生物相容性C60衍生物的合成及其细胞保护活性的研究
|
摘要
利用[C60]富勒烯的各种衍生化方法,将水溶性基团或某些生物活性的组份引入到C_(60)上,合成生物相容的C_(60)衍生物,研究它们的生物活性,已经成为[C60]富勒烯化学及富勒烯生物学应用的一个重要课题。本文利用C_(60)的胺化反应,C_(60)与亚氨基二乙酸酯类的光化学反应,C60 Bingel环加成反应以及C_(60)与叠氮化物的环加成反应,合成和制备了几种未见文献报道的生物相容性的C_(60)衍生物。通过对它们抗氧化、自由基清除及细胞保护等活性的研究,为寻找具有优良抗氧化活性的C_(60)衍生物提供基础性的数据。同时,通过对这些生物学性质的影响因素及构效规律的探讨和分析,为生物相容性C_(60)衍生物分子的设计和合成提供基本的信息。主要内容包括: 1.C_(60)与氨基酸类物质在甲苯/乙醇混和溶剂中的亲核加成反应制得水溶性的C_(60)氨基酸衍生物1_a, 1_b, 1_c和1_d,它们的加成度分别为:n=5(1_a), 5(1_b), 4(1_c)和3(1_d)。C_(60)氨化反应的加成度与氨基酸碳链的空间阻碍及加成产物在反应介质中的溶解性等因素有关。
氧自由基的清除实验、体外培养小鼠胸腺细胞实验、及红细胞氧化性溶血实验表明:1_a, 1_b, 1_c和1_d都具有抗氧化及清除自由基的活性,而且剂量效应明显。
上述实验也表明:C60氨基酸衍生物(1_a和1_b; 1_a, 1_c和1_d)抗氧化活性的大小都有如下规律: 1_a > 1_b ;1_a > 1_c > 1_d
表明,C_(60)氨基酸加成物加成基团的空间位阻及加成度增加所导致的烯键电荷密度增大是影响其抗氧化及自由基清除活性的内在因素。2.C_(60)吡咯烷羧酸衍生物2_b和3_b经由C_(60)与亚氨基二乙酸甲酯(NH(CH_2COOMe)_2的光化学反应,N-烃基化反应及水解和酸化等步聚制得,产率分别为65%和53% (基于C60吡咯烷衍生物2_a和3_a)。
2_b和3_b在0~3×10~(-4) mol/L浓度范围内,能明显清除化学发光体系中产生的超氧阴离子O_2~(-·)和羟基·OH等自由基,它们的清除能力并无明显差异。相同的C_(60)母体结构—单加成[6,6]-闭环结构决定了它们相似的自由基清除能力。
C_(60)吡咯烷二羧酸2_b和三羧酸3_b在极性介质中容易聚集。用电导法测定了2b和3b钠盐的临界聚集浓度(CAC),分别为3.58×10~(-4) mol/L (2_b)和3.33×10~(-4) mol/L (3_b)。透射电子显微镜(TEM)、静态光散射(SLS)、UV-vis等方法进一步证实了2_b和3_b的这一聚集行为。2_b和3_b CAC的差异、聚集体粒径大小的不同,表明C60单加成衍生物加成基团中羧基(COOH)数目的多少对其聚集行为的影响。
氧自由基的清除实验及红细胞氧化性溶血实验表明:2_b和3_b聚集行为的发生导致了它们抗氧化及自由基清除能力下降。
3.合成了C_(60)基Ebselen衍生物7 (产率53%)和10(产率42%,以消耗的[60]富勒烯计)。
MTT法及LDH法测试表明,7和10及相应的C_(60)、和Ebselen衍生物均能抑制H_2O_2诱导的大鼠大脑皮层神经细胞的损伤,而且7和10和保护作用要强于相应的C_(60)、及Ebselen衍生物。NADPH-RD酶偶联分析法的测试表明,7和10的GPx活力也均高于相应的C_(60)、及Ebselen衍生物。
C_(60)基Ebselen衍生物比相应的C_(60)、及Ebselen衍生物表现出更强的抗氧化与神经保护活性,这一活性的增强应归因于它的自由基清除能力的提高及GPX活力的增强。因此,通过选择合适的抗氧化组份并将它们引入到C_(60)是获得具有更强的抗氧化性的C_(60)基衍生物的有效方法。
Making use of various functionalizations of [60]fullerene, introducing solubilising groups or potentially biologically effective components to [60]fullerene to synthesize biologically compatible C_(60) derivatives, and investigating their biological activites have recently become a topic of importance in the fields of [60]fullerene chemistry and its biological applications. In this paper, amination reaction, photochemical reaction, and (Bingel)cycloaddition of C_(60), respectively, with amino-acids, iminodiacetic alkyl esters, azides, and malonates were carried out to prepare a few biologically compatible C_(60) derivatives. Their antioxidative and radical scavenging properties, and their protective effects on culturing cells were studied. The studies may provide basic data for finding better antioxidative C_(60) derivatives. Meanwhile, we also discussed and analyzed influencing factors of these biological properties and structure-activity relationships in order to obtain basic information for designing and synthesizing biologically compatible C60 derivatives.
This paper has the following main aspects:
1. Nucleophilic addition of C_(60) with amino-acids in toluene/ethanol gave the corresponding C_(60) amino-acid adducts (1_a, 1_b, 1_c and 1_d), their addition number (n) determined by elemental analysis: n=5 (1_a), 5 (1_b), 4 (1_c) and 3 (1_d). Addition number (n) of amination reaction of C_(60) was influenced by steric hindering of hydrocarbon chains of amino-acids and solubility of C_(60) adducts in reaction media.
The experimentations of eliminating active oxygen radicals in chemical systems, mouse thymus cell cultures, and H2O2-induced erythrocytes oxidative hemolysis demonstrated that C_(60) amino-acid adducts (1_a, 1_b, 1_c and 1_d ) possess antioxidative and radical scavenging properties. With the increase of concentrations, their antioxidative and radical scavenging abilities increased.
These experimentations also showed that antioxidative potencies of the C_(60) amino-acid adducts were with the same sequence: 1_a > 1_b ; 1_a > 1_c > 1_d
The consistencies in the sequence reveal that steric hindering of addition groups of C60 amino-acid adducts and enhanced electron densities of the conjugated bonds of C_(60) core are intrinsic factors of influencing their antioxidative and radical scavenging abilities.
2. The synthesis of fulleropyrrolidine carboxylic acid 2_b and 3_b were conveniently achieved in a 65% and 53%yield (relative to 2_a and 3_a), by a multiple-step process: photochemical reaction of C_(60) with iminodiacetic methyl ester (NH(CH_2COOMe)_2, further N-Alkylation, hydrolysis and acidification.
2_b and 3_b, in the concentration range of 0 ~3×10~(-4) mol/L, have obvious scavenging activities against superoxide(O_2~(-·))and hydroxyl (·OH) radicals generated in chemiluminescence systems. However, 2_b and 3_b were found to have no obvious differences in radical scavenging efficiency. The similar radical scavenging potencies can reasonably be ascribed to their identical [6,6]-closed structure of parent C_(60).
Fulleropyrrolidine carboxylic acid 2_b and 3_b easily form aggregate in polar media. Critical aggregation concentrations (CAC) of their sodium salts were determined by conductivity measurements, which were 3.58×10~(-4) mol/L (2_b) and 3.33×10~(-4) mol/L (3_b). Their aggregation behaviors were further proved using UV-Vis absorption, static light scattering (SLS) and transmission electron microscopic (TEM) techniques. CAC and aggregate sizes of 2_b and 3_b were different from each other, indicating that the aggregate is effected by the number of carboxyl groups connected to fulleropyrrolidine mono-adduct derivatives.
The experimentations of eliminating active oxygen radicals in chemical systems, and H_2O_2-induced erythrocytes oxidative hemolysis demonstrated that aggregation behavior of 2_b or 3_b resulted in the decline of their antioxidative and radical scavenging potencies. 3. C_(60)-based ebselen derivatives 7 (53%) and 10 (42%, based on consumed C_(60) ) were synthesized.
MTT assay and LDH leakage assay showed that 7 and 10 and their corresponding C_(60), ebselen derivatives can inhibit H_2O_2-induced neuronal injury, and C_(60)-based ebselen derivatives (7, 10) possess stronger nuroprotective potencies than parent C_(60), or ebselen derivatives alone. NADPH-RD coupled enzymatic assay also showed that the GPX activities of 7, or 10 were higher than those of parent C_(60), or ebselen derivatives.
The C_(60)-based ebselen derivatives showed stronger nuroprotective potency than parent C_(60), or ebselen derivatives alone. This enhanced nuroprotective potencies can reasonably be attributed to both improvement of its free radical scavenging capabilities and improvement of GPX-like activities. Therefore, selecting appropriate antioxidant components and introducing them to [60]fullerenes, should be an effective methods of obtaining more biologically effective C_(60)-based antioxidants.
氧自由基的清除实验、体外培养小鼠胸腺细胞实验、及红细胞氧化性溶血实验表明:1_a, 1_b, 1_c和1_d都具有抗氧化及清除自由基的活性,而且剂量效应明显。
上述实验也表明:C60氨基酸衍生物(1_a和1_b; 1_a, 1_c和1_d)抗氧化活性的大小都有如下规律: 1_a > 1_b ;1_a > 1_c > 1_d
表明,C_(60)氨基酸加成物加成基团的空间位阻及加成度增加所导致的烯键电荷密度增大是影响其抗氧化及自由基清除活性的内在因素。2.C_(60)吡咯烷羧酸衍生物2_b和3_b经由C_(60)与亚氨基二乙酸甲酯(NH(CH_2COOMe)_2的光化学反应,N-烃基化反应及水解和酸化等步聚制得,产率分别为65%和53% (基于C60吡咯烷衍生物2_a和3_a)。
2_b和3_b在0~3×10~(-4) mol/L浓度范围内,能明显清除化学发光体系中产生的超氧阴离子O_2~(-·)和羟基·OH等自由基,它们的清除能力并无明显差异。相同的C_(60)母体结构—单加成[6,6]-闭环结构决定了它们相似的自由基清除能力。
C_(60)吡咯烷二羧酸2_b和三羧酸3_b在极性介质中容易聚集。用电导法测定了2b和3b钠盐的临界聚集浓度(CAC),分别为3.58×10~(-4) mol/L (2_b)和3.33×10~(-4) mol/L (3_b)。透射电子显微镜(TEM)、静态光散射(SLS)、UV-vis等方法进一步证实了2_b和3_b的这一聚集行为。2_b和3_b CAC的差异、聚集体粒径大小的不同,表明C60单加成衍生物加成基团中羧基(COOH)数目的多少对其聚集行为的影响。
氧自由基的清除实验及红细胞氧化性溶血实验表明:2_b和3_b聚集行为的发生导致了它们抗氧化及自由基清除能力下降。
3.合成了C_(60)基Ebselen衍生物7 (产率53%)和10(产率42%,以消耗的[60]富勒烯计)。
MTT法及LDH法测试表明,7和10及相应的C_(60)、和Ebselen衍生物均能抑制H_2O_2诱导的大鼠大脑皮层神经细胞的损伤,而且7和10和保护作用要强于相应的C_(60)、及Ebselen衍生物。NADPH-RD酶偶联分析法的测试表明,7和10的GPx活力也均高于相应的C_(60)、及Ebselen衍生物。
C_(60)基Ebselen衍生物比相应的C_(60)、及Ebselen衍生物表现出更强的抗氧化与神经保护活性,这一活性的增强应归因于它的自由基清除能力的提高及GPX活力的增强。因此,通过选择合适的抗氧化组份并将它们引入到C_(60)是获得具有更强的抗氧化性的C_(60)基衍生物的有效方法。
Making use of various functionalizations of [60]fullerene, introducing solubilising groups or potentially biologically effective components to [60]fullerene to synthesize biologically compatible C_(60) derivatives, and investigating their biological activites have recently become a topic of importance in the fields of [60]fullerene chemistry and its biological applications. In this paper, amination reaction, photochemical reaction, and (Bingel)cycloaddition of C_(60), respectively, with amino-acids, iminodiacetic alkyl esters, azides, and malonates were carried out to prepare a few biologically compatible C_(60) derivatives. Their antioxidative and radical scavenging properties, and their protective effects on culturing cells were studied. The studies may provide basic data for finding better antioxidative C_(60) derivatives. Meanwhile, we also discussed and analyzed influencing factors of these biological properties and structure-activity relationships in order to obtain basic information for designing and synthesizing biologically compatible C60 derivatives.
