异咯嗪修饰富勒烯-聚丙烯酸的合成及其与DNA的相互作用

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.     

Synthesis and reversible photocleavage of novel polyurethanes containing coumarin dimer components

Six polyurethanes containing coumarin dimer components in the main chain have been prepared by polyaddition of diisocyanates with anti head-to-head 7-hydroxycoumarin dimer or anti head-to-tail 7-hydroxy-4-methylcoumarin dimer. 7-Acetoxycoumarin and 7-acetoxy-4-methylcoumarin were first prepared and then photodimerized under 350 nm UV light to give anti head-to-head 7-acetoxycoumarin dimer and anti head-to-tail 7-acetoxy-4-methylcoumarin dimer, respectively. After hydrolyzing under acidic conditions to 7-hydroxycoumarin dimer and anti head-to-head 7-hydroxycoumarin dimer, they were polymerized with aliphatic and aromatic diisocyanates in N,N-dimethylacetamide to give the polyurethanes. Addition of dibutyltin dilaurate (T-12) as catalyst increases the polymer yield with the viscosity remaining almost unchanged. It was also found that lithium chloride enhances both the yield and viscosity of the polyurethanes by increasing their solubility possibly through complexation. The polyurethanes are symmetrically photocleaved at cyclobutane rings under 254 nm UV light to dicoumarins. Reversible photodimerization of the photocleaved compounds have also been investigated under 300 and 350 nm UV light. The polyurethanes from aromatic diisocyanates or with 4-methyl substituent exhibit greater reactivity in the photocleavage reaction. © 1997 John Wiley & Sons, Inc.     

Synthesis and photochemical properties of novel multifunctional photopolymers with both pendant epoxy groups and phenacyl ester groups

Novel multifunctional photopolymers with both pendant epoxy groups and phenacyl ester groups were synthesized by the one‐pot method for the reaction of poly(methacrylic acid) with epibromohydrin; this was followed by a reaction with phenacylbromide with 1,8‐diazabicyclo‐[5.4.0]undecene‐7 as a condensation reagent. These esterification reactions proceeded smoothly and quantitatively under mild conditions. Moreover, the photochemical reactions of the resulting polymers were evaluated by UV and IR spectroscopy. The pendant phenacyl ester groups were photocleaved to give corresponding carboxyl groups, and then the produced carboxyl groups reacted with pendant epoxy groups. Furthermore, the baking process promoted a crosslinking reaction because of the addition reaction of epoxy groups with carboxyl groups after irradiation. It was also proven that the photochemical reactivity of the resulting polymers was affected by the structure of the phenacyl ester group. © 2001 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 39: 530–538, 2001     

手性钌(II)配合物与DNA作用性质的计算研究

理论探索了手性钌(II)配合物1和2与DNA作用性质。首先,构建了手性钌(II)配合物1、2与DNA对接模型,并对对接模型进行了优化,通过计算得到的手性钌(II)配合物1、2与DNA的结合能,解释了手性钌(II)配合物1、2与DNA结合力大小次序,即 Kb(Λ-1) < Kb(∆-1) < Kb(Λ-2) < Kb(∆-2)。另外,通过计算得到的电子转移活化能及自然电荷解释了手性钌(II)配合物1和2光裂解DNA的次序,即Λ-2 > ∆-2 > Λ-1> ∆-1。最后,通过计算得到的对接模型的分子轨道分析了光裂解DNA的原因。     

Syntheses, structures and reactivities of designed analogues of cobalt(III)- bleomycinsz : Insight into the mechanism of sequence-specific DNA cleavage upon illumination

Three Co (III) complexes of a designed ligand PMAH that mimics the metal-binding domain of the antitumor antibioticbleomycin (BLM) have been isolated and structurally characterized. The coordination structures of the various forms of Co(III)-BLMs have been established on the basis of spectral similarities between these synthetic analogues and the corresponding Co(III)-BLMs. All three analogues, like Co(III)-BLMs, induce DNA strand scission upon UV illumination. Both DNA cleavage and spin trapping experiments demonstrate that UV irradiation of the analogues generates a C/N-based radical on the ligand framework which rapidly reacts with water to produce -OH radical near the DNA helix and causes strand scission. A similar mechanism could account for the photoactivity of the Co(III)-BLMs. Covalent attachment of DNA-binding groups to these analogues enhances the DNA-affinities and photocleavage efficiencies to a great extent. The hybrid analogues promote sequence-specific DNA photodamage at micromolar concentrations. The metallated cores of the hybrid analogues are the primary determinant of the observed sequence-specificity. Details of the mode of binding of the hybrid analogues to DNA have been explored by NMR techniques.     

带有位阻基团的钌多吡啶配合物与DNA键合及其光断裂DNA性质的研究

合成了两个钌多吡啶配合物[Ru(bpy)₂DMNP](C1O₄)₂ (Ru1)和[Ru(bpy)₂BOPIP](C1O₄)₂ (Ru2), 应用元素分析、核磁共振对配合物结构进行了表征, 通过电子吸收光谱、荧光光谱、粘度实验以及凝胶电泳技术对配合物与DNA相互作用的性质进行了研究. 结果表明, 配合物与DNA分子之间以插入模式结合. 在紫外光照下, 两种配合物均能使质粒pBR322DNA断裂, 机理研究表明, 其光断裂DNA的活性氧化物种为单线态氧.     

