新型巯基化合物分析试剂的设计、合成和分析方法的初步建立
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摘要
巯基化合物是在生物及医药方面有着重要作用的一类有机化合物。它们在人体内的新陈代谢及酶催化过程中起着重要作用。半胱氨酸(Cys)、同型半胱氨酸(Hcys)、谷胱甘肽(GSH)等小分子的巯基化合物含量的高低与人类的某些疾病如艾滋病(AIDS),帕金森综合症(Parkinson's diseases)以及心血管病有关。因此,发展合适的检测试剂来测定巯基化合物有十分重要的意义。本文设计合成了一系列苯磺酸内酯衍生物、香豆素衍生物以及半花菁类衍生物,用于检测巯基化合物。
1.苯磺酸内酯衍生物的合成
以廉价易得的糖精钠为原料,经甲基化、格氏反应、环化,合成苄位多取代的甲苯磺酸内酯,再经硝化、还原,得到相应的硝基衍生物和氨基衍生物;以邻甲酰基苯磺酸钠为原料,经环化、还原合成苯磺酸内酯。初步的探索研究结果表明,所得到的系列苯磺酸内酯衍生物常规反应条件与巯基化合物反应非常缓慢,将其作为巯基化合物的检测试剂存在一定困难。
2.香豆素衍生物的合成
以间苯二酚为原料,经过甲酰化、醚化、碘代、成环、Heck偶联,得到香豆素的丙烯酸甲酯衍生物,但它在常规反应条件与巯基化合物不反应,不能作为巯基检测试剂；以间苯二酚为原料,经环化、甲酰化、醚化、adol反应得到香豆素的adol反应产物,虽能顺利地与巯基化合物反应,但反应前后紫外吸收光谱变化较小,不适于用紫外分光光度法检测硫醇化合物,运用其他分析方法使用该试剂来检测硫醇化合物的分析方法有待建立。
3.半花菁化合物的合成以及对巯基化合物的检测
通过简单的三步方法合成了六个半花菁类化合物,它们能与乙硫醇迅速反应,反应前后紫外吸收光谱变化显著。为此,初步建立了紫外-可见分光光度法测定巯基化合物的分析方法,该方法在10-5～10-4mol／L的巯基化合物检测浓度范围内存在较好的线性关系。
Thiols, which play a crucial role in biology and medicine,and play an important role in metabolic pathways.Low molecular weight thiol-containing compounds such as cysteine (Cys), glutathione (GSH), homocysteine (Hcys), plasma levels of which have been linked to various human diseases such as AIDS, and Parkinson's diseases, as well as cardiovascular diseases. Therefore, it is of importance to detect thiols using appropriate reagents. In this dissertation, it was described the synthesis of novel hemicyanine dyes compounds, benzenesulfolactones and coumarins and their application in detecting thiols.
Part1 Synthesis of benzenesulfolactones
Multi-substituted benzenesulfolactones was synthesized starting from cheap saccharin sodium via methylation, Grignard reaction, cyclization, and further transformed into nitro derivative by nitrification and then amino derivative by reduction. Benzenesulfolactone was sythesized starting from 2-formylbenzenesulfonate via cyclization and then reduction. It was show that by preliminary research, the speed of the obtained benzenesulfolactones reacting with thiols in normal condition is so slow that there are some difficuties to be as detecting thiols'reagents.
Part 2 Synthesis of coumarins
Methyl acrylate of coumarins was synthesized starting from resorcinol via formylation, etherification, iodination, cyclization, Heck cross-coupling reaction. It doesn't react with thiols in normal condition, so this compound cann't be a reagent for detecting thiols.The adol coupound of coumarins was synthesized starting from resorcinol visa cyclization, formylation, etherification,adol reaction.Although it reacts with thiols,the difference value of UV absorbance before and after reaction is small. Hence, the compound also cann't be reagent for detecting thiols by UV analysis. Other analycial mothods to detect thiols with this compound will be established in future.
Part 3 Synthesis of hemicyanine dyescompounds and their application in detecting thiols
Six hemicyanine dyes compounds were designed and prepared concisely via three steps.They can react with ethanethiol quickly, and the difference value of UV absorbance is significant before and after reaction.Hence, the analycal mothod of detecting thiols by UV-visible pectrophotometer was preliminarily established. A linear calibration curve can be observed in the range of 10-5～10-4mol/L.
1.苯磺酸内酯衍生物的合成
以廉价易得的糖精钠为原料,经甲基化、格氏反应、环化,合成苄位多取代的甲苯磺酸内酯,再经硝化、还原,得到相应的硝基衍生物和氨基衍生物;以邻甲酰基苯磺酸钠为原料,经环化、还原合成苯磺酸内酯。初步的探索研究结果表明,所得到的系列苯磺酸内酯衍生物常规反应条件与巯基化合物反应非常缓慢,将其作为巯基化合物的检测试剂存在一定困难。
2.香豆素衍生物的合成
以间苯二酚为原料,经过甲酰化、醚化、碘代、成环、Heck偶联,得到香豆素的丙烯酸甲酯衍生物,但它在常规反应条件与巯基化合物不反应,不能作为巯基检测试剂；以间苯二酚为原料,经环化、甲酰化、醚化、adol反应得到香豆素的adol反应产物,虽能顺利地与巯基化合物反应,但反应前后紫外吸收光谱变化较小,不适于用紫外分光光度法检测硫醇化合物,运用其他分析方法使用该试剂来检测硫醇化合物的分析方法有待建立。
3.半花菁化合物的合成以及对巯基化合物的检测
通过简单的三步方法合成了六个半花菁类化合物,它们能与乙硫醇迅速反应,反应前后紫外吸收光谱变化显著。为此,初步建立了紫外-可见分光光度法测定巯基化合物的分析方法,该方法在10-5～10-4mol／L的巯基化合物检测浓度范围内存在较好的线性关系。
Thiols, which play a crucial role in biology and medicine,and play an important role in metabolic pathways.Low molecular weight thiol-containing compounds such as cysteine (Cys), glutathione (GSH), homocysteine (Hcys), plasma levels of which have been linked to various human diseases such as AIDS, and Parkinson's diseases, as well as cardiovascular diseases. Therefore, it is of importance to detect thiols using appropriate reagents. In this dissertation, it was described the synthesis of novel hemicyanine dyes compounds, benzenesulfolactones and coumarins and their application in detecting thiols.
