4，5-二氮芴-9-酮-2-喹啉甲酰腙合成反应的LC-ESI-MS分析
摘要
近年来随着寻找功能材料及高效催化剂的推动,多吡啶配体及其配合物得到了广泛的研究。本论文以4,5-二氮芴-9-酮(dafo)为原料合成了化合物4,5-二氮芴-9-酮-2-喹啉甲酰腙(dfqh),通过液质联用LC-MS的方法对主产物(dfqh)和原料(dafo)进行定性和定量分析,通过优化条件最终确定：液相条件：选用Eclipse XDB-C18柱(φ4.6×250 mm,5μm),检测波长：240 nm,流动相：甲醇/水(含0.1%的醋酸,V/V)=80/20,流速V=1.0ml·min-1。质谱的条件：电喷雾离子源ESI,正离子模式,雾化器压力40 psi,干燥气温度300℃,干燥气流量9 L·min-1,毛细管端电压-3713V,毛细管出口电压：230.3 V。并且对确定的方法进行线性相关(R=0.9996)、精密度(RSD=0.58%)、稳定性(RSD=1.55%)、重复性(RSD=1.19%)、回收率(RSD=3.70%)等验证,最后对被测样品进行定性定量分析,在线性、定量限、检出限方面比较紫外检测器与质谱检测器的差别,质谱检测器的R为0.9969,当紫外检测器达到检出限S/N=3/1时,但此浓度下质谱检测器的S/N=5.7/1。可见质谱检测器比紫外检测器检测线更低有更高的灵敏度。
采用电喷雾质谱法对咪唑类,联苯类,间苯双胺类三类化合物的MSn规律进行了研究,通过分析它们的质谱图,来寻找质谱裂解规律,为化合物的定性鉴别和定量分析提供可靠的理论依据。结果发现拥有相同的结构骨架的化合物取代基不同则碎片丢失的先后顺序不同,取代基的诱导效应、共轭效应、空间位阻等起了重要的作用,另外特定的结构会有特定的中性丢失。
首先比较八种咪唑类化合物(1-8)的质谱特征,发现在正离子检测方式下,MS1均产生准分子离子[M+H]+峰,双咪唑啉钳形铂配合物8的MS1则脱去Cl-得到强的准分子离子[M-Cl]+峰簇,在它们的MSn中都发生了氢重排而失去中性分子；化合物1、2、7中与咪唑环上N原子相连的基团不含双键,不能形成共轭,所以很容易脱去；化合物3、4中与咪唑环上N原子相连的基团为长链烷烃,与咪唑环的作用力较强,5、6化合物中与咪唑环上N原子相连的基团均含有双键能形成p-π共轭,这些基团不容易脱去。
其次,六种联苯类化合物(9-14)在正离子检测方式下它们的质谱断裂方式存在共性,联苯化合物的MS1得到强的准分子离子[M+H]+峰簇；化合物9、11、12、13的最后一级质谱图均观察到含有稳定结构环庚三烯正离子的m/z166的峰得到了；化合物9、10、11、12的裂解过程中发生H重排后均失去HCN和甲苯中性分子,化合物14的MS2和MS3中均观察到失去中性分子H20。这是因为它们链端的基团很容易发生氢重排而断裂,失去H20中性分子。
最后,间苯双胺类化合物(15-16)在正离子检测方式下,它们的MS1均得到分子离子[M+H]+峰,从化合物16的质谱图上可观察到叔丁氧羰基(Boc)中氢重排导致叔丁基的断裂；在两个化合物的裂解过程中发生环的重排均在出现了环庚三烯正离子的稳定结构。
This Master thesis is divided into two parts. Part one is LC-MS experimental qualitative and quantitative analysis section. Part two is MS" experiment section.
1. LC-MS qualitative and quantitative analysis.
In recent years polypyridine ligands and their complexes have been studied extensively following the search for functional materials and efficient catalyst. This part is focuses on: synthesis of 4,5-diazafluorene -9-one (dafo) compounds from 4,5 diazafluorene -9-one quinaldinoylhydrazone (dfqh), qualitative and quantitative analysis of main product (dfqh) and materials (dafo) by LC-MS.After surveying the linearity, the limit of quantification, the detection limit with UV detector and Mass Spectrometry detector,we come to the conclusion that Mass Spectrometry detector have lower detection limit and higher sensitivity.
2. MS" experiment section.
According to the currently research status, this thesis study on the MS" law of imidazoles, biphenyl, metaphenyldiamine compounds. The compounds in each category have the same skeleton structure and different substituents.The study of the MS" law is through the applying different voltages to produce the target product ion fragmentation and choose the larger molecular weight and ionic strength to break again after the found of the molecular peak. The substituent is conjugated with the backbone or not, the different steric structure of compounds and the different conjugative effect and inductive effect of the substituents will resulent in the different splitting order. Sometimes there will be a splitting of neutral fragment in particular structure.
