单羟基咔咯锰(Ⅲ)配合物的合成及其与DNA的相互作用

以五氟苯基二吡咯烷烃为原料,与对羟基苯甲醛经缩合反应合成了单羟基自由咔咯(1);1与醋酸锰反应合成了一种单羟基咔咯锰配合物——10-(4-羟基苯基)-5,15-二(2,3,4,5,6-五氟苯基)咔咯锰(Ⅲ)配合物,其结构经UV-Vis和HR-MS(ESI)表征。通过紫外滴定、荧光滴定、圆二色谱和琼脂糖凝胶电泳实验探讨了其催化氧化DNA的活性。     

单羟基咔咯锰（III）配合物的合成及其与DNA的相互作用

以五氟苯基二吡咯烷烃为原料,与对羟基苯甲醛经缩合反应合成了单羟基自由咔咯（1）; 1与醋酸锰反应合成了一种单羟基咔咯锰配合物--10-(4-羟基苯基)-5,15-二(2,3,4,5,6-五氟苯基)咔咯锰(III)配合物,其结构经UV-Vis和HR-MS（ESI）表征。通过紫外滴定、荧光滴定、圆二色谱和琼脂糖凝胶电泳实验探讨了其催化氧化DNA的活性。     

三羟基咔咯及其镓配合物与DNA的相互作用、光断裂和光动力抗肿瘤活性

合成了一个三羟基咔咯10-(4-羟基苯基)-5,15-双(4-(2-羟乙基)氨基-2,3,5,6-四氟苯基)咔咯(1)及其镓配合物(1-Ga)。光谱滴定实验、粘度测试和分子对接模拟结果表明,1和1-Ga通过外部结合模式与小牛胸腺DNA发生相互作用。琼脂糖凝胶电泳实验结果表明1和1-Ga显示出良好的光核酸酶活性。2种化合物对A549,HepG2,MCF-7肿瘤细胞有显著的光毒性。光辐照后,它们能通过活性氧物种(ROS)介导的线粒体途径诱导HepG2细胞凋亡。此外,1-Ga能使肿瘤细胞周期阻滞在G2/M期。     

新型吩噻嗪-咔咯锰(Ⅲ)配合物的合成及其催化氧化DNA断裂的活性

以单羟基自由咔咯为起始原料,与吩噻嗪-10-碳酰氯(PTZ)反应制得吩噻嗪-咔咯二元化合物(2);2与醋酸锰反应合成了一种新型5,15-二(2,3,4,5,6)-五氟苯基-10-(4-吩噻嗪苯基)咔咯锰(Ⅲ)配合物(3),收率80.0%,其结构经UV-Vis和HR-MS(ESI)表征。通过琼脂糖凝胶电泳实验探讨了其催化氧化DNA的活性。结果表明:在过氧化氢存在下,3能有效引起超螺旋p BR322 DNA发生氧化断裂,3浓度为250μmol·L~(-1)时,氧化断裂DNA的活性达34%。通过紫外滴定、荧光滴定、圆二色谱推断3与小牛胸腺(ct-DNA)的结合模式为外部结合。     

新型吩噻嗪-咔咯锰（III）配合物的合成及其催化氧化DNA断裂的活性

以单羟基自由咔咯为起始原料,与吩噻嗪-10-碳酰氯（PTZ）反应制得吩噻嗪 咔咯二元化合物(2）; 2与醋酸锰反应合成了一种新型5,15-二（2,3,4,5,6)-五氟苯基-10-(4-吩噻嗪苯基)咔咯锰（Ⅲ）配合物(3),收率80.0%,其结构经UV-Vis和HR-MS（ESI）表征。通过琼脂糖凝胶电泳实验探讨了其催化氧化DNA的活性。结果表明：在过氧化氢存在下,3能有效引起超螺旋pBR322 DNA发生氧化断裂,3浓度为250 μmol·L^-1时,氧化断裂DNA的活性达34%。通过紫外滴定、荧光滴定、圆二色谱推断3与小牛胸腺(ct-DNA）的结合模式为外部结合。     

新型含氯(氟)的A_2B型咔咯化合物的合成及其光学性质

meso-(3-硝基苯基)二吡咯甲烷分别与2,6-二氯(或氟)苯甲醛经酸催化偶联反应和氧化反应合成了两个新型的A2B型咔咯化合物——10-(2,6-二氯苯基)-5,15-二(3-硝基苯基)-咔咯(3a)和10-(2,6-二氟苯基)-5,15-二(3-硝基苯基)-咔咯(3b),其结构经1H NMR,13C NMR,IR和MALDI-TOF-MS表征。采用UV-Vis和荧光光谱研究3的光学性质。结果表明:3a和3b的λmax均位于414 nm,575 nm,610 nm和642 nm附近;λem位于661 nm附近(λex=430 nm)。     