Part1 Synthesis of benzenesulfolactones
Multi-substituted benzenesulfolactones was synthesized starting from cheap saccharin sodium via methylation, Grignard reaction, cyclization, and further transformed into nitro derivative by nitrification and then amino derivative by reduction. Benzenesulfolactone was sythesized starting from 2-formylbenzenesulfonate via cyclization and then reduction. It was show that by preliminary research, the speed of the obtained benzenesulfolactones reacting with thiols in normal condition is so slow that there are some difficuties to be as detecting thiols'reagents.
Part 2 Synthesis of coumarins
Methyl acrylate of coumarins was synthesized starting from resorcinol via formylation, etherification, iodination, cyclization, Heck cross-coupling reaction. It doesn't react with thiols in normal condition, so this compound cann't be a reagent for detecting thiols.The adol coupound of coumarins was synthesized starting from resorcinol visa cyclization, formylation, etherification,adol reaction.Although it reacts with thiols,the difference value of UV absorbance before and after reaction is small. Hence, the compound also cann't be reagent for detecting thiols by UV analysis. Other analycial mothods to detect thiols with this compound will be established in future.
Part 3 Synthesis of hemicyanine dyescompounds and their application in detecting thiols
Six hemicyanine dyes compounds were designed and prepared concisely via three steps.They can react with ethanethiol quickly, and the difference value of UV absorbance is significant before and after reaction.Hence, the analycal mothod of detecting thiols by UV-visible pectrophotometer was preliminarily established. A linear calibration curve can be observed in the range of 10-5～10-4mol/L.
引文
[1]蔡紫阳, 甲硫醇生产、应用与发展, 精细化工原料及中间体。2008,9,40-42
[2]孙保国 著 含硫香料化学,北京,科学出版社,2007
[3]孙艳艳,冯加民,高庆宇等,半胱氨酸和谷胱甘肽氧化反应动力学的研究进展。化学研究与应用,2008,7,799-804
[4]张玉臣,杜永丽,聂翠芳等,还原型谷胱甘肽的临床应用进展。社区医学杂,2005,4,26-27
[5]王瑜,李玉明,高半胱氨酸和血管疾病研究进展。武警医学院学报,2000,1,88-90
[6]Ueland, P. M..; Vollset, S. E. Homocysteine and Folate in Pregnancy. Clin. Chem.2004,50, 1293-1295
[7]Jacobsen, D.W. Homocysteine and vitamins in cardiovascular disease. Clin. Chem.1998,44, 1833-1843
[8]Rasmussen,K.; M(?)ller,J. Total homocysteine measurement in clinical practice. Ann. Clin. Biochem.2000,37,627-648
[9]Nakamura,H.; Tamura,Z. Fluorometric Determination of Thiols by Liquid Chromatography with Post column Derivatizat ion. Anal. Chem.1981,53,2190-2193
[10]Tcherkas,Y.V.; Denisenko, A.D. Simultaneous determination of several amino acids, including homocysteine, cysteine and glutamic acid, in human plasma by isocratic reversed-phase high-performance liquid chromatography with fluorimetric detection. J. Chromatogr. A,2001,913, 309-313
[11]Wang,W.H.; Rusin,OL; Strongin,R.M.;et.al. Detection of Homocysteine and Cysteine. J. Am. Chem. Soc.2005,127,15949-15958
[12]Wang, H.; Liang, S. C.;Zhang, H. S.; et.al.3-Iodoacetylaminobenzanthrone as a fluorescent derivatizing reagent for thiols in high-performance liquid chromatography. Anal. Chim. Acta.2004, 512,281-286
[13]Liang, S. C.; Wang, H.; Zhang, H. S.; et.al. Determination of thiol by high-performance liquid chromatography and fluorescence detection with 5-methyl-(2-(m-iodoacetylaminophenyl) benzoxazole. Anal. Bioanal. Chem.2005,381,1095-1100.
[14]Ivanova. A. R.; Nazimovb. I.V.;. Baratovaa. L.A. Qualitative and quantitative determination of biologically active low-molecular-mass thiols in human blood by reversed-phase high-performance liquid chromatography with photometry and fluorescence detection. J.Chromatogr. A,2000,870, 157-166.
[15]Ivanova. A. R.; Nazimovb. I.V.;. Baratovaa. L.A. Determination of biologically active low-molecular-mass thiols in human blood I. Fast qualitative and quantitative, gradient and isocratic reversed-phase high-performance liquid chromatography with photometric and fluorescence detection. J. Chromatogr. A,2000,870,433-442.
[16]Mare, S.; Penugonda, S.; Ercal, N. High performance liquid chromatography analysis of MESNA (2-mercaptoethane sulfonate) in biological samples using fluorescence detection. Biomed. Chromatogr.2005,19,80-86.
[17]Wu, W.; Goldstein. G.; Ercal, N.; et.al. Separation and quantification of N-acetyl-L-cysteine and Nacetyl-cysteine-amide by HPLC with fluorescence detection. Biomed. Chromatogr.2006,20, 415-422
[18]Oe, T.; Ohyagi, T.; Naganuma, A. Determination of g-glutamylglutathione and other low-molecularmass biological thiol compounds by isocratic high-performance liquid chromatography with fluorimetric detection. J.Chromatogr. B,1998,708,285-289.
[19]Haj-Yehia, A-I.; Assaf, P.; Nassar, T.; et.al. Determination of lipoic acid and dihydrolipoic acid in human plasma and urine by high-performance liquid chromatography with fluorimetric detection. Journal of Chromatogr A,2000,870,381-388.
[20]Bald, E.; Sypniewski, S. Determination of thiol drugs in pharmaceutical formulations as their S-pyridinium derivatives by high-performance liquid chromatography with ultraviolet detection. Fresenius. J. Anal. Chem.1997,358,554-555.
[21]Kaniowska, E.; Chwatko, G.; Bald, E.; et.al. Urinary excretion measurement of cysteine and homocysteine in the form of their S-pyridinium derivatives by high-performance liquid chromatography with ultraviolet detection. J. Chromatogr. A,1998,798,27-35.