采用电喷雾质谱法对咪唑类,联苯类,间苯双胺类三类化合物的MSn规律进行了研究,通过分析它们的质谱图,来寻找质谱裂解规律,为化合物的定性鉴别和定量分析提供可靠的理论依据。结果发现拥有相同的结构骨架的化合物取代基不同则碎片丢失的先后顺序不同,取代基的诱导效应、共轭效应、空间位阻等起了重要的作用,另外特定的结构会有特定的中性丢失。
首先比较八种咪唑类化合物(1-8)的质谱特征,发现在正离子检测方式下,MS1均产生准分子离子[M+H]+峰,双咪唑啉钳形铂配合物8的MS1则脱去Cl-得到强的准分子离子[M-Cl]+峰簇,在它们的MSn中都发生了氢重排而失去中性分子；化合物1、2、7中与咪唑环上N原子相连的基团不含双键,不能形成共轭,所以很容易脱去；化合物3、4中与咪唑环上N原子相连的基团为长链烷烃,与咪唑环的作用力较强,5、6化合物中与咪唑环上N原子相连的基团均含有双键能形成p-π共轭,这些基团不容易脱去。
其次,六种联苯类化合物(9-14)在正离子检测方式下它们的质谱断裂方式存在共性,联苯化合物的MS1得到强的准分子离子[M+H]+峰簇；化合物9、11、12、13的最后一级质谱图均观察到含有稳定结构环庚三烯正离子的m/z166的峰得到了；化合物9、10、11、12的裂解过程中发生H重排后均失去HCN和甲苯中性分子,化合物14的MS2和MS3中均观察到失去中性分子H20。这是因为它们链端的基团很容易发生氢重排而断裂,失去H20中性分子。
最后,间苯双胺类化合物(15-16)在正离子检测方式下,它们的MS1均得到分子离子[M+H]+峰,从化合物16的质谱图上可观察到叔丁氧羰基(Boc)中氢重排导致叔丁基的断裂；在两个化合物的裂解过程中发生环的重排均在出现了环庚三烯正离子的稳定结构。
This Master thesis is divided into two parts. Part one is LC-MS experimental qualitative and quantitative analysis section. Part two is MS" experiment section.
1. LC-MS qualitative and quantitative analysis.
In recent years polypyridine ligands and their complexes have been studied extensively following the search for functional materials and efficient catalyst. This part is focuses on: synthesis of 4,5-diazafluorene -9-one (dafo) compounds from 4,5 diazafluorene -9-one quinaldinoylhydrazone (dfqh), qualitative and quantitative analysis of main product (dfqh) and materials (dafo) by LC-MS.After surveying the linearity, the limit of quantification, the detection limit with UV detector and Mass Spectrometry detector,we come to the conclusion that Mass Spectrometry detector have lower detection limit and higher sensitivity.
2. MS" experiment section.
According to the currently research status, this thesis study on the MS" law of imidazoles, biphenyl, metaphenyldiamine compounds. The compounds in each category have the same skeleton structure and different substituents.The study of the MS" law is through the applying different voltages to produce the target product ion fragmentation and choose the larger molecular weight and ionic strength to break again after the found of the molecular peak. The substituent is conjugated with the backbone or not, the different steric structure of compounds and the different conjugative effect and inductive effect of the substituents will resulent in the different splitting order. Sometimes there will be a splitting of neutral fragment in particular structure.
引文
[1]方晓明,张社.液相色谱-质谱/质谱连用技术新进展及应用.现代仪器,2002.(3)
[2]Liu X D, Liang Q L, Luo G A, et al. The application of Liquid Chromatography-mass Spectrometry in the field of Medicine [J].Pharm Anal,2005,25 (1):110-115
[3]孙毓庆.仪器分析[M].北京：科学出版社,2005
[4]姜艳艳,刘斌,石任兵.高效液相色谱-质谱联用技术在天然产物分离鉴定中的应用[J].药品评价,2005,2(1):111-161.
[5]J Abian.The coupling of gas and liquid chromatography with mass spectrometry .J Mass Spectrom,34:157-168,1999
[6]VL Tal'Roze,GV Karpov,IG Gorodetskii,VE Skurat. Zh Fiz Chim 42:1658,1968
[7]VL Tal'Roze VE Skurat GV Karpov Zh Fiz Chim43:241,1969
[8]MA Baldwin,FW Mclafferty.Org Mass Spectrom7:1111,1973
[9]CR BlaklyJJ Carmody,ML Vestal.Adv Mass Spectrom 8B:1616-1623,1980
[10]CR Blakly, ML Vestal, Anal Chem 55:750,1983
[11]Dole M, Mack LL, Hines RL, et al. [J] Chem Phys 49:2240,1968
[12]Mach LL, Kralik P, Rheude A, et al. [J] Chem Phys 52:4977,1972
[13]张志斐,张兰桐.高效液相色谱-质谱联用技术在药学研究中的应用[J].河北医科大学学报,2005,26(3)：226-229.
[14]刘祥东,梁琼麟,罗国安等.液质联用技术在医药领域中的应用[J].药物分析杂志,2005,25(1)：110-116.
