A novel histidine derivative containing 4-nitroimidazole,(S)-2-(4-((4-nitro-1H-imidazol-1-yl) methyl) benzamido)-3-(1H-imidazol-4-yl)propanoic acid (His-NI),was synthesized and labeled with [99mTc(CO)3(H2O)3]+.The tri...A novel histidine derivative containing 4-nitroimidazole,(S)-2-(4-((4-nitro-1H-imidazol-1-yl) methyl) benzamido)-3-(1H-imidazol-4-yl)propanoic acid (His-NI),was synthesized and labeled with [99mTc(CO)3(H2O)3]+.The tricarbonyl technetium complex,the 99mTc(CO)3-His-NI,showed a 99% yield under mild conditions at a low His-NI ligand concentration of 10-4 molL-1,and its biodistribution in mice bearing S180 tumor had a selective accumulation in tumor (2.01±0.40%ID/g at 1 h postinjection) and a slow clearance.The tumor/muscle ratio was 1.64 at 1 h,3.10 at 4 h,and 3.88 at 24 h,indicating that the 99mTc(CO)3-His-NI has a potential to image tumor hypoxia.展开更多
The voltammetric behaviour of three 5-nitroimidazoles,metronidazole,tinidazole and ornidazole,was investigated,and a method was developed for the simultaneous determination of these compounds,based on their reduction ...The voltammetric behaviour of three 5-nitroimidazoles,metronidazole,tinidazole and ornidazole,was investigated,and a method was developed for the simultaneous determination of these compounds,based on their reduction at a hanging mercury drop electrode（HMDE） in pH 8.95 buffer with differential pulse voltammetric（DPV） approach.Well defined voltammetric waves with peak potentials of -692,-640 and -652 mV were observed for these compounds,respectively.It is difficult to determine them individually from their mixtures without preseparation,for their voltammetric peaks overlapped seriously,so the chemometrics were used to resolve the overlapped voltammogram and quantify the mixtures.The proposed method was successfully applied to the determination of three 5-nitroimidazoles in milk and honey samples.展开更多
A series of natural berberine-derived nitroimidazoles as novel antibacterial agents were designed, synthesized and characterized by nuclear magnetic resonance(NMR), infrared spectra(IR), and high resolution mass spect...A series of natural berberine-derived nitroimidazoles as novel antibacterial agents were designed, synthesized and characterized by nuclear magnetic resonance(NMR), infrared spectra(IR), and high resolution mass spectra(HRMS) spectra. The antimicrobial evaluation showed that some target molecules exhibited moderate to good inhibitory activities against the tested bacteria and fungi including clinical drug-resistant strains isolated from infected patients. Especially, 2-fluorobenzyl derivative8 f not only gave strong activity against drug-resistant E. coli with the minimal inhibitory concentration(MIC) value of0.003 m M, 33-fold more active than norfloxacin, but also exhibited low toxicity toward RAW 264.7 cells and less propensity to trigger resistance. The aqueous solubility and Clog P values of target compounds were investigated to elucidate the structureactivity relationships. Molecular docking and quantum chemical studies for compound 8 f rationally explained its antibacterial effect. The further exploration of antibacterial mechanism revealed that the highly active compound 8 f could effectively permeabilize E. coli cell membrane and intercalate into DNA isolated from resistant E. coli to form 8 f-DNA complex that might block DNA replication to exert the powerful bioactivities. Compound 8 f could also selectively address resistant E. coli from a mixture of various strains.展开更多
2-Azido-4-nitroimidazole and its derivatives have been synthesized for energetic material applications. The synthesized compounds were fully characterized by 1H, 13C NMR spectroscopy and elemental analysis. Most of th...2-Azido-4-nitroimidazole and its derivatives have been synthesized for energetic material applications. The synthesized compounds were fully characterized by 1H, 13C NMR spectroscopy and elemental analysis. Most of them were determined by single crystal X-ray diffraction. The calculated densities of the compounds range between 1.71 and 1.92 g,cm-3. The calculated detonation pressures （P） for these derivatives fall in the range of 25.17 to 32.62 GPa and the detonation velocities （D） are distributed from 7.65 to 8.55 km·s-1.展开更多
