双吡啶单吡咯钌配合物与DNA的相互作用
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摘要
三联吡啶钌配合物和DNA相互作用已有大量报道,但基于类三联吡啶配体,如双吡啶吡咯,稳定的金属配合物和DNA作用却鲜见报道.利用荧光光谱、圆二色谱(CD)和紫外-可见光谱等表征手段,研究了4个已知的双吡啶吡咯钌配合物与DNA结合性质:[(PDP)Ru(COD)X],其中HPDP=2,5-bis(2’-pyridyl)pyrrolide,COD=1,5-环辛二烯,X=Cl~-(1), NO~-_3(2);[(PDP)Ru(COD)(H_2O)](BF_4)(3);[(PDP_(Cl))Ru(COD)Cl](HPDP_(Cl)=2,5-bis(2’-pyridyl)-3,4-dichloropyrrolide(4).发现化合物1以经典嵌插方式和DNA结合,2和3可能为部分或非经典嵌插结合DNA,4主要以静电相互作用结合DNA.此外,通过MTT法考察了配合物1～4对人宫颈癌Hela细胞的体外细胞毒性.
DNA interaction properties of ruthenium complexes with terpyridine ligand have been widely reported, while DNA binding activity of metal complexes based on terpyridine analogous ligand, such as bispyridylpyrrole HPDP(PDP-=2,5-bis(2'-pyridyl)pyrrolide) is seldom reported. In this paper, the DNA interaction properties of known ruthenium complexes [(PDP)Ru(COD)X](COD=1,5-cyclooctadiene, X=Cl~-(1), NO~-_3(2)), [(PDP)Ru(COD)(H_2O)](BF_4)(3) and [(PDP_(Cl))Ru(COD)Cl](HPDP_(Cl)=2,5-bis(2'-pyridyl)-3,4-dichloropyrrolid(4) were studied by the fluorescence, CD and UV-vis spectra. These are different binding mode between 1-4 and ct-DNA. Intercalation and electrostatic binding mode was observed in complex 1 and 4, respectively, and complexes 2 and 3 interacted with ct-DNA probably via a non-classical intercalation. The antitumor activities in vitro of 1-4 against the human ovarian cancer cell line Hela were also evaluated by the MTT assay.
DNA interaction properties of ruthenium complexes with terpyridine ligand have been widely reported, while DNA binding activity of metal complexes based on terpyridine analogous ligand, such as bispyridylpyrrole HPDP(PDP-=2,5-bis(2'-pyridyl)pyrrolide) is seldom reported. In this paper, the DNA interaction properties of known ruthenium complexes [(PDP)Ru(COD)X](COD=1,5-cyclooctadiene, X=Cl~-(1), NO~-_3(2)), [(PDP)Ru(COD)(H_2O)](BF_4)(3) and [(PDP_(Cl))Ru(COD)Cl](HPDP_(Cl)=2,5-bis(2'-pyridyl)-3,4-dichloropyrrolid(4) were studied by the fluorescence, CD and UV-vis spectra. These are different binding mode between 1-4 and ct-DNA. Intercalation and electrostatic binding mode was observed in complex 1 and 4, respectively, and complexes 2 and 3 interacted with ct-DNA probably via a non-classical intercalation. The antitumor activities in vitro of 1-4 against the human ovarian cancer cell line Hela were also evaluated by the MTT assay.
引文
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[2] WANG X Y,GUO Z J.New strategies and trends for the design of metal-based anticancer drugs[J].Progress in Chemistry,2009,21(5):845-855.
[3] WANG J Q,ZHANG P Y,JI L N,et al.A ruthenium(II) complex inhibits tumor growth in vivo with fewer side-effects compared with cisplatin[J].Journal of Inorganic Biochemistry,2015,146:89-96.
[4] YANG J,CAO Q,HU W L,et al.Theranostic TEMPO-functionalized Ru(ii) complexes as photosensitizers and oxidative stress indicators[J].Dalton Transactions,2016,46(2):445-454.
[5] ZHANG D Y,ZHENG Y,ZHANG H,et al.Ruthenium complex-modified carbon nanodots for lysosome-targeted one-and two-photon imaging and photodynamic therapy[J].Nanoscale,2017,9(47):18966-18976.
[6] ZHANG D Y,ZHENG Y,TAN C P,et al.Graphene oxide decorated with Ru(II)-polyethylene glycol complex for lysosome-targeted imaging and photodynamic/photothermal therapy[J].ACS Applied Materials & Interfaces,2017,9(8):6761-6771.
