几种吖啶酯的合成及其应用研究
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摘要
吖啶酯作为一种高效的化学发光试剂,在临床免疫分析,DNA分析,生物酶活性测定等方面有着广泛的应用。本文设计了两个系列的吖啶酯衍生物,第一类是吖啶环无取代的吖啶9-羧酸苯酯三氟甲基磺酸盐衍生物,第二类是吖啶环有取代的吖啶9-羧酸苯酯衍生物,拟将其应用于血液中对氧磷酶的活性测定。第一类化合物以二苯胺为起始原料,在三氯化铝催化下,与草酰氯发生付克酰化反应,得N-苯基茜素,收率78.6%;所得N-苯基茜素在氢氧化钾强碱性条件下重排得到吖啶9-羧酸,收率为94.1%,吖啶9-羧酸经酰氯化,再分别与间甲基苯酚、对甲基苯酚、对硝基苯酚、对乙酰氧基苯酚发生反应,生成相应的吖啶9-羧酸苯酯衍生物(c类化合物),为了增强化学发光效率,缩短发光时间,以及增强试剂的稳定性,将吖啶9-羧酸苯酯衍生物与三氟甲基磺酸甲酯进行反应,得到终产物吖啶9-羧酸苯酯三氟甲基磺酸盐(d类化合物)。中间体和最终产物结构以1HNMR和IR进行结构表征。各反应的总收率分别为:1d(29%)、2d(40%)、3d(31%),4d(22%)。影响反应收率的步骤是吖啶9-酰氯与酚的反应,由于各种酚苯环上取代基的不同,导致生成吖啶酯的收率不同。
在合成吖啶环有取代的吖啶酯的过程中,以合成吖啶环有取代的3-甲基6-硝基吖啶酸为研究对象,通过优化乌尔曼反应制备取代二苯胺,以提高整个反应过程的收率。本课题以氨基酸(L-脯氨酸)为配体,碘化亚铜催化微波加热4h的条件下,制得取代二苯胺,收率76%,结果优于其它条件。所得取代二苯胺经付克酰化反应制得取代N-苯基茜素,然后在氢氧化钾中重排生产取代吖啶9-羧酸,由于N-苯基茜素的结构未能得到确证,以及取代基对重排的影响,最终未能制得取代吖啶9-羧酸。
在确证目标化合物结构的基础上,对各化合物的荧光光谱性质,化学发光动力学进行了测定,结果显示吖啶酯离去基团上斥电子基的存在比吸电子基存在时具有更强的化学发光强度,同时离去基团上取代基的性质也会影响吖啶酯的荧光光谱。在获得所合成的目标化合物的基本化学发光性质后,初步探讨了将其用于血液中对氧磷酶活性测定的可行性,采用的方法是通过对比加入血清样品前后吖啶酯化学发光强度的变化来表征血清中对氧磷酶的活性,结果显示加入血清后,吖啶酯的化学发光强度有非常明显的降低,四个目标化合物化学发光强度降低的强度均超过了90%以上。
As a kind of highly efficient chemiluminescence reagent, Acridine esters are commonly used in clinical immunoassays and biological activity determination of enzymes. In this work two series of acridine ester derivatives were designed: the first class is unsubstituted acridine 9-carboxylic acid benzyl ester derivatives and the second is a substituted acridine 9-carboxylic acid phenyl derivative which was intended for the determination of biological activity of paraoxonase in blood. First class of compounds started from diphenylamine which reacted with oxalyl chloride to generate N-phenyl alizarine with yield of 78.6%; then, N-phenyl alizarine reacted with KOH through rearrangement reaction to give acridine 9 -carboxylic acid with yield of 94.1%. Acridine 9-carboxylic acid reacted with thionyl chloride to parepare Acridine 9-carboxylic chlorides, which reacted with methyl-phenol, cresol, p-nitrophenol, and acetoxy phenol to give corresponding acridine 9 -carboxylic acid benzyl ester derivatives (1c, 2c, 3c, 4c). In order to improve the chemiluminescence efficiency and enhance the stability of Acridine esters, the acridine 9-carboxylic acid benzyl ester derivatives reacted with methyl trifluoromethyl sulfonate to obtain target compounds. All the intermediates and target compounds were characterized by 1HNMR and IR. The total yield of each target coumpound was as follows: 1d (29%), 2d (40%), 3d (31%), 4d (22%).
In the synthesis of substituted acridine esters, Ullman reaction was used to optimize the preparation of substituted diphenylamine to improve the yield of the reaction process. Ullman reactions were carried out according to the latest literature, using amino acids (L-proline) as ligand and cuprous iodide as catalyst under the condition of microwave heating for 4 hours to give substituted diphenylamine with the yield of 76%. Substituted diphenylamine then reacted with oxalyl chloride at the presence of AlCl3 to give substituted N-phenyl alizarine. Rearrangement reaction of N-phenyl alizarine was carried out in the solution of potassium hydroxide to prepare substituted acridine 9-carboxylic acid; however, the target compound was not obtained. It was concluded that the substituted group influenced the rearrangement reaction.
After confirming the structure of target compounds, the fluorescence spectra and chemical luminescence kinetics of each compound were investigated. It was found that acridine ester with electron donating group on its leaving group had stronger CL intensity than that with electron withdrawing group. Meanwhile leaving group also affects the nature of acridine esters’s fluorescence spectrum. After obtaining the chemical luminescence property of target compounds synthesized in this work, we tentatively discussed the determination of paraoxonase activity in blood. The biological activity of paraoxonase was characterized by comparing chemiluminescent intensity change before and after adding the serum into acridine ester. It was showed that after adding serum, acridine ester’s chemiluminescence intensity was significantly reduced, and the chemiluminescence intensity of all four target compounds was reduced by 90%.