新型单羟基氯代咔咯的合成及其光断裂DNA性质

以五氟苯甲醛和吡咯经缩合反应合成了五氟苯基二吡咯烷烃(1); 1与3-氯-4-羟基苯甲醛经缩合反应合成了一个新的10-位苯环被氯原子取代的单羟基自由咔咯--10-(3-氯-4-羟苯基)-5,15-二(五氟苯基)咔咯(〖STHZ〗2〖STBZ〗),收率12.0%,其结构经UV-Vis, ¹H NMR, ¹⁹F NMR, HR-ESI-MS和X-射线单晶衍射表征。琼脂糖凝胶电泳实验发现：2在光照下能够有效引起超螺旋质粒pBR 322 DNA发生断裂,当浓度为100 μmol·L^-1时,活性最强,断裂百分比为68%。     

磺酸咔咯及其镓(Ⅲ)配合物与DNA的相互作用和光核酸酶活性

本文用紫外-可见光谱、荧光光谱、圆二色光谱和粘度法研究了2,17-二(磺酸钠基)-5,10,15-三(五氟苯基)咔咯(1)及其镓配合物(1-Ga)与小牛胸腺DNA(ct-DNA)的相互作用。结果表明1和1-Ga通过外部结合的方式与ct-DNA相互作用, 且结合能力1-Ga比1大。琼脂糖凝胶电泳实验显示1和1-Ga均具较好的光核酸酶活性, 1-Ga光断裂DNA效果比1好, 其光断裂机理与羟基自由基的产生有关。     

咔咯铁(Ⅲ)配合物与DNA的作用及其抗肿瘤活性

本文合成了10-(4-吩噻嗪苯基)-5,15-二(五氟苯基)铁咔咯配合物(2-Fe)。 在H₂O₂存在下,配合物2-Fe能有效抑制人肺癌细胞(A549)增殖。 流式细胞术检测结果显示在H₂O₂和2-Fe共同作用下,A549细胞生长被阻滞在S期和G2期,且有63.76%发生细胞凋亡。 Hoechst-33342细胞核染色实验观察到A549细胞核呈典型的凋亡形态学变化,同时细胞线粒体膜电势发生明显下降。 2-Fe与小牛胸腺DNA(ct-DNA)以外部模式相结合,且能有效催化氧化断裂DNA,此过程中涉及的活性氧物种可能是单线态氧。     

磺酸咔咯及其镓(Ⅲ)配合物与DNA的相互作用和光核酸酶活性

本文用紫外-可见光谱、荧光光谱、圆二色光谱和粘度法研究了2,17-二(磺酸钠基)-5,10,15-三(五氟苯基)咔咯(1)及其镓配合物(1-Ga)与小牛胸腺DNA(ct-DNA)的相互作用。结果表明1和1-Ga通过外部结合的方式与ct-DNA相互作用,且结合能力1-Ga比1大。琼脂糖凝胶电泳实验显示1和1-Ga均具较好的光核酸酶活性,1-Ga光断裂DNA效果比1好,其光断裂机理与羟基自由基的产生有关。     

Corrole光敏剂在光动力治疗中的重原子效应

最近, 我们合成了一系列Corrole衍生物, 经过鼻咽癌(Nasopharyngeal carcinoma,NPC) 细胞的体外PDT试验后, 筛选出了一个具有优良PDT活性的Corrole光敏剂. 本文报道该类Corrole光敏剂在PDT中的重原子效应.     

Mixed ligand ruthenium(II) complexes of bis(pyrid-2-yl)-/bis(benzimidazol-2-yl)-dithioether and diimines: study of non-covalent DNA binding and cytotoxicity