Nitroimidazoles are a family of veterinary drugs containing a 5-nitroimidazole ring structure,which are commonly used antibiotics.In view of their potential genotoxicity and possible coexistence in actual samples,it i...Nitroimidazoles are a family of veterinary drugs containing a 5-nitroimidazole ring structure,which are commonly used antibiotics.In view of their potential genotoxicity and possible coexistence in actual samples,it is necessary to establish a rapid and effective method for the simultaneous determination of multiple nitroimidazoles.In this study,a rapid thin-layer chromatography combined with surface-enhanced Raman spectroscopy(TLC-SER)detection method for 14 nitroimidazole compounds has been established.The theoretical Raman spectra of the nitroimidazoles were calculated using the B3LYP/6-311+G(d)basis set in density functional theory(DFT)and the theoretical Raman spectra of TNZ,NBZ,ONZ,SCZ,DMZ,MNI,2-HMZ,4-HMZ,CMNI,IPZ,MNZ-OH and HMDMZ have been obtained for the first time.SERS detection was carried out on a gold nanoparticles(AuNPs)substrate,which exhibited strong SERS signals and a limit of detection limit of 0.1 mg/L.By optimizing the conditions used for the developing agent in TLC,12 nitroimidazoles were successfully separated,while MNZ and RNZ still could not be separated.When combined with the chemometrics analysis method,the TLC-SERS method can realize the simultaneous detection of 14 nitroimidazoles.Actual pork samples were spiked with nitroimidazoles with a recovery rate of 80%-110%and RSD of 0.74%-16.70%,which showed that SERS and TLC-SERS methods are also effective for detection in actual samples.The detection time of this method is<10 min,which is suitable for the rapid detection of nitroimidazoles,especially for the rapid qualitative identification of nitroimidazoles in situ.展开更多
The 2-azido-4-nitroimidazole-based energetic salts were synthesized in a simple and straightforward manner. The structures of these new salts were determined by IR, 1H NMR and 13C NMR spectroscopy and elemental analys...The 2-azido-4-nitroimidazole-based energetic salts were synthesized in a simple and straightforward manner. The structures of these new salts were determined by IR, 1H NMR and 13C NMR spectroscopy and elemental analysis. These salts also exhibited high positive enthalpies of formation, high nitrogen content, and moderate detonation properties.展开更多
A novel machine learning method, gene expression programming（GEP）, was employed to build quatitative structure-activity relationship（QSAR） models for predicting the enhancement effect of nitroimidazole compounds o...A novel machine learning method, gene expression programming（GEP）, was employed to build quatitative structure-activity relationship（QSAR） models for predicting the enhancement effect of nitroimidazole compounds on irradiation. The models were based on descriptors which were calculated from the molecular structures. Four descriptors were selected from the pool of descriptors by best multiple linear regression（BMLR） method. After that, three regression methods, multiple linear regression（MLR）, support vector machine（SVM） and GEP, were used to build QSAR models. Compared to MLR and SVM, GEP produced a better model with the square of correlation coefficient（R2）, 0.9203 and 0.9014, and the root mean square error（RMSE）, 0.6187 and 0.6875, for training set and test set, respectively. The results show that the GEP model has better predictive ability and more reliable than the MLR and SVM models. This indicates that GEP is a promising method on relevant researches in radiation area.展开更多
基金Supported by the National Natural Science Foundation of China(Grant No.20771011and21071010)
文摘A novel histidine derivative containing 4-nitroimidazole,(S)-2-(4-((4-nitro-1H-imidazol-1-yl) methyl) benzamido)-3-(1H-imidazol-4-yl)propanoic acid (His-NI),was synthesized and labeled with [99mTc(CO)3(H2O)3]+.The tricarbonyl technetium complex,the 99mTc(CO)3-His-NI,showed a 99% yield under mild conditions at a low His-NI ligand concentration of 10-4 molL-1,and its biodistribution in mice bearing S180 tumor had a selective accumulation in tumor (2.01±0.40%ID/g at 1 h postinjection) and a slow clearance.The tumor/muscle ratio was 1.64 at 1 h,3.10 at 4 h,and 3.88 at 24 h,indicating that the 99mTc(CO)3-His-NI has a potential to image tumor hypoxia.
文摘The voltammetric behaviour of three 5-nitroimidazoles,metronidazole,tinidazole and ornidazole,was investigated,and a method was developed for the simultaneous determination of these compounds,based on their reduction at a hanging mercury drop electrode（HMDE） in pH 8.95 buffer with differential pulse voltammetric（DPV） approach.Well defined voltammetric waves with peak potentials of -692,-640 and -652 mV were observed for these compounds,respectively.It is difficult to determine them individually from their mixtures without preseparation,for their voltammetric peaks overlapped seriously,so the chemometrics were used to resolve the overlapped voltammogram and quantify the mixtures.The proposed method was successfully applied to the determination of three 5-nitroimidazoles in milk and honey samples.
