手性三菲咯啉合镍与DNA的立体选择性研究

有关 DNA与金属配合物反应机理和作用模式的探讨是生物无机化学研究的重要内容之一 .目前的研究 [1～ 4] 表明 ,有大共轭配体配位的八面体金属配合物以静电作用或插入方式与DNA结合 .外消旋 [Ni( phen) 3]2 +及其旋光异构体与 DNA作用机理的研究曾有报道 [4] .但用电化学方法研究其旋光异构体与 DNA作用则未见详细报道 .本文用电化学方法和 CD谱研究了 Δ- ,∧ - [Ni( phen) 3]2 +配合物与 DNA的作用 .两种方法所得结果均表明 Δ- ,∧ - [Ni( phen) 3]2 +与 DNA作用时 ,Δ构型配合物的插入作用比∧构型配合物的强 .该法与平衡透析…     

硫杂蒽酮类稀土配合物的合成、表征及与DNA的作用(Ⅰ)

合成了新的O-(硫杂蒽酮-[2]-基)-氧乙酸及其稀土配合物.通过元素分析,IR,1H NMR,UV,DTA-TG和13C NMR谱对其结构进行了表征.研究表明:配体羧羰基脱质子后与金属离子配位,2位氧原子也与金属离子配位,配合物中含有一定量的配位水,配合物为非电解质类型.同时,研究了O-(硫杂蒽酮-[2]-基)-氧乙酸稀土配合物对质粒DNA的切割作用.结果表明:铕的配合物对DNA的切割较明显,且当配合物浓度增加时,质粒DNA的超螺旋构型逐渐减少,而缺刻、开环型构型逐渐增多.在相同条件下,Eu(Ⅲ)离子对质粒pBR322DNA几乎没有切割作用;配体O-(硫杂蒽酮-[2]-基)-氧乙酸对质粒pBR322DNA也有切割作用,但配合物EuL3对质粒pBR322DNA的切割作用明显强于配体,表明稀土离子Eu(Ⅲ)与配体生成配合物后有较好的协同切割作用.     

硫杂蒽酮类稀土配合物的合成、表征及与DNA的作用(I)

合成了新的O-(硫杂蒽酮-[2]-基)-氧乙酸及其稀土配合物.通过元素分析,IR,1HNMR,UV,DTA-TG和13CNMR谱对其结构进行了表征.研究表明:配体羧羰基脱质子后与金属离子配位,2位氧原子也与金属离子配位,配合物中含有一定量的配位水,配合物为非电解质类型.同时,研究了O-(硫杂蒽酮-[2]-基)-氧乙酸稀土配合物对质粒DNA的切割作用.结果表明:铕的配合物对DNA的切割较明显,且当配合物浓度增加时,质粒DNA的超螺旋构型逐渐减少,而缺刻、开环型构型逐渐增多.在相同条件下,Eu(III)离子对质粒pBR322DNA几乎没有切割作用;配体O-(硫杂蒽酮-[2]-基)-氧乙酸对质粒pBR322DNA也有切割作用,但配合物EuL3对质粒pBR322DNA的切割作用明显强于配体,表明稀土离子Eu(III)与配体生成配合物后有较好的协同切割作用.     

钌（Ⅱ）多吡啶配合物的合成、荧光性质及与脱氧核糖核酸DNA的作用机制研究

设计合成含多个配位中心的多吡啶配体ODCIP(3,4-二氯基苯并咪唑并[4,5-f][1,10]邻菲咯啉)及其钌(Ⅱ)多吡啶配合物[Ru(bpy)2ODCIP]2 .运用元素分析、红外光谱、核磁谱和质谱对配体及配合物进行结构表征.利用紫外吸收光谱、荧光光谱和粘度法研究了[Ru(bpy)2ODCIP]2 与DNA(脱氧核糖核酸)的作用机制、与Co2 配位后与DNA的作用机制及其荧光变化情况.结果表明[Ru(bpy)2ODCIP]2 与DNA通过部分插入模式作用,[Ru(bpy)2ODCIP]2 与Co2 配位形成的双核配合物[Ru(bpy)2(ODCIP)Co]4 也能与DNA插入结合.进一步利用稳态荧光发射光谱、荧光淬灭实验等方法研究了单核配合物[Ru(bpy)2ODCIP]2 和双核配合物[Ru(bpy)2(ODCIP)Co]4 的荧光性质.     

