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2020 Volume 78 Issue 3
2020, 78(3): 193-216
doi: 10.6023/A20010002
Abstract:
P-Chiral phosphine oxides are a class of privileged structures, which have important applications in the field of medicinal chemistry, organic synthesis, life and material science. Recent years have witnessed significant progress in the catalytic asymmetric construction of such scaffolds. These advances are summarized in this review according to the following three major strategies:desymmetrization of prochiral tertiary phosphine oxides, (dynamic) kinetic resolution of tertiary phosphine oxides, and catalytic asymmetric reactions involving secondary phosphine oxides, and discusses the possible reaction mechanism, the advantage and disadvantage of each type of reactions, which would provide reference and inspiration for the researchers engaged in organic synthesis and organic phosphorus chemistry.
P-Chiral phosphine oxides are a class of privileged structures, which have important applications in the field of medicinal chemistry, organic synthesis, life and material science. Recent years have witnessed significant progress in the catalytic asymmetric construction of such scaffolds. These advances are summarized in this review according to the following three major strategies:desymmetrization of prochiral tertiary phosphine oxides, (dynamic) kinetic resolution of tertiary phosphine oxides, and catalytic asymmetric reactions involving secondary phosphine oxides, and discusses the possible reaction mechanism, the advantage and disadvantage of each type of reactions, which would provide reference and inspiration for the researchers engaged in organic synthesis and organic phosphorus chemistry.
2020, 78(3): 217-231
doi: 10.6023/A19110411
Abstract:
In recent years, the efficiency of perovskite solar cells has developed rapidly, but its stability is limited by the influence of heat, light and water. All-inorganic perovskite formed by inorganic cations instead of organic cations shows improved thermal stability, high light absorption and adjustable band gap. The photoelectric conversion efficiency of all-inorganic perovskite solar cells has been improved to 19.03% at present. Among them, CsPbI3 perovskite solar cells have good photoelectric performance but poor stability, while CsPbBr3 perovskite solar cells have excellent stability but poor photoelectric performance of devices. In this paper, the influence of preparation method, film doping and interface modification on the stability of inorganic perovskite solar cells is systematically summarized. The reasons behind the instability of inorganic perovskite and the improvement methods are emphatically analyzed. In conclusion, improving the stability of inorganic perovskite light absorbing materials by film doping, surface passivation and morphology control such as low dimensional materials preparation can effectively improve the stability of the overall device, which provides the basis for further commercialization. In addition, it is of great significance to study the theory of charge transfer and recombination and establish a complete theoretical system for improving the performance and stability of the device. At present, most of perovskite contains harmful elements Pb. How to replace Pb and find new materials applied in perovskite solar cells is also the future development trend. In a word, as a new type of solar cell, inorganic perovskite solar cell is expected to contribute to the photovoltaic development of the future society.
In recent years, the efficiency of perovskite solar cells has developed rapidly, but its stability is limited by the influence of heat, light and water. All-inorganic perovskite formed by inorganic cations instead of organic cations shows improved thermal stability, high light absorption and adjustable band gap. The photoelectric conversion efficiency of all-inorganic perovskite solar cells has been improved to 19.03% at present. Among them, CsPbI3 perovskite solar cells have good photoelectric performance but poor stability, while CsPbBr3 perovskite solar cells have excellent stability but poor photoelectric performance of devices. In this paper, the influence of preparation method, film doping and interface modification on the stability of inorganic perovskite solar cells is systematically summarized. The reasons behind the instability of inorganic perovskite and the improvement methods are emphatically analyzed. In conclusion, improving the stability of inorganic perovskite light absorbing materials by film doping, surface passivation and morphology control such as low dimensional materials preparation can effectively improve the stability of the overall device, which provides the basis for further commercialization. In addition, it is of great significance to study the theory of charge transfer and recombination and establish a complete theoretical system for improving the performance and stability of the device. At present, most of perovskite contains harmful elements Pb. How to replace Pb and find new materials applied in perovskite solar cells is also the future development trend. In a word, as a new type of solar cell, inorganic perovskite solar cell is expected to contribute to the photovoltaic development of the future society.