Photo-activated cytotoxicity of a pyrenyl-terpyridine copper(II) complex in HeLa cells

Terpyridine copper(II) complexes [Cu(L)₂](NO₃)₂, where L is (4′-phenyl)-2,2′:6′,2′′-terpyridine (ph-tpy in 1) and [4′-(1-pyrenyl)]-2,2′:6′,2′′-terpyridine (py-tpy in 2), are prepared, characterized and their photocytotoxic activity studied. The crystal structure of complex 1 shows distorted octahedral CuN₆ coordination geometry. The 1:2 electrolytic and one-electron paramagnetic complexes show a visible band near 650 nm in DMF–H₂O. The complexes show emission band at 352 nm for 1 and 425 nm for 2 when excited at 283 and 346 nm, respectively. The Cu(II)–Cu(I) redox couple is observed near −0.2 V versus SCE in DMF–0.1 M TBAP. The complexes are avid partial-intercalative binders to calf thymus DNA giving binding constant (K_b) values of ∼10⁶ M⁻¹. Complex 2 with its photoactive pyrenyl moiety exhibits significant photocleavage of pUC19 DNA in red light via singlet oxygen pathway. Complex 2 also exhibits significant photo-activated cytotoxicity in HeLa cancer cells in visible light giving IC₅₀ value of 11.9 μM, while being non-toxic in dark with an IC₅₀ value of 130.5 μM.     

Green Algae as a Drug Delivery System for the Controlled Release of Antibiotics

New strategies to efficiently treat bacterial infections are crucial to circumvent the increase of resistant strains and to mitigate side effects during treatment. Skin and soft tissue infections represent one of the areas suffering the most from these resistant strains. We developed a new drug delivery system composed of the green algae, Chlamydomonas reinhardtii, which is generally recognized as safe, to target specifically skin diseases. A two-step functionalization strategy was used to chemically modify the algae with the antibiotic vancomycin. Chlamydomonas reinhardtii was found to mask vancomycin and the insertion of a photocleavable linker was used for the release of the antibiotic. This living drug carrier was evaluated in presence of Bacillus subtilis and, only upon UVA1-mediated release, growth inhibition of bacteria was observed. These results represent one of the first examples of a living organism used as a drug delivery system for the release of an antibiotic by UVA1-irradiation.     

Synthesis,DNA binding mode,singlet oxygen photogeneration and DNA photocleavage activity of ruthenium compounds with porphyrin–imidazo[4,5‐f]phenanthroline conjugated ligand

Using 1,10‐phenanothroline‐5,6‐dione and 10,20‐bis(4‐methylphenyl)porphyrin copper as starting materials, a conjugated porphyrin–imidazo[4,5‐f]‐1,10‐phenanothroline ligand (Por 1 ) was prepared. Subsequently, the copper complex of Por 1 was reacted with Ru(1,10‐phenanothroline)₂Cl₂ to yield ruthenium compound Por 2 . After removal of copper metal under acid condition, the free base porphyrin of Por 2 (Por 3 ) was prepared. The structure of these compounds was confirmed using UV–visible, ¹H NMR, mass and infrared spectroscopies and elemental analysis. Through UV–visible, fluorescence and circular dichroism analyses, the interaction modes between Por 1 – 3 and calf thymus DNA were investigated. Por 1 interacted with DNA via outside groove face, but Por 2 and Por 3 showed intercalative interaction with DNA. Binding constants between Por 1 – 3 and DNA were 7.79 × 10⁵, 1.29 × 10⁶ and 1.32 × 10⁶ M^?1, respectively. With 5,10,15,20‐tetraphenylporphyrin (H₂TPP) as a control, the singlet oxygen (¹O₂) generation of Por 1 – 3 was measured using the 1,3‐diphenylisobenzofuran method. The ¹O₂ generation rate of Por 1 – 3 followed the order: Por 3 >Por 1 >H₂TPPP >Por 2 . Por 1 and Por 3 showed better ¹O₂ quantum yields than Por 2 , which were almost threefold higher than that of H₂TPP. The DNA cleavage ability of Por 1 – 3 was analyzed using gel electrophoresis. Por 3 showed higher DNA photocleavage activity, with more than 50% photocleavage rate at 20 μM. These results suggest that amphipathic (hydrophilic/lipophilic) Por 3 with conjugated Por 1 ligand is a potential photosensitizer in cancer therapy.     

Deciphering Photoluminescence Dynamics and Reactivity of the Luminescent Metal–Metal‐Bonded Excited State of a Binuclear Gold(I) Phosphine Complex Containing Open Coordination Sites

Luminescent metal complexes having open coordination sites hold promise in the design of sensory materials and photocatalysts. As a prototype example, [Au₂(dcpm)₂)]²⁺ (dcpm = bis(dicyclohexylphosphanyl) is known for its intriguing environmental sensitive photoluminescence. By integrating a range of complementary ultrafast time‐resolved spectroscopy to interrogate the excited state dynamics, this study uncovers that the events occurring in extremely rapid timescales and which are modulated strongly by environmental conditions play a pivotal role in the luminescence behavior and photochemical outcomes. Formed independent of the phase and solvent property within ～0.15 ps, the metal–metal bonded ³5dσ*6pσ state is highly reactive possessing strong propensity toward increasing coordination number at Au^I center, and with ～510 ps lifetime in dichloromethane is able to mediate light induced C–X bond cleavage.