A series of mixed ligand ruthenium(II) complexes [Ru(pdto)(diimine)](ClO4)2/(PF6)2 1-3 and [Ru(bbdo)(diimine)](ClO4), 4-6, where pdto is 1,8-bis(pyrid-2-yl)-3,6-dithiooctane, bbdo is 1,8-bis(benzimidazol-2-yl)-3,6-dithiooctane and diimine is 1,10-phenanthroline (phen), dipyrido-[3,2-d:2',3'-f]-quinoxaline (dpq) and dipyrido[3,2-a:2',3'-c]phenazine (dppz), have been isolated and characterised by analytical and spectral methods. The complexes [Ru(pdto)(phen)](PF6)2 la, [Ru(pdto)(dpq)(Cl](PF6) 2a, [Ru(bbdo)(phen)](PF6)2 4a and [Ru(bbdo)(dpq)](ClO4)2 5 have been structurally characterized and their coordination geometries around ruthenium(II) are described as distorted octahedral. In la, 4a and 5 the two thioether sulfur and two py/bzim nitrogen atoms of the tetradentate pdto/bbdo ligand are folded around Ru(II) to give predominantly a "cis-alpha" configuration. (I)H NMR spectral data of the complexes support this configuration in solution. In [Ru(pdto)(dpq)Cl](PF6) 2a with a distorted octahedral coordination geometry, one of the two py nitrogens of pdto is not coordinated. The DNA binding constants (Kb: 2, 2.00 +/- 0.02 x 10(4) M(-1), s = 1.0; 3, 3.00 +/- 0.01 x 10(6) M(-1), s = 1.3) determined by absorption spectral titrations of the complexes with CT DNA reveal that 3 interacts with DNA more tightly than 2 through partial intercalation of the extended planar ring of coordinated dppz with the DNA base stack. The DNA binding affinities of the complexes increase with increase in the number of planar aromatic rings in the co-ligand, and on replacing both the py moieties in pdto complexes (1-3) by bzim moieties to give bbdo complexes (4-6). Upon interaction with CT DNA the complexes 1, 2, 5 and 6 show a decrease in anodic current in the cyclic voltammograms. On the other hand, interestingly, 3 and 4 show an increase in anodic current suggesting their involvement in electrocatalytic guanine oxidation. Interestingly, of all the complexes, only 6 alters the superhelicity of DNA upon binding with supercoiled pBR322 DNA. The cytotoxicities of the dppz complexes 3 and 6, which avidly bind to DNA, have been examined by screening them against cell lines of different cancer origins. It is noteworthy that 6 exhibits selectivity with higher cytotoxicity against the melanoma cancer cell line (A375) than other cell lines, potency approximately twice that of cisplatin and toxicity to normal cells 3 and 90 times less than cisplatin and adriamycin respectively.     

1，4，7-三氮环壬烷衍生物铜、锌配合物切割DNA及催化对硝基苯磷酸单酯水解

系统研究了1,4,7-三(2-羟基丙基)-1,4,7-三氮环壬烷(L1)和1,2-双[N,N′-二(2-羟基丙基)-1,4,7-三氮杂环壬基]乙烷(L2)铜配合物([CuL1](ClO4)(NO3)和[Cu2L2](ClO4)4])以及锌配合物([ZnL1](ClO4)2)与CT-DNA的相互作用以及核酸酶活性和催化磷酸酯水解功能。两个铜配合物对DNA切割具有浓度、时间和pH依赖性。荧光和CD光谱实验表明[Cu2L2](ClO4)4能插入DNA双螺旋中。配位饱和的[ZnL1](ClO4)2和[Cu2L2](ClO4)4能催化对硝基苯磷酸单酯水解生成对硝基苯,[ZnL1](ClO4)2和[Cu2L2](ClO4)4催化磷酸单酯水解的表观一级反应速率常数分别为2.8×10-5min-1和5.9×10-6min-1。     

Synthesis of binaphthyl bridged chiral bis-corrole

Chiral bis-corrole 1 and 2 were prepared by reaction of(s)-2,2′-bis(bromomethyl)-1,1′-binaphthyl and 10-(4-hydroxylphenyl)- 5,15-bis(pentafluorophenyl)corrole or 10-(3-hydroxylphenyl)-5,15-bis(pentafluorophenyl)corrole in DMF at 60℃in the presence of anhydrous K_2CO_3 with an isolated yield～8%.Both 1 and 2 exhibit unsymmetrical induced circular dichroism(ICD)in the soret band with positive exciton chirality.     

Methyl Benzoate Gallium(III) corrole complexes: DNA‐binding,Photocleavage Activity,Cytotoxicity on Tumor Cells

Two new gallium corrole complexes, 10‐(4‐Methoxycarbonylphenyl) ‐5, 15‐bis(pentafluorophenyl)corrolatogallium(III)( 1 ‐Ga) and 5,15‐bis(4‐Methoxycarbonylphenyl)‐10‐(pentafluorophenyl)corrolatogallium(III)( 2 ‐Ga), were synthesized and characterized. The interaction of these gallium corrole complexes with CT‐DNA was studied by fluorescence methods, UV–visible, viscosity measurements, molecular docking as well as agarose gel electrophoresis. The results revealed that both 1 ‐Ga and 2 ‐Ga interact with DNA via major groove binding and could cleavage the supercoiled plasmid DNA efficiently under irradiation. The inhibitor and singlet oxygen test indicated that singlet oxygen was the reactive oxygen species involved in the photocleavage DNA initiated by 1 ‐Ga or 2 ‐Ga. Cell viability experiments indicated that 1 ‐Ga and 2 ‐Ga show high photocytotoxicity and low dark toxicity towards tested QGY‐7701 and MHCC‐H/L tumor cell lines. Fluorescence probe tests showed the absorbed 1 ‐Ga and 2 ‐Ga in tumor cells are mainly localized in mitochondria, and the mitochondria membrane potential disruption was observed after irradiation.     