2020, 78(3): 232-244
doi: 10.6023/A20010006
Abstract:
Cyclodextrins (CDs) are a family of macrocyclic oligosaccharides composed of α-1, 4-linked D-glucopyranose units. The most commonly used CDs are α-, β-, and γ-CD, which consist of 6, 7, and 8 D-glucose units, respectively. They possess a relative hydrophobic inner cavity and a hydrophilic outer surface and can form inclusion complexes with various small molecules, metal ions and polymers, tailoring the physicochemical property of the guests, and thus have been widely used in the fields of pharmacy, food, chemistry, chromatography, catalysis, biotechnology, agriculture, cosmetics, hygiene, medicine, textiles and the environment, etc. However, it is difficult to manipulate the native CDs in some specific applications, they are crystallized solid and soluble in water but insoluble in most organic solvents. CD polymers (CDPs), such as crosslinked CDs or CD based hydrogels with various crosslinkers by chemical reactions, and CD based supramolecular polymers formed by physical interactions, can achieve the integration effect and synergy effect of CDs, crosslinkers and guest polymers, not only possessing the inclusion capacity of CDs, but also endowing CDs with other properties introduced by crosslinkers. The CDPs can be easily manipulated and they exhibit unique features that native CDs are lack of. Hence, the design, synthesis and applications of CDPs have attracted broad interests in recent years. This review focuses on the recent progress in CDPs, and different types of CDPs are identified and classified based on the structures and functions, namely CD based polyrotaxane, grafted CDs, crosslinked CDs and linear CDs, etc. Besides, the synthetic methodologies of CDPs are highlighted. Particular attention is paid to the breakthrough on the CDPs in the past five years, and their applications in biomedicine, such as drug delivery, gene delivery, target delivery, controlled release and cell imaging are discussed in detail. The typical applications in other fields such as absorption, environment remediation, thermal insulation, catalysis and slid-ring gels are also discussed in brief. Finally, the review provides brief summary and prospect of CDPs.
Cyclodextrins (CDs) are a family of macrocyclic oligosaccharides composed of α-1, 4-linked D-glucopyranose units. The most commonly used CDs are α-, β-, and γ-CD, which consist of 6, 7, and 8 D-glucose units, respectively. They possess a relative hydrophobic inner cavity and a hydrophilic outer surface and can form inclusion complexes with various small molecules, metal ions and polymers, tailoring the physicochemical property of the guests, and thus have been widely used in the fields of pharmacy, food, chemistry, chromatography, catalysis, biotechnology, agriculture, cosmetics, hygiene, medicine, textiles and the environment, etc. However, it is difficult to manipulate the native CDs in some specific applications, they are crystallized solid and soluble in water but insoluble in most organic solvents. CD polymers (CDPs), such as crosslinked CDs or CD based hydrogels with various crosslinkers by chemical reactions, and CD based supramolecular polymers formed by physical interactions, can achieve the integration effect and synergy effect of CDs, crosslinkers and guest polymers, not only possessing the inclusion capacity of CDs, but also endowing CDs with other properties introduced by crosslinkers. The CDPs can be easily manipulated and they exhibit unique features that native CDs are lack of. Hence, the design, synthesis and applications of CDPs have attracted broad interests in recent years. This review focuses on the recent progress in CDPs, and different types of CDPs are identified and classified based on the structures and functions, namely CD based polyrotaxane, grafted CDs, crosslinked CDs and linear CDs, etc. Besides, the synthetic methodologies of CDPs are highlighted. Particular attention is paid to the breakthrough on the CDPs in the past five years, and their applications in biomedicine, such as drug delivery, gene delivery, target delivery, controlled release and cell imaging are discussed in detail. The typical applications in other fields such as absorption, environment remediation, thermal insulation, catalysis and slid-ring gels are also discussed in brief. Finally, the review provides brief summary and prospect of CDPs.