[15]梁振,段继诚,张维冰等.毛细管电泳-电喷雾质谱联用中缓冲液pH对质谱检测灵敏度的影响.色谱.2003,21(1)：9-12
[16]Colby BN, Evans CA. Anal Chem 45:1884,1973
[17]Cook KD. Mass Spectrom Rev 5:467,1986
[18]Blades AT, Ikonomou MG, Kebarle P. Mechanism of electrospray mass spectromet-ry. Electrospray as an electrolysis cell.Anal Chem 63:2109-2114,1991
[19]Charbonnier F, Rolando C, Saru F, et al. J Pinson. Short time-scale observation of an electrpspray ion current. Rapid Commun Mass Spectrom 7:707-710,1993
[20]Van Berkel GJ, McLuckey SA, Glish GL, et al. Electrospray ionization of prorphyrins using a quadrupole ion trap for mass analysis,Anal Chem 63:1098-1109,1991
[21]Van Berkel GJ, McLuckey SA, Glish GL, et al. Preforming ions in solution via charge-transfer complexation for analysis by electrospray ionization mass spectrometry. Anal Chem 63:2064-2068,1991
[22]Van Breemen RB. Electrospray liquid chromatography-mass spectrometry of caroteno-ids. Anal Chem 67: 2004-2009, 1995
[23]Van Berkel GJ, McLuckey SA, Glish GL, et al. Electrochemical origin of radical cations observed in electrospray ionization mass spectra.Anal Chem 64:1586-1593,1992
[24]Xu X, Lu W, Cole RB, et al. On-line probe for fast electrochemistry/electrospray mass spectrometry.Investigation of polycyclic aromatic hydrocarbons.Anal Chem 68:4244-4253,1996
[25]Van Berkel GJ, Quirke JME, Tigani RA, et al. Derivatization for electrspray ionization mass spectometry-Electrochemically ionizable drivatives.Anal 70:1544-1554,1998
[26]Van Berkel GJ, Zhou F. Characterization of an electrospray ion source as a controlled-current electrolytic cell.Anal Chem67:2916-2923,1995
[27]Gomez A, Tang K. Phys Fluids 6:404,1994
[28]Tang K, Gomez A. Phys Fluids 6:2317,1994
[29]Kebarle P, Tang L. From ions in solution to ions in the gas phase. The mechanism of electrospray mass spectrometry. Anal Chem 65:927A-986A,1993
[30]Kebarle P, Ho Y. On the mechanism of electrospray mass spectrometry, In:RB Cole,ed. Electrospray mass spectrometry. New York:Wiley,1997, Chap7
[31]Hager DB, Dovichi NJ, Klassen J, et al. Droplet electro-spray mass spectrometry. Anal Chem 66:3944,1994
[32]Schmelzeisen-Redecker G, Buttering L, Rollgen F W, et al. Int J Mass Spectrom Ion Proc. 1989,90: 139
[33]Irbarne J V, Thomson B A. On the evaporation of smalll ions from charged droplets J Ch-em Phys.1976,64 (6):2287-2294
[34]Thomson B A, Iribarne J V. Field-induced ion evaporation from liquid surfaces at atmospheric pressure. [J] Chem Phys.1979,71:4451-4463
[35]Yamashita M, Fenn J B. Electrospray ion source. Another variation on the free-jet theme. [J] Chem Phys. 1984, 88 (20):4451-4459
[36]Guevremont R, Le Blanc J C Y, SiuKWM. Electrospray mass spectrometry:ethylene glycol as a solvent and its effects on ion desorption. Org Mass Spectrom.1993,28(11): 1345-1352
[37]Siu K W M, Guevremont R, Le Blanc JCY, et al. Is droplet evaporation crucial in the mechanism of electospray mass spectrometry. Org Mass Spectrom.1993,28 (5):579-584
[38]Kebarle, Pang L. The mechanism of electrospray mass spectrometry. Anal Chem.1993, 65:972A-986A
[39]Fenn JB, Roswell J, Meng CK. In electrospray ionization, how much pull does an ion need to escape its droplet prison? [J] Am Soc Mass Spectrom 8:1147-1157,1997
[40]Gamero-Castano M, Fernandez dela Mora J. Modulations in the abundance of salt clusters in electrosprays. Anal Chem 72:1426-1429,2000
[41]Sakairi M, Yergey AL, Siu KWM, et al. Electrospray mass spectrometry:Application of ion evaporation theory to amino acids. Anal Chem 63:1488-1490,1991
[42]Bruins AP. ESI source design and dynamic range considerations. In:RP Cole, ed. Electro-spray Ionization Mass Spectromery. New York:Wiley,1997, Chap 3
[43]Feng X, Agnes GR. Single isolated droplets with net charge as a source of ions. [J] Am Soc Mass Spectrom 11:393-399,2000
[44]Shaffer SA, Tang K, Anderson GA, et al. A novel ion funnel for focusing ions at elevated pressure using electrospray ionization mass spectrometry . Rapid Commun Mass Spectrometry. Rapid Commun Mass Spectrom 11:1813-1817,1997
[45]Shaffer SA, Prior DC, Anderson GA, et al. An ion funnel interface for improved ion focusing and sensitivity using electrospray ionization mass spectrometry. Anal Chem 70:4111-4119,1998
[46](a) Shaffer SA, Tolmachev AV, Pior DC, et al. Characterization of an improved electrodynamic ion funnel interface for electrosperay ionization mass spectronmetry.Anal-Chem 71:2957-2964,1999. (b)Kim T, Tolmachev AV, Harkewicz R, et al. Design and implementation of a new electrodynamic ion funnel.Anal Chem 72:2247-2255,2000
[47]Belov ME, Gorshkov MV, Udseth HK, et al. Initial implementation of electrometry. [J] Am Soc Mass Spectrom 11:19-23,2000
[48]Carr SA, Huddleston MJ, Bean MF. Selective identification and differentiation of N-andO-linked oligosaccharides in glycoproteins by liquid chromatography-mass spectrometry. Protein Sci 2:183-196,1993
[49]Huddleston MJ, Annan RS, Bean MF, et al. Selective detection of phosphopeptides in complex mixtures by electrospray liquid chromatography/mass spectrometry. [J] Am Soc Mass Spectrom 4:710-717,1993
[50]Jedrzejewski PT, Lehmann WD. Detection of modified peptides in enzymatic digests by capillary liquid chromatography / electrospray mass spectrometry and a programmable skimmer CID acquisition routine. Anal Chem69:294-301,1997.