Cobalt(II) complexes of terpyridine bases as photochemotherapeutic agents showing cellular uptake and photocytotoxicity in visible light

Cobalt(II) complexes of terpyridine bases [Co(L)?](ClO?)? (1-3), where L is 4'-phenyl-2,2':6',2'-terpyridine (ph-tpy in 1), 4'-(9-anthracenyl)-2,2':6',2'-terpyridine (an-tpy in 2) and 4'-(1- pyrenyl)-2,2':6',2'-terpyridine (py-tpy in 3), are prepared and their photo-induced DNA and protein cleavage activity and photocytotoxic property in HeLa cells studied. The 1?:?2 electrolytic and three-electron paramagnetic complexes show a visible band near 550 nm in DMF-Tris-HCl buffer. The complexes 1-3 show emission spectral bands at 355, 421 and 454 nm, respectively, when excited at 287, 368 and 335 nm. The quantum yield values for 1-3 in DMF-H?O (2?:?1 v/v) are 0.025, 0.060 and 0.28, respectively. The complexes are redox active in DMF-0.1 M TBAP. The Co(III)-Co(II) and Co(II)-Co(I) couples appear as quasi-reversible cyclic voltammetric responses near 0.2 and -0.7 V vs. SCE, respectively. Complexes 2 and 3 are avid binders to calf thymus DNA giving K(b) value of ～10? M?1. The complexes show chemical nuclease activity. Complexes 2 and 3 exhibit oxidative cleavage of pUC19 DNA in UV-A and visible light. The DNA photocleavage reaction of 3 at 365 nm shows formation of singlet oxygen and hydroxyl radical species, while only hydroxyl radical formation is evidenced in visible light. Complexes 2 and 3 show non-specific photo-induced bovine serum albumin protein cleavage activity at 365 nm. The an-tpy and py-tpy complexes exhibit significant photocytotoxicity in HeLa cervical cancer cells on exposure to visible light giving IC?? values of 24.2 and 7.6 μM, respectively. Live cell imaging study shows accumulation of the complexes in the cytosol of HeLa cancer cells.     

Dual triggering of DNA binding and fluorescence via photoactivation of a dinuclear ruthenium(II) arene complex

The dinuclear RuII arene complexes [{(eta6-arene)RuCl}2(mu-2,3-dpp)](PF6)2, arene=indan (1), benzene (2), p-cymene (3), or hexamethylbenzene (4) and 2,3-dpp=2,3-bis(2-pyridyl)pyrazine, have been synthesized and characterized. Upon irradiation with UVA light, complexes 1 and 2 readily underwent arene loss, while complexes 3 and 4 did not. The photochemistry of 1 was studied in detail. In the X-ray structure of [{(eta6-indan)RuCl}2(mu-2,3-dpp)](PF6)2 (1), 2,3-dpp bridges two RuII centers 6.8529(6) A apart. In water, aquation of 1 in the dark occurs with replacement of chloride with biexponential kinetics and decay constants of 100+/-1 min-1 and 580+/-11 min-1. This aquation was suppressed by 0.1 M NaCl. UV or visible irradiation of 1 in aqueous or methanolic solution led to arene loss. The fluorescence of the unbound arene is approximately 40 times greater than when it is complexed. Irradiation of 1 also had a significant effect on its interactions with DNA. The DNA binding of 1 is increased after irradiation. The non-irradiated form of 1 preferentially formed DNA adducts that only weakly blocked RNA polymerase, while irradiation of 1 transformed the adducts into stronger blocks for RNA polymerase. The efficiency of irradiated 1 to form DNA interstrand cross-links was slightly greater than that of cisplatin in both 10 mM NaClO4 and 0.1 M NaCl. In contrast, the interstrand cross-linking efficiency of non-irradiated 1 in 10 mM NaClO4 was relatively low. An intermediate amount of cross-linking was observed when the sample of DNA already modified by non-irradiated 1 was irradiated. DNA unwinding measurements supported the conclusion that both mono- and bifunctional adducts with DNA can form. These results show that photoactivation of dinuclear RuII arene complexes can simultaneously produce a highly reactive ruthenium species that can bind to DNA and a fluorescent marker (the free arene). Importantly, the mechanism of photoreactivity is also independent of oxygen. These complexes, therefore, have the potential to combine both photoinduced cell death and fluorescence imaging of the location and efficiency of the photoactivation process.