2020, 78(3): 245-249
doi: 10.6023/A20010019
Abstract:
Optically pure pyrrolidine ring systems are core structural motifs found in a range of bioactive compounds, natural products, pharmaceuticals and catalysts. The synthesis of optically pure pyrrolidine ring systems is no longer mysterious as a great number of studies concerning the catalytic asymmetric 1, 3-dipolar cycloaddition of iminoesters have been reported. Overall, the transition-metal-catalyzed asymmetric 1, 3-dipolar cycloaddition of iminoesters with electron-deficient alkenes is one of the most powerful and straightforward synthetic tools for the optically pure pyrrolidines. However, high diastereo-and enantioselectivities are requested simultaneously during the synthesis of chiral substituted pyrrolidine and it still remains a big challenge to develop an efficient way to achieve both of them. Recently, we developed a novel chiral sulfinamide mono-phosphine (Ming-Phos) which performed well in copper-catalyzed intermolecular cycloaddition of iminoesters with β-trifluoromethyl β, β-disubstituted enones or α-trifluoromethyl α, β-unsaturated esters. Encouraged by the satisfying results, herein we report the Ming-Phos/Cu-catalyzed asymmetric intermolecular[3+2] cycloaddition of azomethine ylides with nitroalkenes. To our delight, a new Ming-Phos M3 bearing a trifluoromethyl showed good performance in this type of inter-molecular cycloaddition with high diastereo-and enantioselectivities (up to 13:1 dr, 98% ee and 95% yield). High efficiency, high diastereo-and enantioselectivity, a novel ligand, an inexpensive copper catalyst, and good functional group tolerance make it worth to be considered as an efficient, reliable and atom-economic strategy for the synthesis of optically pyrrolidines. The general procedure is as following:the solution of M3 (5.5 mol%) and Cu(CH3CN)4BF4 (5 mol%) in methyl tert-butyl ether (MTBE, 6 mL) was stirred at room temperature for 2 h. After the reaction temperature was dropped to -30℃, azomethine ylides 2 (0.6 mmol), Cs2CO3 (0.15 mmol) and nitroalkene 1 (0.3 mmol) were added sequentially. After the nitroalkene 1 was consumed completely, the solvent was removed under reduced pressure. The crude product was analyzed with 1H NMR to determine the diastereomeric ratio. Then the crude product was then purified by flash column chromatography on silica gel to afford the desired product.
Optically pure pyrrolidine ring systems are core structural motifs found in a range of bioactive compounds, natural products, pharmaceuticals and catalysts. The synthesis of optically pure pyrrolidine ring systems is no longer mysterious as a great number of studies concerning the catalytic asymmetric 1, 3-dipolar cycloaddition of iminoesters have been reported. Overall, the transition-metal-catalyzed asymmetric 1, 3-dipolar cycloaddition of iminoesters with electron-deficient alkenes is one of the most powerful and straightforward synthetic tools for the optically pure pyrrolidines. However, high diastereo-and enantioselectivities are requested simultaneously during the synthesis of chiral substituted pyrrolidine and it still remains a big challenge to develop an efficient way to achieve both of them. Recently, we developed a novel chiral sulfinamide mono-phosphine (Ming-Phos) which performed well in copper-catalyzed intermolecular cycloaddition of iminoesters with β-trifluoromethyl β, β-disubstituted enones or α-trifluoromethyl α, β-unsaturated esters. Encouraged by the satisfying results, herein we report the Ming-Phos/Cu-catalyzed asymmetric intermolecular[3+2] cycloaddition of azomethine ylides with nitroalkenes. To our delight, a new Ming-Phos M3 bearing a trifluoromethyl showed good performance in this type of inter-molecular cycloaddition with high diastereo-and enantioselectivities (up to 13:1 dr, 98% ee and 95% yield). High efficiency, high diastereo-and enantioselectivity, a novel ligand, an inexpensive copper catalyst, and good functional group tolerance make it worth to be considered as an efficient, reliable and atom-economic strategy for the synthesis of optically pyrrolidines. The general procedure is as following:the solution of M3 (5.5 mol%) and Cu(CH3CN)4BF4 (5 mol%) in methyl tert-butyl ether (MTBE, 6 mL) was stirred at room temperature for 2 h. After the reaction temperature was dropped to -30℃, azomethine ylides 2 (0.6 mmol), Cs2CO3 (0.15 mmol) and nitroalkene 1 (0.3 mmol) were added sequentially. After the nitroalkene 1 was consumed completely, the solvent was removed under reduced pressure. The crude product was analyzed with 1H NMR to determine the diastereomeric ratio. Then the crude product was then purified by flash column chromatography on silica gel to afford the desired product.