[22]Kaniowska, G.; Bald. E. Determination of cysteine in human plasma by high-performance liquid chromatography and ultraviolet detection after pre-column derivatization with 2-chloro-l-methylpyridinium iodide. Talanta.2000.52.509-515
[23]Chwatko,G.; Bald. E. Determination of different species of homocysteine in human plasma by high-performance liquid chromatography with ultraviolet detection. J.Chromatogr. A,2002,949, 141-151.
[24]Bald. E.; Glowacki, R. Analysis of saliva for glutathione and metabolically related thiols by liquid chromatography with ultraviolet detection. Amino. Acids.2005,28,431-433.
[25]D'Eramol, J.; Finkelstein, A.; Fridman, O.; et.al. Total homocysteine levels in plasma: high-performance liquid chromatographic determination with electrochemical detection and glassy carbon electrode. J. Chromatogr. B.1998,720,205-210.
[26]Houze, P.; Gamra, S.; Madelaine, I.; et.al. Simultaneous Determination of Total Plasma Glutathione, Homocysteine, Cysteinylglycine, and Methionine by High-Performance Liquid Chromatography With Electrochemical Detection. J. Clin. Lab. Anal.2001,15,144-153.
[27]Liu, M. C.;Li, P.;Cheng,Y. X.; et.al. Determination of thiol compounds in rat striatum microdialysate by HPLC with a nanosized CoHCF-modified electrode. Anal. Bioanal. Chem.2004, 380,742-750.
[28]Cao, X. N.;Li, J. H.;Jin. L.T.; et.al. Platinum particles-modified electrode for HPLC with amperometric detection of thiols in rat striatum. Biomed. Chromatogr.2004,18,564-569.
[29]Guan, X.M,.; Hoffman, B.; Dwivedi, C.; et.al. A simultaneous liquid chromatography/mass spectrometric assay of glutathione, cysteine, homocysteine and their disulfides in biological samples. J. Pharm. Biomed. Anal.2003,31,251-261.
[30]Braga, P.; Montes-Bayo'n, M.; Alvarez, J.; et al. Characterization, biological interactions and in-vivo detection of selenotrisulfide derivatives of glutathion, cysteine and homocysteine by HPLC-ICP-MS. J. Anal. At. Spectrom.,2004,19,1128-1133.
[31]Kang, S. H.;Wei, W.; Yeung. E. S. On-column derivatization for the analysis of homocysteine and other thiols by capillary electrophoresis with laser-induced fluorescence detection. J. Chromatogr. B,2000,744,149-156.
[32]Zinellu, A.; Sotgial, S.; Posadino, A.; et.al. Highly sensitive simultaneous detection of cultured cellular thiols by laser induced fluorescencecapillary electrophoresis. Electrophoresis 2005,26, 1063-1070
[33]Musenga, A.; Mandrioli, R.; Bonifazi, P.; et.al. Sensitive and selective determination of glutathione in probiotic bacteria by capillary electrophoresis-laser induced fluorescence. Anal Bioanal Chem.2007,387,917-924.
[34]Ivanov, A. R.; Nazimov, I. V.; Baratova, L. A. Determination of biologically active low-molecular-mass thiols in human blood Ⅱ. High-performance capillary electrophoresis with photometric detection. J. Chromatogr. A,2000,895,167-171.
[35]Pasas, S.; Lacher, N.; Davies, M.; et.al. Detection of homocysteine by conventional and microchip capillary electrophoresis/electrochemistry. Electrophoresis.2002,23,759-766.
[36]Inoue, T.; Kirchhoff, J. Determination of Thiols by Capillary Electrophoresis with Amperometric Detection at a Coenzyme Pyrroloquinoline Quinone Modified Electrode. Anal. Chem. 2002,74,1349-1354.
[37]Allison, L. A.; Shoup, R. E. Dual electrode liquid chromatography detector for thiols and disulfides. Anal. Chem.1983,55,8-12.
[38]Lawrence, N.; Deo, R.;Wang, J. Detection of homocysteine at carbon nanotube paste electrodes. Talanta.2004,63,443-449.
[39]Deng, C, Y.;Chen, J. H.; Chen, H, L.; et.al. Electrochemical detection of 1-cysteine using a boron-doped carbon nanotube-modified electrode. Electrochim. Acta,2009,54,3298-3302.
[40]Fei, S, D.; Chen, J, H.; Yao, S, Z.; et.al. Electrochemical behavior of L-cysteine and its detection at carbon nanotube electrode modiWed with platinum. Anal. Biochem.2005.339.29-35.
[41]Kafi, A.K.M.; Yin, F.; Kwon, Y. S.; et.al. Amperometric thiol sensor based on Prussian blue-modified glassy carbon electrode. CurrAppl. Physi.2007,7,496-499.
[42]Lima, P. R.; Santos, W. J.R.; Kubota, L. T.; et.al. An amperometric sensor based on electrochemically triggered reaction:Redox-active Ar-NO/Ar-NHOH from 4-nitrophthalonitrile-modified electrode for the low voltage cysteine detection. J. Electroanal. Chem.2008,612,87-96.
[43]Lawrence, N, S.; Davis, J.; Compton, R. J. Electrochemical detection of thiols in biological media. Talanta,2001,53,1089-1094.
[44]Nekrassova, O.; White, P. C.; Compton, R. G.; et.al. An electrochemical adaptation of Ellman's test. Analyst,2002,127,797-802.
[45]Wen. M.; Liu, H. Q.; Tian, Y.; et.al. Amorphous FeNiPt nanoparticles with tunable length for electrocatalysis and electrochemical determination of thiols. Chem. Commun.,2009,4530-4532.
[46]Wang, W.; Li, L.; Zhang, S, S.; et.al. Determination of Physiological Thiols by Electrochemical Detection with Piazselenole and Its Application in Rat Breast Cancer Cells 4T-1. J. Am. Chem. Soc. 2008,130,10846-10847.
[47]Capitan, p.; Malmezat, T.; Obled, C.; et.al. Gas chromatographic-mass spectrometric analysis of stable isotopes of cysteine and glutathione in biological samples. J. Chromatogr. B,1999,732, 127-135.
[48]Guo, Y.; Shao, S. J.; Jiang, S. X.; et.al. A specific colorimetric cysteine sensing probe based on dipyrromethane-TCNQ assembly. Tetrahedron Lett.2004,45,6477-6480.