This paper has the following main aspects:
1. Nucleophilic addition of C_(60) with amino-acids in toluene/ethanol gave the corresponding C_(60) amino-acid adducts (1_a, 1_b, 1_c and 1_d), their addition number (n) determined by elemental analysis: n=5 (1_a), 5 (1_b), 4 (1_c) and 3 (1_d). Addition number (n) of amination reaction of C_(60) was influenced by steric hindering of hydrocarbon chains of amino-acids and solubility of C_(60) adducts in reaction media.
The experimentations of eliminating active oxygen radicals in chemical systems, mouse thymus cell cultures, and H2O2-induced erythrocytes oxidative hemolysis demonstrated that C_(60) amino-acid adducts (1_a, 1_b, 1_c and 1_d ) possess antioxidative and radical scavenging properties. With the increase of concentrations, their antioxidative and radical scavenging abilities increased.
These experimentations also showed that antioxidative potencies of the C_(60) amino-acid adducts were with the same sequence: 1_a > 1_b ; 1_a > 1_c > 1_d
The consistencies in the sequence reveal that steric hindering of addition groups of C60 amino-acid adducts and enhanced electron densities of the conjugated bonds of C_(60) core are intrinsic factors of influencing their antioxidative and radical scavenging abilities.
2. The synthesis of fulleropyrrolidine carboxylic acid 2_b and 3_b were conveniently achieved in a 65% and 53%yield (relative to 2_a and 3_a), by a multiple-step process: photochemical reaction of C_(60) with iminodiacetic methyl ester (NH(CH_2COOMe)_2, further N-Alkylation, hydrolysis and acidification.
2_b and 3_b, in the concentration range of 0 ~3×10~(-4) mol/L, have obvious scavenging activities against superoxide(O_2~(-·))and hydroxyl (·OH) radicals generated in chemiluminescence systems. However, 2_b and 3_b were found to have no obvious differences in radical scavenging efficiency. The similar radical scavenging potencies can reasonably be ascribed to their identical [6,6]-closed structure of parent C_(60).
Fulleropyrrolidine carboxylic acid 2_b and 3_b easily form aggregate in polar media. Critical aggregation concentrations (CAC) of their sodium salts were determined by conductivity measurements, which were 3.58×10~(-4) mol/L (2_b) and 3.33×10~(-4) mol/L (3_b). Their aggregation behaviors were further proved using UV-Vis absorption, static light scattering (SLS) and transmission electron microscopic (TEM) techniques. CAC and aggregate sizes of 2_b and 3_b were different from each other, indicating that the aggregate is effected by the number of carboxyl groups connected to fulleropyrrolidine mono-adduct derivatives.
The experimentations of eliminating active oxygen radicals in chemical systems, and H_2O_2-induced erythrocytes oxidative hemolysis demonstrated that aggregation behavior of 2_b or 3_b resulted in the decline of their antioxidative and radical scavenging potencies. 3. C_(60)-based ebselen derivatives 7 (53%) and 10 (42%, based on consumed C_(60) ) were synthesized.
MTT assay and LDH leakage assay showed that 7 and 10 and their corresponding C_(60), ebselen derivatives can inhibit H_2O_2-induced neuronal injury, and C_(60)-based ebselen derivatives (7, 10) possess stronger nuroprotective potencies than parent C_(60), or ebselen derivatives alone. NADPH-RD coupled enzymatic assay also showed that the GPX activities of 7, or 10 were higher than those of parent C_(60), or ebselen derivatives.
The C_(60)-based ebselen derivatives showed stronger nuroprotective potency than parent C_(60), or ebselen derivatives alone. This enhanced nuroprotective potencies can reasonably be attributed to both improvement of its free radical scavenging capabilities and improvement of GPX-like activities. Therefore, selecting appropriate antioxidant components and introducing them to [60]fullerenes, should be an effective methods of obtaining more biologically effective C_(60)-based antioxidants.
引文
[1] Prato M, Li Q C, Wudl F. Addition of Azides to C_(60): Synthesis of Azafulleroids. J. Am. Chem. Soc., 1993, 115: 1148~1150.
[2] Banks M. R, Cadogan J. I, Gosney I. Aziridino[2’,3’:1,2]fullerene. J. Chem. Commun., 1994, 11: 1365~1366.
[3] Averdung J, Mattay J. Exohedral Functionalization of [60]Fullerene by [3+2] Cycloadditions: Synthesis and Chemical Properties of Triazolino-[60]fullerenes. Tetrachedron, 1996, 52 (15): 5407~5420.
[4] Tsuda M, Ishida T, Nogami T, et al. C_(61)Cl_2 Synthesis and Characterization of Dichlorocarbene Adducts of C_(60). Tetrahedron Lett., 1993, 34: 6911~6912.
[5] Benito A B, Darwish A D, Kroto H W, et al. Synthesis and Characterization of tre Methanofullerenes, C_(60) (CHCN) and C_(60) (CBr_2). Tetrahedron Lett., 1996, 37: 1085~1086.
[6] Isaacs L, Diederich F. Structures and Chemistry Methanofullerenes: A Versatile Route into N-[(Methanofullerene)carbonyl]–Substituted Amino Acids. Helv. Chim. Acta., 1993, 76: 2454~2464.
[7] Vaseiia A, Uhlmann P, Diederich F. Fullerene Sugar: Preparation of Spiro-Linked C-Glycosides of C_(60). Angew.Chem., Int. Ed. Engl., 1992, 31: 1388~1390.
[8] Tokuyama H, Nakamura M, Nakamura E, Tetrahedron Lett., 1997, 34: 6911.
[9] Shu L H, Wang G W, Wu S H., et al. Reaction of [60]fullerene with 1-(4-methoxyphenyl)-1-(trimethylsilyloxy)ethylene. J. Chem. Soc., Chem.Commun.., 1995, 367~368.
[10] (a) Wang Y, Cao J, Schuster D I, et al. A Superior Synthesis of [6,6]- Methanofullerenes: the Reaction of Sulfonium Ylides with C_(60) . Tetrahedron Lett., 1995, 36: 6843~6846 . (b) Hirsch A. Synthesis, 1995, 8: 895 . (c) Hamada M, Hino T, Kinbara K, et al. Synthesis and transformation of a novel methano[60]fullerene having a formyl group. Tetrahedron Lett., 2001, 42: 5069~5071.
[11] Nierengarten F J, Habicher T, Kessinger R, et al. Macrocyclization on the FullereneCore: Synthesis of Fullerene–dendrimer Dervatives. Helv. Chim. Acta, 1997, 80: 2238~2276.
[12] Nierengarten J F, Gramlich V, Cardullo F, et al. Angew. Chem., Int. Ed. Engl. 1996, 35, 2242.
[13] Camps X, Hirsch A. Efficient cyclopropanation of C_(60) starting from Malonates. J. Chem. Soc., Perkin Trans. 1, 1997, 1595~1596.
[14] Cheng F, Yang X, Zhu H, et al. Synthesis and optical properties of tetraethyl methano[60]fullerenediphosphonate . Tetrahedron Lett., 2000, 41, 3947~3950 .
[15] Zhou D, Tan H, Luo C, et al. Fullerene induced c-n bond breaking and formation: synthesis of fullerene pyrrolidine and methanofullerene sarcosine derivatives by photochemical addition of sarcosine ester to C_(60) . Tetrahedron Lett., 1995, 36, 9169~9172.
[16] (a) Gan L B, Jiang J F, Zhang W, et al. Synthesis of Pyrrolidine Ring-Fused Fullerene Multicarboxylates by Photoreaction. J. Org. Chem., 1998 , 63 (13): 4240~4247. (b ) Gan L B, Zhou D, Luo C, Tan H, et al. Synthesis of Fullerene Amino Acid Derivatives by Direct Interaction of Amino Acid Ester with C_(60). J. Org. Chem., 1996, 61(6): 1954~1961. [17 ] Maggini M, Scorrano G. Addition of Azomethine Ylides to CM: Synthesis, Characterization, and Functionalization of Fullerene Pyrrolidines. J. Am. Chem. Soc., 1993, 115: 9798~9799.
[18] (a) Laborde E. 3-Arylpyrrolidines via azomethine ylide 1,3-dipolar cycloaddition to styrenes . Tetrahedron Lett., 1992, 6607~6610. (b ) Wu S-H, Sun W-Q, Zhang D-W., et al. 1,3-Dipolar cycloaddition of several azomethine ylides to [60]fullerene: synthesis of derivatives of 2 ,5 -dihydro-1 H-pyrrolo[3 ,4 : 1,2][60]fullerene. J. Chem. Soc., Perkin trans.1, 1998,1733~1738 .
[19] (a) Bernstein R, Foote C S. Singlet Oxygen Involvement in the Photochemical Reaction of C_(60) and Amines. Synthesis of an Alkyne-Containing Fullerene. J. Phys. Chem. A, 1999, 103, 7244~7247. (b) Takcda K, Kajii Y, Shibuya K, J. Photochem. and Photobiol. A: Chem., 1995, 92: 69~72.
[20] Seshadri R, Govindaraj A, Nagarajan R, Addition of amines and halogens to fullerenes C_(60) and C70. Tetrahedron Lett., 1992, 33 (15): 2069~2070.
[21] Gan L B, Luo C P, Xu L B, et al. Water-Soluble Fullerene Derivatives,Synthesis andCharacterization ofβ一alanine C_(60) adducts. Chinese Chem. Lett., 1994, 5: 275~278.
[22]孙涛,徐铸德,贾之慎.功能化基团对C60-β一丙氨酸衍生物清除超氧阴离子自由基能力的影响.高等学校化学学报, 2003, 24(7): 1231~1233.
[23] Peng H, Lam J. W. Y., Leug F. S. M., et al. Synthesis of Fullerene-Containing Sol-Gel Glasses. Journal of Sol-gel Science and Technology, 2001, 22: 205~218.
[24] Davey S.N., Leigh D.A., Moody A.E. C_(60)–Azacrown Ethers: the First Monoaminated Fullerene Derivatives J. Chem. Soc.,Chem.Commun.1994, 397~398.
[25] Hirsch A., Wudl Q. L I F. Globe-trotting Hydrogens on the Surface of the Fullerene Compound C_(60)H_6(N(CH_2CH_2)_2O)_6. Angew. Chem., Int. Ed. Engl., 1991, 30: 1309~1310.
[26] Vaknin D., Wang J.Y., Uphous R.A.. C_(60)-propylamine Adduct Monolayers at the Air-Water. Interface. Langmir, 1995, 11: 1435~1438.
[27] Schick G., Kampe K.D., Hirsch A. Reaction of [60]fullerene with morpholine and piperidine: preferred 1,4-additions and fullerene dimer formation. J. Chem. Soc., Chem. Commun., 1995, 2023~2024.
[28] Beiik P, Gugel A. Spickermann J, et al. Reaction of Buckminsterfullerene with ortho-Quinodimethane: a New Access to Stable C_(60) Derivatives. Angew. Chem. Int. Ed. Engl.,1993, 32: 78~80.
[29] (a) Boulle C, Cariou M., Bainville A., et al. [4+2] Cycloaddition of C_(60) to -(thi)oxo-4,5-bis(methylene)-1,3-dithioles : en Route to the bis-Linking of Tetrathiafulvalene to C_(60) Tetrahedron Lett.,1997, 8: 8l~84. (b) Llacay J, Mas M., Molins E., et al. The first Diels–Alder adduct of [60]fullerene with a tetrathiafulvalene. Chem.Commun,1997, 659~660. (c) Ferndndez P, Martin N. Thermal and Microwave-Assisted Synthesis of Diels-Alder Adducts of [60]Fullerene with 2,3-Pyrazinoquinodimethanes: Characterization and Electrochemical Properties. J.Org.Chem., 1997, 62:3705~3710.