2020, 78(3): 250-255
doi: 10.6023/A19120449
Abstract:
The pressure-swing adsorption (PSA) technology is the promising approach for O2/N2 separation because of its low cost and facile manipulation, in which adsorbents dominate the separation performance. In recent years, metal-organic frameworks (MOFs) have been recognized as the most potential adsorbents in gas adsorption and separation due to their ultrahigh surface area. In this work, MIL-101(Cr) with different weight percentages of graphene oxide (5%, 15% and 35%) was prepared by growing MIL-101(Cr) on pre-synthesized GO materials. The final product was activated under vacuum at 180℃ for 12 h. Structure characterization of different MIL-101(Cr)/GO composites revealed that MIL-101(Cr)/GO-15 with 15% GO additive exhibited the highest specific surface area (3486 m2·g-1) and pore volume (2.39 cm3·g-1) compared with pristine MIL-101(Cr) and the composites with 5% and 35% GO additives. The high surface area and pore volume are beneficial for the O2 uptake of MIL-101(Cr)/GO-15. Compared with the O2 uptake of MIL-101(Cr)/GO-5 (0.35 mmol·g-1) and MIL-101(Cr)/GO-35 (0.31 mmol·g-1), MIL-101(Cr)/GO-15 exhibited the highest uptake of 0.54 mmol·g-1. Further pore size distribution analysis demonstrated that the enhanced O2 uptake of MIL-101(Cr)/GO-15 can be ascribed to its increased fraction of mesopores. On the other hand, O2/N2 selectivity of different MIL-101(Cr)/GO composites was also calculated according to ideal adsorbed solution theory (IAST), from which it was found that MIL-101(Cr)/GO-15 displayed the highest O2/N2 selectivity (1.2) in a binary gas mixture with the volume fraction of O2/N2=1/4. Compared with pristine MIL-101, O2/N2 selectivity of MIL-101(Cr)/GO-15 was increased by 17.65%. Recyclability is one of the most important criteria to evaluate the gas adsorption performance of adsorbents. Therefore, the recyclability of MIL-101(Cr)/GO-15 was tested by measuring the O2 adsorption and desorption isotherms for three cycles. It was revealed that 80% of O2 uptake of MIL-101(Cr)/GO-15 was remained after three adsorp-tion/desorption cycles, implicating the outstanding recyclability of MIL-101(Cr)/GO-15.