[51]Rundlett KL, Armstrong DW. Mechanism of singal suppression by anionic surfactants in capillary electrophoresis-electrospray ionization mass spectrometry. Anal Chem68:3493-3497,1996
[52]Kuhlmann FE, Apffel A, Fischer SM, et al. Signal enhancement for gradient reverse- phase high-performance liquid chromatography-electrospray ionization mass spectro- metry with trifluoroacetic and other strong acid modifiers by postcolumn addition of propionic acid and isopropanol. [J] Am Soc Mass Spectrom6:1221-1225,1995
[53]Bier ME, Schwartz JC. Electrospray ionization quadrupole ion-trap mass spectro metr-y. In:RB Cole,ed.Electrospray Ionization Mass Spectrometry. New York:Wiley,1997, Chap7
[54]Hart KJ, McLuckey SA, Glish GL. Evidence of isomerization during isolation in the quadrupole ion trap. J Am Soc Mass Spectrom3:680-682,1992
[55]Sadagopan N, Watson JT. Investigation of the tris(trimethoxyphenyl)phosphonium acetyl charged derivatives of peptides by electrospray ionization mass spectrometry and tandem mass spectrometry. J Am Soc Mass Spectrom11: 107-119,2000
[56]Kim SH, Lee JH, Yun SY, et al. React ionMonitoring of Succinylation of Collagen With Matrix-A ssisted Laser Desorption/Ionization Mass Spectrometry [J].Rapid-Commun-Mass Spectrom.2000,14 (22):2125-2128
[57]牛长群,祝仕清.氨苄西林、阿莫西林相关物质的LC-MS分析药学学报,2001,36(10)：758-761
[58]胡敏,胡昌勤.LC-MS法分析头孢硫脒降解产物[J].药学学报,2006,41(10)1015-1019
[59]吉文亮,马永建,仓公敖.高效液相色谱串联质谱法测定蜂蜜中残留氯霉素[J]. 药物分析杂志,2006,26(12)：1814-1817
[60]谢文,丁慧瑛,黄雷芳,等.高效液相色谱-电喷雾电离三级四极杆质谱检测动物源食品中氯霉素、甲砜霉素、氟苯尼考残留量.分析试验室,2006,25(12)：1-7
[61]张志荣.现代仪器联用分析,成都科技大学出版社,1986
[62]孙毓庆.现代色谱法及其在医药中的应用.人民卫生出版社.1998
[63]徐秉玖.仪器分析与药物和临床医学.1、色谱部分.生命科学仪器,2003.Vol.1 No.21-6
[64]马栋,刘伟.液相色谱-质谱连用技术在毒物分析法中的应用.中国司法鉴定,671-2072(2005)03-0021-03
[65]靖静,刘倩茹,史晓凡.液-质联用技术在微量物证分析中的应用[J].广东公安科技,2009,97(4)
[66]Chen X Y, Xing J, Zhong D F. Rearrangement Process Occurring in the Fragmetation of Adefovir Derivatives [J]. Mass Spect rom,2004,39:145-152
[67]Zhong D F, Xing J, Zhang S Q, et al. Study of the Electrospray Ionization Tandem Mass Spectrometry of Sildenafil Derivatives [J]. Rapid Commun Mass Spectrom,2002,16: 1836-1843
[68]董宇,仇峰,张玉峰等.氨基甲酸酯类化合物电喷雾多级质谱分析中一种特殊的中型丢失CO2的重排反应[J].质谱学报.2005,26(1)：629
[69]Anari MR, Bakhitar R, Franklin RB, et al. Study of the Fragmentation Mechanism of 6-Hydroxychlorzoxazone:Application in Simultaneous Analysis of CYP-E1 Activity with Major Human Cytochrome P450s [J]. Anal Chem,2003,75 (3):469-478.
[70]薛松主编.有机结构分析.第1版[M].胡祥壁泽.合肥：中国科学技术大学出版社,2005.72
[71]渠琛玲,张寒琦,张华蓉,等.电喷雾质谱法研究氨基酸的质谱碎裂及其与人参皂苷Rb3的相互作用.高等学校化学学报.2008,29(9)：1721-1726
[72]刘国强,董静,王弘.4种儿茶素类化合物电喷雾质谱裂解规律的研究[J].高等学校化学学报,2009,No.8.566-1570
[73]张志涛.5种吡咯烷酮衍生物的电喷雾离子阱质谱分析初探[J].安徽医药.2009,13(5)494-495
[74]陈笑艳,钟大放等.电喷雾离子阱质谱法直接测定几种药物的葡萄糖苷酸型代谢物.药学学报Acta Pharmaceutica Sinica.1998,33 (11):849-854
[75]Summers L A. Advances in hetrocyclic chemistry[M]. Academic Press, New York.1978, 22,1-69
[76]John G J, weijnen Arie K, Johan F J. Engbersen. Carboxylic and phosphate ester hydrolysis catalysed by bivalent zinc and copper metallosufactants [J]. J chem soc Perkin Trans,1991, 2,1121-1126
[77]Guo D F, He J, Zengzz. Studies on interaction between ternary rare earth complexes of cinnamic acid and phenanthroline with DNA by spectroscopy[J]. J Chinese Rare Ealt hso-c,2004,22,55-60
[78]Taixs, Yin J, Feng Y M.1,10-phenanthroline pyridinium perchlorate[J]. Acta Cryst,2007, E61,01037-01038
[79]徐筱杰.超分子建筑-从分子到材料[M].科学技术文献出版社,2000.