在合成吖啶环有取代的吖啶酯的过程中,以合成吖啶环有取代的3-甲基6-硝基吖啶酸为研究对象,通过优化乌尔曼反应制备取代二苯胺,以提高整个反应过程的收率。本课题以氨基酸(L-脯氨酸)为配体,碘化亚铜催化微波加热4h的条件下,制得取代二苯胺,收率76%,结果优于其它条件。所得取代二苯胺经付克酰化反应制得取代N-苯基茜素,然后在氢氧化钾中重排生产取代吖啶9-羧酸,由于N-苯基茜素的结构未能得到确证,以及取代基对重排的影响,最终未能制得取代吖啶9-羧酸。
在确证目标化合物结构的基础上,对各化合物的荧光光谱性质,化学发光动力学进行了测定,结果显示吖啶酯离去基团上斥电子基的存在比吸电子基存在时具有更强的化学发光强度,同时离去基团上取代基的性质也会影响吖啶酯的荧光光谱。在获得所合成的目标化合物的基本化学发光性质后,初步探讨了将其用于血液中对氧磷酶活性测定的可行性,采用的方法是通过对比加入血清样品前后吖啶酯化学发光强度的变化来表征血清中对氧磷酶的活性,结果显示加入血清后,吖啶酯的化学发光强度有非常明显的降低,四个目标化合物化学发光强度降低的强度均超过了90%以上。
As a kind of highly efficient chemiluminescence reagent, Acridine esters are commonly used in clinical immunoassays and biological activity determination of enzymes. In this work two series of acridine ester derivatives were designed: the first class is unsubstituted acridine 9-carboxylic acid benzyl ester derivatives and the second is a substituted acridine 9-carboxylic acid phenyl derivative which was intended for the determination of biological activity of paraoxonase in blood. First class of compounds started from diphenylamine which reacted with oxalyl chloride to generate N-phenyl alizarine with yield of 78.6%; then, N-phenyl alizarine reacted with KOH through rearrangement reaction to give acridine 9 -carboxylic acid with yield of 94.1%. Acridine 9-carboxylic acid reacted with thionyl chloride to parepare Acridine 9-carboxylic chlorides, which reacted with methyl-phenol, cresol, p-nitrophenol, and acetoxy phenol to give corresponding acridine 9 -carboxylic acid benzyl ester derivatives (1c, 2c, 3c, 4c). In order to improve the chemiluminescence efficiency and enhance the stability of Acridine esters, the acridine 9-carboxylic acid benzyl ester derivatives reacted with methyl trifluoromethyl sulfonate to obtain target compounds. All the intermediates and target compounds were characterized by 1HNMR and IR. The total yield of each target coumpound was as follows: 1d (29%), 2d (40%), 3d (31%), 4d (22%).
In the synthesis of substituted acridine esters, Ullman reaction was used to optimize the preparation of substituted diphenylamine to improve the yield of the reaction process. Ullman reactions were carried out according to the latest literature, using amino acids (L-proline) as ligand and cuprous iodide as catalyst under the condition of microwave heating for 4 hours to give substituted diphenylamine with the yield of 76%. Substituted diphenylamine then reacted with oxalyl chloride at the presence of AlCl3 to give substituted N-phenyl alizarine. Rearrangement reaction of N-phenyl alizarine was carried out in the solution of potassium hydroxide to prepare substituted acridine 9-carboxylic acid; however, the target compound was not obtained. It was concluded that the substituted group influenced the rearrangement reaction.
After confirming the structure of target compounds, the fluorescence spectra and chemical luminescence kinetics of each compound were investigated. It was found that acridine ester with electron donating group on its leaving group had stronger CL intensity than that with electron withdrawing group. Meanwhile leaving group also affects the nature of acridine esters’s fluorescence spectrum. After obtaining the chemical luminescence property of target compounds synthesized in this work, we tentatively discussed the determination of paraoxonase activity in blood. The biological activity of paraoxonase was characterized by comparing chemiluminescent intensity change before and after adding the serum into acridine ester. It was showed that after adding serum, acridine ester’s chemiluminescence intensity was significantly reduced, and the chemiluminescence intensity of all four target compounds was reduced by 90%.
引文
[1] Gamiz-Gracia L, Garcia-Campana A M, Huertas-Perez, J F. Chemiluminescence detection in liquid chromatography: Applications to clinical, pharmaceutical, environmental and food analysis-A review[J]. Analytica Chimica Acta, 2009, 640(1-2): 7-28.
[2] Vilim V, Wilhelm J. What do we measure by a luminol-dependent chemi-luminescence of phagocytes[J]. Free radical Biology and Medicine, 1989, 6(6): 623-629.
[3]吴秋华,李正平,方正.鲁米诺化学发光体系的应用新进展[J].化学试剂, 2005, 27(4): 212-216.
[4]杜建修,刘文侠,吕九如.高锰酸钾-鲁米诺反应体系中碱土金属离子Mg2+, Ca2+, Sr2+ , Ba2+,化学发光行为研究[J].化学学报, 2004, 62(14): 1323-1326.
[5]李丽清.鲁米诺化学发光反应在贵金属分析中的应用[J].泰安师专学报, 2000, 22(6): 30-31.
[6]吕九如,贾生华.鲁米诺-AuCl4-H2O2体系化学发光反应的研究-矿石中痕量金的测定[J].化学学报, 1984, 42(6): 562.
[7]吕小虎,陆明刚.过氧化氢-次氯酸钠氧化鲁米诺发光的研究[J].光谱学与光谱分析, 1994, 14(1): 123-127.
[8]石文兵. AuCl4-鲁米诺体系测定氨苄西林钠[J].分析试验室, 2009, 28(9): 35-36.
[9]石文兵. KIO4-鲁米诺化学发光体系测定青霉素钠[J].分析试验室, 2009, 28(7): 75.
[10]石文兵.鲁米诺-AuCl4体系化学发光法测定美洛西林钠,分析试验室, 2009, 28(8): 29-30.
[11]符冠烨.鲁米诺化学发光体系在药物分析中的应用[J].海南医学院学报, 2002, 8(3): 187-189.
[12]杨季冬.铁氰化钾-鲁米诺化学发光体系测定盐酸异丙嗪和盐酸氯丙嗪[J].分析化学, 2002, 30(12): 1529.
[13]郑行望,章竹君,王琦.基于电还原鲁米诺电化学发光分析法测定水样中钼VI[J].分析化学, 2003, 31(9): 1076-1078.
[14]吴晓静,高守华,陈园园,刘彩芬. Tl(I)-H2O2-鲁米诺体系气相色谱法测定微量铊[J].合肥工业大学学报(自然科学版), 2007, 30(4): 465-467.