[30] Ohno M, Azuma T, Eguchi S., et al. Buckminsterfullerene C_(60)– o-Quinone Methide Cycloadduct. Chem. Lett.,1993: 1833~1834.
[31] Taki M, Nakamura Y, Kasashima E., et al. Selective Functionalization on [60]Fullerene Governed by Tether Length. J. Am. Chem. Soc., 1997, 119: 926~932.
[32] (a) Lang F, Cruz P, Espildora E., et al. Fullerene chemistry under microwaveirradiation. Carbon, 2000,38:1641~1646. (b) Pilar C, Angle D O., García J. J., et al. Synthesis of new C_(60)---donor dyads by reaction of pyrazolylhydrazones with [60]fullerene under microwave irradiation. Tetrahedron Lett,1999, 40: 1587~1590. (c) Cruz P, Hoz A. Synthetic Metals, 1997, 86: 2283~2284. (d) Cruz P, Hoz A., Langa F., et al. Cycloadditions to [60]fullerene using microwave irradiation: A convenient and expeditious procedure . Tetrahedron,1996,52:2599~2608. (e) Illescas B, Martín N, Seoane C, et al. A Facile Formation of Electroactive Fullerene Adducts from Sultines via a Diels-Alder Reaction. Tetrahedron Lett., 1995, 36: 8307~8310.
[33] Lerestif J M, Bazureau J P, Hamelin J. Cycloaddition with stabilized imidates as potential azomethines ylides : A new route to 2-imidazoline and 4-yliden-s-imidazolinone. Tetrahedron Lett., 1993, 34: 4639~4642.
[34] Pierre L, Yhou Z, Echegoyen L. A new route for the selective synthesis of [6,6]-methanofullerenes.Electrosynthesis of C61HCMe3 and C61HCN. Chem.Commun., 1996: 1547~1548.
[35] Bingel C. Cyclopropanierung von Fullerenen. Chem. Ber., 1993, 126: 1957~1959.
[36] Moonen N, Thilgen C, Diedeich F., et al. The chemical retro-Bingel reaction: selective removal of bis(alkoxycarbonyl)methano addends from C_(60) and C70 with amalgamated magnesium. Chem.Commun., 2000, 335~336.
[37] Fender N. S., Nuber B., Schuster D. I., et al. Preparation of [60]fullerene tris-malonate adducts by addend removal from higher adducts via the electrochemical retro-Bingel reaction. J. Chem. Soc., Perkin Trans. 2, 2000, 1924~1928.
[38] Kamat J.P., Devasagayam T. P. A., Priyadarsini K. I., et al. Oxidative damage induced by the fullerene C_(60) on photosensitization in rat liver microsomes . Chem. Biol. Interact., 1998, 114: 145~159.
[39] Arbogast J. W., Foote C. S., Kao M. Electron transfer to triplet fullerene C_(60). J. Am. Chem. Soc., 1992, 114: 2277~2279.
[40]方渊清,蔡瑞芳.富勒烯[60]的光化学反应研究.化学通报, 2000, 5:25~33.
[41] Akasaka T., Maeda Y., Wakahara T., et al. A First Photochemical Bis-germylation of C_(60) with Digermirane . Org. Lett., 2000, 2(17): 2671~2674.
[42] Wang G. W., Komatsu K., Murata Y., et al. Synthesis and X-ray structure ofdumb-bell-shaped C_(120) , Nature, 1997, 387:583~586.
[43] Murata Y., Kato N., Fujiwara K., et al. Solid-State [4 + 2] Cycloaddition of Fullerene C_(60) with Condensed Aromatics Using a High-Speed Vibration Milling Technique. J. Org. Chem., 1996, 64: 3483~3488.
[44] Koichi F., Noriyuki K. Syn.Commun., 1999,29 (24):4397~4402.
[45] Dugan L.L., Turetsky D.M., Wheeler M. Proc. Natl. Acad. Sci. U.S.A.,1997, 94:9434.
[46] Hsu S.C., Wu C.C., Luh T.Y., et al. Apoptotic Signal of Fas Is Not Mediated by Ceramide. Blood, 1998, 91:2658~2663.
[47] Huang Y.L., Shen C.K., Luh T.Y., et al. Blockage of apoptotic signaling of transforming growth factor-βin human hepatoma cells by carboxyfullerene. Eur. J. Biochem., 1998, 254: 38~43.
[48] Da Ros T., Prato M., NovelloF., et al. Easy Access to Water-Soluble Fullerene Derivatives via 1,3-Dipolar Cycloadditions of Azomethine Ylides to C_(60). J.Org. Chem. ,1996, 61: 9070~9072.
[49] Bosi S., Da Ros T., Castellano S., et al. Antimycobacterial activity of ionic fullerene derivatives. Bioorg. Med. Chem. Lett., 2000, 10: 1043~1045.
[50] Takcnaka S., Yamashita K., Takagi M., et al. Photo-induced DNA Cleavage by Water-soluble Cationic Fullerene Derivatives. Chem. Lett., 1999, 321~322.
[51] Yang X.L., Fan C.H., Zhu H.S. Photo-induced cytotoxicity of malonic acid [C60]fullerene derivatives and its mechanism . Toxicology in Vitro, 2002,16: 41~46.
[52] Friedman S H, DeCamp D L, Sijbesma R P, et a1. Inhibition of the HIV-1 protease by fullerene derivatives: model building studies and experimental verification. J. Am. Chem. Soc., 1993, 115: 6506~6509.
[53] Ueng T.H., Kang J.J., Wang H.W.,et al. Suppression of microsomal cytochrome P450-dependent monooxygenases and mitochondrial oxidative phosphorylation by fullerenol, a polyhydroxylated fullerene C_(60) . Toxicol. Lett., 1997, 93: 29~37.
[54] Lin Y.-L., Lei H.-Y., Wen Y.-Y., et al. Light-Independent Inactivation of Dengue-2 Virus by Carboxyfullerene C3 Isomer . Virology, 2000, 275: 258~262.
[55] Tsai M.C., Chen Y.H., Chiang L.Y. J. Pharm. Pharmacol., 1997, 49:438~445.
[56] Huang S.S., Tsai S.K., Chih C.L., et al. Neuroprotective effect of hexasulfobutylatedC60 on rats subjected to focal cerebral ischemia. Free Radic. Biol. Med., 2001, 30: 643~649.
[57] Lin A.M.-Y., Fang S.-F., Lin Sh.Z., et al. Neuroscience Research, 2002, 43: 317~321.
[58] Dugan L.L., Lovett E.G., Quick K.L., et al. Fullerene-based antioxidants and neurodegenerative disorders. Parkinsonism and Related Disorders, 2001, 7: 243~246.
[59] Chiang L.Y., Lu F.J., Lin J.T., Free radical scavenging activity of water-soluble fullerenols. J.Chem.Soc.,Chem.Commun., 1995, 1283~1284.
[60]祝严师,孙大勇,刘桂珍, et al.富勒醇清除·OH~ˉ自由基的ESR研究.高等学校化学学报, 1996, 17(7):1127~1129.
[61] Cheng F., Yang X., Zhu H., et al. Synthesis of oligoadducts of malonic acid C_(60) and their scavenging effects on hydroxyl radical. J. Phys. Chem. Solids, 2000, 61: 1145~1148.
[62] Okuda K., Mashino T., Hirobe M. Superoxide radical quenching and cytochrome C peroxidase-like activity of C_(60)-dimalonic acid, C_(62)(COOH)_4 . Bioorg. Med. Chem. Lett., 1996, 6 (5): 539~542.
[63] Sun T., Xu. Zh. Radical scavenging activities ofα-alanine C_(60) adduct . Bioorg. Med. Chem. Lett., 2006, 16 : 3731~3734.
[64] Guldi D.M., Asmus K.-D. Activity of water-soluble fullerenes towards OH-radicals and molecular oxygen. Radiation Physics and Chemistry, 1999, 56: 449~456.
[65]Guo L.W., Gao X., Zhang D.W., et al. Easy Access to [60]Fulleroalkaloids via Photoinduced Reactions of Tertiary Amines with [60]Fullerene. Chem. Lett., 1999, 5: 411~413.
[66] (a) Janis R. A., Silver P. J., Triggle D. J. Adv. Drug Res., 1987, 16: 309~91. (b) Bossert F., Vater W., Med. Res. Rev., 1989, 9:291~324.
[67] Illescas B., Martinez-Grau M. A.,Torres M. L., et al. Synthesis of new C_(60) derivatives containing biologically active 4-aryl-1,4-dihydropyridines . Tetrahedron Lett., 2002, 43: 4133~4136
[68] Yashiro A., Nishida Y., Ohno M., et al. Fullerene glycoconjugates: A general synthetic approach via cycloaddition of per-O-acetyl glycosyl azides to [60]fullerene . Tetrahedron Lett., 1998, 39: 9031~9034.
[69] Wilson S.R., Lu Q., Cao L. Proc. Electrochem. Soc ., 1995,95-10,1179.
[70] Sofou P., Elemes Y., Panou-Pomonis E., et al. Synthesis of a proline-rich
[60]fullerene peptide with potential biological activity. Tetrahedron, 2004, 60: 2823~2828
[71] Boutorine A. S., Tokuyama H., Takasugi M., , et al. Fullerene-Oligonucleotide Conjugates: Photoinduced Sequence-Specific DNA Cleavage. Angew. Chem. Int. Ed. Engl., 1994, 33: 2462~2465.
[72] An Y.Z., Chen C-H.B., Anderson J.L., et al. Sequence-specific modification of guanosine in DNA by a C_(60)-linked deoxyoligonucleotide: Evidence for a non-singlet oxygen mechanism. Tetrahedron, 1996, 52 (14): 5179~5189.
[73] Chi Y., Bhonsle J.B. Canteenwala T ., et al. Novel Water-soluble Hexa(sulfobutyl)fullerenes as Potent Free Radical Scavengers. Chem. Lett., 1998, 465~466.
[74] Hirsch A., Lampartn J., Karfunkel H. R. Fullerene Chemistry in Three Dimensions: Isolation of Seven Regioisomeric Bisadducts and Chiral Trisadducts of C_(60) and Di(ethoxycarbonyl)methylene. Angew. Chem. Int. Ed. Engl, 1994, 33: 437~438.
[75] Chiang L.Y., Bhonsk J.B., wang L., et al. Efficient one-flask synthesis of water-soluble [60]fullerenols. Tetrahedron, 1996, 52: 4963~4972.
[76] (a) Yamago S., Tokuyama H., Nakamura E., et al. Chemical derivatization of organofullerenes through oxidation, reduction, and carbon-oxygen and carbon-carbon bond-forming reactions . J. Org. Chem., 1993, 58 (18): 4796~4798. (b) Tokuyama H., Yamago S., Nakamura E., et al. Photoinduced biochemical activity of fullerene carboxylic acid . J. Am. Chem. Soc., 1993, 115 (17): 7918~7919. (c) Sijbesma R., Srdanov G., Wudl F., et al. Synthesis of a fullerene derivative for the inhibition of HIV enzymes . J. Am. Chem. Soc., 1993, 115 (15): 6510~6512.
[77] (a)Richardson C. F., Schuster O.I., Wilson S.R. Synthesis and Characterization of Water-Soluble Amino Fullerene Derivatives. Org, Lett. 2000, 2: 1011~1014. (b) Murakami H., Shirakusa M., Sagara T ., et al. Synthesis, Aggregate Structure and Electrochemical Properties of a Water-Soluble Fullerene-Bearing Ammonium Amphiphile. Chem. Lett., 1999, 815~816.
[78] (a)Tamberli V., Tatiana K.R., Bosi S., et al. Synthetic approaches towards thepreparation of water-soluble fulleropyrrolidines. Carbon, 2000, 38: 1551~1555. (b) Hawker C.J., Saville P. M., White J. W. The Synthesis and Characterization of a Self-Assembling Amphiphilic Fullerene. J.Org. Chem ,1994, 59: 3503~3505.
[79] Polese A., Mondini S., Bianco A., et al. Solvent-Dependent Intramolecular Electron Transfer in a Peptide-Linked [Ru(bpy)3]2+-C60 Dyad. J. Am. Chem. Soc., 1999, 121(14): 3446~3452.