[80]Wang Y X, Rillema D P. Altering the reaction pathways of aminopyridine with 4, 5-diazafluore none:metal ion control [J]. Tetrahedron Letters,1997,38 (38); 6627-6630
[81]Rajasekharan M V, Menon S. A. channel-forming ployiodide network in[Cu(dafon-e)3]I12.A trischelate of dafone and a new planer structure for the I122- ion(dafone=4,5-diaz afluoren-9-one)[J]. Inorg Chem,1997,36; 4983-4987
[82]Wang Y X, Perez W, Zheng G Y, et al. Syntheses and electrochemical. Photophysical, and Photochemical properties of ruthenium(II)4,5-diazafluorenone complexes and their ketal derivatives[J]. Ingorg Chem.1998.37:2051-2059
[83]Wang Y X, Perez w, Zheng G Y, et al. Preparmion, purification, and characterization of binuclear ruthenium (Ⅱ) complexes:bridging ligands based on diazafluorenes [J]. Inorg Ch-em,1998:2227-2234
[84]钟义添,吴建中.双(4,5-二氮杂芴酮)缩对,对-二氨基二苯甲烷桥联的二(邻菲罗啉)合铜(Ⅱ)的合成及其与DNA作用的光谱研究[J].无机化学学报,2003,19(2)：196-200
[85]Kraft B J j, Eppley H J, Huffman J C, et al. Cu(II)-mediated intramolecular carbene cation radical formation:relevance to unimolecular metal-ligand radical intermediates [J]. J Am Chem Soc,2002,124 (2):272-280
[86]Zhou G C, Harruna I. Synthesis of ligand monomers derived from 4,5-diazafluoren-9-one [J]. Tetrahedron Letters,2003,44; 4617-4619
[87]邵奎占.4,5-二氮芴-9-酮衍生物及配位聚合物的合成、结构与性质研究. [硕士学位论文].东北师范大学化学学院.2005
[88]Lehrer M. The role of gas chromatography/mass spectrometry. Instrumental techniques in forensicurine drug testing [J]. Clin Lab Med,1998,18 (4):631.
[89]毛红艳.多吡啶,多羧酸构筑的功能性配合物的结构和性能研究[D].[博十学位论文].沈阳：东北师范大学,2005
[90](a)T Hosokawa, T. Uno, S. lnui, S, et al. Palladium(II)-catalyzed asymmetric oxidative cyclization of 2-allylphenols in the presence of copper (II) acetate and molecular o-xygen. Study of the catalysis of the wacker-type oxidation. J Am. Chem. Soc.1981,103,2318- 2323; (b)T Hosokawa, C. Okuda, S.-I. Murahashi, Substituent effects on palladium(Ⅱ)-catalyzed enantioselective cyclization of a series of 2-(2-buten-y)phenol-s. J. Org. Chem. 1985,50,1282-1287
[91]Uozumi Y, Kato K. Hayashi T, Catalytic asymmetric wacker-type cyclization. J. Am. Che-m. Soc. 1997, 119, 5063-5064
[92]Elliott M, Jane NF. Synthetic pyrethroids-a new class of insecticide [J]. Chem. Soc. Rev. 1978, 7: 473-505
[93]Still J K, Arnold F E. Polyquinoxalines. [J]. Journal of Polymer Science Part A:Polymer Chemistry, 1966,4 (3):551-562
[94]Jerry J H, Marvel C S. Benzimidazole polymers from aldehydes and tetraamines [J]. Journal of Polymer Science Part A:Polymer Chemistry,1970,8(1):171-177
[95]Harry Adams, Darren Bradshaw, David E. Fenton Eur. J. Inorg. Chem.2002535-538
[96]Huynh H, Wong V, L.R.Ng, P.S.Organometallics 2008,27,2231
[97]McGuinness DS, Mueller W, WasserscheidP, et al. Englert, U. Organometallics 2002, 21,175
[2]Liu X D, Liang Q L, Luo G A, et al. The application of Liquid Chromatography-mass Spectrometry in the field of Medicine [J].Pharm Anal,2005,25 (1):110-115
[3]孙毓庆.仪器分析[M].北京：科学出版社,2005
[4]姜艳艳,刘斌,石任兵.高效液相色谱-质谱联用技术在天然产物分离鉴定中的应用[J].药品评价,2005,2(1):111-161.
[5]J Abian.The coupling of gas and liquid chromatography with mass spectrometry .J Mass Spectrom,34:157-168,1999
[6]VL Tal'Roze,GV Karpov,IG Gorodetskii,VE Skurat. Zh Fiz Chim 42:1658,1968
[7]VL Tal'Roze VE Skurat GV Karpov Zh Fiz Chim43:241,1969
[8]MA Baldwin,FW Mclafferty.Org Mass Spectrom7:1111,1973
[9]CR BlaklyJJ Carmody,ML Vestal.Adv Mass Spectrom 8B:1616-1623,1980
[10]CR Blakly, ML Vestal, Anal Chem 55:750,1983
[11]Dole M, Mack LL, Hines RL, et al. [J] Chem Phys 49:2240,1968
[12]Mach LL, Kralik P, Rheude A, et al. [J] Chem Phys 52:4977,1972
[13]张志斐,张兰桐.高效液相色谱-质谱联用技术在药学研究中的应用[J].河北医科大学学报,2005,26(3)：226-229.