[15]黄梓平,王建宁.鲁米诺-过氧化氢体系对敌敌畏的检测分析[J].农药, 2002, 43(9): 19-20.
[16]高岐.尿酸-铁氰化钾-鲁米诺化学发光测定亚硝酸盐[J].分析化学, 2002, 30(7): 812-814.
[17]翁元凯.发光剂鲁米诺的合成[J].江苏化工, 1990, 1: 17-18.
[18] Lin J M, Shan X, Haracka S. Luminol chemiluminescence in unbuffered solutions with a cobalt(II)-ethanolamine complex immobilized on resin as catalyst and its application toanalysis[J]. Analytical Chemistry. 2001, 73: 5043-5051.
[19]蒋滋慧,田亚平.生物素-氨基丁基乙基异鲁米诺与亲和素的结合特性及其在发光免疫中的应用[J].中国生物化学与分子生物学报, 1989, 5: 456-458.
[20]王琼娥,庄惠生,张帆.新试剂N-(β-羧酸丙酰基)异鲁米诺标记抗体的研究[J].高等学校化学学报, 1996, 25(3): 1035-1038.
[21]庄惠生,王琼娥,张帆.异硫氰酸异鲁米诺的电致化学发光性质及其机理[J]. 1997, 25(3): 330-333.
[22]任荣芳,卫洪清,柴宜民,韩素琴.光泽精化学发光分析进展[J].山西师范大学学报(自然科学版), 2003, 17(2): 53-55.
[23]李光浩.光泽精化学发光体系的研究与应用[J].光谱实验室2002, 19(6): 736-739.
[24]庄惠生,王琼娥,陈国南,黄金陵,林培诚.测定癌胚抗原的化学发光免疫分析新方法[J].光谱学与光谱分析, 2000, 6: 889-891.
[25] Ceoffrey T, Gore, J. Preparation of biological labels with acetylenic linker arms[J]. Tetrahedron, 1997, 53(4): 1505-1522.
[26]庄惠生,陈国南,黄金陵. 9,9'-双吖啶衍生物的化学发光反应新机理[J].福州大学学报(自然科学版), 1999, (27): 56-57.
[27] Zhang H M, Guo X Q, Zhao Y B, Wang D Y, Xu J G. Study on the dimer–monomer equilibrium of a fluorescent dye and its application in nucleic acids determination[J]. Analytica Chimica Acta, 1998, 361(12): 9.
[28] Guo X Q, Zhang Z L, Zhao Y B, Wang D Y, Xu J G. DNA-dye fluorescence enhancement based on shifting the dimer-monomer equilibrium of fluorescent dye[J]. Applied Spectroscopy, 1997, 51(7): 1002.
[29]林金明.化学发光基础理论与应用[M].化学工业出版社化学与应用化学出版中心, 2004.
[30]支正良,于山江,华万森,陈守文.过氧草酸酯类化学发光体系的研究进展[J].化学世界, 1997, 12: 619-621.
[31]玉山江.过氧草酸酯的发光机理[J].《新疆师范大学学报》(自然科学版). 2002, 21(4): 27-28.
[32]支正良,杨绪杰,陆路德,汪信.具有发绿光的过氧草酸酯类化学发光体系的研究[J].淮海工学院学报, 1998, 1: 36-37.
[33] Gamiz-Gracia, L, Garcia-Campana, A M, Huertas-Perez J F. Chemiluminescence detection in liquid chromatography: Applications to clinical, pharmaceutical, environmental and food analysis-A review[J]. Analytica Chimica Acta, 2009, 640(1-2): 7-28.
[34] Meseguer L, Molins L C, Verdu A J. Sensitive Determination of Aliphatic Amines in Water by High- performance Liquid Chromatography with Chemiluminescence Detection[J]. Journal ofChromatogh A, 2004, 1035(1): 75- 82.
[35] Olesen C E M, Yan Y X, Liu B. Novel methods for chemiluminescent detection of reporter enzymes[J]. Applications of Chimeric Genes and Hybrid Proteins, 2000, 326: 175-202.
[36] Ana L P, Nery D, Luiz H. Studies on the IntramoleeularElectron Transfer Catalysed Thermolysis of 1,2-Dioxetanes[J]. Tetrahedron, 2000,56(30): 5317-5327.
[37] Nobuko W, Yasuhim N, Takahim Y. Fluoride-induced chemiluminescent decomposion of dioxetanes bearing a siloxysryl moiety to produce an alky1 arylketone as an emitter[J]. Tetrahedron, 2003, 59: 4811-4819.
[38] Adam D, Reinhardt C, Sahamoler R. From the firefly bioluminescence to the dioxemne-based (AMPPD) chemiluminescevce immunoassay: a retroanalysis[J]. Analyst, 1996, 121: 1527- 1531.
[39]赵利霞,林金明,屈锋.微板式磁化学发光酶免疫分析法对人绒毛膜促性腺激素HCG的灵敏快速测定[J].化学学报, 2004, 62: 71-77.
[40] Olesen, C E M, Mosier, J, Voyta J C. Chemiluminescent immunodetection protocols with 1,2-dioxetane substrates[J]. Bioluminescence and Chemiluminescence, 2000, 305: 417-427.
[41] Olesen, C E M, Martin, C S, Mosier J. Chemiluminescent reporter gene assays with 1,2-dioxetane enzyme substrates[J]. Bioluminescence and Chemiluminescence, 2000, 305: 428-450.
[42] Mario D F, Ingle J D. Ion exchange separation of cobalt from alkaline earth and selected transition metals with lophine chemiluminescence detection[J]. Analytical Chemistry, 1981, 53: 294.
[43] Kimura M, Nishikawa H, Kura H. Maximization of the chemiluminescence efficiency of 1,4,5-triarylhydroperoxy4-isoimidazoles[J]. Chemistry Letters, 1993, 15: 505-508.
[44] Kuroda N, Takatani M, Nakashima K, Akiyama S, Ohkura Y. Preparation and evaluation of fatty acid esters of 2-(4-hydroxyphenyl)-4,5-diphenylimidazole as fluorescent substrates for measurement of lipase activity[J]. Biological and Pharmaceutical Bulletin, 1993, 16: 220.
