectively. The new online 2DLC-1C technology can simplify the purification process and lower the separation cost. It is easy to realize automation and scale-up to preparative scale. Therefore, this new technology has a broad application prospect in the fast separation and preparation of active protein.
2016, 74(3): 271-276
doi: 10.6023/A15100687
Abstract:
Bipolar fuel cell (BPFC) is a new kind polymer electrolyte membrane fuel cell (PEMFC) with acidic-alkaline bipolar interface formed by acidic and alkaline polyelectrolyte both used in one cell. BPFC has shown some novel characterizations: (1) water generated at the bipolar interface would provide the possibility to devise self-humidification over the entire cell, which would simplify the water manager system; (2) alkaline cathode with facilitated electrokinetics allows for the use of lower catalyst loading or non-noble catalysts, such as silver and nickel. In our previous work, the effect of bipolar membrane electrode configuration on the cell output performance was evaluated and the optimal configuration was achieved. The BPFC with optimal membrane electrode configuration has been operated under completely self-humidifying conditions for prolonged periods successfully. However, there exists a big gap with the cell performance between BPFC and the state-of-art PEMFC. In order to improve the fuel cell performance, optimization of the membrane electrode configurations and further advances in fabricating bipolar interface had been conducted in our previous work. Another issue that affects the performance of the fuel cell is the structure and composition of the catalyst layer. Since the oxygen reduction reaction (ORR) at cathode influenced the fuel cell performance a lot, the improvement of electrode was mainly focused on the cathode catalyst layer. In the present work, thin hydrophilic electrode and thick hydrophobic electrode were used as cathode for BPFC. The influence of ionomer binder, quaternary ammonium polysulfone (QAPSF) in thin hydrophilic electrode and polytetrafluoroethylene (PTFE) in thick hydrophobic electrode, concentration on BPFC performance was studied. The results indicated that the optimal content of QAPSF in thin hydrophilic cathode was 20 wt%, and the peak power density of BPFC reached to 186.1 mW/cm2 at 25 ℃ without humidification. While the PTFE in the thick hydrophobic cathode was also 20 wt% with a peak power density of 461.5 mW/cm2 at 40 ℃ without humidification. Due to the high demand of alkaline cathode for drainage, the thick hydrophobic electrode behaved better than thin hydrophilic electrode in BPFC.
Bipolar fuel cell (BPFC) is a new kind polymer electrolyte membrane fuel cell (PEMFC) with acidic-alkaline bipolar interface formed by acidic and alkaline polyelectrolyte both used in one cell. BPFC has shown some novel characterizations: (1) water generated at the bipolar interface would provide the possibility to devise self-humidification over the entire cell, which would simplify the water manager system; (2) alkaline cathode with facilitated electrokinetics allows for the use of lower catalyst loading or non-noble catalysts, such as silver and nickel. In our previous work, the effect of bipolar membrane electrode configuration on the cell output performance was evaluated and the optimal configuration was achieved. The BPFC with optimal membrane electrode configuration has been operated under completely self-humidifying conditions for prolonged periods successfully. However, there exists a big gap with the cell performance between BPFC and the state-of-art PEMFC. In order to improve the fuel cell performance, optimization of the membrane electrode configurations and further advances in fabricating bipolar interface had been conducted in our previous work. Another issue that affects the performance of the fuel cell is the structure and composition of the catalyst layer. Since the oxygen reduction reaction (ORR) at cathode influenced the fuel cell performance a lot, the improvement of electrode was mainly focused on the cathode catalyst layer. In the present work, thin hydrophilic electrode and thick hydrophobic electrode were used as cathode for BPFC. The influence of ionomer binder, quaternary ammonium polysulfone (QAPSF) in thin hydrophilic electrode and polytetrafluoroethylene (PTFE) in thick hydrophobic electrode, concentration on BPFC performance was studied. The results indicated that the optimal content of QAPSF in thin hydrophilic cathode was 20 wt%, and the peak power density of BPFC reached to 186.1 mW/cm2 at 25 ℃ without humidification. While the PTFE in the thick hydrophobic cathode was also 20 wt% with a peak power density of 461.5 mW/cm2 at 40 ℃ without humidification. Due to the high demand of alkaline cathode for drainage, the thick hydrophobic electrode behaved better than thin hydrophilic electrode in BPFC.
2016, 74(3): 277-284
doi: 10.6023/A15110704
Abstract:
Fluorescent and phosphorescent techniques have been widely used in the fields of food, biology, environment, chemistry, medicine, life science and so on. However, the spectral background drift often occurs in the spectral excitation dimension, creating the need for new methods to process this phenomenon. There are many different factors which may lead to this common phenomenon, such as the changes in background noise of instrument or temperature. In the work, a new technique for removal of background drift in three-dimensional spectral arrays is proposed. The basic idea is to perform trilinear decomposition based on the alternating trilinear decomposition (ATLD) algorithm on the instrumental response data. In model building, the background drift is modeled as an additional component or factor as well as the analytes of interest and the interferents. As the optimum number of factors (N) is provided by the core consistency diagnostic (CORCONDIA), the ATLD algorithm is applied to decompose the raw data (Xraw) with the factor number of N, then three profile matrices A, B and C can be obtained. Vectors an, bn and cn that representing the signal of the background drift can be extracted from these matrices to construct a 3-D background drift data array (Xdrift ). After subtracting the Xdrift from the Xraw, the background drift is removed, leaving the new data on a flat baseline. Two simulated data sets were firstly employed to demonstrate the reasonability of the new method. The same and different levels of background drifts along the excitation dimension are added into the two simulated data sets, respectively. Then, it is successfully used to analyze two experimental data sets in which significant background drift are present. These results highlight the fact that this technique yields a good removal of background drift. In addition, the good result is obtained by secondary removal for serious background drift. The proposed method can be viewed as a good spectral pretreatment technique.
Fluorescent and phosphorescent techniques have been widely used in the fields of food, biology, environment, chemistry, medicine, life science and so on. However, the spectral background drift often occurs in the spectral excitation dimension, creating the need for new methods to process this phenomenon. There are many different factors which may lead to this common phenomenon, such as the changes in background noise of instrument or temperature. In the work, a new technique for removal of background drift in three-dimensional spectral arrays is proposed. The basic idea is to perform trilinear decomposition based on the alternating trilinear decomposition (ATLD) algorithm on the instrumental response data. In model building, the background drift is modeled as an additional component or factor as well as the analytes of interest and the interferents. As the optimum number of factors (N) is provided by the core consistency diagnostic (CORCONDIA), the ATLD algorithm is applied to decompose the raw data (Xraw) with the factor number of N, then three profile matrices A, B and C can be obtained. Vectors an, bn and cn that representing the signal of the background drift can be extracted from these matrices to construct a 3-D background drift data array (Xdrift ). After subtracting the Xdrift from the Xraw, the background drift is removed, leaving the new data on a flat baseline. Two simulated data sets were firstly employed to demonstrate the reasonability of the new method. The same and different levels of background drifts along the excitation dimension are added into the two simulated data sets, respectively. Then, it is successfully used to analyze two experimental data sets in which significant background drift are present. These results highlight the fact that this technique yields a good removal of background drift. In addition, the good result is obtained by secondary removal for serious background drift. The proposed method can be viewed as a good spectral pretreatment technique.