[80] (a)Fullerene Sci.Technol.,1997,5,989.(b)Photochem. Photobiol.1997,66: 301. (c) Sun Y. P., Liu B., Moton D. K. Preparation and characterization of a highly water-soluble pendant fullerene polymer. Chem. Commun. 1996, 2699~2700.
[81] Brettreich M., Hirsch A. A highly water-soluble dendro[60]fullerene. Tetrahedron Lett., 1998, 39 : 2731~2734.
[82] Wharton T., Kini V. U., Mortis R. A., et al. New non-ionic, highly water-soluble derivatives of C_(60) designed for biological compatibility . Tetrahedron Lett., 2001, 42: 5159~5162.
[83] (a) Yang J., Wang Y., Rassat A, et al. Synthesis of novel highly water-soluble 2:1 cyclodextrin/fullerene conjugates involving the secondary rim ofβ-cyclodextrin . Tetrahedron, 2004, 60: 12163~12168. (b) Samal S, Geckeler K. E. Cyclodextrin–fullerenes: a new class of water-soluble fullerenes.Chem. Commun. 2000, 1101~1102.
[84] Ikeda A., HatanoT., Kawaguchi M., et al. Water-soluble [60]fullerene–cationic homooxacalix[3]arene complex which is applicable to the photocleavage of DNA. Chem. Commun. 1999, 1403~1404.
[85]Yamakoshi Y.N., Yagama T., Fukuhara K. Solubilization of fullerenes into water with polyvinylpyrrolidone applicable to biological tests. J. Chem. Soc., Chem. Commun. 1994, 517~518.
[86] Farman D. Free Radical in Biology. New York: Academic Press, 1982. 255~258.
[87]赵葆路.氧自由基和天然抗氧化剂.北京:科学出版社, 1999. 7~10.
[88] Lin A. M-Y., Fang S.- F., Lin S. Z., et al. Local carboxyfullerene protects cortical infarction in rat brain. Neurosci. Res., 2002, 43: 317~321.
[89] Monti D., Moretti L., Salvioli S., et al. C_(60) Carboxyfullerene Exerts a ProtectiveActivity against Oxidative Stress-Induced Apoptosis in Human Peripheral Blood Mononuclear Cells. Biochem. Biophys. Res. Commun., 2000, 277: 711~717.
[90] Lai H.S., Chen Y., Chen W. J., et al. Free radical scavenging activity of fullerenol on grafts after small bowel transplantation in dogs. Transplant. Proc., 2000, 32:1272~1274.
[91] Stephens A.H.H., Green M.L.H. Adv. Inorg. Chem., 1997, 44: 1~5.
[92] (a) West R., Oka K., Takahashi H., et al. in Inorganic and Organometallic Polymers II. Washington, D.C.: American Chemical Society, 1994. Chapter 9. (b) Olah G.A., Bucsi I., Lambert C., et al. Polyarenefullerenes, C_(60)(H-Ar)n, obtained by acid-catalyzed fullerenation of aromatics. J. Am. Chem. Soc., 1991, 113: 9387~9388.
[93] Miller G. P., Millar J. M., Liang B., et al. The absence of globe-trotting hydrogen on the surfaces of aminated fullerenes: 3-D hydrogen bonding between aminated fullerenes and water revealed. J.Chem. Soc. Chem. Commun. 1993, 897~899.
[94]郭霭光,王振镒.邻苯三酚自氧化-化学发光法测定SOD活性.植物生理学通讯, 1989, 3: 54~57.
[95]陈季武,胡天喜.测定·0H产生与清除的化学发光体系.生物化学与生物物理进展, l992, l9:136~140.
[96] Mosmann T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J.Immuno. Methods, 1983, 65(1): 55~63.
[97] Wu Y.J., Li W.G., Zhang Z.M., et al. Antioxidative activity of 4-oxyand 4- hydroxy- nitroxides in tissues and eyethrocytes from rats. Acta Pharmacol Sin , 1997 ,18 :150.
[98]周林珠,杨祥良等.多糖抗氧化作用研究进展.中国生化药物杂志, 2002, 23(4): 210~212.
[99]马兰萍,刘在群,周波.绿茶多酚对自由基诱导的红细胞氧化性溶血的抑制作用.科学通报, 2000, 45(12): l271~1275.
[100] Nakamura E., Tokuyama H., Yamago S., et al. Biological Activity of Water-Soluble Fullerenes. Structural Dependence of DNA Cleavage, Cytotoxicity, and Enzyme Inhibitory Activities Including HIV-Protease Inhibitio. Bull. Chem. Soc. Jpn., 1996, 69: 2143~2151.
[101] (a) Okamura H., Miyazono K., Minoda M., et al. J. Polym. Sci. Part A: Pol. Chem., 2000, 38, 3578. (b)Brough P., Bonifazi D., Prato M. Self-organization of amphiphilic [60]fullerene derivatives in nanorod-like morphologies. Tetrahedron , 2006, 62:2110~2114.
[102] Guldi D.M., Hungerbuhler H., Asmus K.-D. Unusual redox behavior of a water soluble malonic acid derivative of C_(60): evidence for possible cluster formation. J. Phys. Chem., 1995, 99: 13487~13493.
[103] (a) Guldi D.M. Capped Fullerenes: Stabilization of Water-Soluble Fullerene Monomers As Studied by Flash Photolysis and Pulse Radiolysis. J. Phys. Chem. A., 1997, 101: 3895~3900. (b) Guldi D.M. Res. Chem.Intermed. 1997, 23: 653.
[104] (a)Song T., Daib S., Tamb K.C., et al. Aggregation behavior of two-arm fullerene-containing poly(ethylene oxide). Polymer 2003, 44: 2529~2536. (b) Brettreich M., Burghardt S., Bottcher C., et al. Globular Amphiphiles: Membrane-Forming Hexaadducts of C_(60). Angew. Chem. Int. Ed. 2000, 39: 1845~1848.
[105] KerckhoffsJ. M. C. A., Leeuwen F. W. B., Spek A. L., et al. Regulatory Strategies in the Complexation and Release of a Noncovalent Guest Trimer by a Self-Assembled Molecular Cage. Angew. Chem. Int. Ed., 2003, 42: 5717~5722.
[106] Guo X., Szoka F. C. Chemical Approaches to Triggerable Lipid Vesicles for Drug and Gene Delivery. Acc. Chem. Res., 2003, 36: 335~341.
[107] Eastoe J., Crooks E., Beeby A., et al. Structure and photophysics in C_(60)-micellar solutions. Chem.Phys.Lett., 1995, 245: 571~577.
[108] Samal S., Geckeler K. E. Unexpected solute aggregation in water on dilution. Chem.Commun., 2001, 2224~2225. (b) Burger C., Hao J., Ying Q., et al. Multilayer vesicles and vesicle clusters formed by the fullerene-based surfactant C_(60)(CH3)5K . J. Colloid. Interface. Sci., 2004, 275: 632~641.
[109] Langa F., Cruz P., Espíldora E., et al. Fullerene chemistry under microwave irradiation . Carbon, 2000, 38: 1641~1646.
[110] Cruz P., Hoz A., Font L. M., et al. Solvent-free phase transfer catalysis under microwaves in fullerene chemistry. A convenient preparation of N-alkylpyrrolidino[60]fullerenes. Tetrahedron Lett. 1998, 39: 6053~6056.
[111] Lamparth I., Hirsch A. Water-soluble malonic acid derivatives of C_(60) with a defined three-dimensional structure. J. Chem. Soc., Chem. Commun., 1994, 1727~1728.
[112]浙江大学,南京大学等.综合化学实验.第一版.北京:高等教育出版社, 2001年.94~97.
[113] Mashino T., Shimotohno K., Ikegami N., et al. Human immunodeficiency virus-reverse transcriptase inhibition and hepatitis C virus RNA-dependent RNA polymerase inhibition activities of fullerene derivatives. Bioorg. Med. Chem. Lett., 2005, 15: 1107~1109.
[114] (a) Da Ros T., Prato M., Novello F., et al. Easy Access to Water-Soluble Fullerene Derivatives via 1,3-Dipolar Cycloadditions of Azomethine Ylides to C_(60). J. Org. Chem. 1996, 61, 9070~9072. (b) Guldi D.M., Hungerbu1hler H., Asmus K-D. Radiolytic Reduction of a Water-Soluble Fullerene Cluster. J. Phys. Chem. A, 1997, 101: 1783~1786.
[115]左榘.激光光散射原理及其在高分子科学中的应用.第一版.郑州:河南科学技术出版社, 1994. 48~229.
[116]马兰萍,刘在群,周波.绿茶多酚对自由基诱导的红细胞氧化性溶血的抑制作用.科学通报, 2000, 45 (12): l271~1275.
[117] (a) Mattson M.P., Chan S.L. Dysregulation of cellular calcium homeostasis in Alzheimer's disease: bad genes and bad habits. J Mol. Neurosci., 2001, 17(2): 205~224. (b)Mattson M. P. Oxidative stress, perturbed calcium homeostasis, and immune dysfunction in Alzheimer's disease. J. Neurovirol., 2002, 8 (6): 539~550.
[118] (a) Cui J., Holmes E.H., Greene T.G., et al. Oxidative DNA damage precedes DNA fragmentation after experimental stroke in rat brain. FASEB J., 2000,14 (7): 955~967. (b)赵丹洋,吴伟康.氧化应激在脑缺血损伤中的作用机制.中国病理生理杂志, 2004, 20 (4): 679~682. (c) Stadtman, E.R. Protein oxidation and ageing. Science, 1992, 257: 1220~1224.
[119] Mahura I.S. Cerebral ischemia-hypoxia and biophysical mechanisms of neurodegeneration and neuroprotection effects. Fizio.l Zh., 2003, 49 (2): 7~12.
[120] (a)Aronowski J., Grotta J. C. Ca~(2+)/calmodulin-dependent protein kinase II in postsynaptic densities after reversible cerebral ischemia in rats. Brain Res.,1996, 709 (1):103~110. (b)Colomer J. M, Mao L., Rockman H. A., et al. Pressure Overload Selectively Up-Regulates Ca~(2+)/Calmodulin-Dependent Protein Kinase II in Vivo. Mol. Endocrinol., 2003, 17 (2):183~192.
[121] (a)LaFerla F.M. Calcium dyshomeostasis and intracellular signalling inAlzheimer'sdisease. Nat. Rev. Neurosci., 2002, 3(11): 862~872. (b) Palotas A., Kalman J., Palotas M., et al. Long-term exposition of cells to beta-amyloid results in decreased intracellular calcium concentration. Neurochem. Int., 2003, 42 (7): 543~547.
[122] (a)Nishizawa Y. Glutamate release and neuronal damage in ischemia. Life Sci, 2001, 69 (4):369~381. (b)Roy M., Sapolsky R. M. The exacerbation of hippocampal excitotoxicity by glucocorticoids is not mediated by apoptosis. Neuroendocrinology, 2003, 77(1): 24~31.
[123] Kuwako K., Nishimura I., Uetsuki T., et al. Activation of calpain in cultured neurons overexpressing Alzheimer amyloid precursor protein. Brain Res. Mol. Brain Res., 2002, 107 (2):166~175.
[124] Frantseva M. V., Carlen P.L., Perez V. J.L. Dynamics of intracellular calcium and free radical production during ischemia in pyramidal neurons. Free Radic. Biol. Med., 2001, 31 (10): 1216~1227.
[125] Dubinsky J. M., Kristal B. S., Elizondo-Fournier M., et al. An obligate role for oxygen in the early stages of glutamate-induced, delayed neuronal death. J. Neurosci., 1995, 15: 7071~7078.
[126] Porter N.A., Caldwell S.E., Mills K.A. Mechanisms of free radical oxidation of unsaturated lipids. Lipids, 1995, 30: 277~290.
[127] Ikeda Y., Long D.M. The molecular basis of brain injury and brain edema the role of oxygen free radicals. Neurosurgery, 1990, 27 (1): 1~11.