[49]Chen, H, L.; Zhao, Q.; Wu, Y, B.; et.al. Selective Phosphorescence Chemosensor for Homocysteine Based on an Iridium(Ⅲ) Complex. Inorg. Chem.2007,46,11075-11081.
[50]Ros-Lis, J. V.; Garci'a, B.; Jime'nez, D.; et.al. Squaraines as Fluoro-Chromogenic Probes for Thiol-Containing Compounds and Their Application to the Detection of Biorelevant Thiols. J. Am. Chem. Soc.2004,126,4064-4065.
[51]Han, M. S.; Kim, D. H. Rationally designed chromogenic chemosensor that detects cysteine in aqueous solution with remarkable selectivity. Tetrahedron,2004,60,11251-11257.
[52]Zhang, D. Q.; Zhang, M.; Huang, C. H.; et.al. Highly selective colorimetric sensor for cysteine and homocysteine based on azo derivatives. Tetrahedron Lett.2006,47,7093-7096.
[53]Zeng, Y; Zhang, G. X.; Zhang, D. Q. A selective colorimetric chemosensor for thiols based on intramolecular charge transfer mechanism. Anal Chim. Acta.2008,627,254-257.
[54]Zeng, Y.; Zhang, G. X.; Zhang, D. Q. A dual-function colorimetric chemosensor for thiols and transition metal ions based on ICT mechanism. Tetrahedron Lett.2008,49,7391-7394.
[55]Huo, F. J.; Sun, Y. Q.; Yin, C. X.; et.al. Colorimetric Detection of Thiols Using a Chromene Molecule. Org.Lett.2008,11,1918-4921.
[56]Zhang, M.; Yu, M. X.; Huang, C. H.; et al. A Highly Selective Fluorescence Turn-on Sensor for Cysteine/Homocysteine and Its Application in Bioimaging. J. Am.Chem. Soc.,2007,129, 10322-10323.
[57]Sreejith, S.; Divya, K. P. Ajayaghosh, A. A Near-Infrared Squaraine Dye as a Latent Ratiometric Fluorophore for the Detection of Aminothiol Content in Blood Plasma. Angew. Chem. Int. Ed.2008, 47,7883-7887.
[58]Ellman, G. L. Tissue sulfhydryl groups. Arch. Biochem. Biophys.1959,82,70-77.
[59]Zhu J, G,; Dhimitruka. I; Pei, D.5-(2-Aminoethyl)dithio-2-nitrobenzoate as a More Base-Stable Alternative to Ellman's Reagent. Org.Lett.2004,6,3809-3812.
[60]Kanaoka, Y.C.; Machida, M.; Ando, K.; et.al. Fluorescence and structures of proteins as measured by incorporation of fluorophore:IV. Synthesis and fluorescence characteristics of N-(p-(2-benzimidazolyl)phenyl) maleimide. Biochi. Biophys. Acta.1970,207,269-277.
[61]Machida, M.; Ushijima. N.; Takahashi, T.; et.al. A Novel Fluorescent Thiol Reagent:Syntheses and Electronic Spectra of N-(7-Dimethylamino-4-methyl-3-coumarinyl)-maleimide (DACM-3) and the Related Compounds. Chem. Pharm. Bull,1977,25,1289-1294.
[62]Liang, S. C.; Wang, H.; Zhang, H. S.; et.al. Direct spectrofluorimetric determination of glutathione in biological samples using 5-maleimidyl-2-(m-methylphenyl) benzoxazole. Anal. Chim. Acta,2002,45,211-219.
[63]Matsumoto, T. Urano, Y.; Nagano, T. A Thiol-Reactive Fluorescence Probe Based on Donor-Excited Photoinduced Electron Transfer:Key Role of Ortho Substitution. Org. Lett.,2007,9, 3375-3377.
[64]Huanga, S. T.; Ting, K.N.; Wang, K. L. Development of a long-wavelength fluorescent probe based on quinone-methide-type reaction to detect physiologically significant thiols. Anal. Chim. Acta.2008,620,120-126.
[65]Lin, W. Y.; Yuan, L.; Cao, Z. M.; et.al. A Sensitive and Selective Fluorescent Thiol Probe in Water Based on the Conjugate 1,4-Addition of Thiols to a,b-Unsaturated Ketones. Chem. Eur. J. 2009,15,5096-5103.
[66]Tang. B.; Xing. Y. L.; Li P.; et.al. A Rhodamine-Based Fluorescent Probe Containing a Se-N Bond for Detecting Thiols and Its Application in Living Cells. J. Am. Chem. Soc.,2007,129, 11666-11667.
[67]Ahn, Y. H.; Lee, J. S.; Chang, Y. T. Combinatorial Rosamine Library and Application to in Vivo Glutathione Probe. J. Am. Chem. Soc.,2007,129,4510-4511.
[68]Maeda, H.; Matsuno H.; Ushida, M.; et.al. 2,4-Dinitrobenzenesulfonyl Fluoresceins as Fluorescent Alternatives to Ellman's Reagent in Thiol-Quantification Enzyme Assays. Angew. Chem. Int. Ed.2005,44,2922-2925.
[69]Shibata, A.; Furukawa, K.; Abe, H.; et.al. Rhodamine-based fluorogenic probe for imaging biological thiol. Bioorg.Med. Chem. Lett.2008,18,2246-2249.
[70]Jiang, W.; Fu, Q. Q.; Wang, W.; et.al. A Highly Selective Fluorescent Probe for Thiophenols. Angew. Chem. Int. Ed.2001,46,8445-8448.
[71]Bouffard, J.; Kim, Y.; Hilderbrand, S. A.; et.al. A Highly Selective Fluorescent Probe for Thiol Bioimaging. Org. Lett.,2008,10,37-40.
[72]Zhang, M.; Li, M. Y.; Huang, C. H.; et.al. Novel Y-type two-photon active fluorophore: synthesis and application in fluorescent sensor for cysteine and homocysteine. Tetrahedron Lett. 2007,48,2329-2333.
[73]Kim, T-K.; Lee, D-M.; Kim, H-J. Highly selective fluorescent sensor for homocysteine and cysteine. Tetrahedron Lett.2008,49,4879-4881.