[14]刘祥东,梁琼麟,罗国安等.液质联用技术在医药领域中的应用[J].药物分析杂志,2005,25(1)：110-116.
[15]梁振,段继诚,张维冰等.毛细管电泳-电喷雾质谱联用中缓冲液pH对质谱检测灵敏度的影响.色谱.2003,21(1)：9-12
[16]Colby BN, Evans CA. Anal Chem 45:1884,1973
[17]Cook KD. Mass Spectrom Rev 5:467,1986
[18]Blades AT, Ikonomou MG, Kebarle P. Mechanism of electrospray mass spectromet-ry. Electrospray as an electrolysis cell.Anal Chem 63:2109-2114,1991
[19]Charbonnier F, Rolando C, Saru F, et al. J Pinson. Short time-scale observation of an electrpspray ion current. Rapid Commun Mass Spectrom 7:707-710,1993
[20]Van Berkel GJ, McLuckey SA, Glish GL, et al. Electrospray ionization of prorphyrins using a quadrupole ion trap for mass analysis,Anal Chem 63:1098-1109,1991
[21]Van Berkel GJ, McLuckey SA, Glish GL, et al. Preforming ions in solution via charge-transfer complexation for analysis by electrospray ionization mass spectrometry. Anal Chem 63:2064-2068,1991
[22]Van Breemen RB. Electrospray liquid chromatography-mass spectrometry of caroteno-ids. Anal Chem 67: 2004-2009, 1995
[23]Van Berkel GJ, McLuckey SA, Glish GL, et al. Electrochemical origin of radical cations observed in electrospray ionization mass spectra.Anal Chem 64:1586-1593,1992
[24]Xu X, Lu W, Cole RB, et al. On-line probe for fast electrochemistry/electrospray mass spectrometry.Investigation of polycyclic aromatic hydrocarbons.Anal Chem 68:4244-4253,1996
[25]Van Berkel GJ, Quirke JME, Tigani RA, et al. Derivatization for electrspray ionization mass spectometry-Electrochemically ionizable drivatives.Anal 70:1544-1554,1998
[26]Van Berkel GJ, Zhou F. Characterization of an electrospray ion source as a controlled-current electrolytic cell.Anal Chem67:2916-2923,1995
[27]Gomez A, Tang K. Phys Fluids 6:404,1994
[28]Tang K, Gomez A. Phys Fluids 6:2317,1994
[29]Kebarle P, Tang L. From ions in solution to ions in the gas phase. The mechanism of electrospray mass spectrometry. Anal Chem 65:927A-986A,1993
[30]Kebarle P, Ho Y. On the mechanism of electrospray mass spectrometry, In:RB Cole,ed. Electrospray mass spectrometry. New York:Wiley,1997, Chap7
[31]Hager DB, Dovichi NJ, Klassen J, et al. Droplet electro-spray mass spectrometry. Anal Chem 66:3944,1994
[32]Schmelzeisen-Redecker G, Buttering L, Rollgen F W, et al. Int J Mass Spectrom Ion Proc. 1989,90: 139
[33]Irbarne J V, Thomson B A. On the evaporation of smalll ions from charged droplets J Ch-em Phys.1976,64 (6):2287-2294
[34]Thomson B A, Iribarne J V. Field-induced ion evaporation from liquid surfaces at atmospheric pressure. [J] Chem Phys.1979,71:4451-4463
[35]Yamashita M, Fenn J B. Electrospray ion source. Another variation on the free-jet theme. [J] Chem Phys. 1984, 88 (20):4451-4459
[36]Guevremont R, Le Blanc J C Y, SiuKWM. Electrospray mass spectrometry:ethylene glycol as a solvent and its effects on ion desorption. Org Mass Spectrom.1993,28(11): 1345-1352
[37]Siu K W M, Guevremont R, Le Blanc JCY, et al. Is droplet evaporation crucial in the mechanism of electospray mass spectrometry. Org Mass Spectrom.1993,28 (5):579-584
[38]Kebarle, Pang L. The mechanism of electrospray mass spectrometry. Anal Chem.1993, 65:972A-986A
[39]Fenn JB, Roswell J, Meng CK. In electrospray ionization, how much pull does an ion need to escape its droplet prison? [J] Am Soc Mass Spectrom 8:1147-1157,1997
[40]Gamero-Castano M, Fernandez dela Mora J. Modulations in the abundance of salt clusters in electrosprays. Anal Chem 72:1426-1429,2000
[41]Sakairi M, Yergey AL, Siu KWM, et al. Electrospray mass spectrometry:Application of ion evaporation theory to amino acids. Anal Chem 63:1488-1490,1991
[42]Bruins AP. ESI source design and dynamic range considerations. In:RP Cole, ed. Electro-spray Ionization Mass Spectromery. New York:Wiley,1997, Chap 3
[43]Feng X, Agnes GR. Single isolated droplets with net charge as a source of ions. [J] Am Soc Mass Spectrom 11:393-399,2000
[44]Shaffer SA, Tang K, Anderson GA, et al. A novel ion funnel for focusing ions at elevated pressure using electrospray ionization mass spectrometry . Rapid Commun Mass Spectrometry. Rapid Commun Mass Spectrom 11:1813-1817,1997
[45]Shaffer SA, Prior DC, Anderson GA, et al. An ion funnel interface for improved ion focusing and sensitivity using electrospray ionization mass spectrometry. Anal Chem 70:4111-4119,1998
[46](a) Shaffer SA, Tolmachev AV, Pior DC, et al. Characterization of an improved electrodynamic ion funnel interface for electrosperay ionization mass spectronmetry.Anal-Chem 71:2957-2964,1999. (b)Kim T, Tolmachev AV, Harkewicz R, et al. Design and implementation of a new electrodynamic ion funnel.Anal Chem 72:2247-2255,2000
[47]Belov ME, Gorshkov MV, Udseth HK, et al. Initial implementation of electrometry. [J] Am Soc Mass Spectrom 11:19-23,2000
[48]Carr SA, Huddleston MJ, Bean MF. Selective identification and differentiation of N-andO-linked oligosaccharides in glycoproteins by liquid chromatography-mass spectrometry. Protein Sci 2:183-196,1993
[49]Huddleston MJ, Annan RS, Bean MF, et al. Selective detection of phosphopeptides in complex mixtures by electrospray liquid chromatography/mass spectrometry. [J] Am Soc Mass Spectrom 4:710-717,1993
[50]Jedrzejewski PT, Lehmann WD. Detection of modified peptides in enzymatic digests by capillary liquid chromatography / electrospray mass spectrometry and a programmable skimmer CID acquisition routine. Anal Chem69:294-301,1997.