The pressure-swing adsorption (PSA) technology is the promising approach for O2/N2 separation because of its low cost and facile manipulation, in which adsorbents dominate the separation performance. In recent years, metal-organic frameworks (MOFs) have been recognized as the most potential adsorbents in gas adsorption and separation due to their ultrahigh surface area. In this work, MIL-101(Cr) with different weight percentages of graphene oxide (5%, 15% and 35%) was prepared by growing MIL-101(Cr) on pre-synthesized GO materials. The final product was activated under vacuum at 180℃ for 12 h. Structure characterization of different MIL-101(Cr)/GO composites revealed that MIL-101(Cr)/GO-15 with 15% GO additive exhibited the highest specific surface area (3486 m2·g-1) and pore volume (2.39 cm3·g-1) compared with pristine MIL-101(Cr) and the composites with 5% and 35% GO additives. The high surface area and pore volume are beneficial for the O2 uptake of MIL-101(Cr)/GO-15. Compared with the O2 uptake of MIL-101(Cr)/GO-5 (0.35 mmol·g-1) and MIL-101(Cr)/GO-35 (0.31 mmol·g-1), MIL-101(Cr)/GO-15 exhibited the highest uptake of 0.54 mmol·g-1. Further pore size distribution analysis demonstrated that the enhanced O2 uptake of MIL-101(Cr)/GO-15 can be ascribed to its increased fraction of mesopores. On the other hand, O2/N2 selectivity of different MIL-101(Cr)/GO composites was also calculated according to ideal adsorbed solution theory (IAST), from which it was found that MIL-101(Cr)/GO-15 displayed the highest O2/N2 selectivity (1.2) in a binary gas mixture with the volume fraction of O2/N2=1/4. Compared with pristine MIL-101, O2/N2 selectivity of MIL-101(Cr)/GO-15 was increased by 17.65%. Recyclability is one of the most important criteria to evaluate the gas adsorption performance of adsorbents. Therefore, the recyclability of MIL-101(Cr)/GO-15 was tested by measuring the O2 adsorption and desorption isotherms for three cycles. It was revealed that 80% of O2 uptake of MIL-101(Cr)/GO-15 was remained after three adsorp-tion/desorption cycles, implicating the outstanding recyclability of MIL-101(Cr)/GO-15.
2020, 78(3): 256-262
doi: 10.6023/A19120427
Abstract:
The photo-controllable third-order nonlinear optical (NLO) switches have drawn ever-increasing attention due to considerable research potential in the emerging field of nonlinear optics. A class of materials, which contain photosensitive groups but cannot express directly switching properties under light conditions, can also exhibit the characteristics of excellent photo-controllable NLO switches after external regulation. Azobenzene is a kind of classic photo-isomerized molecule and has good π coplanar property and excellent electron channel, which can engender third-order NLO response under push and pull electron action. It is a feasible strategy to design photo-controlled NLO switch materials by introducing azo groups. Nevertheless, the trans-cis isomerization behaviors of some azobenzene derivatives are interfered by other groups or external factors, further inhibiting the conversion of photo-controllable third-order NLO properties. Once these external interference factors are found and removed, the photo-controllable NLO behaviors of such azobenzene derivatives will be opened. In our work, a special azobenzene derivative was synthesized and reported, which was unable to produce cis-trans isomerization due to the H+ effect of self-dissociation, and the H+ effect could be shield by introducing organic groups or bases. The adjusted materials can easily undergo reversible cis-trans isomerization reaction, and the Z-scan test shows the complete inversions of third-order NLO properties before and after UV irradiation. The adjusted materials in trans configuration show the reverse saturation absorption (RSA) and self-defocusing properties. After UV irradiation, the materials convert into cis configuration and exhibit saturation absorption (SA) and strong self-focusing behaviors. To gain a deeper understanding of the light-adjusted third-order NLO switch behaviors, density functional theory (DFT) calculations of (CH3)2L were carried out. For trans-(CH3)2L, HOMO and LUMO are mainly localized on the azobenzene unit, where π-π* transition between the two orbitals is displayed. The azobenzene unit in the trans-(CH3)2L is considered to have considerable contribution to the generation of third-order nonlinear-ity. For cis-(CH3)2L, the electron cloud density of HOMO is mainly populated on the azobenzene unit, whereas the electron cloud density distribution of LUMO appears on the entire molecule, suggesting significant intramolecular charge transfer (ICT) from azobenzene to the entire molecule. The effect of ICT in the cis structure dominants the generation of third-order nonlinearity. The remarkable third-order NLO transformation result from the rearrangement of the electronic structures, which makes them generate different response mechanisms under the laser stimulation.