[45] Nakashima K, Yamasaki H, Kuroda N, Akiyama S. Evaluation of lophine derivatives as chemiluminogens by a flow-injection method[J]. Analytica Chimica Acta, 1995, 303: 103.
[46] Al-Dirbashi O, Kuroda N, Inuzuka S, Menichini F, Nakashima K. HPLC with fluorescence detection of methamphetamine and amphetamine in segmentally analyzed human hair[J]. Analyst, 1999, 124: 493.
[47] Okamoto M, Owari M, Kimura. Preparation of a crown ether-modified lophine peroxide as a guest-sensitive novel chemiluminophore and modulation of its chemiluminescence by metal cations[J]. Tetrahedron Leters, 2001, 42(42): 7453-7455.
[48] Francis P S, Adcock, J L. Chemiluminescence methods for the determination of ofloxacin[J]. Analytica Chimica Acta, 2005, 541(1-2): 3-12.
[49]何云华,聂峰. KMnO4-甲醛-茚三酮化学发光体系的研究[J].分析试验室, 2007, 26(6): 96-98.
[50]李丽清,杨敏丽,封满良,吕九如. L-酪氨酸-高锰酸钾-过氧化氢流动注射化学发光体系的研究[J].陕西师范大学学报(自然科学版), 1997, 25(3): 67-69.
[51]何云华,杜建修,封满良,吕九如.高锰酸钾-甲醛-Fe化学发光新体系的研究[J].高等学校化学学报, 1999, l(7): 1049-1051.
[52]何云华,杜建修,封满良,吕九如.高锰酸钾-甲醛-氨基比林化学发光体系的研究[J].分析试验室, 1999, 18(1): 13-15.
[53]何云华,王志银,吕九如.高锰酸钾甲醛-碘化学发光新体系的研究[J].分析试验室, 2001, 20(1): 70-72.
[54]何树华,吕弋,何德勇.高锰酸钾-甲醛-多巴酚丁胺化学发光体系的研究[J].西南师范大学学报(自然科学版), 2003, 28(5): 802-804.
[55]刘梅,何云华,吕九如.高锰酸钾-甲醛-尿酸化学发光体系的研究[J].分析化学, 2005, 33(4): 535-537.
[56] Brown A J, Francis P S, Adcock J L. Manganese(III) and manganese(IV) as chemilumines -cence reagents: A review[J]. Analytica Chimica Acta, 2008, 624(2): 175-183.
[57]李丽清,周艳梅,封满良,吕九如.高锰酸钾-硫代硫酸钠-延胡索乙素化学发光体系的研究[J].山东大学学报(自然科学版), 2002, 37(1): 78-79.
[58]刘卫兵,黄玉明.高锰酸钾直接氧化化学发光法测定甲磺酸酚妥拉明[J].西南师范大学学报(自然科学版), 2004, 29(3): 415-417.
[59]林金明,赵利霞,王栩.化学发光免疫分析[M]. 2008,化学工业出版社.
[60]穆小静,刘敏,严淑珊. 10-甲基吖啶苯酚酯衍生物的和合成表征及化学发光特性[J].影像科学与光化学, 2008, 4(26): 257-264.
[61] Kagiamarnioti K, Triantis T, Papadopoulos K. Synthesis and chemiluminescent properties of novel biotinylated acridinium esters[J]. Acta Chim Slovenica, 2004, 51 (1): 67-76.
[62] Sikorski, A, Krzyminski, K, Bialonska, A. 10-Methyl-9-(2-methylphenoxycarbonyl) acridinium trifluoromethanesulfonate[J]. Acta Crystallographica Section E-structure Reports Online, 2006, 62: 822-824.
[63] Weeks L, Bebeshti L, Mccapra F, Ambory K. Acridinium esters as high specific activity labels in immunoassay[J]. Clinical Chemistry, 1983, 29(8): 1474.
[64] Week M, Campbel A K, Wood J S. 2-site immunochemiluminometric assay for human alpha1-fetoprotein[J]. Clinical Chemistry, 1983, 29(8): 1480.
[65] Richardson A P, Kim J B, Barnard G J. Chemiluminescence immunoassay of plasma progesterone, with progesterone-acridinium ester used as the labeled antigen[J]. Clinical Chemistry, 1985, 31(10): 1664-1668.
[66]罗世能,奚月芬,金坚,谢敏浩,王博诚,张满达,张志斌.化学发光免疫分析试剂10-甲基吖啶9-甲酸对氨乙基苯酯(AEP-MAC)的合成化学试剂[J].化学试剂, 1992, 14(5): 274.
[67]庄惠生,王琼娥,陈国南,张帆.化学发光免疫分析试剂吖啶酯的合成新路线[J].高等学校化学学报, 1998, 19(12): 1933-1936.
[68]尹东光,贺佑丰,刘一兵.促甲状腺激素化学发光免疫分析的研究[J].分析化学, 2004, 32(7): 893-896.
[69]蒋滋慧,刘农乐.吖啶酯标记抗体应用于结核病人抗体水平的测定[J].军事医学科学院院刊, 1991, (4): 45.
[70]刘农乐,蒋滋慧.神经生长因子的发光免疫分析法[J].中国生物化学与分子生物学报, 1994, (05): 616-617.
[71]刘农乐,蒋滋慧.表皮生长因子的发光免疫测定法-吖啶酯标记抗体的应用[J].生物化学与生物物理进展, 1993, (1): 43-44.
[72]徐秀英,刘农乐.吖啶酯发光法测定组织型纤溶酶原激活剂活性的研究[J].中华血液学杂志, 1996, (03): 157-158.
[73] Gion M, Mione R, Leon A E. Clinical chemistry, Comparison of the diagnostic accuracy of CA27.29 and CA15.3 in primary breast cancer[J]. 1999, 45(5): 630-637.
[74]庄惠生,王琼娥,陈国南,黄金陵,林培诚.测定癌胚抗原的化学发光免疫分析新方法[J].光谱学与光谱分析, 2000, (6): 889-891.
[75]卢建忠,曹志娟.化学发光技术在蛋白质和DNA分析中的新进展[J].世界科技研究与发展, 2004, 26(4): 97-104.
[76] Goto S, Takahashi A, Kamisango K, Matsubara K. Single-nu-cleotide polymorphism analysis by hybridization protection assay onsolid support[J]. Analytical Biochemistry, 2002, 307: 25-32.