钌(II)多吡啶配合物的合成、荧光性质及与脱氧核糖核酸DNA的 作用机制研究

设计合成含多个配位中心的多吡啶配体ODCIP (3,4-二氯基苯并咪唑并[4,5-f][1,10]邻菲咯啉)及其钌(II)多吡啶配合物[Ru(bpy)2ODCIP]2＋. 运用元素分析、红外光谱、核磁谱和质谱对配体及配合物进行结构表征. 利用紫外吸收光谱、荧光光谱和粘度法研究了[Ru(bpy)2ODCIP]2＋与DNA(脱氧核糖核酸)的作用机制、与Co2＋配位后与DNA的作用机制及其荧光变化情况. 结果表明[Ru(bpy)2ODCIP]2＋与DNA通过部分插入模式作用, [Ru(bpy)2ODCIP]2＋与Co2＋配位形成的双核配合物[Ru(bpy)2(ODCIP)Co]4＋也能与DNA插入结合. 进一步利用稳态荧光发射光谱、荧光淬灭实验等方法研究了单核配合物[Ru(bpy)2ODCIP]2＋和双核配合物[Ru(bpy)2(ODCIP)Co]4＋的荧光性质.     

多吡啶钴(Ⅲ)配合物与Zn2+形成的新型“关-开”荧光探针

近十几年来,对小分子过渡金属配合物与大分子DNA键合与识别机理的研究一直是国际上生物无机化学领域十分活跃的研究课题[1￣3],已发展了一系列具有特定功能的配合物,如DNA结构探针和DNA荧光探针等。与其他类型的金属配合物相比,八面体过渡金属多吡啶配合物具有丰富的光化学和光物理信息,当这些配合物与DNA相互作用时,由于结构匹配或微环境的差异,配合物的光谱特征会出现不同程度的改变,从而达到对DNA的检测。传统的DNA荧光探针有[Ru(bpy)2dppz]2 和[Ru(phen)2dppz]2 (bpy=2,2′-联吡啶,phen=1,10-菲咯啉,dppz=二吡啶[3,2-a∶2′,3′…     

1,10-邻菲啰啉衍生物钌配合物的合成、 表征及与DNA和BSA的相互作用

通过2-(4-吡啶)-咪唑[4,5-f]-1,10-邻菲啰啉(L₁)与[Ru(η⁶-cymene)(μ-Cl)Cl]₂反应合成了3种新型芳基钌配合物, 并利用新配体2-(4-咪唑基苯基)咪唑[4,5-f]-1,10-邻菲啰啉(L₂)与RuCl₃反应合成了配合物4. 利用核磁共振波谱、 质谱等对配合物进行了表征. 通过紫外光谱和圆二色谱研究了配合物在缓冲溶液中的稳定性及与CT-DNA的相互作用, 利用荧光光谱研究了配合物与牛血清蛋白的作用, 用乌氏黏度计测试了配合物对DNA黏度的影响, 并通过荧光光谱、 凝胶电泳研究了配合物4在不同pH条件下的荧光响应及与pBR322 DNA的作用. 结果表明, 配合物通过嵌入的方式与DNA作用, 并对DNA的二级结构产生影响; 配合物1~4均可与牛血清蛋白的一个位点发生相互作用并使其发生静态荧光猝灭. 配合物4在光照条件下有活性氧生成, 可以使pBR322 DNA断裂并在酸性溶液中荧光增强.     

光谱法研究[Ce(NO_3)_3(Phen)_2]配合物晶体结构及其与DNA之间的相互作用

对配合物[Ce(NO3)3(Phen)2]的吸收光谱、荧光光谱和拉曼光谱进行了归属,研究了该配合物的晶体结构。同时,用光谱法研究了该配合物与DNA之间的相互作用。研究发现,DNA加入后,配合物的紫外吸收峰和表面增强拉曼峰明显降低,而荧光强度明显增强。配合物对EB与DNA作用有竞争。这些表明配合物与DNA有较强的相互作用,并且主要键合模式是插入作用。测得配合物与DNA的键合常数为1·7×105。     