[74]Huang, G. G.; Hossain, M. K.; Ozaki, Y.; et.al. A novel reversed reporting agent method for surface-enhanced Raman scattering; highly sensitive detection of glutathione in aqueous solutions. Analyst,2009,134,2468-2474.
[75]Chen, S, J.; Chang, H, T.; Nile Red-Adsorbed Gold Nanoparticles for Selective Determination of Thiols Based on Energy Transfer and Aggregation. Anal. Chem.,2004,76,3727-3734.
[76]Chow, C. F.; Chiu, B-K. W.; Lam, M-H. W.; et.al. A Trinuclear Heterobimetallic Ru(Ⅱ)/Pt(Ⅱ) Complex as a Chemodosimeter Selective for Sulfhydryl-Containing Amino Acids and Peptides. J. Am. Chem. Soc.2003,125,7802-7803.
[77]Lee, J. H.; Lim.C. C.; Cho, B. R..; et.al. A Two-Photon Fluorescent Probe for Thiols in Live Cells and Tissues. J. Am. Chem. Soc.,2010,132,1216-1217.
[78]Riiegg, U.; Jarvis, D.; Rudinger, J.2-Sulphobenzyl, a New Solubilizing and Reversible Protecting Group for Cysteine in Proteins. Biochem. J.1979,179,127-134.
[79]Shashidhar, M. S.; Bhatt, M. V. Aspects of tautomerism. Part 16. Influence of the γ-keto function on the reactions of sulphonic acids. Proc. Indian Acad. Sci. (Chem. Sci.),1989,4,319-326.
[80]Zinnes, H.; Sircar, J.C.; Lindo, N.; et.al. Isoxicam and related 4-Hydroxy-N-isoxazolyl-2H-1, 2-benzothiazine-3-carboxamide 1,1-Dioxides. Potent nonsteroidal antiinflammatory agents. J.Med.Chem.,1982,25,12-18.
[81]Wagenaar, A.;. Engberts, J-B-F-N. Intramolecular Nucleophilic Catalysis by the Neighboring Hydroxyl Group in Acid-and Base-Catalyzed Hydrolysis of Aromatic Sulfonamides and Sultones. Mechanism of Intramolecular Nucleophilic Substitution at Sulfonyl Sulfur. J. Org. Chem.1988,53, 768-772.
[82]杨金会,孟丽聪。天然产物1,3-二-(2-羟基-4-甲氧基苯基)丙烷和1,3-二-(2,4-二羟基苯基)丙烷的合成。有机化学,2008,5,918～921.
[83]Luo, Q. L.; Eibauer, S. Reiser, O. Novel Bis(oxazole) Pincer Ligands and their Application in Suzuki-Miyaura Cross Coupling Reactions under Aerobic Conditions. J. Mol. Catal. A,2007,268, 65-69
[84]Alexander, V-M.; Bhat, R-P.; Samant, S-D. Bismuth(Ⅲ) nitrate pentahydrate-a mild and inexpensive reagent for synthesis of coumarins under mild conditions. Tetrahedron Lett.2005,46, 6957-6959.
[85]Kulkarni, A.; Patil, S-A.; Badami, P-S. Synthesis, characterization, DNA cleavage and in vitro antimicrobial studies of La(Ⅲ), Th(Ⅳ) and VO(Ⅳ) complexes with Schiff bases of coumarin derivatives. Eur. J. Med. Chem,2009,44,2904-2912.
[86]Mohammadpoor-Baltork, I.; Khosropour, A. R.; Hojati, S. F. ZrOCl2.8H2O as an efficient, environmentally friendly and reusable catalyst'for synthesis of benzoxazoles, benzothiazoles, benzimidazoles and oxazolo[4,5-b]pyridines under solvent-free conditions. Catal. Commun.2007,8, 1865-1870.
[87]Jcdrzejewska, B.; Kabatc, J.; Paczkkowski J.; et al. Hemicyanine dyes:synthesis, structure and photophysical properties. Dye and Pigments,2003,58,47-58.
[2]孙保国 著 含硫香料化学,北京,科学出版社,2007
[3]孙艳艳,冯加民,高庆宇等,半胱氨酸和谷胱甘肽氧化反应动力学的研究进展。化学研究与应用,2008,7,799-804
[4]张玉臣,杜永丽,聂翠芳等,还原型谷胱甘肽的临床应用进展。社区医学杂,2005,4,26-27
[5]王瑜,李玉明,高半胱氨酸和血管疾病研究进展。武警医学院学报,2000,1,88-90
[6]Ueland, P. M..; Vollset, S. E. Homocysteine and Folate in Pregnancy. Clin. Chem.2004,50, 1293-1295
[7]Jacobsen, D.W. Homocysteine and vitamins in cardiovascular disease. Clin. Chem.1998,44, 1833-1843
[8]Rasmussen,K.; M(?)ller,J. Total homocysteine measurement in clinical practice. Ann. Clin. Biochem.2000,37,627-648
[9]Nakamura,H.; Tamura,Z. Fluorometric Determination of Thiols by Liquid Chromatography with Post column Derivatizat ion. Anal. Chem.1981,53,2190-2193
[10]Tcherkas,Y.V.; Denisenko, A.D. Simultaneous determination of several amino acids, including homocysteine, cysteine and glutamic acid, in human plasma by isocratic reversed-phase high-performance liquid chromatography with fluorimetric detection. J. Chromatogr. A,2001,913, 309-313
[11]Wang,W.H.; Rusin,OL; Strongin,R.M.;et.al. Detection of Homocysteine and Cysteine. J. Am. Chem. Soc.2005,127,15949-15958
[12]Wang, H.; Liang, S. C.;Zhang, H. S.; et.al.3-Iodoacetylaminobenzanthrone as a fluorescent derivatizing reagent for thiols in high-performance liquid chromatography. Anal. Chim. Acta.2004, 512,281-286
[13]Liang, S. C.; Wang, H.; Zhang, H. S.; et.al. Determination of thiol by high-performance liquid chromatography and fluorescence detection with 5-methyl-(2-(m-iodoacetylaminophenyl) benzoxazole. Anal. Bioanal. Chem.2005,381,1095-1100.