The photo-controllable third-order nonlinear optical (NLO) switches have drawn ever-increasing attention due to considerable research potential in the emerging field of nonlinear optics. A class of materials, which contain photosensitive groups but cannot express directly switching properties under light conditions, can also exhibit the characteristics of excellent photo-controllable NLO switches after external regulation. Azobenzene is a kind of classic photo-isomerized molecule and has good π coplanar property and excellent electron channel, which can engender third-order NLO response under push and pull electron action. It is a feasible strategy to design photo-controlled NLO switch materials by introducing azo groups. Nevertheless, the trans-cis isomerization behaviors of some azobenzene derivatives are interfered by other groups or external factors, further inhibiting the conversion of photo-controllable third-order NLO properties. Once these external interference factors are found and removed, the photo-controllable NLO behaviors of such azobenzene derivatives will be opened. In our work, a special azobenzene derivative was synthesized and reported, which was unable to produce cis-trans isomerization due to the H+ effect of self-dissociation, and the H+ effect could be shield by introducing organic groups or bases. The adjusted materials can easily undergo reversible cis-trans isomerization reaction, and the Z-scan test shows the complete inversions of third-order NLO properties before and after UV irradiation. The adjusted materials in trans configuration show the reverse saturation absorption (RSA) and self-defocusing properties. After UV irradiation, the materials convert into cis configuration and exhibit saturation absorption (SA) and strong self-focusing behaviors. To gain a deeper understanding of the light-adjusted third-order NLO switch behaviors, density functional theory (DFT) calculations of (CH3)2L were carried out. For trans-(CH3)2L, HOMO and LUMO are mainly localized on the azobenzene unit, where π-π* transition between the two orbitals is displayed. The azobenzene unit in the trans-(CH3)2L is considered to have considerable contribution to the generation of third-order nonlinear-ity. For cis-(CH3)2L, the electron cloud density of HOMO is mainly populated on the azobenzene unit, whereas the electron cloud density distribution of LUMO appears on the entire molecule, suggesting significant intramolecular charge transfer (ICT) from azobenzene to the entire molecule. The effect of ICT in the cis structure dominants the generation of third-order nonlinearity. The remarkable third-order NLO transformation result from the rearrangement of the electronic structures, which makes them generate different response mechanisms under the laser stimulation.
2020, 78(3): 263-270
doi: 10.6023/A19110403
Abstract:
DNA is an important target for antitumor drugs, hence investigation of the interaction between drug molecules and DNA can help to design targeted DNA antitumor drugs. New ternary copper(Ⅱ) complex[Cu(Sf)(PyTA)(H2O)]·ClO4· 3.5H2O[Sf=sparfloxacin, 5-amino-1-cyclopropyl-7-(cis-3, 5-dimethyl-1-piperazinyl)-6, 8-difluoro-1, 4-dihydro-4-oxoquino-line-3-carboxylic acid, PyTA=2, 4-diamino-6-(2'-pyridyl)-1, 3, 5-triazine] was synthesized and characterized by elemental analyses, molar conductivity measurement and various spectroscopic techniques such as infrared, ultraviolet-visible, and electrospray ionization mass spectra. The interaction of the complex with DNA was investigated using electronic absorption spectroscopy, KI fluorescence quench, viscosity measurement and molecular docking techniques. It was found that the complex could bind to DNA through an intercalation mode being related with the quinoline ring of ligand Sf, and the corresponding binding constant Kb is 1.23×104 L/mol. Moreover, the antitumor activity of the complex was evaluated using the MTT[3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide] method, revealing that the complex displayed favorable cytotoxic effects[IC50=(57.0±1.6)~(77.6±1.4) μmol/L] toward cancer cells (A549, Bel-7402 and Eca-109) and less toxic towards normal cells (3T3). Most importantly, the cytotoxic mechanism of the complex towards Eca-109 cells was explored by single cell gel electrophoresis assay, Hoechst 33342 staining, Annexin V-FITC/PI double dye flow cytometry, measurement of mitochondrial membrane potential change, detection of intracellular cytochrome C and Ca2+ levels, and test of cell cycle arrest. Single cell gel electrophoresis assay (comet assays) demonstrated that the complex could damage DNA and cause apoptosis. Double staining analysis showed that the complex could induce apoptosis in Eca-109 cells. Cell cycle arrest studies revealed the cell growth arrest at S and G2/M phases. The complex also could induce a reduction in the mitochondrial membrane potential and release of the cytochrome C, and increase the intracellular Ca2+ level. The results demonstrated that the complex could induce apoptosis in Eca-109 cells through DNA-binding mitochondrial dysfunctional pathways, which was accompanied by the cell growth arrest at S and G2/M phases and damage of DNA.