三齿多吡啶钴(Ⅱ)配合物的合成、表征及其与DNA的相互作用研究

合成了两种三齿多吡啶钴(Ⅱ)配合物[Co(DMPhTPY)2]2+(ClO-4)2(A)和[Co(H2Bzimpy)2]Cl2(B),用元素分析、IR对配合物的组成和结构进行了表征,测定了配合物A的晶体结构.用电子吸收光谱、荧光光谱、循环伏安法及凝胶电泳实验等方法研究了配合物与DNA的相互作用.结果表明配合物A和B与小牛胸腺(CTDNA)的作用属部分插入和静电结合,凝胶电泳实验表明配合物A在310nm光辐射15min,可使超螺旋pBR322DNA断裂为开环缺口型和线型DNA.     

硫杂蒽酮类稀土配合物的合成、表征及与DNA的作用(I)

合成了新的O-(硫杂蒽酮-[2]-基)-氧乙酸及其稀土配合物. 通过元素分析, IR, ¹H NMR, UV, DTA-TG和¹³C NMR谱对其结构进行了表征. 研究表明: 配体羧羰基脱质子后与金属离子配位, 2位氧原子也与金属离子配位, 配合物中含有一定量的配位水, 配合物为非电解质类型. 同时, 研究了O-(硫杂蒽酮-[2]-基)-氧乙酸稀土配合物对质粒DNA的切割作用. 结果表明: 铕的配合物对DNA的切割较明显, 且当配合物浓度增加时, 质粒DNA的超螺旋构型逐渐减少, 而缺刻、开环型构型逐渐增多. 在相同条件下, Eu(III)离子对质粒pBR322DNA几乎没有切割作用; 配体O-(硫杂蒽酮-[2]-基)-氧乙酸对质粒pBR322DNA也有切割作用, 但配合物EuL₃对质粒pBR322DNA的切割作用明显强于配体, 表明稀土离子Eu(III)与配体生成配合物后有较好的协同切割作用.     

不同配体对钌多吡啶配合物与DNA的作用和荧光性质的影响

Two polypyridyl ligands DCHIP (2-hydro-3，5-dichlorophenyl-imidazo[4，5-f][1，10] phenanthroline)，MDHIP(2，4-dihydrophenyl-imidazo[4，5-f][1，10]phenanthroline) and their ruthenium(Ⅱ) complexes [Ru(phen)₂MDHIP]²⁺ and [Ru(phen)₂DCHIP]²⁺ were prepared. Their DNA-binding properties were studied by spectroscopic methods and viscosity measurements. The results indicated that the complexes both bound to DNA by partial intercalation mode， but [Ru(phen)₂DCHIP]²⁺ exhibited stronger binding affinity for DNA than [Ru(phen)₂MDHIP]²⁺ due to the different planarities and steric effects of ligands. On the other hand， after binding to DNA， the fluorescence intensity of [Ru(phen)₂MDHIP]²⁺ decreased， while the fluorescence intensity of [Ru(phen)₂ DCHIP]²⁺ increased.     

Synthesis and spectroscopic DNA binding studies of [Ru(phen)2(tbtc)]2+ and [Ru(2,9-dmp)2(tbtc)]2+

A new polypyridyl ligand tbtc (tbtc=4,5,9,14-tetraaza-benzo[b]triphenylene-11-carboxylic acid methyl ester) and its complexes [Ru(phen)2(tbtc)]2+ (1) (phen=1,10-phenanthroline) and [Ru(2,9-dmp)2(tbtc)]2+ (2) (2,9-dmp=2,9-dimethyl-1,10-phenanthroline) were synthesized and characterized by element analysis, MS, and 1H NMR. The DNA binding properties of both complexes to calf thymus DNA (CT-DNA) were investigated by different spectrophotometric methods and viscosity measurements. The results suggest that both complexes bind to DNA via an intercalative mode, and the DNA binding affinity of complex 1 is much greater than that of complex 2. This difference in binding affinity probably was caused by the different ancillary ligands. Also, when irradiated at 365 nm, complex 1 was found to be a more-effective DNA-cleaving agent than complex 2.     