[14]Ivanova. A. R.; Nazimovb. I.V.;. Baratovaa. L.A. Qualitative and quantitative determination of biologically active low-molecular-mass thiols in human blood by reversed-phase high-performance liquid chromatography with photometry and fluorescence detection. J.Chromatogr. A,2000,870, 157-166.
[15]Ivanova. A. R.; Nazimovb. I.V.;. Baratovaa. L.A. Determination of biologically active low-molecular-mass thiols in human blood I. Fast qualitative and quantitative, gradient and isocratic reversed-phase high-performance liquid chromatography with photometric and fluorescence detection. J. Chromatogr. A,2000,870,433-442.
[16]Mare, S.; Penugonda, S.; Ercal, N. High performance liquid chromatography analysis of MESNA (2-mercaptoethane sulfonate) in biological samples using fluorescence detection. Biomed. Chromatogr.2005,19,80-86.
[17]Wu, W.; Goldstein. G.; Ercal, N.; et.al. Separation and quantification of N-acetyl-L-cysteine and Nacetyl-cysteine-amide by HPLC with fluorescence detection. Biomed. Chromatogr.2006,20, 415-422
[18]Oe, T.; Ohyagi, T.; Naganuma, A. Determination of g-glutamylglutathione and other low-molecularmass biological thiol compounds by isocratic high-performance liquid chromatography with fluorimetric detection. J.Chromatogr. B,1998,708,285-289.
[19]Haj-Yehia, A-I.; Assaf, P.; Nassar, T.; et.al. Determination of lipoic acid and dihydrolipoic acid in human plasma and urine by high-performance liquid chromatography with fluorimetric detection. Journal of Chromatogr A,2000,870,381-388.
[20]Bald, E.; Sypniewski, S. Determination of thiol drugs in pharmaceutical formulations as their S-pyridinium derivatives by high-performance liquid chromatography with ultraviolet detection. Fresenius. J. Anal. Chem.1997,358,554-555.
[21]Kaniowska, E.; Chwatko, G.; Bald, E.; et.al. Urinary excretion measurement of cysteine and homocysteine in the form of their S-pyridinium derivatives by high-performance liquid chromatography with ultraviolet detection. J. Chromatogr. A,1998,798,27-35.
[22]Kaniowska, G.; Bald. E. Determination of cysteine in human plasma by high-performance liquid chromatography and ultraviolet detection after pre-column derivatization with 2-chloro-l-methylpyridinium iodide. Talanta.2000.52.509-515
[23]Chwatko,G.; Bald. E. Determination of different species of homocysteine in human plasma by high-performance liquid chromatography with ultraviolet detection. J.Chromatogr. A,2002,949, 141-151.
[24]Bald. E.; Glowacki, R. Analysis of saliva for glutathione and metabolically related thiols by liquid chromatography with ultraviolet detection. Amino. Acids.2005,28,431-433.
[25]D'Eramol, J.; Finkelstein, A.; Fridman, O.; et.al. Total homocysteine levels in plasma: high-performance liquid chromatographic determination with electrochemical detection and glassy carbon electrode. J. Chromatogr. B.1998,720,205-210.
[26]Houze, P.; Gamra, S.; Madelaine, I.; et.al. Simultaneous Determination of Total Plasma Glutathione, Homocysteine, Cysteinylglycine, and Methionine by High-Performance Liquid Chromatography With Electrochemical Detection. J. Clin. Lab. Anal.2001,15,144-153.
[27]Liu, M. C.;Li, P.;Cheng,Y. X.; et.al. Determination of thiol compounds in rat striatum microdialysate by HPLC with a nanosized CoHCF-modified electrode. Anal. Bioanal. Chem.2004, 380,742-750.
[28]Cao, X. N.;Li, J. H.;Jin. L.T.; et.al. Platinum particles-modified electrode for HPLC with amperometric detection of thiols in rat striatum. Biomed. Chromatogr.2004,18,564-569.
[29]Guan, X.M,.; Hoffman, B.; Dwivedi, C.; et.al. A simultaneous liquid chromatography/mass spectrometric assay of glutathione, cysteine, homocysteine and their disulfides in biological samples. J. Pharm. Biomed. Anal.2003,31,251-261.
[30]Braga, P.; Montes-Bayo'n, M.; Alvarez, J.; et al. Characterization, biological interactions and in-vivo detection of selenotrisulfide derivatives of glutathion, cysteine and homocysteine by HPLC-ICP-MS. J. Anal. At. Spectrom.,2004,19,1128-1133.
[31]Kang, S. H.;Wei, W.; Yeung. E. S. On-column derivatization for the analysis of homocysteine and other thiols by capillary electrophoresis with laser-induced fluorescence detection. J. Chromatogr. B,2000,744,149-156.
[32]Zinellu, A.; Sotgial, S.; Posadino, A.; et.al. Highly sensitive simultaneous detection of cultured cellular thiols by laser induced fluorescencecapillary electrophoresis. Electrophoresis 2005,26, 1063-1070
[33]Musenga, A.; Mandrioli, R.; Bonifazi, P.; et.al. Sensitive and selective determination of glutathione in probiotic bacteria by capillary electrophoresis-laser induced fluorescence. Anal Bioanal Chem.2007,387,917-924.
[34]Ivanov, A. R.; Nazimov, I. V.; Baratova, L. A. Determination of biologically active low-molecular-mass thiols in human blood Ⅱ. High-performance capillary electrophoresis with photometric detection. J. Chromatogr. A,2000,895,167-171.
[35]Pasas, S.; Lacher, N.; Davies, M.; et.al. Detection of homocysteine by conventional and microchip capillary electrophoresis/electrochemistry. Electrophoresis.2002,23,759-766.
[36]Inoue, T.; Kirchhoff, J. Determination of Thiols by Capillary Electrophoresis with Amperometric Detection at a Coenzyme Pyrroloquinoline Quinone Modified Electrode. Anal. Chem. 2002,74,1349-1354.
[37]Allison, L. A.; Shoup, R. E. Dual electrode liquid chromatography detector for thiols and disulfides. Anal. Chem.1983,55,8-12.
[38]Lawrence, N.; Deo, R.;Wang, J. Detection of homocysteine at carbon nanotube paste electrodes. Talanta.2004,63,443-449.