DNA is an important target for antitumor drugs, hence investigation of the interaction between drug molecules and DNA can help to design targeted DNA antitumor drugs. New ternary copper(Ⅱ) complex[Cu(Sf)(PyTA)(H2O)]·ClO4· 3.5H2O[Sf=sparfloxacin, 5-amino-1-cyclopropyl-7-(cis-3, 5-dimethyl-1-piperazinyl)-6, 8-difluoro-1, 4-dihydro-4-oxoquino-line-3-carboxylic acid, PyTA=2, 4-diamino-6-(2'-pyridyl)-1, 3, 5-triazine] was synthesized and characterized by elemental analyses, molar conductivity measurement and various spectroscopic techniques such as infrared, ultraviolet-visible, and electrospray ionization mass spectra. The interaction of the complex with DNA was investigated using electronic absorption spectroscopy, KI fluorescence quench, viscosity measurement and molecular docking techniques. It was found that the complex could bind to DNA through an intercalation mode being related with the quinoline ring of ligand Sf, and the corresponding binding constant Kb is 1.23×104 L/mol. Moreover, the antitumor activity of the complex was evaluated using the MTT[3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide] method, revealing that the complex displayed favorable cytotoxic effects[IC50=(57.0±1.6)~(77.6±1.4) μmol/L] toward cancer cells (A549, Bel-7402 and Eca-109) and less toxic towards normal cells (3T3). Most importantly, the cytotoxic mechanism of the complex towards Eca-109 cells was explored by single cell gel electrophoresis assay, Hoechst 33342 staining, Annexin V-FITC/PI double dye flow cytometry, measurement of mitochondrial membrane potential change, detection of intracellular cytochrome C and Ca2+ levels, and test of cell cycle arrest. Single cell gel electrophoresis assay (comet assays) demonstrated that the complex could damage DNA and cause apoptosis. Double staining analysis showed that the complex could induce apoptosis in Eca-109 cells. Cell cycle arrest studies revealed the cell growth arrest at S and G2/M phases. The complex also could induce a reduction in the mitochondrial membrane potential and release of the cytochrome C, and increase the intracellular Ca2+ level. The results demonstrated that the complex could induce apoptosis in Eca-109 cells through DNA-binding mitochondrial dysfunctional pathways, which was accompanied by the cell growth arrest at S and G2/M phases and damage of DNA.