[7] DA SILVEIRA CARVALHO J M,DE MORAIS BATISTA A H,NOGUEIRA N A P,et al.A biphosphinic ruthenium complex with potent anti-bacterial and anti-cancer activity[J].New Journal of Chemistry,2017,41(21):■,et al.Light controllable TiO2-Ru nanocomposite system encapsulated in phospholipid unilamellar vesicles for anti-cancer photodynamic therapy[J].Optical and Quantum Electronics,2018,50(6):232-240.
[9] TAN L F,LIU J,SHEN J L,et al.First ruthenium(II) polypyridyl complex as a true molecular “light switch” for triplex RNA structure:[Ru(phen)2(mdpz)]2+ enhances the stability of poly(U)·poly(A)*poly(U)[J].Inorganic Chemistry,2012,51(8):4417-4419.
[10] BARTON J K,GOLDBERG J M,KUMAR C V,et al.Binding modes and base specificity of tris(phenanthroline)ruthenium(II) enantiomers with nucleic acids:tuning the stereoselectivity[J].Journal of American Chemical Society,1986,108(8):2081-2088.
[11] SONG H,KAISER J T,BARTON J K.Crystal structure of Δ-[Ru(bpy)2dppz]2+ bound to mismatched DNA reveals side-by-side metalloinsertion and intercalation[J].Nature Chemistry,2012,4(8):615-620.
[12] NIYAZI H,HALL J P,O’SULLIVAN K,et al.Crystal structures of Λ-[Ru(phen)2dppz]2+ with oligonucleotides containing TA/TA and AT/AT steps show two intercalation modes[J].Nature Chemistry,2012,4(8):621-628.
[13] GRUESO E,LóPEZ-PéREZ G,CASTELLANO M,et al.Thermodynamic and structural study of phenanthroline derivative ruthenium complex/DNA interactions:Probing partial intercalation and binding properties[J].Journal of Inorganic Biochemistry,2012,106(1):1-9.
[14] HARTSHORN R M,BARTON J K.Novel dipyridophenazine complexes of ruthenium(II):exploring luminescent reporters of DNA[J].Journal of Amercian Chemical Society,1992,114(15):5919-5925.
[15] WU L,REYMER A,PERSSON C,et al.Initial DNA interactions of the binuclear threading intercalator Λ,Λ-[μ-bidppz(bipy)4Ru2]4+:An NMR study with [d(CGCGAATTCGCG)]2[J].Chemistry-A European Journal,2013,19(17):5401-5410.
[16] ZHONG Y Q,XIAO H Q,YI X Y.Synthesis,structural characterization and catalysis of ruthenium(ii) complexes based on 2,5-bis(2’-pyridyl)pyrrole ligand [J].Dalton Transactions,2016,45(45):18113-18119.
[17] ALVAREZ N,VEIGA N,IGLESIAS S,et al.Synthesis,structural characterization and DNA interaction of new copper-terpyridine complexes[J].Polyhedron,2014,68(2014):295-302.
[18] BARONE G,GENNARO G,GIULIANI A M,et al.Interaction of Cd(ii) and Ni(ii) terpyridine complexes with model polynucleotides:a multidisciplinary approach[J].RSC Advances,2016,6(6):4936-4945.
[19] NOVALES J,JONKHOFF N,ACQUAYE J H.Synthesis,characterization and X-ray crystal structures of ruthenium polypyridyl and 2-(2’-hydroxyphenyl)-benzoxazole complexes:Reactivity with 1-methylimidazole,purine,glutathione and CT-DNA[J].Polyhedron,2013,62:148-157.
[20] MIN R,HU X H,YI X Y,et al.Synthesis,structure,DNA binding and cleavage activity of a new copper(II) complex of bispyridylpyrrole[J].Journal of Central South University,2015,22(5),1619-1625.
[21] MARMUR J.A procedure for the isolation of deoxyribonucleic acid from micro-organisms[J].Journal of Molecular Biology,1961,3(1):208-218.
[22] REICHMANN M E,RICE S A,THOMAS C A,et al.A further examination of the molecular weight and size of desoxypentose nucleic acid[J].Journal of American Chemical Society,1954,76(11):3047-3053.
[23] FRIEDMAN A E,CHAMBRON J C,SAUVAGE J P,et al.A molecular light switch for DNA:Ru(bpy)2(dppz)2+[J].Journal American Chemical Society,1990,112(12):4960-4962.