[128] Takei N., EndoY. Ca~(2+) ionophore-induced apoptosis on cultured embryonicratcorticalneurons. Brain Res,1994, 652 (1): 65~70
[129] Chueh S.C., Lai M.K., Lee M.S., et al. Decrease of free radical level in organ perfusate by a novel water-soluble carbon-sixty, hexa(sulfobutyl)fullerenes. Transplantation Proceedings, 1999, 31: 1976~1977.
[130] Xiao L., Takada H., Maeda K., et al. Antioxidant effects of water-soluble fullerene derivatives against ultraviolet ray or peroxylipid through their action of scavenging the reactive oxygen species in human skin keratinocytes. Biomedicine & Pharmacotherapy. 2005, 59: 351~358.
[131] Lin A.M.Y., Chyi B.Y., Wang S.D., et al. Carboxyfullerene Prevents Iron-InducedOxidative Stress in Rat Brain. J. Neurochem., 1999, 72: 1634~1640.
[132] Bisaglia M., Natalini B., Pellicciari R., et al. C_3-Fullero-tris-Methanodicarboxylic Acid Protects Cerebellar Granule Cells from Apoptosis. J. Neurochem., 2000, 74: 1197~1204.
[133] (a)Dugan L. L., Turetsky D. M., Du C., et al. Proc. Natl. Acad. Sci. USA 1997, 94, 9434. (b) Dugan L.L., Gabrielsen J.K., Yu S.P., et al. Buckminsterfullerenol Free Radical Scavengers Reduce Excitotoxic and Apoptotic Death of Cultured Cortical Neurons. Neurobiology of Disease, 1996, 3:129~135.
[134] Lai H-Sh., ChenW-J., Chiang L-Y. Free Radical Scavenging Activity of Fullerenol on the Ischemia-reperfusion Intestine in Dogs. World J. Surg., 2000, 24: 450~454.
[135] (a) Chi Y., Bhonsle J. B., Canteenwala. T ., et al. Novel Water-soluble Hexa(sulfobutyl)fullerenes as Potent Free Radical Scavengers. Chem Lett. 1998, 465~466. (b) Lee Y. T., Chiang L. Y., Chen W. J., et al. PSEBM, 2000, 224, 69.
[136] Huang S.S., Tsai S.K., Chih C.L., et al. Neuroprotective effect of hexasulfobutylated C_(60) on rats subjected to focal cerebral ischemia. Free Radic. Biol. Med., 2001, 30: 643~649.
[137] Chien Ch.T., Chen Ch-F., Hsu Su-M., et al. Fuller.Sci.Tech., 2001, 9(1): 77.
[138] (a) Krusic P.J., Wasserman E., Ketzer P.N., et al. Radical Reactions of C_(60). Science 1991, 254, 1183~1185. (b) McEwen C.N., McKay R.G., Larsen B. S. C_(60) as a radical sponge. J. Am. Chem. Soc., 1992, 114, 4412~4414. (c) Morton J. R., Negri F., PrestonK. F. Addition of Free Radicals to C_(60). Acc. Chem. Res., 1998, 31: 63~69.
[139] (a) Sies H., Masumoto H. Adv. Pharmacol. 1997, 38: 229. (b) Ren X.J., Yang L., Liu J., et al. A Novel Glutathione Peroxidase Mimic with Antioxidant Activity. Arch. Physiol. Biochem., 2001,387(2): 250~256.
[140] Li Y, Cao Z. The neuroprotectant ebselen inhibits oxidative DNA damage induced by dopamine in the presence of copper ions. Neurosci. Lett., 2002 , 330 (1): 69~73.
[141] Imai H., Graham D.I., Masayasu H ., et al. Antioxidant ebselen reduces oxidative damage in focal cerebral ischemia . Free Radic. Biol. Med., 2003, 34 (1) : 56~63.
[142] Porciuncula L. O., Rocha J.B., Boeck C. R ., et al. Ebselen prevents excitotoxicity provoked by glutamate in rat cerebellar granule neurons . Neurosci. Lett., 2001, 299 (3):217~220.
[143] Farina M., Dahm K.C.S., Schwalm F.D., et al. Methylmercury Increases Glutamate Release from Brain Synaptosomes and Glutamate Uptake by Cortical Slices from Suckling Rat Pups: Modulatory Effect of Ebselen . Toxicol. Sci., 2003, 73:135~140.
[144] Cabrera J., Reiter R.J., Tan D.X ., et al. Melatonin reduces oxidative neurotoxicity due to quinolinic acid : in vitro and in vivo findings. Neuropharmacology, 2000, 39 (3) : 507~514.
[145] Rossato J. I., Zeni G., Mello C.F., et al. Ebselen blocks the quinolinic acid induced production of thiobarbituric acid reactive species but does not prevent the behavioral alterations produced by intrastriatal quinolinic acid administration in the rat. Neurosci. Lett., 2002 , 318 (3):137~140.
[146] Burger M.E., Alves A., Callegari L., et al. Ebselen attenuates reserpine induced orofacial dyskinesia and oxidative stress in rat striatum. Prog. Neuropsychopharmacol Biol. Psychiatry., 2003, 27 (1) :135~140.
[147] Kalayci M., Coskun O., Cagavi F., et al. Neuroprotective Effects of Ebselen on Experimental Spinal Cord Injury in Rats. Neurochem. Res., 2005, 30 (3): 403~410.
[148] Perottoni J., Flavia C.M., Folmer V., et al. Ebselen and diphenyl diselenide do not change the inhibitory effect of lead acetate on delta-aminolevulinate dehidratase. Environ.Toxicol. Pharmacol., 2005, 19: 239~248.
[149] Wende1 A. Glutathione peroxidase. Methods Enzymol., 198l, 77: 325~333.
[150] Lown J. W., Joshua A.V., McLaughlin L.W.. Novel antitumor nitrosoureas and related compounds and their reactions with DNA. J. Med. Chem. 1980, 23: 798~805.
[151] Schewe T. Molecular actions of Ebselen—an antiinflammatory antioxidant. Gen. Pharmac., 1995, 26:1153~1169.
[152] Adems R., Press J., Deegan E. Synthetic Communications, 1991, 21: 675.
[153] Hawker C. J., Saville P. M., White J. W. The Synthesis and Characterization of a Self-Assembling Amphiphilic Fullerene. J. Org. Chem., 1994, 59: 3503~3505.
[154] Diederich F., Isaacs L., Philp D. Syntheses, structures, and properties of methanofullerenes. Chem. Soc. Rev., 1994, 243~255.
[155] IsaacsL., Wehrsig A., Diederich F. Improved Purification of C_(60) and Formation of- and -Homoaromatic methano-bridged fullerenes by reaction with alkyl diazoacetates. Helv. Chim. Acta., 1993, 76: 1231~1250.
[156]胡惟孝.有机化合物制备手册.第1版.天津:天津科技翻译公司, 1995, 431~435.
[157] Osajda M., M?ochowski J. The reactions of 2-(chloroseleno)benzoyl chloride with nucleophiles. Tetrahedron, 2002, 58: 7531~7537.
[158] (a) Schena M., Shalon D., Dais R.W. Quantitative Monitoring of Gene Expression Patterns with a Complementary DNA Microarray. Science, 1995, 270 (20): 467~470. (b)聂荣庆,李扣华,胡国柱.黄芪抗新生大鼠大脑皮层神经细胞缺氧性凋亡研究.中国中医基础医学杂志, 2004, 10(11): 34~37.
[159] Alley M.C., Scudieco A., Monks M.L., et al. Cancer Res., 1988, 48: 589.
[160] Behl C., Davis J.B., Lesley R., et al. Hydrogen peroxide mediates amyloidβprotein toxicity. Cell, 1994, 77: 817~827.
[161] (a)赵善正.临床生化检验.上海:上海科学技术出版社,1979. 314~319. (b) Hartnett K.A., Stout A.K., Rajdev S., et al. Neurochem., 1997, 68: 1836.
[162] Wilson S.R., Sucker P. A., Hung R.C. , et al. Development of synthetic compounds with glutathione peroxidase activity. J. Am. Chem. Soc. 1989, 111: 5936~5939.
[163] Okuda K., Mashino T., Hirobe M. Superoxide radical quenching and cytochrome C peroxidase-like activity of C_(60)-dimalonic acid, C_(62)(COOH)_4. Bioorg. Med. Chem. Lett., 1996, 6 (5): 539~542.
[2] Banks M. R, Cadogan J. I, Gosney I. Aziridino[2’,3’:1,2]fullerene. J. Chem. Commun., 1994, 11: 1365~1366.
[3] Averdung J, Mattay J. Exohedral Functionalization of [60]Fullerene by [3+2] Cycloadditions: Synthesis and Chemical Properties of Triazolino-[60]fullerenes. Tetrachedron, 1996, 52 (15): 5407~5420.
[4] Tsuda M, Ishida T, Nogami T, et al. C_(61)Cl_2 Synthesis and Characterization of Dichlorocarbene Adducts of C_(60). Tetrahedron Lett., 1993, 34: 6911~6912.
[5] Benito A B, Darwish A D, Kroto H W, et al. Synthesis and Characterization of tre Methanofullerenes, C_(60) (CHCN) and C_(60) (CBr_2). Tetrahedron Lett., 1996, 37: 1085~1086.
[6] Isaacs L, Diederich F. Structures and Chemistry Methanofullerenes: A Versatile Route into N-[(Methanofullerene)carbonyl]–Substituted Amino Acids. Helv. Chim. Acta., 1993, 76: 2454~2464.
[7] Vaseiia A, Uhlmann P, Diederich F. Fullerene Sugar: Preparation of Spiro-Linked C-Glycosides of C_(60). Angew.Chem., Int. Ed. Engl., 1992, 31: 1388~1390.
[8] Tokuyama H, Nakamura M, Nakamura E, Tetrahedron Lett., 1997, 34: 6911.
[9] Shu L H, Wang G W, Wu S H., et al. Reaction of [60]fullerene with 1-(4-methoxyphenyl)-1-(trimethylsilyloxy)ethylene. J. Chem. Soc., Chem.Commun.., 1995, 367~368.
[10] (a) Wang Y, Cao J, Schuster D I, et al. A Superior Synthesis of [6,6]- Methanofullerenes: the Reaction of Sulfonium Ylides with C_(60) . Tetrahedron Lett., 1995, 36: 6843~6846 . (b) Hirsch A. Synthesis, 1995, 8: 895 . (c) Hamada M, Hino T, Kinbara K, et al. Synthesis and transformation of a novel methano[60]fullerene having a formyl group. Tetrahedron Lett., 2001, 42: 5069~5071.
[11] Nierengarten F J, Habicher T, Kessinger R, et al. Macrocyclization on the FullereneCore: Synthesis of Fullerene–dendrimer Dervatives. Helv. Chim. Acta, 1997, 80: 2238~2276.
[12] Nierengarten J F, Gramlich V, Cardullo F, et al. Angew. Chem., Int. Ed. Engl. 1996, 35, 2242.
[13] Camps X, Hirsch A. Efficient cyclopropanation of C_(60) starting from Malonates. J. Chem. Soc., Perkin Trans. 1, 1997, 1595~1596.
[14] Cheng F, Yang X, Zhu H, et al. Synthesis and optical properties of tetraethyl methano[60]fullerenediphosphonate . Tetrahedron Lett., 2000, 41, 3947~3950 .
[15] Zhou D, Tan H, Luo C, et al. Fullerene induced c-n bond breaking and formation: synthesis of fullerene pyrrolidine and methanofullerene sarcosine derivatives by photochemical addition of sarcosine ester to C_(60) . Tetrahedron Lett., 1995, 36, 9169~9172.
[16] (a) Gan L B, Jiang J F, Zhang W, et al. Synthesis of Pyrrolidine Ring-Fused Fullerene Multicarboxylates by Photoreaction. J. Org. Chem., 1998 , 63 (13): 4240~4247. (b ) Gan L B, Zhou D, Luo C, Tan H, et al. Synthesis of Fullerene Amino Acid Derivatives by Direct Interaction of Amino Acid Ester with C_(60). J. Org. Chem., 1996, 61(6): 1954~1961. [17 ] Maggini M, Scorrano G. Addition of Azomethine Ylides to CM: Synthesis, Characterization, and Functionalization of Fullerene Pyrrolidines. J. Am. Chem. Soc., 1993, 115: 9798~9799.