新型双核配合物的形成及荧光性质研究

利用光谱学方法研究了[Ru(bpy)2TPPHZ]2+(TPPHZ=四吡啶[3,2-a: 2',3'-c: 3",2"-h: 2'",3'"-j]吩嗪)和[Ru(bpy)2ODHIP]2+(ODHIP=3,4-二羟基-咪唑并[4,5-f][1,10]邻菲咯啉)与Ni2+的配位情况及配位后的荧光性质变化, 探讨了配合物与Ni2+配位形成双核配合物后与DNA的作用机制变化. 结果表明, [Ru(bpy)2TPPHZ]2+和[Ru(bpy)2ODHIP]2+均可与Ni2+配位, 形成双核配合物[Ru(bpy)2(TPPHZ)Ni]4+和[Ru(bpy)2(ODHIP)Ni]4+, 配合物的荧光强度随着Ni2+浓度的增加而减弱. 与DNA作用后, 配合物仍可与Ni2+配位形成双核配合物, [Ru(bpy)2(TPPHZ)Ni]4+的荧光几乎完全消失, 同时配合物与DNA保持插入模式作用, 而配合物[Ru(bpy)2(ODHIP)Ni]4+与DNA的作用则由沟面结合改为插入结合, 同时配合物的荧光减弱.     

Comparison of the binding stoichiometries of positively charged DNA-binding drugs using positive and negative ion electrospray ionization mass spectrometry

Positive and negative ion electrospray ionization (ESI) mass spectra of complexes of positively charged small molecules (distamycin, Hoechst 33258, [Ru(phen)2dpq]Cl2 and [Ru(phen)2dpqC]Cl2) have been compared. [Ru(phen)2dpq]Cl2 and [Ru(phen)2dpqC]Cl2 bind to DNA by intercalation. Negative ion ESI mass spectra of mixtures of [Ru(phen)2dpq]Cl2 or [Ru(phen)2dpqC]Cl2 with DNA showed ions from DNA-ligand complexes consistent with solution studies. In contrast, only ions from free DNA were present in positive ion ESI mass spectra of mixtures of [Ru(phen)2dpq]Cl2 or [Ru(phen)2dpqC]Cl2 with DNA, highlighting the need for obtaining ESI mass spectra of non-covalent complexes under a range of experimental conditions. Negative ion spectra of mixtures of the minor groove binder Hoechst 33258 with DNA containing a known minor groove binding sequence were dominated by ions from a 1:1 complex. In contrast, in positive ion spectra there were also ions present from a 2:1 (Hoechst 33258: DNA) complex, suggesting an alternative binding mode was possible either in solution or in the gas phase. When Hoechst 33258 was mixed with a DNA sequence lacking a high affinity minor groove binding site, the negative ion ESI mass spectra showed that 1:1 and 2:1 complexes were formed, consistent with existence of binding modes other than minor groove binding. The data presented suggest that comparison of positive and negative ion ESI-MS spectra might provide an insight into various binding modes in both solution and the gas phase.     

Synthesis and spectroscopic DNA binding studies of homoleptic and heteroleptic ruthenium(II) complexes with imidazo[4,5-f] [1,10]phenanthroline or its derivatives

Two series of new complexes, [Ru(phen)2L]2+ and [RuL3]2+, where phen = 1,10-phenanthroline, and L denotes imidazo[4,5-f][1,10]phenanthroline (IP) or 2-(4-R-phenyl)imidazo[4,5-f][1,10]phenanthroline(PIP, R = H; HOP, R = –OH; MOP, R = –OMe; DMNP, R = NMe2; CLP, R = Cl; NOP, R = NO2), were synthesized and characterized. Their binding to calf thymus DNA was investigated using electronic absorption and emission spectroscopy. [Ru(IP)3]2+ and each [Ru(phen)2 L]2+ showed dramatic absorption hypochromism and bathochromicity, as well as steady-state emission intensity and excited-state lifetime enhancements {except nonluminescent [Ru(phen)2NOP]2+} associated with the presence of DNA, inferring that they bind to DNA by intercalation. These phenomena were not observed for [RuL3]2+ type complexes (except L = IP), indicating that they bind to DNA at most through electrostatic interactions.     