[51]Rundlett KL, Armstrong DW. Mechanism of singal suppression by anionic surfactants in capillary electrophoresis-electrospray ionization mass spectrometry. Anal Chem68:3493-3497,1996
[52]Kuhlmann FE, Apffel A, Fischer SM, et al. Signal enhancement for gradient reverse- phase high-performance liquid chromatography-electrospray ionization mass spectro- metry with trifluoroacetic and other strong acid modifiers by postcolumn addition of propionic acid and isopropanol. [J] Am Soc Mass Spectrom6:1221-1225,1995
[53]Bier ME, Schwartz JC. Electrospray ionization quadrupole ion-trap mass spectro metr-y. In:RB Cole,ed.Electrospray Ionization Mass Spectrometry. New York:Wiley,1997, Chap7
[54]Hart KJ, McLuckey SA, Glish GL. Evidence of isomerization during isolation in the quadrupole ion trap. J Am Soc Mass Spectrom3:680-682,1992
[55]Sadagopan N, Watson JT. Investigation of the tris(trimethoxyphenyl)phosphonium acetyl charged derivatives of peptides by electrospray ionization mass spectrometry and tandem mass spectrometry. J Am Soc Mass Spectrom11: 107-119,2000
[56]Kim SH, Lee JH, Yun SY, et al. React ionMonitoring of Succinylation of Collagen With Matrix-A ssisted Laser Desorption/Ionization Mass Spectrometry [J].Rapid-Commun-Mass Spectrom.2000,14 (22):2125-2128
[57]牛长群,祝仕清.氨苄西林、阿莫西林相关物质的LC-MS分析药学学报,2001,36(10)：758-761
[58]胡敏,胡昌勤.LC-MS法分析头孢硫脒降解产物[J].药学学报,2006,41(10)1015-1019
[59]吉文亮,马永建,仓公敖.高效液相色谱串联质谱法测定蜂蜜中残留氯霉素[J]. 药物分析杂志,2006,26(12)：1814-1817
[60]谢文,丁慧瑛,黄雷芳,等.高效液相色谱-电喷雾电离三级四极杆质谱检测动物源食品中氯霉素、甲砜霉素、氟苯尼考残留量.分析试验室,2006,25(12)：1-7
[61]张志荣.现代仪器联用分析,成都科技大学出版社,1986
[62]孙毓庆.现代色谱法及其在医药中的应用.人民卫生出版社.1998
[63]徐秉玖.仪器分析与药物和临床医学.1、色谱部分.生命科学仪器,2003.Vol.1 No.21-6
[64]马栋,刘伟.液相色谱-质谱连用技术在毒物分析法中的应用.中国司法鉴定,671-2072(2005)03-0021-03
[65]靖静,刘倩茹,史晓凡.液-质联用技术在微量物证分析中的应用[J].广东公安科技,2009,97(4)
[66]Chen X Y, Xing J, Zhong D F. Rearrangement Process Occurring in the Fragmetation of Adefovir Derivatives [J]. Mass Spect rom,2004,39:145-152
[67]Zhong D F, Xing J, Zhang S Q, et al. Study of the Electrospray Ionization Tandem Mass Spectrometry of Sildenafil Derivatives [J]. Rapid Commun Mass Spectrom,2002,16: 1836-1843
[68]董宇,仇峰,张玉峰等.氨基甲酸酯类化合物电喷雾多级质谱分析中一种特殊的中型丢失CO2的重排反应[J].质谱学报.2005,26(1)：629
[69]Anari MR, Bakhitar R, Franklin RB, et al. Study of the Fragmentation Mechanism of 6-Hydroxychlorzoxazone:Application in Simultaneous Analysis of CYP-E1 Activity with Major Human Cytochrome P450s [J]. Anal Chem,2003,75 (3):469-478.