[18] (a) Laborde E. 3-Arylpyrrolidines via azomethine ylide 1,3-dipolar cycloaddition to styrenes . Tetrahedron Lett., 1992, 6607~6610. (b ) Wu S-H, Sun W-Q, Zhang D-W., et al. 1,3-Dipolar cycloaddition of several azomethine ylides to [60]fullerene: synthesis of derivatives of 2 ,5 -dihydro-1 H-pyrrolo[3 ,4 : 1,2][60]fullerene. J. Chem. Soc., Perkin trans.1, 1998,1733~1738 .
[19] (a) Bernstein R, Foote C S. Singlet Oxygen Involvement in the Photochemical Reaction of C_(60) and Amines. Synthesis of an Alkyne-Containing Fullerene. J. Phys. Chem. A, 1999, 103, 7244~7247. (b) Takcda K, Kajii Y, Shibuya K, J. Photochem. and Photobiol. A: Chem., 1995, 92: 69~72.
[20] Seshadri R, Govindaraj A, Nagarajan R, Addition of amines and halogens to fullerenes C_(60) and C70. Tetrahedron Lett., 1992, 33 (15): 2069~2070.
[21] Gan L B, Luo C P, Xu L B, et al. Water-Soluble Fullerene Derivatives,Synthesis andCharacterization ofβ一alanine C_(60) adducts. Chinese Chem. Lett., 1994, 5: 275~278.
[22]孙涛,徐铸德,贾之慎.功能化基团对C60-β一丙氨酸衍生物清除超氧阴离子自由基能力的影响.高等学校化学学报, 2003, 24(7): 1231~1233.
[23] Peng H, Lam J. W. Y., Leug F. S. M., et al. Synthesis of Fullerene-Containing Sol-Gel Glasses. Journal of Sol-gel Science and Technology, 2001, 22: 205~218.
[24] Davey S.N., Leigh D.A., Moody A.E. C_(60)–Azacrown Ethers: the First Monoaminated Fullerene Derivatives J. Chem. Soc.,Chem.Commun.1994, 397~398.
[25] Hirsch A., Wudl Q. L I F. Globe-trotting Hydrogens on the Surface of the Fullerene Compound C_(60)H_6(N(CH_2CH_2)_2O)_6. Angew. Chem., Int. Ed. Engl., 1991, 30: 1309~1310.
[26] Vaknin D., Wang J.Y., Uphous R.A.. C_(60)-propylamine Adduct Monolayers at the Air-Water. Interface. Langmir, 1995, 11: 1435~1438.
[27] Schick G., Kampe K.D., Hirsch A. Reaction of [60]fullerene with morpholine and piperidine: preferred 1,4-additions and fullerene dimer formation. J. Chem. Soc., Chem. Commun., 1995, 2023~2024.
[28] Beiik P, Gugel A. Spickermann J, et al. Reaction of Buckminsterfullerene with ortho-Quinodimethane: a New Access to Stable C_(60) Derivatives. Angew. Chem. Int. Ed. Engl.,1993, 32: 78~80.
[29] (a) Boulle C, Cariou M., Bainville A., et al. [4+2] Cycloaddition of C_(60) to -(thi)oxo-4,5-bis(methylene)-1,3-dithioles : en Route to the bis-Linking of Tetrathiafulvalene to C_(60) Tetrahedron Lett.,1997, 8: 8l~84. (b) Llacay J, Mas M., Molins E., et al. The first Diels–Alder adduct of [60]fullerene with a tetrathiafulvalene. Chem.Commun,1997, 659~660. (c) Ferndndez P, Martin N. Thermal and Microwave-Assisted Synthesis of Diels-Alder Adducts of [60]Fullerene with 2,3-Pyrazinoquinodimethanes: Characterization and Electrochemical Properties. J.Org.Chem., 1997, 62:3705~3710.
[30] Ohno M, Azuma T, Eguchi S., et al. Buckminsterfullerene C_(60)– o-Quinone Methide Cycloadduct. Chem. Lett.,1993: 1833~1834.
[31] Taki M, Nakamura Y, Kasashima E., et al. Selective Functionalization on [60]Fullerene Governed by Tether Length. J. Am. Chem. Soc., 1997, 119: 926~932.
[32] (a) Lang F, Cruz P, Espildora E., et al. Fullerene chemistry under microwaveirradiation. Carbon, 2000,38:1641~1646. (b) Pilar C, Angle D O., García J. J., et al. Synthesis of new C_(60)---donor dyads by reaction of pyrazolylhydrazones with [60]fullerene under microwave irradiation. Tetrahedron Lett,1999, 40: 1587~1590. (c) Cruz P, Hoz A. Synthetic Metals, 1997, 86: 2283~2284. (d) Cruz P, Hoz A., Langa F., et al. Cycloadditions to [60]fullerene using microwave irradiation: A convenient and expeditious procedure . Tetrahedron,1996,52:2599~2608. (e) Illescas B, Martín N, Seoane C, et al. A Facile Formation of Electroactive Fullerene Adducts from Sultines via a Diels-Alder Reaction. Tetrahedron Lett., 1995, 36: 8307~8310.
[33] Lerestif J M, Bazureau J P, Hamelin J. Cycloaddition with stabilized imidates as potential azomethines ylides : A new route to 2-imidazoline and 4-yliden-s-imidazolinone. Tetrahedron Lett., 1993, 34: 4639~4642.
[34] Pierre L, Yhou Z, Echegoyen L. A new route for the selective synthesis of [6,6]-methanofullerenes.Electrosynthesis of C61HCMe3 and C61HCN. Chem.Commun., 1996: 1547~1548.
[35] Bingel C. Cyclopropanierung von Fullerenen. Chem. Ber., 1993, 126: 1957~1959.
[36] Moonen N, Thilgen C, Diedeich F., et al. The chemical retro-Bingel reaction: selective removal of bis(alkoxycarbonyl)methano addends from C_(60) and C70 with amalgamated magnesium. Chem.Commun., 2000, 335~336.
[37] Fender N. S., Nuber B., Schuster D. I., et al. Preparation of [60]fullerene tris-malonate adducts by addend removal from higher adducts via the electrochemical retro-Bingel reaction. J. Chem. Soc., Perkin Trans. 2, 2000, 1924~1928.
[38] Kamat J.P., Devasagayam T. P. A., Priyadarsini K. I., et al. Oxidative damage induced by the fullerene C_(60) on photosensitization in rat liver microsomes . Chem. Biol. Interact., 1998, 114: 145~159.
[39] Arbogast J. W., Foote C. S., Kao M. Electron transfer to triplet fullerene C_(60). J. Am. Chem. Soc., 1992, 114: 2277~2279.
[40]方渊清,蔡瑞芳.富勒烯[60]的光化学反应研究.化学通报, 2000, 5:25~33.
[41] Akasaka T., Maeda Y., Wakahara T., et al. A First Photochemical Bis-germylation of C_(60) with Digermirane . Org. Lett., 2000, 2(17): 2671~2674.
[42] Wang G. W., Komatsu K., Murata Y., et al. Synthesis and X-ray structure ofdumb-bell-shaped C_(120) , Nature, 1997, 387:583~586.
[43] Murata Y., Kato N., Fujiwara K., et al. Solid-State [4 + 2] Cycloaddition of Fullerene C_(60) with Condensed Aromatics Using a High-Speed Vibration Milling Technique. J. Org. Chem., 1996, 64: 3483~3488.
[44] Koichi F., Noriyuki K. Syn.Commun., 1999,29 (24):4397~4402.
[45] Dugan L.L., Turetsky D.M., Wheeler M. Proc. Natl. Acad. Sci. U.S.A.,1997, 94:9434.
[46] Hsu S.C., Wu C.C., Luh T.Y., et al. Apoptotic Signal of Fas Is Not Mediated by Ceramide. Blood, 1998, 91:2658~2663.
[47] Huang Y.L., Shen C.K., Luh T.Y., et al. Blockage of apoptotic signaling of transforming growth factor-βin human hepatoma cells by carboxyfullerene. Eur. J. Biochem., 1998, 254: 38~43.
[48] Da Ros T., Prato M., NovelloF., et al. Easy Access to Water-Soluble Fullerene Derivatives via 1,3-Dipolar Cycloadditions of Azomethine Ylides to C_(60). J.Org. Chem. ,1996, 61: 9070~9072.
[49] Bosi S., Da Ros T., Castellano S., et al. Antimycobacterial activity of ionic fullerene derivatives. Bioorg. Med. Chem. Lett., 2000, 10: 1043~1045.
[50] Takcnaka S., Yamashita K., Takagi M., et al. Photo-induced DNA Cleavage by Water-soluble Cationic Fullerene Derivatives. Chem. Lett., 1999, 321~322.
[51] Yang X.L., Fan C.H., Zhu H.S. Photo-induced cytotoxicity of malonic acid [C60]fullerene derivatives and its mechanism . Toxicology in Vitro, 2002,16: 41~46.
[52] Friedman S H, DeCamp D L, Sijbesma R P, et a1. Inhibition of the HIV-1 protease by fullerene derivatives: model building studies and experimental verification. J. Am. Chem. Soc., 1993, 115: 6506~6509.
[53] Ueng T.H., Kang J.J., Wang H.W.,et al. Suppression of microsomal cytochrome P450-dependent monooxygenases and mitochondrial oxidative phosphorylation by fullerenol, a polyhydroxylated fullerene C_(60) . Toxicol. Lett., 1997, 93: 29~37.
[54] Lin Y.-L., Lei H.-Y., Wen Y.-Y., et al. Light-Independent Inactivation of Dengue-2 Virus by Carboxyfullerene C3 Isomer . Virology, 2000, 275: 258~262.
[55] Tsai M.C., Chen Y.H., Chiang L.Y. J. Pharm. Pharmacol., 1997, 49:438~445.
[56] Huang S.S., Tsai S.K., Chih C.L., et al. Neuroprotective effect of hexasulfobutylatedC60 on rats subjected to focal cerebral ischemia. Free Radic. Biol. Med., 2001, 30: 643~649.
[57] Lin A.M.-Y., Fang S.-F., Lin Sh.Z., et al. Neuroscience Research, 2002, 43: 317~321.
[58] Dugan L.L., Lovett E.G., Quick K.L., et al. Fullerene-based antioxidants and neurodegenerative disorders. Parkinsonism and Related Disorders, 2001, 7: 243~246.
[59] Chiang L.Y., Lu F.J., Lin J.T., Free radical scavenging activity of water-soluble fullerenols. J.Chem.Soc.,Chem.Commun., 1995, 1283~1284.
[60]祝严师,孙大勇,刘桂珍, et al.富勒醇清除·OH~ˉ自由基的ESR研究.高等学校化学学报, 1996, 17(7):1127~1129.
[61] Cheng F., Yang X., Zhu H., et al. Synthesis of oligoadducts of malonic acid C_(60) and their scavenging effects on hydroxyl radical. J. Phys. Chem. Solids, 2000, 61: 1145~1148.
[62] Okuda K., Mashino T., Hirobe M. Superoxide radical quenching and cytochrome C peroxidase-like activity of C_(60)-dimalonic acid, C_(62)(COOH)_4 . Bioorg. Med. Chem. Lett., 1996, 6 (5): 539~542.
[63] Sun T., Xu. Zh. Radical scavenging activities ofα-alanine C_(60) adduct . Bioorg. Med. Chem. Lett., 2006, 16 : 3731~3734.
[64] Guldi D.M., Asmus K.-D. Activity of water-soluble fullerenes towards OH-radicals and molecular oxygen. Radiation Physics and Chemistry, 1999, 56: 449~456.
[65]Guo L.W., Gao X., Zhang D.W., et al. Easy Access to [60]Fulleroalkaloids via Photoinduced Reactions of Tertiary Amines with [60]Fullerene. Chem. Lett., 1999, 5: 411~413.
[66] (a) Janis R. A., Silver P. J., Triggle D. J. Adv. Drug Res., 1987, 16: 309~91. (b) Bossert F., Vater W., Med. Res. Rev., 1989, 9:291~324.