[77]王晓娟,漆红兰,张成孝.利用吖啶酯化学发光研究甲醛和乙醛对DNA的损伤[J].陕西师范大学学报, 2006, 34(3): 73-76.
[78] Arnold L J, Hammond J P W, Wiese W A. NC Nelson. Assay formats involving acridinium-ester-labeled DNA probes[J]. Clinical Chemistry, 1989, 35 (8): 1588-1594.
[79] Ou C Y, McDonough S H, Sherrol H. Rapid and quantitative detection of enzymatically amplified HIV-1 DNA using chemiluminescent oligonucleotide probes. Retroviruses[J]. AIDS Research and Human Retroviruses, 1990, 6 (11): 1323-1325.
[80] Martinelli R, Arruda J C, Dwivedi P. Chemiluminescent hybridization-ligation assays for Delta F508 and Delta 1507 cystic fibrosis mutations[J]. Clinical Chemistry, 1996, 42 (1): 14-18.
[81]庄慧生,陈国南,张帆.化学发光免疫分析试剂吖啶酯的合成新路线[J].高等学校化学学报, 1998, 19(12): 1933-1936.
[82] LEE, Yeon-soo. Method For synthesizing hydroquinonone monoester compound[P], WO 03/ 033449, 2002.
[83] Urakami T, Yoshida C, Akaike T, Maeda H, Nishigori H, Niki E. Synthesis of monoesters of pyrroloquinoline quinone and imidazopyrroloquinoline, and radical scavenging activities using electron spin resonance in vitro and pharmacological activity in vivo[J]. Journal of Nutritional Science and Vitaminology, 1997, 43(1): 19-33.
[84]谢小安. CuI催化氨基酸促进的Ullmann类碳—碳键交叉偶联反应研究[D].有机化学博士论文,复旦大学, 2008.
[85] Veverkova E, Toma S. Study of CuI catalyzed coupling reactions of aryl bromides with imidazole and aliphatic amines under microwave dielectric heating[J]. Chemical Papers, 2008, 62(3): 334-338.
[86] Mc Capra F. Chemical mechanisms in bioluminescence[J]. Acc Chemistry Research, 1976, 9: 201-208.
[87] Natrajan A, Jiang Q, Sharpe D. Improved heterogeneous immunoassay for detection or quantification of analyte, using hydrophilic, high quantum yield acridinium compound containing electron-donating functional groups at C-2 and/or C-7 position of acridinium ring[P], WO: 20061307362 A2, 2006.
[88]赵赞梅,王汉斌.对氧磷酶的某些研究进展[J].毒理学杂志, 2005, 19 (1) : 64-65.
[89]腾霞,孙曼霁.对氧磷酶研究进展[J].生命科学, 2002, 14(2): 107-109.
[90]钱书红,王诗瑾,张情,刘新郑,王玉萍.糖尿病患者血清芳香醋酶活性与脂类关系的研究[J].河南医科大学学报, 1994, 29(1): 49-50.
[91]钱书虹,刘新郑.非胰岛素依赖型糖尿病患者血清芳香酯酶的临床观察[J].中华内分泌代谢杂志, 1994, 10(2): 111.
[92]孙艳,周长邵,胡望平.血清中芳香醋酶的特性及其与疾病的关系[J].国外医学临床生物化学与检验学分册, 2003, 24(4): 206-207.
[93] Lorentz K, Flatter B, Augustin E. A rylesterase in serum: elaborationand clinical application of a fixed-incubation m ethod[J]. Clinical Chemistry, 1979, 25(10): 1714-1720.
[94]钱庆文,钱书虹,王书君.慢性肾功能衰竭血清芳香酯酶活性改变的研究[J].中国现代医学杂志, 2002, 12(3): 38-42.
[95]钱庆文,钱书虹.不同原因慢性肾功能衰竭芳香酯酶与脂代谢紊乱的关系[J].天津医药, 2004, 32(10): 596-598.
[96]王书君,钱书虹,钱庆文.慢性肾衰竭血清芳香酯酶活性的变化及临床意义[J].临床荟萃, 2001, 16(21): 965.
[97] Gao H, Girard-Globa A, Bert-Hezene F. Paraoxonase protection of LDL against peroxidation is independent of is its esterase activity towards paraoxon and is unaffected by the Q→R genetie polymorphism[J]. Journal of Lipid Research, 1999, 40: 133-139.
[98] Lorentz K, Flatter B, Augustin E. A rylesterase in serum: elaborationand clinical application of a fixed-incubation m ethod [J]. Clinical Chemistry, 1979, 25(10): 1714-1720.
[99]邬红梅,周志俊,胡云平,薛寿征.血清芳香酯酶活性测定方法研究[J].工业卫生与职业病, 2001, 27(5): 270-272.
[100]周长邵,胡望平,孙艳.一种芳香酯酶检测新方法及其应用[J].江西医学检验, 2003, 21(3): 151-154.
[101]周志俊,邬红梅,胡云平,薛寿征.血清对氧磷酶活性测定方法研究[J].中国公共卫生, 2000, 16(4): 303-304.
[2] Vilim V, Wilhelm J. What do we measure by a luminol-dependent chemi-luminescence of phagocytes[J]. Free radical Biology and Medicine, 1989, 6(6): 623-629.
[3]吴秋华,李正平,方正.鲁米诺化学发光体系的应用新进展[J].化学试剂, 2005, 27(4): 212-216.
[4]杜建修,刘文侠,吕九如.高锰酸钾-鲁米诺反应体系中碱土金属离子Mg2+, Ca2+, Sr2+ , Ba2+,化学发光行为研究[J].化学学报, 2004, 62(14): 1323-1326.
[5]李丽清.鲁米诺化学发光反应在贵金属分析中的应用[J].泰安师专学报, 2000, 22(6): 30-31.
[6]吕九如,贾生华.鲁米诺-AuCl4-H2O2体系化学发光反应的研究-矿石中痕量金的测定[J].化学学报, 1984, 42(6): 562.
[7]吕小虎,陆明刚.过氧化氢-次氯酸钠氧化鲁米诺发光的研究[J].光谱学与光谱分析, 1994, 14(1): 123-127.