[70]薛松主编.有机结构分析.第1版[M].胡祥壁泽.合肥：中国科学技术大学出版社,2005.72
[71]渠琛玲,张寒琦,张华蓉,等.电喷雾质谱法研究氨基酸的质谱碎裂及其与人参皂苷Rb3的相互作用.高等学校化学学报.2008,29(9)：1721-1726
[72]刘国强,董静,王弘.4种儿茶素类化合物电喷雾质谱裂解规律的研究[J].高等学校化学学报,2009,No.8.566-1570
[73]张志涛.5种吡咯烷酮衍生物的电喷雾离子阱质谱分析初探[J].安徽医药.2009,13(5)494-495
[74]陈笑艳,钟大放等.电喷雾离子阱质谱法直接测定几种药物的葡萄糖苷酸型代谢物.药学学报Acta Pharmaceutica Sinica.1998,33 (11):849-854
[75]Summers L A. Advances in hetrocyclic chemistry[M]. Academic Press, New York.1978, 22,1-69
[76]John G J, weijnen Arie K, Johan F J. Engbersen. Carboxylic and phosphate ester hydrolysis catalysed by bivalent zinc and copper metallosufactants [J]. J chem soc Perkin Trans,1991, 2,1121-1126
[77]Guo D F, He J, Zengzz. Studies on interaction between ternary rare earth complexes of cinnamic acid and phenanthroline with DNA by spectroscopy[J]. J Chinese Rare Ealt hso-c,2004,22,55-60
[78]Taixs, Yin J, Feng Y M.1,10-phenanthroline pyridinium perchlorate[J]. Acta Cryst,2007, E61,01037-01038
[79]徐筱杰.超分子建筑-从分子到材料[M].科学技术文献出版社,2000.
[80]Wang Y X, Rillema D P. Altering the reaction pathways of aminopyridine with 4, 5-diazafluore none:metal ion control [J]. Tetrahedron Letters,1997,38 (38); 6627-6630
[81]Rajasekharan M V, Menon S. A. channel-forming ployiodide network in[Cu(dafon-e)3]I12.A trischelate of dafone and a new planer structure for the I122- ion(dafone=4,5-diaz afluoren-9-one)[J]. Inorg Chem,1997,36; 4983-4987
[82]Wang Y X, Perez W, Zheng G Y, et al. Syntheses and electrochemical. Photophysical, and Photochemical properties of ruthenium(II)4,5-diazafluorenone complexes and their ketal derivatives[J]. Ingorg Chem.1998.37:2051-2059
[83]Wang Y X, Perez w, Zheng G Y, et al. Preparmion, purification, and characterization of binuclear ruthenium (Ⅱ) complexes:bridging ligands based on diazafluorenes [J]. Inorg Ch-em,1998:2227-2234
[84]钟义添,吴建中.双(4,5-二氮杂芴酮)缩对,对-二氨基二苯甲烷桥联的二(邻菲罗啉)合铜(Ⅱ)的合成及其与DNA作用的光谱研究[J].无机化学学报,2003,19(2)：196-200
[85]Kraft B J j, Eppley H J, Huffman J C, et al. Cu(II)-mediated intramolecular carbene cation radical formation:relevance to unimolecular metal-ligand radical intermediates [J]. J Am Chem Soc,2002,124 (2):272-280
[86]Zhou G C, Harruna I. Synthesis of ligand monomers derived from 4,5-diazafluoren-9-one [J]. Tetrahedron Letters,2003,44; 4617-4619
[87]邵奎占.4,5-二氮芴-9-酮衍生物及配位聚合物的合成、结构与性质研究. [硕士学位论文].东北师范大学化学学院.2005
[88]Lehrer M. The role of gas chromatography/mass spectrometry. Instrumental techniques in forensicurine drug testing [J]. Clin Lab Med,1998,18 (4):631.
[89]毛红艳.多吡啶,多羧酸构筑的功能性配合物的结构和性能研究[D].[博十学位论文].沈阳：东北师范大学,2005
[90](a)T Hosokawa, T. Uno, S. lnui, S, et al. Palladium(II)-catalyzed asymmetric oxidative cyclization of 2-allylphenols in the presence of copper (II) acetate and molecular o-xygen. Study of the catalysis of the wacker-type oxidation. J Am. Chem. Soc.1981,103,2318- 2323; (b)T Hosokawa, C. Okuda, S.-I. Murahashi, Substituent effects on palladium(Ⅱ)-catalyzed enantioselective cyclization of a series of 2-(2-buten-y)phenol-s. J. Org. Chem. 1985,50,1282-1287
[91]Uozumi Y, Kato K. Hayashi T, Catalytic asymmetric wacker-type cyclization. J. Am. Che-m. Soc. 1997, 119, 5063-5064
[92]Elliott M, Jane NF. Synthetic pyrethroids-a new class of insecticide [J]. Chem. Soc. Rev. 1978, 7: 473-505
[93]Still J K, Arnold F E. Polyquinoxalines. [J]. Journal of Polymer Science Part A:Polymer Chemistry, 1966,4 (3):551-562
[94]Jerry J H, Marvel C S. Benzimidazole polymers from aldehydes and tetraamines [J]. Journal of Polymer Science Part A:Polymer Chemistry,1970,8(1):171-177
[95]Harry Adams, Darren Bradshaw, David E. Fenton Eur. J. Inorg. Chem.2002535-538
[96]Huynh H, Wong V, L.R.Ng, P.S.Organometallics 2008,27,2231
[97]McGuinness DS, Mueller W, WasserscheidP, et al. Englert, U. Organometallics 2002, 21,175