[39]Deng, C, Y.;Chen, J. H.; Chen, H, L.; et.al. Electrochemical detection of 1-cysteine using a boron-doped carbon nanotube-modified electrode. Electrochim. Acta,2009,54,3298-3302.
[40]Fei, S, D.; Chen, J, H.; Yao, S, Z.; et.al. Electrochemical behavior of L-cysteine and its detection at carbon nanotube electrode modiWed with platinum. Anal. Biochem.2005.339.29-35.
[41]Kafi, A.K.M.; Yin, F.; Kwon, Y. S.; et.al. Amperometric thiol sensor based on Prussian blue-modified glassy carbon electrode. CurrAppl. Physi.2007,7,496-499.
[42]Lima, P. R.; Santos, W. J.R.; Kubota, L. T.; et.al. An amperometric sensor based on electrochemically triggered reaction:Redox-active Ar-NO/Ar-NHOH from 4-nitrophthalonitrile-modified electrode for the low voltage cysteine detection. J. Electroanal. Chem.2008,612,87-96.
[43]Lawrence, N, S.; Davis, J.; Compton, R. J. Electrochemical detection of thiols in biological media. Talanta,2001,53,1089-1094.
[44]Nekrassova, O.; White, P. C.; Compton, R. G.; et.al. An electrochemical adaptation of Ellman's test. Analyst,2002,127,797-802.
[45]Wen. M.; Liu, H. Q.; Tian, Y.; et.al. Amorphous FeNiPt nanoparticles with tunable length for electrocatalysis and electrochemical determination of thiols. Chem. Commun.,2009,4530-4532.
[46]Wang, W.; Li, L.; Zhang, S, S.; et.al. Determination of Physiological Thiols by Electrochemical Detection with Piazselenole and Its Application in Rat Breast Cancer Cells 4T-1. J. Am. Chem. Soc. 2008,130,10846-10847.
[47]Capitan, p.; Malmezat, T.; Obled, C.; et.al. Gas chromatographic-mass spectrometric analysis of stable isotopes of cysteine and glutathione in biological samples. J. Chromatogr. B,1999,732, 127-135.
[48]Guo, Y.; Shao, S. J.; Jiang, S. X.; et.al. A specific colorimetric cysteine sensing probe based on dipyrromethane-TCNQ assembly. Tetrahedron Lett.2004,45,6477-6480.
[49]Chen, H, L.; Zhao, Q.; Wu, Y, B.; et.al. Selective Phosphorescence Chemosensor for Homocysteine Based on an Iridium(Ⅲ) Complex. Inorg. Chem.2007,46,11075-11081.
[50]Ros-Lis, J. V.; Garci'a, B.; Jime'nez, D.; et.al. Squaraines as Fluoro-Chromogenic Probes for Thiol-Containing Compounds and Their Application to the Detection of Biorelevant Thiols. J. Am. Chem. Soc.2004,126,4064-4065.
[51]Han, M. S.; Kim, D. H. Rationally designed chromogenic chemosensor that detects cysteine in aqueous solution with remarkable selectivity. Tetrahedron,2004,60,11251-11257.
[52]Zhang, D. Q.; Zhang, M.; Huang, C. H.; et.al. Highly selective colorimetric sensor for cysteine and homocysteine based on azo derivatives. Tetrahedron Lett.2006,47,7093-7096.
[53]Zeng, Y; Zhang, G. X.; Zhang, D. Q. A selective colorimetric chemosensor for thiols based on intramolecular charge transfer mechanism. Anal Chim. Acta.2008,627,254-257.
[54]Zeng, Y.; Zhang, G. X.; Zhang, D. Q. A dual-function colorimetric chemosensor for thiols and transition metal ions based on ICT mechanism. Tetrahedron Lett.2008,49,7391-7394.
[55]Huo, F. J.; Sun, Y. Q.; Yin, C. X.; et.al. Colorimetric Detection of Thiols Using a Chromene Molecule. Org.Lett.2008,11,1918-4921.
[56]Zhang, M.; Yu, M. X.; Huang, C. H.; et al. A Highly Selective Fluorescence Turn-on Sensor for Cysteine/Homocysteine and Its Application in Bioimaging. J. Am.Chem. Soc.,2007,129, 10322-10323.
[57]Sreejith, S.; Divya, K. P. Ajayaghosh, A. A Near-Infrared Squaraine Dye as a Latent Ratiometric Fluorophore for the Detection of Aminothiol Content in Blood Plasma. Angew. Chem. Int. Ed.2008, 47,7883-7887.
[58]Ellman, G. L. Tissue sulfhydryl groups. Arch. Biochem. Biophys.1959,82,70-77.
[59]Zhu J, G,; Dhimitruka. I; Pei, D.5-(2-Aminoethyl)dithio-2-nitrobenzoate as a More Base-Stable Alternative to Ellman's Reagent. Org.Lett.2004,6,3809-3812.
[60]Kanaoka, Y.C.; Machida, M.; Ando, K.; et.al. Fluorescence and structures of proteins as measured by incorporation of fluorophore:IV. Synthesis and fluorescence characteristics of N-(p-(2-benzimidazolyl)phenyl) maleimide. Biochi. Biophys. Acta.1970,207,269-277.
[61]Machida, M.; Ushijima. N.; Takahashi, T.; et.al. A Novel Fluorescent Thiol Reagent:Syntheses and Electronic Spectra of N-(7-Dimethylamino-4-methyl-3-coumarinyl)-maleimide (DACM-3) and the Related Compounds. Chem. Pharm. Bull,1977,25,1289-1294.
[62]Liang, S. C.; Wang, H.; Zhang, H. S.; et.al. Direct spectrofluorimetric determination of glutathione in biological samples using 5-maleimidyl-2-(m-methylphenyl) benzoxazole. Anal. Chim. Acta,2002,45,211-219.
[63]Matsumoto, T. Urano, Y.; Nagano, T. A Thiol-Reactive Fluorescence Probe Based on Donor-Excited Photoinduced Electron Transfer:Key Role of Ortho Substitution. Org. Lett.,2007,9, 3375-3377.
[64]Huanga, S. T.; Ting, K.N.; Wang, K. L. Development of a long-wavelength fluorescent probe based on quinone-methide-type reaction to detect physiologically significant thiols. Anal. Chim. Acta.2008,620,120-126.