Luminescence properties of [Ru(bpy)2MDHIP]2+ modulated by the introduction of DNA,copper(II) ion and EDTA

The luminescence properties of [Ru(bpy)₂MDHIP]²⁺ (bpy = 2,2′-bipyridine, MDHIP = 2,4-dihydrophenyl-imidazo[4,5-f][1,10]phenanthroline) in the absence and presence of DNA modulated by the introduction of Cu²⁺ ion and EDTA have been investigated. It is found that the ruthenium(II) complex can insert and stack between the base pairs of calf thymus DNA with MDHIP ligand, and the intramolecular hydrogen bond is located inside of the DNA. The presence of DNA can enhance the luminescence intensities of [Ru(bpy)₂MDHIP]²⁺ both in buffer solution and on an ITO surface. Moreover, the luminescence intensities of [Ru(bpy)₂MDHIP]²⁺ and DNA-bound [Ru(bpy)₂MDHIP]²⁺ are quenched by Cu²⁺, and next recovered by the addition of EDTA. The repetitive luminescence-modulations have been achieved through the introduction of equimolar Cu²⁺ and EDTA, respectively. In addition, it becomes evident that the number of luminescence-modulation cycles for [Ru(bpy)₂MDHIP]²⁺ in the absence and presence of DNA is influenced by the cumulative concentrations of CuEDTA, generated successively by the strong coordination of Cu²⁺ to EDTA.     

meso-[{Ru(phen)2}2(mu-HAT)]4+: a high-affinity DNA hairpin probe {HAT = 1,4,5,8,9,12-hexaazatriphenylene; phen = 1,10-phenanthroline}

1H NMR spectroscopy and fluorescent intercalator displacement (FID) assays have been used to investigate the DNA-binding abilities of two series of dinuclear polypyridyl ruthenium(II) complexes of the form [{Ru(L)2}2(mu-BL)]4+ {L = 2,2'-bipyridine (bpy), 4,4'-dimethyl-2,2'-bipyridine (Me2bpy), 1,10-phenanthroline (phen), or 4,7-dimethyl-1,10-phenanthroline (Me2phen); BL = 2,2'-bipyrimidine (bpm) or 1,4,5,8,9,12-hexaazatriphenylene (HAT)}. Preliminary FID surveys of these metal complexes against a variety of different oligonucleotides revealed that those complexes based upon the HAT bridging ligand induced greater fluorescence decreases in dye-bound DNA than did their bpm-bridged counterparts, suggesting a higher binding affinity by the HAT-bridged species. Furthermore, the greatest fluorescence decreases were typically observed in an oligonucleotide featuring a six-base hairpin loop. The apparent binding affinity of the metal complexes was also found to be a function of the stereochemistry and identity of the terminal ligands of the complex. The meso (DeltaLambda) stereoisomer generally induced greater fluorescence decreases than did either enantiomer (DeltaDelta or LambdaLambda), phen-based terminal ligands performed better than bpy-based terminal ligands, and those terminal ligands with methyl substituents demonstrated stronger apparent binding than did their non-methylated analogues. NMR experiments on meso-[{Ru(phen)2}2(mu-HAT)]4+ and meso-[{Ru(Me2phen)2}2(mu-HAT)]4+ demonstrated that both complexes bound with high affinity to the six-base hairpin oligonucleotide at the stem-loop interface and provided evidence to support stronger binding by the methylated species. meso-[{Ru(phen)2}2(mu-HAT)]4+ was found to bind poorly to duplex DNA and smaller four-base hairpin loops in FID and NMR experiments, whereas FID data suggest that the methylated analogue binds relatively strongly to most oligonucleotide sequences (the four- and six-base hairpins in particular). These results demonstrate that binding affinity can come at the expense of selectivity, with meso-[{Ru(phen)2}2(mu-HAT)]4+ proving to be an efficient compromise between the two as a high-affinity DNA hairpin probe.     