[67] Illescas B., Martinez-Grau M. A.,Torres M. L., et al. Synthesis of new C_(60) derivatives containing biologically active 4-aryl-1,4-dihydropyridines . Tetrahedron Lett., 2002, 43: 4133~4136
[68] Yashiro A., Nishida Y., Ohno M., et al. Fullerene glycoconjugates: A general synthetic approach via cycloaddition of per-O-acetyl glycosyl azides to [60]fullerene . Tetrahedron Lett., 1998, 39: 9031~9034.
[69] Wilson S.R., Lu Q., Cao L. Proc. Electrochem. Soc ., 1995,95-10,1179.
[70] Sofou P., Elemes Y., Panou-Pomonis E., et al. Synthesis of a proline-rich
[60]fullerene peptide with potential biological activity. Tetrahedron, 2004, 60: 2823~2828
[71] Boutorine A. S., Tokuyama H., Takasugi M., , et al. Fullerene-Oligonucleotide Conjugates: Photoinduced Sequence-Specific DNA Cleavage. Angew. Chem. Int. Ed. Engl., 1994, 33: 2462~2465.
[72] An Y.Z., Chen C-H.B., Anderson J.L., et al. Sequence-specific modification of guanosine in DNA by a C_(60)-linked deoxyoligonucleotide: Evidence for a non-singlet oxygen mechanism. Tetrahedron, 1996, 52 (14): 5179~5189.
[73] Chi Y., Bhonsle J.B. Canteenwala T ., et al. Novel Water-soluble Hexa(sulfobutyl)fullerenes as Potent Free Radical Scavengers. Chem. Lett., 1998, 465~466.
[74] Hirsch A., Lampartn J., Karfunkel H. R. Fullerene Chemistry in Three Dimensions: Isolation of Seven Regioisomeric Bisadducts and Chiral Trisadducts of C_(60) and Di(ethoxycarbonyl)methylene. Angew. Chem. Int. Ed. Engl, 1994, 33: 437~438.
[75] Chiang L.Y., Bhonsk J.B., wang L., et al. Efficient one-flask synthesis of water-soluble [60]fullerenols. Tetrahedron, 1996, 52: 4963~4972.
[76] (a) Yamago S., Tokuyama H., Nakamura E., et al. Chemical derivatization of organofullerenes through oxidation, reduction, and carbon-oxygen and carbon-carbon bond-forming reactions . J. Org. Chem., 1993, 58 (18): 4796~4798. (b) Tokuyama H., Yamago S., Nakamura E., et al. Photoinduced biochemical activity of fullerene carboxylic acid . J. Am. Chem. Soc., 1993, 115 (17): 7918~7919. (c) Sijbesma R., Srdanov G., Wudl F., et al. Synthesis of a fullerene derivative for the inhibition of HIV enzymes . J. Am. Chem. Soc., 1993, 115 (15): 6510~6512.
[77] (a)Richardson C. F., Schuster O.I., Wilson S.R. Synthesis and Characterization of Water-Soluble Amino Fullerene Derivatives. Org, Lett. 2000, 2: 1011~1014. (b) Murakami H., Shirakusa M., Sagara T ., et al. Synthesis, Aggregate Structure and Electrochemical Properties of a Water-Soluble Fullerene-Bearing Ammonium Amphiphile. Chem. Lett., 1999, 815~816.
[78] (a)Tamberli V., Tatiana K.R., Bosi S., et al. Synthetic approaches towards thepreparation of water-soluble fulleropyrrolidines. Carbon, 2000, 38: 1551~1555. (b) Hawker C.J., Saville P. M., White J. W. The Synthesis and Characterization of a Self-Assembling Amphiphilic Fullerene. J.Org. Chem ,1994, 59: 3503~3505.
[79] Polese A., Mondini S., Bianco A., et al. Solvent-Dependent Intramolecular Electron Transfer in a Peptide-Linked [Ru(bpy)3]2+-C60 Dyad. J. Am. Chem. Soc., 1999, 121(14): 3446~3452.
[80] (a)Fullerene Sci.Technol.,1997,5,989.(b)Photochem. Photobiol.1997,66: 301. (c) Sun Y. P., Liu B., Moton D. K. Preparation and characterization of a highly water-soluble pendant fullerene polymer. Chem. Commun. 1996, 2699~2700.
[81] Brettreich M., Hirsch A. A highly water-soluble dendro[60]fullerene. Tetrahedron Lett., 1998, 39 : 2731~2734.
[82] Wharton T., Kini V. U., Mortis R. A., et al. New non-ionic, highly water-soluble derivatives of C_(60) designed for biological compatibility . Tetrahedron Lett., 2001, 42: 5159~5162.
[83] (a) Yang J., Wang Y., Rassat A, et al. Synthesis of novel highly water-soluble 2:1 cyclodextrin/fullerene conjugates involving the secondary rim ofβ-cyclodextrin . Tetrahedron, 2004, 60: 12163~12168. (b) Samal S, Geckeler K. E. Cyclodextrin–fullerenes: a new class of water-soluble fullerenes.Chem. Commun. 2000, 1101~1102.
[84] Ikeda A., HatanoT., Kawaguchi M., et al. Water-soluble [60]fullerene–cationic homooxacalix[3]arene complex which is applicable to the photocleavage of DNA. Chem. Commun. 1999, 1403~1404.
[85]Yamakoshi Y.N., Yagama T., Fukuhara K. Solubilization of fullerenes into water with polyvinylpyrrolidone applicable to biological tests. J. Chem. Soc., Chem. Commun. 1994, 517~518.
[86] Farman D. Free Radical in Biology. New York: Academic Press, 1982. 255~258.
[87]赵葆路.氧自由基和天然抗氧化剂.北京:科学出版社, 1999. 7~10.
[88] Lin A. M-Y., Fang S.- F., Lin S. Z., et al. Local carboxyfullerene protects cortical infarction in rat brain. Neurosci. Res., 2002, 43: 317~321.
[89] Monti D., Moretti L., Salvioli S., et al. C_(60) Carboxyfullerene Exerts a ProtectiveActivity against Oxidative Stress-Induced Apoptosis in Human Peripheral Blood Mononuclear Cells. Biochem. Biophys. Res. Commun., 2000, 277: 711~717.
[90] Lai H.S., Chen Y., Chen W. J., et al. Free radical scavenging activity of fullerenol on grafts after small bowel transplantation in dogs. Transplant. Proc., 2000, 32:1272~1274.
[91] Stephens A.H.H., Green M.L.H. Adv. Inorg. Chem., 1997, 44: 1~5.
[92] (a) West R., Oka K., Takahashi H., et al. in Inorganic and Organometallic Polymers II. Washington, D.C.: American Chemical Society, 1994. Chapter 9. (b) Olah G.A., Bucsi I., Lambert C., et al. Polyarenefullerenes, C_(60)(H-Ar)n, obtained by acid-catalyzed fullerenation of aromatics. J. Am. Chem. Soc., 1991, 113: 9387~9388.
[93] Miller G. P., Millar J. M., Liang B., et al. The absence of globe-trotting hydrogen on the surfaces of aminated fullerenes: 3-D hydrogen bonding between aminated fullerenes and water revealed. J.Chem. Soc. Chem. Commun. 1993, 897~899.
[94]郭霭光,王振镒.邻苯三酚自氧化-化学发光法测定SOD活性.植物生理学通讯, 1989, 3: 54~57.
[95]陈季武,胡天喜.测定·0H产生与清除的化学发光体系.生物化学与生物物理进展, l992, l9:136~140.
[96] Mosmann T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J.Immuno. Methods, 1983, 65(1): 55~63.
[97] Wu Y.J., Li W.G., Zhang Z.M., et al. Antioxidative activity of 4-oxyand 4- hydroxy- nitroxides in tissues and eyethrocytes from rats. Acta Pharmacol Sin , 1997 ,18 :150.
[98]周林珠,杨祥良等.多糖抗氧化作用研究进展.中国生化药物杂志, 2002, 23(4): 210~212.
[99]马兰萍,刘在群,周波.绿茶多酚对自由基诱导的红细胞氧化性溶血的抑制作用.科学通报, 2000, 45(12): l271~1275.
[100] Nakamura E., Tokuyama H., Yamago S., et al. Biological Activity of Water-Soluble Fullerenes. Structural Dependence of DNA Cleavage, Cytotoxicity, and Enzyme Inhibitory Activities Including HIV-Protease Inhibitio. Bull. Chem. Soc. Jpn., 1996, 69: 2143~2151.
[101] (a) Okamura H., Miyazono K., Minoda M., et al. J. Polym. Sci. Part A: Pol. Chem., 2000, 38, 3578. (b)Brough P., Bonifazi D., Prato M. Self-organization of amphiphilic [60]fullerene derivatives in nanorod-like morphologies. Tetrahedron , 2006, 62:2110~2114.
[102] Guldi D.M., Hungerbuhler H., Asmus K.-D. Unusual redox behavior of a water soluble malonic acid derivative of C_(60): evidence for possible cluster formation. J. Phys. Chem., 1995, 99: 13487~13493.
[103] (a) Guldi D.M. Capped Fullerenes: Stabilization of Water-Soluble Fullerene Monomers As Studied by Flash Photolysis and Pulse Radiolysis. J. Phys. Chem. A., 1997, 101: 3895~3900. (b) Guldi D.M. Res. Chem.Intermed. 1997, 23: 653.
[104] (a)Song T., Daib S., Tamb K.C., et al. Aggregation behavior of two-arm fullerene-containing poly(ethylene oxide). Polymer 2003, 44: 2529~2536. (b) Brettreich M., Burghardt S., Bottcher C., et al. Globular Amphiphiles: Membrane-Forming Hexaadducts of C_(60). Angew. Chem. Int. Ed. 2000, 39: 1845~1848.
[105] KerckhoffsJ. M. C. A., Leeuwen F. W. B., Spek A. L., et al. Regulatory Strategies in the Complexation and Release of a Noncovalent Guest Trimer by a Self-Assembled Molecular Cage. Angew. Chem. Int. Ed., 2003, 42: 5717~5722.
[106] Guo X., Szoka F. C. Chemical Approaches to Triggerable Lipid Vesicles for Drug and Gene Delivery. Acc. Chem. Res., 2003, 36: 335~341.
[107] Eastoe J., Crooks E., Beeby A., et al. Structure and photophysics in C_(60)-micellar solutions. Chem.Phys.Lett., 1995, 245: 571~577.
[108] Samal S., Geckeler K. E. Unexpected solute aggregation in water on dilution. Chem.Commun., 2001, 2224~2225. (b) Burger C., Hao J., Ying Q., et al. Multilayer vesicles and vesicle clusters formed by the fullerene-based surfactant C_(60)(CH3)5K . J. Colloid. Interface. Sci., 2004, 275: 632~641.
[109] Langa F., Cruz P., Espíldora E., et al. Fullerene chemistry under microwave irradiation . Carbon, 2000, 38: 1641~1646.
[110] Cruz P., Hoz A., Font L. M., et al. Solvent-free phase transfer catalysis under microwaves in fullerene chemistry. A convenient preparation of N-alkylpyrrolidino[60]fullerenes. Tetrahedron Lett. 1998, 39: 6053~6056.
[111] Lamparth I., Hirsch A. Water-soluble malonic acid derivatives of C_(60) with a defined three-dimensional structure. J. Chem. Soc., Chem. Commun., 1994, 1727~1728.
[112]浙江大学,南京大学等.综合化学实验.第一版.北京:高等教育出版社, 2001年.94~97.
[113] Mashino T., Shimotohno K., Ikegami N., et al. Human immunodeficiency virus-reverse transcriptase inhibition and hepatitis C virus RNA-dependent RNA polymerase inhibition activities of fullerene derivatives. Bioorg. Med. Chem. Lett., 2005, 15: 1107~1109.
[114] (a) Da Ros T., Prato M., Novello F., et al. Easy Access to Water-Soluble Fullerene Derivatives via 1,3-Dipolar Cycloadditions of Azomethine Ylides to C_(60). J. Org. Chem. 1996, 61, 9070~9072. (b) Guldi D.M., Hungerbu1hler H., Asmus K-D. Radiolytic Reduction of a Water-Soluble Fullerene Cluster. J. Phys. Chem. A, 1997, 101: 1783~1786.