2020, 78(3): 271-278
doi: 10.6023/A19120435
Abstract:
Due to the lower redox potential comparing with guanine, it is the 8-azaguanine (8-AG) as the hole trap to form 8-azaguanine radical cation (8-AG·+) after one-electron oxidation of DNA containing 8-azaguanine. In generally, the 8-AG·+ may suffer from deprotonation to generate 8-AG(-H)·. In this text, we were stimulated to investigate the deprotonation reaction of 8-AG·+ generating by one-electron oxidation at M06-2X/6-31+G(d) level with explicit water molecules and polarized continuum model (PCM) to simulate the solvent effect. By building deprotonation model with different number of explicit water molecules, we found that these four water molecules locating around N(1)-H, O(6), N(2)-H of 8-AG·+ as well as the one locating in the second water shell which was hydrogen-bonding with the water around O(6) were necessary. If the water in the second water shell was not included, the imino proton (N(1)-H) would not transfer into the bulk water. In parallel, the N(1)-H would transfer to the O(6) of 8-AG·+ by intramolecular proton transfer. If the water molecule locating around N(2)-H was removed, the 8-AG·+ deprotonation would continue but the energy barrier would be lowered from 24.8 kJ/mol to 16.3 kJ/mol. In addition, the site of the water molecule in the second water shell was also studied. If putting the water in the second water shell around N(2)-H of 8-AG·+, the proton would be stabilized between the N(1) of 8-AG·+ and the oxygen of water molecule around N(1)-H meaning the proton would not be transferred into bulk water. Further, in order to test the influence of water number on 8-AG·+ deprotonation, the fifth water molecule, which is hydrogen-bonding with the water molecule around N(2)-H and another N(2)-H, was added. The potential energy surface with 5H2O revealed that it is almost no effect on the deprotonation pathway and energy barrier (25.5 kJ/mol). Lastly, so as to obtain the exact energy barrier of 8-AG·+ deprotonation, the deprotonation model with more explicit water molecules (9H2O) was proposed, where the additional water molecules were placed around N(2)-H, N(3), O(6), N(7) and N(8). From the potential energy surface, the deprotonation energy barrier of 8-AG·+ was confirmed to be 19.5 kJ/mol. These theoretical results provide valuable dynamics information and mechanistic insights for further understanding the properties of nucleic acid base analogues and one-electron oxidation of DNA.
Due to the lower redox potential comparing with guanine, it is the 8-azaguanine (8-AG) as the hole trap to form 8-azaguanine radical cation (8-AG·+) after one-electron oxidation of DNA containing 8-azaguanine. In generally, the 8-AG·+ may suffer from deprotonation to generate 8-AG(-H)·. In this text, we were stimulated to investigate the deprotonation reaction of 8-AG·+ generating by one-electron oxidation at M06-2X/6-31+G(d) level with explicit water molecules and polarized continuum model (PCM) to simulate the solvent effect. By building deprotonation model with different number of explicit water molecules, we found that these four water molecules locating around N(1)-H, O(6), N(2)-H of 8-AG·+ as well as the one locating in the second water shell which was hydrogen-bonding with the water around O(6) were necessary. If the water in the second water shell was not included, the imino proton (N(1)-H) would not transfer into the bulk water. In parallel, the N(1)-H would transfer to the O(6) of 8-AG·+ by intramolecular proton transfer. If the water molecule locating around N(2)-H was removed, the 8-AG·+ deprotonation would continue but the energy barrier would be lowered from 24.8 kJ/mol to 16.3 kJ/mol. In addition, the site of the water molecule in the second water shell was also studied. If putting the water in the second water shell around N(2)-H of 8-AG·+, the proton would be stabilized between the N(1) of 8-AG·+ and the oxygen of water molecule around N(1)-H meaning the proton would not be transferred into bulk water. Further, in order to test the influence of water number on 8-AG·+ deprotonation, the fifth water molecule, which is hydrogen-bonding with the water molecule around N(2)-H and another N(2)-H, was added. The potential energy surface with 5H2O revealed that it is almost no effect on the deprotonation pathway and energy barrier (25.5 kJ/mol). Lastly, so as to obtain the exact energy barrier of 8-AG·+ deprotonation, the deprotonation model with more explicit water molecules (9H2O) was proposed, where the additional water molecules were placed around N(2)-H, N(3), O(6), N(7) and N(8). From the potential energy surface, the deprotonation energy barrier of 8-AG·+ was confirmed to be 19.5 kJ/mol. These theoretical results provide valuable dynamics information and mechanistic insights for further understanding the properties of nucleic acid base analogues and one-electron oxidation of DNA.