基金supported by the National Natural Science Foundation of China(21672173,21372186)Research Fund for International Young Scientists from International(Regional)Cooperation and Exchange Program of NSFC(81650110529)+3 种基金Chongqing Special Foundation for Postdoctoral Research Proposal(Xm2016039,Xm2017185)Program for Overseas Young Talents from State Administration of Foreign Experts Affairs,China(WQ2017XNDX047)the Doctoral Fund of Southwest University(SWU111075)the Research Funds for the Central Universities(XDJK2017B015)
文摘A series of natural berberine-derived nitroimidazoles as novel antibacterial agents were designed, synthesized and characterized by nuclear magnetic resonance(NMR), infrared spectra(IR), and high resolution mass spectra(HRMS) spectra. The antimicrobial evaluation showed that some target molecules exhibited moderate to good inhibitory activities against the tested bacteria and fungi including clinical drug-resistant strains isolated from infected patients. Especially, 2-fluorobenzyl derivative8 f not only gave strong activity against drug-resistant E. coli with the minimal inhibitory concentration(MIC) value of0.003 m M, 33-fold more active than norfloxacin, but also exhibited low toxicity toward RAW 264.7 cells and less propensity to trigger resistance. The aqueous solubility and Clog P values of target compounds were investigated to elucidate the structureactivity relationships. Molecular docking and quantum chemical studies for compound 8 f rationally explained its antibacterial effect. The further exploration of antibacterial mechanism revealed that the highly active compound 8 f could effectively permeabilize E. coli cell membrane and intercalate into DNA isolated from resistant E. coli to form 8 f-DNA complex that might block DNA replication to exert the powerful bioactivities. Compound 8 f could also selectively address resistant E. coli from a mixture of various strains.
文摘2-Azido-4-nitroimidazole and its derivatives have been synthesized for energetic material applications. The synthesized compounds were fully characterized by 1H, 13C NMR spectroscopy and elemental analysis. Most of them were determined by single crystal X-ray diffraction. The calculated densities of the compounds range between 1.71 and 1.92 g,cm-3. The calculated detonation pressures （P） for these derivatives fall in the range of 25.17 to 32.62 GPa and the detonation velocities （D） are distributed from 7.65 to 8.55 km·s-1.
基金supported by National Natural Science Foundation of China(32172326)National Key R&D Program of China(2018YFC1602300,2020YFC1606800)+2 种基金Modern agriculture in Jiangsu Province-key and general projects(BE2019362)Science and technology planning project of Jiangsu market supervision and Administration Bureau(KJ204132,KJ21125006)Suzhou science and technology development plan(SS2019016).
文摘Nitroimidazoles are a family of veterinary drugs containing a 5-nitroimidazole ring structure,which are commonly used antibiotics.In view of their potential genotoxicity and possible coexistence in actual samples,it is necessary to establish a rapid and effective method for the simultaneous determination of multiple nitroimidazoles.In this study,a rapid thin-layer chromatography combined with surface-enhanced Raman spectroscopy(TLC-SER)detection method for 14 nitroimidazole compounds has been established.The theoretical Raman spectra of the nitroimidazoles were calculated using the B3LYP/6-311+G(d)basis set in density functional theory(DFT)and the theoretical Raman spectra of TNZ,NBZ,ONZ,SCZ,DMZ,MNI,2-HMZ,4-HMZ,CMNI,IPZ,MNZ-OH and HMDMZ have been obtained for the first time.SERS detection was carried out on a gold nanoparticles(AuNPs)substrate,which exhibited strong SERS signals and a limit of detection limit of 0.1 mg/L.By optimizing the conditions used for the developing agent in TLC,12 nitroimidazoles were successfully separated,while MNZ and RNZ still could not be separated.When combined with the chemometrics analysis method,the TLC-SERS method can realize the simultaneous detection of 14 nitroimidazoles.Actual pork samples were spiked with nitroimidazoles with a recovery rate of 80%-110%and RSD of 0.74%-16.70%,which showed that SERS and TLC-SERS methods are also effective for detection in actual samples.The detection time of this method is<10 min,which is suitable for the rapid detection of nitroimidazoles,especially for the rapid qualitative identification of nitroimidazoles in situ.
文摘The 2-azido-4-nitroimidazole-based energetic salts were synthesized in a simple and straightforward manner. The structures of these new salts were determined by IR, 1H NMR and 13C NMR spectroscopy and elemental analysis. These salts also exhibited high positive enthalpies of formation, high nitrogen content, and moderate detonation properties.
基金Supported by the National Natural Science Foundation of China（No.81202153）, the Research Fund for Youth Scholars of Union Medical College of China（No.2012D03）, the Research Fund for the Doctoral Program of Higher Education of China （No.20121106120042） and the Development Fund of Institute of Radiation Medicine, Chinese Academy of Medical Sciences （No.SF1227）.
文摘A novel machine learning method, gene expression programming（GEP）, was employed to build quatitative structure-activity relationship（QSAR） models for predicting the enhancement effect of nitroimidazole compounds on irradiation. The models were based on descriptors which were calculated from the molecular structures. Four descriptors were selected from the pool of descriptors by best multiple linear regression（BMLR） method. After that, three regression methods, multiple linear regression（MLR）, support vector machine（SVM） and GEP, were used to build QSAR models. Compared to MLR and SVM, GEP produced a better model with the square of correlation coefficient（R2）, 0.9203 and 0.9014, and the root mean square error（RMSE）, 0.6187 and 0.6875, for training set and test set, respectively. The results show that the GEP model has better predictive ability and more reliable than the MLR and SVM models. This indicates that GEP is a promising method on relevant researches in radiation area.