[115]左榘.激光光散射原理及其在高分子科学中的应用.第一版.郑州:河南科学技术出版社, 1994. 48~229.
[116]马兰萍,刘在群,周波.绿茶多酚对自由基诱导的红细胞氧化性溶血的抑制作用.科学通报, 2000, 45 (12): l271~1275.
[117] (a) Mattson M.P., Chan S.L. Dysregulation of cellular calcium homeostasis in Alzheimer's disease: bad genes and bad habits. J Mol. Neurosci., 2001, 17(2): 205~224. (b)Mattson M. P. Oxidative stress, perturbed calcium homeostasis, and immune dysfunction in Alzheimer's disease. J. Neurovirol., 2002, 8 (6): 539~550.
[118] (a) Cui J., Holmes E.H., Greene T.G., et al. Oxidative DNA damage precedes DNA fragmentation after experimental stroke in rat brain. FASEB J., 2000,14 (7): 955~967. (b)赵丹洋,吴伟康.氧化应激在脑缺血损伤中的作用机制.中国病理生理杂志, 2004, 20 (4): 679~682. (c) Stadtman, E.R. Protein oxidation and ageing. Science, 1992, 257: 1220~1224.
[119] Mahura I.S. Cerebral ischemia-hypoxia and biophysical mechanisms of neurodegeneration and neuroprotection effects. Fizio.l Zh., 2003, 49 (2): 7~12.
[120] (a)Aronowski J., Grotta J. C. Ca~(2+)/calmodulin-dependent protein kinase II in postsynaptic densities after reversible cerebral ischemia in rats. Brain Res.,1996, 709 (1):103~110. (b)Colomer J. M, Mao L., Rockman H. A., et al. Pressure Overload Selectively Up-Regulates Ca~(2+)/Calmodulin-Dependent Protein Kinase II in Vivo. Mol. Endocrinol., 2003, 17 (2):183~192.
[121] (a)LaFerla F.M. Calcium dyshomeostasis and intracellular signalling inAlzheimer'sdisease. Nat. Rev. Neurosci., 2002, 3(11): 862~872. (b) Palotas A., Kalman J., Palotas M., et al. Long-term exposition of cells to beta-amyloid results in decreased intracellular calcium concentration. Neurochem. Int., 2003, 42 (7): 543~547.
[122] (a)Nishizawa Y. Glutamate release and neuronal damage in ischemia. Life Sci, 2001, 69 (4):369~381. (b)Roy M., Sapolsky R. M. The exacerbation of hippocampal excitotoxicity by glucocorticoids is not mediated by apoptosis. Neuroendocrinology, 2003, 77(1): 24~31.
[123] Kuwako K., Nishimura I., Uetsuki T., et al. Activation of calpain in cultured neurons overexpressing Alzheimer amyloid precursor protein. Brain Res. Mol. Brain Res., 2002, 107 (2):166~175.
[124] Frantseva M. V., Carlen P.L., Perez V. J.L. Dynamics of intracellular calcium and free radical production during ischemia in pyramidal neurons. Free Radic. Biol. Med., 2001, 31 (10): 1216~1227.
[125] Dubinsky J. M., Kristal B. S., Elizondo-Fournier M., et al. An obligate role for oxygen in the early stages of glutamate-induced, delayed neuronal death. J. Neurosci., 1995, 15: 7071~7078.
[126] Porter N.A., Caldwell S.E., Mills K.A. Mechanisms of free radical oxidation of unsaturated lipids. Lipids, 1995, 30: 277~290.
[127] Ikeda Y., Long D.M. The molecular basis of brain injury and brain edema the role of oxygen free radicals. Neurosurgery, 1990, 27 (1): 1~11.
[128] Takei N., EndoY. Ca~(2+) ionophore-induced apoptosis on cultured embryonicratcorticalneurons. Brain Res,1994, 652 (1): 65~70
[129] Chueh S.C., Lai M.K., Lee M.S., et al. Decrease of free radical level in organ perfusate by a novel water-soluble carbon-sixty, hexa(sulfobutyl)fullerenes. Transplantation Proceedings, 1999, 31: 1976~1977.
[130] Xiao L., Takada H., Maeda K., et al. Antioxidant effects of water-soluble fullerene derivatives against ultraviolet ray or peroxylipid through their action of scavenging the reactive oxygen species in human skin keratinocytes. Biomedicine & Pharmacotherapy. 2005, 59: 351~358.
[131] Lin A.M.Y., Chyi B.Y., Wang S.D., et al. Carboxyfullerene Prevents Iron-InducedOxidative Stress in Rat Brain. J. Neurochem., 1999, 72: 1634~1640.
[132] Bisaglia M., Natalini B., Pellicciari R., et al. C_3-Fullero-tris-Methanodicarboxylic Acid Protects Cerebellar Granule Cells from Apoptosis. J. Neurochem., 2000, 74: 1197~1204.
[133] (a)Dugan L. L., Turetsky D. M., Du C., et al. Proc. Natl. Acad. Sci. USA 1997, 94, 9434. (b) Dugan L.L., Gabrielsen J.K., Yu S.P., et al. Buckminsterfullerenol Free Radical Scavengers Reduce Excitotoxic and Apoptotic Death of Cultured Cortical Neurons. Neurobiology of Disease, 1996, 3:129~135.
[134] Lai H-Sh., ChenW-J., Chiang L-Y. Free Radical Scavenging Activity of Fullerenol on the Ischemia-reperfusion Intestine in Dogs. World J. Surg., 2000, 24: 450~454.
[135] (a) Chi Y., Bhonsle J. B., Canteenwala. T ., et al. Novel Water-soluble Hexa(sulfobutyl)fullerenes as Potent Free Radical Scavengers. Chem Lett. 1998, 465~466. (b) Lee Y. T., Chiang L. Y., Chen W. J., et al. PSEBM, 2000, 224, 69.
[136] Huang S.S., Tsai S.K., Chih C.L., et al. Neuroprotective effect of hexasulfobutylated C_(60) on rats subjected to focal cerebral ischemia. Free Radic. Biol. Med., 2001, 30: 643~649.
[137] Chien Ch.T., Chen Ch-F., Hsu Su-M., et al. Fuller.Sci.Tech., 2001, 9(1): 77.
[138] (a) Krusic P.J., Wasserman E., Ketzer P.N., et al. Radical Reactions of C_(60). Science 1991, 254, 1183~1185. (b) McEwen C.N., McKay R.G., Larsen B. S. C_(60) as a radical sponge. J. Am. Chem. Soc., 1992, 114, 4412~4414. (c) Morton J. R., Negri F., PrestonK. F. Addition of Free Radicals to C_(60). Acc. Chem. Res., 1998, 31: 63~69.
[139] (a) Sies H., Masumoto H. Adv. Pharmacol. 1997, 38: 229. (b) Ren X.J., Yang L., Liu J., et al. A Novel Glutathione Peroxidase Mimic with Antioxidant Activity. Arch. Physiol. Biochem., 2001,387(2): 250~256.
[140] Li Y, Cao Z. The neuroprotectant ebselen inhibits oxidative DNA damage induced by dopamine in the presence of copper ions. Neurosci. Lett., 2002 , 330 (1): 69~73.
[141] Imai H., Graham D.I., Masayasu H ., et al. Antioxidant ebselen reduces oxidative damage in focal cerebral ischemia . Free Radic. Biol. Med., 2003, 34 (1) : 56~63.
[142] Porciuncula L. O., Rocha J.B., Boeck C. R ., et al. Ebselen prevents excitotoxicity provoked by glutamate in rat cerebellar granule neurons . Neurosci. Lett., 2001, 299 (3):217~220.
[143] Farina M., Dahm K.C.S., Schwalm F.D., et al. Methylmercury Increases Glutamate Release from Brain Synaptosomes and Glutamate Uptake by Cortical Slices from Suckling Rat Pups: Modulatory Effect of Ebselen . Toxicol. Sci., 2003, 73:135~140.
[144] Cabrera J., Reiter R.J., Tan D.X ., et al. Melatonin reduces oxidative neurotoxicity due to quinolinic acid : in vitro and in vivo findings. Neuropharmacology, 2000, 39 (3) : 507~514.
[145] Rossato J. I., Zeni G., Mello C.F., et al. Ebselen blocks the quinolinic acid induced production of thiobarbituric acid reactive species but does not prevent the behavioral alterations produced by intrastriatal quinolinic acid administration in the rat. Neurosci. Lett., 2002 , 318 (3):137~140.
[146] Burger M.E., Alves A., Callegari L., et al. Ebselen attenuates reserpine induced orofacial dyskinesia and oxidative stress in rat striatum. Prog. Neuropsychopharmacol Biol. Psychiatry., 2003, 27 (1) :135~140.
[147] Kalayci M., Coskun O., Cagavi F., et al. Neuroprotective Effects of Ebselen on Experimental Spinal Cord Injury in Rats. Neurochem. Res., 2005, 30 (3): 403~410.
[148] Perottoni J., Flavia C.M., Folmer V., et al. Ebselen and diphenyl diselenide do not change the inhibitory effect of lead acetate on delta-aminolevulinate dehidratase. Environ.Toxicol. Pharmacol., 2005, 19: 239~248.
[149] Wende1 A. Glutathione peroxidase. Methods Enzymol., 198l, 77: 325~333.
[150] Lown J. W., Joshua A.V., McLaughlin L.W.. Novel antitumor nitrosoureas and related compounds and their reactions with DNA. J. Med. Chem. 1980, 23: 798~805.
[151] Schewe T. Molecular actions of Ebselen—an antiinflammatory antioxidant. Gen. Pharmac., 1995, 26:1153~1169.
[152] Adems R., Press J., Deegan E. Synthetic Communications, 1991, 21: 675.
[153] Hawker C. J., Saville P. M., White J. W. The Synthesis and Characterization of a Self-Assembling Amphiphilic Fullerene. J. Org. Chem., 1994, 59: 3503~3505.
[154] Diederich F., Isaacs L., Philp D. Syntheses, structures, and properties of methanofullerenes. Chem. Soc. Rev., 1994, 243~255.
[155] IsaacsL., Wehrsig A., Diederich F. Improved Purification of C_(60) and Formation of- and -Homoaromatic methano-bridged fullerenes by reaction with alkyl diazoacetates. Helv. Chim. Acta., 1993, 76: 1231~1250.
[156]胡惟孝.有机化合物制备手册.第1版.天津:天津科技翻译公司, 1995, 431~435.
[157] Osajda M., M?ochowski J. The reactions of 2-(chloroseleno)benzoyl chloride with nucleophiles. Tetrahedron, 2002, 58: 7531~7537.
[158] (a) Schena M., Shalon D., Dais R.W. Quantitative Monitoring of Gene Expression Patterns with a Complementary DNA Microarray. Science, 1995, 270 (20): 467~470. (b)聂荣庆,李扣华,胡国柱.黄芪抗新生大鼠大脑皮层神经细胞缺氧性凋亡研究.中国中医基础医学杂志, 2004, 10(11): 34~37.
[159] Alley M.C., Scudieco A., Monks M.L., et al. Cancer Res., 1988, 48: 589.
[160] Behl C., Davis J.B., Lesley R., et al. Hydrogen peroxide mediates amyloidβprotein toxicity. Cell, 1994, 77: 817~827.
[161] (a)赵善正.临床生化检验.上海:上海科学技术出版社,1979. 314~319. (b) Hartnett K.A., Stout A.K., Rajdev S., et al. Neurochem., 1997, 68: 1836.
[162] Wilson S.R., Sucker P. A., Hung R.C. , et al. Development of synthetic compounds with glutathione peroxidase activity. J. Am. Chem. Soc. 1989, 111: 5936~5939.
[163] Okuda K., Mashino T., Hirobe M. Superoxide radical quenching and cytochrome C peroxidase-like activity of C_(60)-dimalonic acid, C_(62)(COOH)_4. Bioorg. Med. Chem. Lett., 1996, 6 (5): 539~542.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |