异咯嗪修饰富勒烯-聚丙烯酸的合成及其与DNA的相互作用

doi:10.7517/j.issn.1674-0475.2011.03.181

摘要/Abstract

摘要： 利用自由基聚合反应合成了聚丙烯酸修饰的富勒烯(C₆₀-PAA),进一步通过酯化反应将核黄素类似物6,7-二甲基-9-(2’-羟乙基)-异咯嗪(DHIX)与C₆₀-PAA共价连接,得到C₆₀-PAA-DHIX.利用傅立叶红外光谱(FT-IR)、核磁共振氢谱(¹HNMR)、紫外-可见吸收光谱(UV-Vis)、荧光光谱对产物的化学结构进行了表征.循环伏安法表明,C₆₀-PAA-DHIX中富勒烯基团的第一还原电位要高于DHIX基团的第一还原电位.ESR实验表明C₆₀-PAA-DHIX能与N,N-二甲基苯胺发生多步光诱导电子转移反应,即DHIX基团与N,N-二甲基苯胺发生光诱导电子转移生成DHIX负离子自由基(DHIX^-·),DHIX^-·能进一步将电子传递给富勒烯生成富勒烯负离子自由基.DNA熔解曲线、紫外-可见吸收光谱和荧光光谱结果表明,C₆₀-PAA-DHIX通过沟槽结合与CTDNA作用,而C₆₀-PAA与DNA的作用较弱.无氧条件下,C₆₀-PAA-DHIX具有比C₆₀-PAA更强的DNA光损伤能力.

关键词: 富勒烯聚合物, 异咯嗪, 光诱导电子转移, 沟槽结合, DNA光损伤

Abstract: Poly(acrylic acid) conjugated fullerene(C₆₀-PAA) is synthesized by free-radical polymerization.C₆₀-PAA is covalently linked with riboflavin analogue 6,7-Dimethyl-9-(2’-hydroxyethyl)-isoalloxazine through esterification reaction,affording C₆₀-PAA-DHIX.The products are characterized by Fourier transform infrared spectroscopy(FT-IR),proton nuclear magnetic resonance(¹HNMR),UV-visible absorption spectroscopy(UV-Vis),and fluorescence spectroscopy.Cyclic voltammetry results show that the first reduction potential of fullerene moiety is higher than that of DHIX moiety in C₆₀-PAA-DHIX.ESR results indicate that multi-step photoinduced electron-transfer processes may occur between C₆₀-PAA-DHIX and N,N-dimethyl aniline under irradiation.One-electron transfer from N,N-dimethyl aniline to excited-state DHIX induces the generation of DHIX^-· radical,followed by electron transfer from the DHIX^-· radical to C₆₀,forming the corresponding anion radical of C₆₀(C₆₀^-·).The results obtained from DNA melting experiments,UV-Vis absorption and fluorescence spectra suggest that C₆₀-PAA-DHIX could interact with CT DNA through groove binding mechanism.However,C₆₀-PAA can only weakly interact with DNA.C₆₀-PAA-DHIX exhibited stronger DNA photodamage ability on plasma DNA than C₆₀-PAA under anaerobic condition.

Key words: fullerene polymer, isoalloxazine, photoinduced electron transfer, groove binding, DNA photocleavage

中图分类号:

王中丽, 高云燕, 欧植泽, 郭创龙, 李海霞, 金和林. 异咯嗪修饰富勒烯-聚丙烯酸的合成及其与DNA的相互作用[J]. 影像科学与光化学, 2011, 29(3): 181-193.

WANG Zhong-li, GAO Yun-yan, OU Zhi-ze, GUO Chuang-long, LI Hai-xia, JIN He-lin. Synthesis of Isoalloxazine Modified C₆₀-polypropylene Acid and Its Interaction with DNA[J]. Imaging Science and Photochemistry, 2011, 29(3): 181-193.

参考文献

[1] Guldi D M,Illescas B M,Atienza C M,et al.Fullerene for organic electronics[J].Chem.Soc.Rev.,2009,40(37):1587-1597.
[2] Thompson B C,Frechet J M.Polymer-fullerene composite solar cells[J].J.Angew.Chem.Int.Edit.,2008,47(1):58-77.
[3] Nakamura E,Isobe H.Functionalized fullerenes in water.the first 10 years of their chemistry,biology,andnanoscience[J].Acc.Chem.Res.,2003,36(11):807-815.
[4] Ros T D,Prato M.Medicinal chemistry with fullerenes and fullerene derivatives[J].Chem.Commun.,1999,(8):663-669.
[5] Murthy C N,Geckeler K E.The water-soluble-βcyclodextrin-[60] fullerene complex[J].Chem.Commun.,2001,(13):1194-1195.
[6] 高云燕,刘丽华,欧植泽,等.胆固醇修饰富勒烯/β-环糊精包结复合物的生物活性[J].物理化学学报,2010,26(2):495-501.Gao Y,Liu L,Ou Z,et al.Biological activity of a cholesterol modified fullerene/-γcyclodextrin inclusion com-plex[J].Acta Phys.-Chim.Sin.,2010,26(2):495-501.
[7] Ikeda A,Hatano T,Kawaguchi M,et al.Water-soluble[60] fullerene?cationic homooxacalix[3] arene com-plex which is applicable to the photocleavage of DNA[J].Chem.Commun.,1999,(15):1403 1404.
[8] Spiotto M T,Banh A,Papandreou I,et al.Visualization of the unfolded protein response in primary tumors re-veals unique microenvironments that reflect metabolic variations and predict for tumor growth[J].Cancer Res.,2010,70(1):78-88.
[9] Seshadri M,Bellnier D A,Vaughan L A,et al.Light delivery over extended time periods enhances the effec-tiveness of photodynamic therapy[J].Clin.Cancer Res.,2008,14(9):2796-2805.
[10] Liu Y,Wang H,Liang P,et al.Water-soluble supramolecular fullerene assembly mediated by metallobridged-βcyclodextrins[J].Angew.Chem.,2004,116(20):2744-2748.
[11] Yamakoshi Y,Umezawa N,Ryu A,et al.Active oxygen species generated from photoexcited fullerene(C₆₀)as potential medicines:O^2-·versus¹O₂[J].J.Am.Chem.Soc.,2003,125(42):12803-12809.
[12] Yamakoshi Y N,Yagami T,Sueyoshi S,et al.Acridine adduct of[60] fullerene with enhanced DNA-cleavingactivity[J].J.Org.Chem.,1996,61(21):7236-7237.
[13] Gao Y,Ou Z,Yang G,et al.Efficient photocleavage of DNA utilizing water soluble riboflavin/naphthaleneac-etate substituted fullerene complex[J],J.Photochem.Photobiol.A:Chem.,2009,203(2-3):105-111.
[14] Kumar A,Rao M V,Menon S K.Photoinduced DNA cleavage by fullerene lysine conjugate[J].TetrahedronLett.,2009,50(47):6526-6530.
[15] Silva E,Edwards A M.Flavins-Photochemistry and Photobiology[M].Cambridge:Royal Society of Chemis-try,2006.
[16] Thomas T P,Choi S K,Li M H,et al.Design of riboflavin-presenting PAMAM dendrimers as a new nano-platform for cancer-targeted delivery[J].Bioorg.Med.Chem.,2010,20(17):5191-5194.
[17] Ou Z,Chen J,Wang X,et al.Synthesis of a water-soluble cyclodextrin modified hypocrellin and ESR study ofits photodynamic therapy properties[J].New J.Chem.,2002,26(9):1130 1136.
[18] Karlsson H J,Eriksson M,Perzon E,et al.Groove-binding unsymmetrical cyanine dyes for staining of DNA:syntheses and characterization of the DNA-binding[J].Nucleic.Acids.Res.,2003,31(21):6227-6234.
[19] Fall H H,Peterin H G.Metabolite inhibitors.i.6,7-dimethyl-9-formylmethylisoalloxazine,6,7-dimethyl-9-(2'-hydroxyethyl)-isoalloxazine and derivatives[J].J.Am.Chem.Soc.,1956,78(2):377-380.
[20] 姚威,吴宝燕,高丽华,等.一种含芴基的钌(II)配合物的合成及DNA键合性质[J].物理化学学报,2007,23(2):237-241.Yao W,Wu B Y,Gao L H,et al.DNA-binding properties of a fluorenyl-containing ru(ii)complex[J].ActaPhys.-Chim.Sin.,2007,23(2):237-241.
[21] Zeng Y,Montrichok A,Zocchi G.Bubble nucleation and cooperativity in DNA melting[J].J.Mol.Biol.,2004,339(1):67-75.
[22] Giacalone F,Martin N.Fullerene polymers:synthesis and properties[J].Chem.Rev.,2006,106(12):5136-5190.
[23] Li G,Glusac K D.Light-triggered proton and electron transfer in flavin cofactors[J].J.Phys.Chem.A.,2008,112(20):4573-4583.
[24] Mansoorabadi S O,Thibodeaux C J,Liu H.The diverse roles of flavin coenzymesnature's most versatile thes-pians[J].J.Org.Chem.,2007,72(17):6329-6342.
[25] 官文超,段标,余俊.富勒烯(C_60/70)-丙烯酸的自由基共聚[J].高等学校化学学报,1998,19(3):492-493.Guan W C,Duan B,Yu J.Free radical copolymerization of fullerenes(c_60/70)with acrylic acid[J].Chim.Jour.Chin.Univer.,1998,19(3):492-493.
[26] Wang Z Y,Kuang L,Meng,X S,et al.New route to incorporation of[60] fullerene into polymers via thebenzocyclobutenone group[J].Macromolecules,1998,31(16):5556 5558.
[27] Hermann D T,Schindler A C,Polborn K,et al.Synthesis,spectroscopy,and semiempirical study of a novelporphyrin flavin dyad[J].Chem.Eur.J.,1999,5(11):3208-3220.
[28] 袁钊,曾毅,陈金平,等.以尼罗红为探针对新型两亲性树枝形聚合物微环境的研究[J],影像科学与光化学,2010,28(5):343-353.Yuan Z,Zeng Y,Chen J P,et al.Investigation of the microenvironment of novel amphiphilic dendrimers withnile red as a probe[J].Imaging Science and Photochemistry,2010,28(5):343-353.
[29] Gao Y,Ou Z,Chen J,et al.Photodynamic properties of supramolecular assembly constructed by magnesiumcomplex of hypocrellin A and fullerene C₆₀[J].New J.Chem.,2008,32(9):1555-1560.
[30] Sun Y P,Bunker C E,Ma B.Quantitative studies of ground and excited state charge transfer complexes offullerenes with N,N-dimethylaniline and N,N-diethylaniline[J].J.Am.Chem.Soc.,1994,116(21):9692-9699.
[31] Kowalczyk R M,Schleicher E,Bittl R,et al.The photoinduced triplet of flavins and its protonation states[J].J.Am.Chem.Soc.,2004,126(36):11393-11399.
[32] Kumar C V,Turener R S,Asuncion E H.Groove binding of a styrylcyanine dye to the DNA double helix:thesalt effect[J].J.Photochem.Photobiol.A,1993,74(2):231-238.
[33] Hianik T,Wang X,Tashlitsky V,et al.Thompson M.Interaction of cationic surfactants with DNA detectedby spectroscopic and acoustic wave techniques[J].Analyst,2010,135(5):980-986.
[34] Rosa M,Dias R,Miguel M G,et al.DNA-cationic surfactant interactions are different for doubleand single-stranded DNA[J].Biomacromolecules,2005,6(4):2164-2171.
[35] Mikhailenko I,Shlyakhtenko L.A study of DNA melting in concentrated water-alcohol solutions[J].J.Bio-mol.Struct.Dyn.,1984,1(6):1501-1510.
[36] McFarland G D,Borer P N.Separation of oligo-RNA by reverse-phase HPLC[J].Nucleic Acids Res.,1979,7(6):1067-1080.
[37] Qiao C,Bi S,Sun Y,et al.Study of interactions of anthraquinones with DNA using ethidium bromide as a flu-orescence probe[J].Spectrochim.Acta,Part A,2008,70(1):136-143.
[38] Zhen Q X,Ye B H,Zhang Q L,et al.Synthesis,characterization and the effect of ligand planarity of[Ru(bpy)₂L]²⁺ on DNA binding affinity[J].J.Inorg.Biochem.,1999,76(1):47-53.