[65]Lin, W. Y.; Yuan, L.; Cao, Z. M.; et.al. A Sensitive and Selective Fluorescent Thiol Probe in Water Based on the Conjugate 1,4-Addition of Thiols to a,b-Unsaturated Ketones. Chem. Eur. J. 2009,15,5096-5103.
[66]Tang. B.; Xing. Y. L.; Li P.; et.al. A Rhodamine-Based Fluorescent Probe Containing a Se-N Bond for Detecting Thiols and Its Application in Living Cells. J. Am. Chem. Soc.,2007,129, 11666-11667.
[67]Ahn, Y. H.; Lee, J. S.; Chang, Y. T. Combinatorial Rosamine Library and Application to in Vivo Glutathione Probe. J. Am. Chem. Soc.,2007,129,4510-4511.
[68]Maeda, H.; Matsuno H.; Ushida, M.; et.al. 2,4-Dinitrobenzenesulfonyl Fluoresceins as Fluorescent Alternatives to Ellman's Reagent in Thiol-Quantification Enzyme Assays. Angew. Chem. Int. Ed.2005,44,2922-2925.
[69]Shibata, A.; Furukawa, K.; Abe, H.; et.al. Rhodamine-based fluorogenic probe for imaging biological thiol. Bioorg.Med. Chem. Lett.2008,18,2246-2249.
[70]Jiang, W.; Fu, Q. Q.; Wang, W.; et.al. A Highly Selective Fluorescent Probe for Thiophenols. Angew. Chem. Int. Ed.2001,46,8445-8448.
[71]Bouffard, J.; Kim, Y.; Hilderbrand, S. A.; et.al. A Highly Selective Fluorescent Probe for Thiol Bioimaging. Org. Lett.,2008,10,37-40.
[72]Zhang, M.; Li, M. Y.; Huang, C. H.; et.al. Novel Y-type two-photon active fluorophore: synthesis and application in fluorescent sensor for cysteine and homocysteine. Tetrahedron Lett. 2007,48,2329-2333.
[73]Kim, T-K.; Lee, D-M.; Kim, H-J. Highly selective fluorescent sensor for homocysteine and cysteine. Tetrahedron Lett.2008,49,4879-4881.
[74]Huang, G. G.; Hossain, M. K.; Ozaki, Y.; et.al. A novel reversed reporting agent method for surface-enhanced Raman scattering; highly sensitive detection of glutathione in aqueous solutions. Analyst,2009,134,2468-2474.
[75]Chen, S, J.; Chang, H, T.; Nile Red-Adsorbed Gold Nanoparticles for Selective Determination of Thiols Based on Energy Transfer and Aggregation. Anal. Chem.,2004,76,3727-3734.
[76]Chow, C. F.; Chiu, B-K. W.; Lam, M-H. W.; et.al. A Trinuclear Heterobimetallic Ru(Ⅱ)/Pt(Ⅱ) Complex as a Chemodosimeter Selective for Sulfhydryl-Containing Amino Acids and Peptides. J. Am. Chem. Soc.2003,125,7802-7803.
[77]Lee, J. H.; Lim.C. C.; Cho, B. R..; et.al. A Two-Photon Fluorescent Probe for Thiols in Live Cells and Tissues. J. Am. Chem. Soc.,2010,132,1216-1217.
[78]Riiegg, U.; Jarvis, D.; Rudinger, J.2-Sulphobenzyl, a New Solubilizing and Reversible Protecting Group for Cysteine in Proteins. Biochem. J.1979,179,127-134.
[79]Shashidhar, M. S.; Bhatt, M. V. Aspects of tautomerism. Part 16. Influence of the γ-keto function on the reactions of sulphonic acids. Proc. Indian Acad. Sci. (Chem. Sci.),1989,4,319-326.
[80]Zinnes, H.; Sircar, J.C.; Lindo, N.; et.al. Isoxicam and related 4-Hydroxy-N-isoxazolyl-2H-1, 2-benzothiazine-3-carboxamide 1,1-Dioxides. Potent nonsteroidal antiinflammatory agents. J.Med.Chem.,1982,25,12-18.
[81]Wagenaar, A.;. Engberts, J-B-F-N. Intramolecular Nucleophilic Catalysis by the Neighboring Hydroxyl Group in Acid-and Base-Catalyzed Hydrolysis of Aromatic Sulfonamides and Sultones. Mechanism of Intramolecular Nucleophilic Substitution at Sulfonyl Sulfur. J. Org. Chem.1988,53, 768-772.
[82]杨金会,孟丽聪。天然产物1,3-二-(2-羟基-4-甲氧基苯基)丙烷和1,3-二-(2,4-二羟基苯基)丙烷的合成。有机化学,2008,5,918～921.
[83]Luo, Q. L.; Eibauer, S. Reiser, O. Novel Bis(oxazole) Pincer Ligands and their Application in Suzuki-Miyaura Cross Coupling Reactions under Aerobic Conditions. J. Mol. Catal. A,2007,268, 65-69
[84]Alexander, V-M.; Bhat, R-P.; Samant, S-D. Bismuth(Ⅲ) nitrate pentahydrate-a mild and inexpensive reagent for synthesis of coumarins under mild conditions. Tetrahedron Lett.2005,46, 6957-6959.
[85]Kulkarni, A.; Patil, S-A.; Badami, P-S. Synthesis, characterization, DNA cleavage and in vitro antimicrobial studies of La(Ⅲ), Th(Ⅳ) and VO(Ⅳ) complexes with Schiff bases of coumarin derivatives. Eur. J. Med. Chem,2009,44,2904-2912.
[86]Mohammadpoor-Baltork, I.; Khosropour, A. R.; Hojati, S. F. ZrOCl2.8H2O as an efficient, environmentally friendly and reusable catalyst'for synthesis of benzoxazoles, benzothiazoles, benzimidazoles and oxazolo[4,5-b]pyridines under solvent-free conditions. Catal. Commun.2007,8, 1865-1870.
[87]Jcdrzejewska, B.; Kabatc, J.; Paczkkowski J.; et al. Hemicyanine dyes:synthesis, structure and photophysical properties. Dye and Pigments,2003,58,47-58.