新型双核配合物的形成、与DNA的作用机制及荧光性质研究

利用紫外、荧光和粘度等方法研究了含不同配体的钌(II)配合物[Ru(phen)₂CImP]^2＋(CImP＝3,4-二羟基-咪唑并[4,5-i][1,10]邻菲咯啉)和[Ru(phen)₂TPPZ]^2＋(TPPZ＝四吡啶[3,2-a:2',3'-c:3',2'-h:2'',3''-j]吩嗪)与DNA的作用机制, 并研究了配合物与Zn^2＋配合后荧光性质变化. 结果表明[Ru(phen)₂TPPZ]^2＋与DNA以插入模式作用, 而[Ru(phen)₂CImP]^2＋与DNA则以沟面结合模式作用. 向配合物溶液中滴加Zn^2＋后, 配合物[Ru(phen)₂TPPZ]^2＋和[Ru(phen)₂CImP]^2＋均可以与Zn^2＋形成双核配合物[Ru(phen)₂(TPPZ)Zn]^4＋和[Ru(phen)₂(CImP)Zn]^4＋, 配合物的荧光减弱. 与DNA作用后, 配合物仍可以与Zn^2＋配位形成双核配合物, 但[Ru(phen)₂(TPPZ)Zn]^4＋保持插入模式与DNA作用, 配合物的荧光减弱. 而[Ru(phen)₂(CImP)Zn]^4＋与DNA则由沟面结合改为插入结合, 配合物的荧光增强.     

Ruthenium(II) complexes of 6,7-dicyanodipyridoquinoxaline: synthesis, luminescence studies, and DNA interaction

The hexaflurophosphate and chloride salts of a series of ruthenium(II) complexes incorporating a new dipyridophenazine-based ligand, dicnq (6,7-dicyanodipyrido[2,2-d:2',3'-f]quinoxaline), are synthesized in good-to-moderate yields. These mono ([Ru(phen)2(dicnq)]2+; phen = 1,10-phenanthroline), bis ([Ru(phen)(dicnq)2]2+), and tris ([Ru(dicnq)3]2+) complexes are fully characterized by elemental analysis, infrared, FAB-MS, 1H NMR, and cyclic voltammetric methods. Results of absorption titration and thermal denaturation studies reveal that these complexes are moderately strong binders of calf-thymus (CT) DNA, with their binding constants spanning the range (1-3) x 10(4) M-1. On the other hand, under the identical set of experimental conditions of light and drug dose, the DNA (pBR 322)-photocleavage abilities of these ruthenium(II) complexes follow the order [Ru(phen)2(dicnq)]2+ > [Ru(phen)(dicnq)2]2+ > [Ru(dicnq)3]2+, an order which is the same as that observed for their MLCT emission quantum yields. Steady-state emission studies carried out in nonaqueous solvents and in aqueous media with or without DNA reveal that while [Ru(dicnq)3]2+ is totally nonemissive under these solution conditions, both [Ru(phen)2(dicnq)]2+ and [Ru(phen)(dicnq)2]2+ are luminescent and function as "molecular light switches" for DNA. Successive addition of CT DNA to buffered aqueous solutions containing the latter two complexes results in an enhancement of the emission in each case, with the enhancement factors at saturation being approximately 16 and 8 for [Ru(phen)2(dicnq)]2+ and [Ru(phen)(dicnq)2]2+, respectively. These results are discussed in light of the relationship between the structure-specific deactivations of the MLCT excited states of these metallointercalators and the characteristic features of their DNA interactions, and attempts are made to compare and contrast their properties with those of analogous dipyridophenazine-based complexes, including the ones reported in the preceding paper.     

Synthesis,characterization, and DNA binding of ruthenium(II) complexes with 2-benzo[b] furan-2-yl-1H-imidazo[4,5f][1,10]phenanthroline as an intercalative ligand

DNA-binding properties of a number of ruthenium complexes with different polypyridine ligands are reported. The new polypyridine ligand BFIP (=2-benzo[b] furan-2-yl-1H-imidazo[4,5-f][1,10]phenanthroline) and its ruthenium complexes [Ru(bpy)₂BFIP]²⁺ (bpy = 2,2′-bipyridine), [Ru(dmb)₂BFIP]²⁺ (dmb = 4,4′-dimethyl-2,2′-bipyridine), and [Ru(phen)₂BFIP]²⁺ (phen = 1,10-phenanthroline) have been synthesized and characterized by elemental analysis, mass spectra, IR, UV-Vis, ¹H- and ¹³C-NMR, and cyclic voltammetry. The DNA binding of these complexes to calf-thymus DNA (CT-DNA) was investigated by spectrophotometric, fluorescence, and viscosity measurements. The results suggest that ruthenium(II) complexes bind to CT-DNA through intercalation. Photocleavage of pBR 322 DNA by these complexes was also studied, and [Ru(phen)₂BFIP]²⁺ was found to be a much better photocleavage agent than the other two complexes.