[8]石文兵. AuCl4-鲁米诺体系测定氨苄西林钠[J].分析试验室, 2009, 28(9): 35-36.
[9]石文兵. KIO4-鲁米诺化学发光体系测定青霉素钠[J].分析试验室, 2009, 28(7): 75.
[10]石文兵.鲁米诺-AuCl4体系化学发光法测定美洛西林钠,分析试验室, 2009, 28(8): 29-30.
[11]符冠烨.鲁米诺化学发光体系在药物分析中的应用[J].海南医学院学报, 2002, 8(3): 187-189.
[12]杨季冬.铁氰化钾-鲁米诺化学发光体系测定盐酸异丙嗪和盐酸氯丙嗪[J].分析化学, 2002, 30(12): 1529.
[13]郑行望,章竹君,王琦.基于电还原鲁米诺电化学发光分析法测定水样中钼VI[J].分析化学, 2003, 31(9): 1076-1078.
[14]吴晓静,高守华,陈园园,刘彩芬. Tl(I)-H2O2-鲁米诺体系气相色谱法测定微量铊[J].合肥工业大学学报(自然科学版), 2007, 30(4): 465-467.
[15]黄梓平,王建宁.鲁米诺-过氧化氢体系对敌敌畏的检测分析[J].农药, 2002, 43(9): 19-20.
[16]高岐.尿酸-铁氰化钾-鲁米诺化学发光测定亚硝酸盐[J].分析化学, 2002, 30(7): 812-814.
[17]翁元凯.发光剂鲁米诺的合成[J].江苏化工, 1990, 1: 17-18.
[18] Lin J M, Shan X, Haracka S. Luminol chemiluminescence in unbuffered solutions with a cobalt(II)-ethanolamine complex immobilized on resin as catalyst and its application toanalysis[J]. Analytical Chemistry. 2001, 73: 5043-5051.
[19]蒋滋慧,田亚平.生物素-氨基丁基乙基异鲁米诺与亲和素的结合特性及其在发光免疫中的应用[J].中国生物化学与分子生物学报, 1989, 5: 456-458.
[20]王琼娥,庄惠生,张帆.新试剂N-(β-羧酸丙酰基)异鲁米诺标记抗体的研究[J].高等学校化学学报, 1996, 25(3): 1035-1038.
[21]庄惠生,王琼娥,张帆.异硫氰酸异鲁米诺的电致化学发光性质及其机理[J]. 1997, 25(3): 330-333.
[22]任荣芳,卫洪清,柴宜民,韩素琴.光泽精化学发光分析进展[J].山西师范大学学报(自然科学版), 2003, 17(2): 53-55.
[23]李光浩.光泽精化学发光体系的研究与应用[J].光谱实验室2002, 19(6): 736-739.
[24]庄惠生,王琼娥,陈国南,黄金陵,林培诚.测定癌胚抗原的化学发光免疫分析新方法[J].光谱学与光谱分析, 2000, 6: 889-891.
[25] Ceoffrey T, Gore, J. Preparation of biological labels with acetylenic linker arms[J]. Tetrahedron, 1997, 53(4): 1505-1522.
[26]庄惠生,陈国南,黄金陵. 9,9'-双吖啶衍生物的化学发光反应新机理[J].福州大学学报(自然科学版), 1999, (27): 56-57.
[27] Zhang H M, Guo X Q, Zhao Y B, Wang D Y, Xu J G. Study on the dimer–monomer equilibrium of a fluorescent dye and its application in nucleic acids determination[J]. Analytica Chimica Acta, 1998, 361(12): 9.
[28] Guo X Q, Zhang Z L, Zhao Y B, Wang D Y, Xu J G. DNA-dye fluorescence enhancement based on shifting the dimer-monomer equilibrium of fluorescent dye[J]. Applied Spectroscopy, 1997, 51(7): 1002.
[29]林金明.化学发光基础理论与应用[M].化学工业出版社化学与应用化学出版中心, 2004.
[30]支正良,于山江,华万森,陈守文.过氧草酸酯类化学发光体系的研究进展[J].化学世界, 1997, 12: 619-621.
[31]玉山江.过氧草酸酯的发光机理[J].《新疆师范大学学报》(自然科学版). 2002, 21(4): 27-28.
[32]支正良,杨绪杰,陆路德,汪信.具有发绿光的过氧草酸酯类化学发光体系的研究[J].淮海工学院学报, 1998, 1: 36-37.
[33] Gamiz-Gracia, L, Garcia-Campana, A M, Huertas-Perez J F. Chemiluminescence detection in liquid chromatography: Applications to clinical, pharmaceutical, environmental and food analysis-A review[J]. Analytica Chimica Acta, 2009, 640(1-2): 7-28.
[34] Meseguer L, Molins L C, Verdu A J. Sensitive Determination of Aliphatic Amines in Water by High- performance Liquid Chromatography with Chemiluminescence Detection[J]. Journal ofChromatogh A, 2004, 1035(1): 75- 82.
[35] Olesen C E M, Yan Y X, Liu B. Novel methods for chemiluminescent detection of reporter enzymes[J]. Applications of Chimeric Genes and Hybrid Proteins, 2000, 326: 175-202.
[36] Ana L P, Nery D, Luiz H. Studies on the IntramoleeularElectron Transfer Catalysed Thermolysis of 1,2-Dioxetanes[J]. Tetrahedron, 2000,56(30): 5317-5327.
[37] Nobuko W, Yasuhim N, Takahim Y. Fluoride-induced chemiluminescent decomposion of dioxetanes bearing a siloxysryl moiety to produce an alky1 arylketone as an emitter[J]. Tetrahedron, 2003, 59: 4811-4819.
[38] Adam D, Reinhardt C, Sahamoler R. From the firefly bioluminescence to the dioxemne-based (AMPPD) chemiluminescevce immunoassay: a retroanalysis[J]. Analyst, 1996, 121: 1527- 1531.
[39]赵利霞,林金明,屈锋.微板式磁化学发光酶免疫分析法对人绒毛膜促性腺激素HCG的灵敏快速测定[J].化学学报, 2004, 62: 71-77.
[40] Olesen, C E M, Mosier, J, Voyta J C. Chemiluminescent immunodetection protocols with 1,2-dioxetane substrates[J]. Bioluminescence and Chemiluminescence, 2000, 305: 417-427.
[41] Olesen, C E M, Martin, C S, Mosier J. Chemiluminescent reporter gene assays with 1,2-dioxetane enzyme substrates[J]. Bioluminescence and Chemiluminescence, 2000, 305: 428-450.
[42] Mario D F, Ingle J D. Ion exchange separation of cobalt from alkaline earth and selected transition metals with lophine chemiluminescence detection[J]. Analytical Chemistry, 1981, 53: 294.
[43] Kimura M, Nishikawa H, Kura H. Maximization of the chemiluminescence efficiency of 1,4,5-triarylhydroperoxy4-isoimidazoles[J]. Chemistry Letters, 1993, 15: 505-508.
[44] Kuroda N, Takatani M, Nakashima K, Akiyama S, Ohkura Y. Preparation and evaluation of fatty acid esters of 2-(4-hydroxyphenyl)-4,5-diphenylimidazole as fluorescent substrates for measurement of lipase activity[J]. Biological and Pharmaceutical Bulletin, 1993, 16: 220.
[45] Nakashima K, Yamasaki H, Kuroda N, Akiyama S. Evaluation of lophine derivatives as chemiluminogens by a flow-injection method[J]. Analytica Chimica Acta, 1995, 303: 103.
[46] Al-Dirbashi O, Kuroda N, Inuzuka S, Menichini F, Nakashima K. HPLC with fluorescence detection of methamphetamine and amphetamine in segmentally analyzed human hair[J]. Analyst, 1999, 124: 493.
[47] Okamoto M, Owari M, Kimura. Preparation of a crown ether-modified lophine peroxide as a guest-sensitive novel chemiluminophore and modulation of its chemiluminescence by metal cations[J]. Tetrahedron Leters, 2001, 42(42): 7453-7455.
[48] Francis P S, Adcock, J L. Chemiluminescence methods for the determination of ofloxacin[J]. Analytica Chimica Acta, 2005, 541(1-2): 3-12.
[49]何云华,聂峰. KMnO4-甲醛-茚三酮化学发光体系的研究[J].分析试验室, 2007, 26(6): 96-98.
[50]李丽清,杨敏丽,封满良,吕九如. L-酪氨酸-高锰酸钾-过氧化氢流动注射化学发光体系的研究[J].陕西师范大学学报(自然科学版), 1997, 25(3): 67-69.
[51]何云华,杜建修,封满良,吕九如.高锰酸钾-甲醛-Fe化学发光新体系的研究[J].高等学校化学学报, 1999, l(7): 1049-1051.
[52]何云华,杜建修,封满良,吕九如.高锰酸钾-甲醛-氨基比林化学发光体系的研究[J].分析试验室, 1999, 18(1): 13-15.
[53]何云华,王志银,吕九如.高锰酸钾甲醛-碘化学发光新体系的研究[J].分析试验室, 2001, 20(1): 70-72.
[54]何树华,吕弋,何德勇.高锰酸钾-甲醛-多巴酚丁胺化学发光体系的研究[J].西南师范大学学报(自然科学版), 2003, 28(5): 802-804.
[55]刘梅,何云华,吕九如.高锰酸钾-甲醛-尿酸化学发光体系的研究[J].分析化学, 2005, 33(4): 535-537.
[56] Brown A J, Francis P S, Adcock J L. Manganese(III) and manganese(IV) as chemilumines -cence reagents: A review[J]. Analytica Chimica Acta, 2008, 624(2): 175-183.
[57]李丽清,周艳梅,封满良,吕九如.高锰酸钾-硫代硫酸钠-延胡索乙素化学发光体系的研究[J].山东大学学报(自然科学版), 2002, 37(1): 78-79.
[58]刘卫兵,黄玉明.高锰酸钾直接氧化化学发光法测定甲磺酸酚妥拉明[J].西南师范大学学报(自然科学版), 2004, 29(3): 415-417.
[59]林金明,赵利霞,王栩.化学发光免疫分析[M]. 2008,化学工业出版社.
[60]穆小静,刘敏,严淑珊. 10-甲基吖啶苯酚酯衍生物的和合成表征及化学发光特性[J].影像科学与光化学, 2008, 4(26): 257-264.
[61] Kagiamarnioti K, Triantis T, Papadopoulos K. Synthesis and chemiluminescent properties of novel biotinylated acridinium esters[J]. Acta Chim Slovenica, 2004, 51 (1): 67-76.
[62] Sikorski, A, Krzyminski, K, Bialonska, A. 10-Methyl-9-(2-methylphenoxycarbonyl) acridinium trifluoromethanesulfonate[J]. Acta Crystallographica Section E-structure Reports Online, 2006, 62: 822-824.
[63] Weeks L, Bebeshti L, Mccapra F, Ambory K. Acridinium esters as high specific activity labels in immunoassay[J]. Clinical Chemistry, 1983, 29(8): 1474.
[64] Week M, Campbel A K, Wood J S. 2-site immunochemiluminometric assay for human alpha1-fetoprotein[J]. Clinical Chemistry, 1983, 29(8): 1480.
[65] Richardson A P, Kim J B, Barnard G J. Chemiluminescence immunoassay of plasma progesterone, with progesterone-acridinium ester used as the labeled antigen[J]. Clinical Chemistry, 1985, 31(10): 1664-1668.
[66]罗世能,奚月芬,金坚,谢敏浩,王博诚,张满达,张志斌.化学发光免疫分析试剂10-甲基吖啶9-甲酸对氨乙基苯酯(AEP-MAC)的合成化学试剂[J].化学试剂, 1992, 14(5): 274.
[67]庄惠生,王琼娥,陈国南,张帆.化学发光免疫分析试剂吖啶酯的合成新路线[J].高等学校化学学报, 1998, 19(12): 1933-1936.
[68]尹东光,贺佑丰,刘一兵.促甲状腺激素化学发光免疫分析的研究[J].分析化学, 2004, 32(7): 893-896.
[69]蒋滋慧,刘农乐.吖啶酯标记抗体应用于结核病人抗体水平的测定[J].军事医学科学院院刊, 1991, (4): 45.
[70]刘农乐,蒋滋慧.神经生长因子的发光免疫分析法[J].中国生物化学与分子生物学报, 1994, (05): 616-617.
[71]刘农乐,蒋滋慧.表皮生长因子的发光免疫测定法-吖啶酯标记抗体的应用[J].生物化学与生物物理进展, 1993, (1): 43-44.
[72]徐秀英,刘农乐.吖啶酯发光法测定组织型纤溶酶原激活剂活性的研究[J].中华血液学杂志, 1996, (03): 157-158.
[73] Gion M, Mione R, Leon A E. Clinical chemistry, Comparison of the diagnostic accuracy of CA27.29 and CA15.3 in primary breast cancer[J]. 1999, 45(5): 630-637.
[74]庄惠生,王琼娥,陈国南,黄金陵,林培诚.测定癌胚抗原的化学发光免疫分析新方法[J].光谱学与光谱分析, 2000, (6): 889-891.
[75]卢建忠,曹志娟.化学发光技术在蛋白质和DNA分析中的新进展[J].世界科技研究与发展, 2004, 26(4): 97-104.
[76] Goto S, Takahashi A, Kamisango K, Matsubara K. Single-nu-cleotide polymorphism analysis by hybridization protection assay onsolid support[J]. Analytical Biochemistry, 2002, 307: 25-32.
[77]王晓娟,漆红兰,张成孝.利用吖啶酯化学发光研究甲醛和乙醛对DNA的损伤[J].陕西师范大学学报, 2006, 34(3): 73-76.
[78] Arnold L J, Hammond J P W, Wiese W A. NC Nelson. Assay formats involving acridinium-ester-labeled DNA probes[J]. Clinical Chemistry, 1989, 35 (8): 1588-1594.
[79] Ou C Y, McDonough S H, Sherrol H. Rapid and quantitative detection of enzymatically amplified HIV-1 DNA using chemiluminescent oligonucleotide probes. Retroviruses[J]. AIDS Research and Human Retroviruses, 1990, 6 (11): 1323-1325.
[80] Martinelli R, Arruda J C, Dwivedi P. Chemiluminescent hybridization-ligation assays for Delta F508 and Delta 1507 cystic fibrosis mutations[J]. Clinical Chemistry, 1996, 42 (1): 14-18.
[81]庄慧生,陈国南,张帆.化学发光免疫分析试剂吖啶酯的合成新路线[J].高等学校化学学报, 1998, 19(12): 1933-1936.
[82] LEE, Yeon-soo. Method For synthesizing hydroquinonone monoester compound[P], WO 03/ 033449, 2002.
[83] Urakami T, Yoshida C, Akaike T, Maeda H, Nishigori H, Niki E. Synthesis of monoesters of pyrroloquinoline quinone and imidazopyrroloquinoline, and radical scavenging activities using electron spin resonance in vitro and pharmacological activity in vivo[J]. Journal of Nutritional Science and Vitaminology, 1997, 43(1): 19-33.
[84]谢小安. CuI催化氨基酸促进的Ullmann类碳—碳键交叉偶联反应研究[D].有机化学博士论文,复旦大学, 2008.
[85] Veverkova E, Toma S. Study of CuI catalyzed coupling reactions of aryl bromides with imidazole and aliphatic amines under microwave dielectric heating[J]. Chemical Papers, 2008, 62(3): 334-338.
[86] Mc Capra F. Chemical mechanisms in bioluminescence[J]. Acc Chemistry Research, 1976, 9: 201-208.
[87] Natrajan A, Jiang Q, Sharpe D. Improved heterogeneous immunoassay for detection or quantification of analyte, using hydrophilic, high quantum yield acridinium compound containing electron-donating functional groups at C-2 and/or C-7 position of acridinium ring[P], WO: 20061307362 A2, 2006.
[88]赵赞梅,王汉斌.对氧磷酶的某些研究进展[J].毒理学杂志, 2005, 19 (1) : 64-65.
[89]腾霞,孙曼霁.对氧磷酶研究进展[J].生命科学, 2002, 14(2): 107-109.
[90]钱书红,王诗瑾,张情,刘新郑,王玉萍.糖尿病患者血清芳香醋酶活性与脂类关系的研究[J].河南医科大学学报, 1994, 29(1): 49-50.
[91]钱书虹,刘新郑.非胰岛素依赖型糖尿病患者血清芳香酯酶的临床观察[J].中华内分泌代谢杂志, 1994, 10(2): 111.
[92]孙艳,周长邵,胡望平.血清中芳香醋酶的特性及其与疾病的关系[J].国外医学临床生物化学与检验学分册, 2003, 24(4): 206-207.
[93] Lorentz K, Flatter B, Augustin E. A rylesterase in serum: elaborationand clinical application of a fixed-incubation m ethod[J]. Clinical Chemistry, 1979, 25(10): 1714-1720.
[94]钱庆文,钱书虹,王书君.慢性肾功能衰竭血清芳香酯酶活性改变的研究[J].中国现代医学杂志, 2002, 12(3): 38-42.
[95]钱庆文,钱书虹.不同原因慢性肾功能衰竭芳香酯酶与脂代谢紊乱的关系[J].天津医药, 2004, 32(10): 596-598.
[96]王书君,钱书虹,钱庆文.慢性肾衰竭血清芳香酯酶活性的变化及临床意义[J].临床荟萃, 2001, 16(21): 965.
[97] Gao H, Girard-Globa A, Bert-Hezene F. Paraoxonase protection of LDL against peroxidation is independent of is its esterase activity towards paraoxon and is unaffected by the Q→R genetie polymorphism[J]. Journal of Lipid Research, 1999, 40: 133-139.
[98] Lorentz K, Flatter B, Augustin E. A rylesterase in serum: elaborationand clinical application of a fixed-incubation m ethod [J]. Clinical Chemistry, 1979, 25(10): 1714-1720.
[99]邬红梅,周志俊,胡云平,薛寿征.血清芳香酯酶活性测定方法研究[J].工业卫生与职业病, 2001, 27(5): 270-272.
[100]周长邵,胡望平,孙艳.一种芳香酯酶检测新方法及其应用[J].江西医学检验, 2003, 21(3): 151-154.
[101]周志俊,邬红梅,胡云平,薛寿征.血清对氧磷酶活性测定方法研究[J].中国公共卫生, 2000, 16(4): 303-304.