卟啉类第二代光敏剂的发展

本文对目前用于光动力治疗的以卟啉为基础的第二代光敏剂进行了综述，这些光敏剂中的大部分已进入临床或临床前试验，光物理性质研究表明它们是很有前途的光动力药物。本文同样介绍了连接生物分子和硼烷的卟啉衍生物，作为光序剂，它们具有非常光明的前途。     

卟啉类化合物作为光敏剂在治疗癌症方面的研究概况

卟啉及金属卟啉对癌细胞有特殊的亲合性,能够在肿瘤细胞中有选择性的滞留,因而被作为癌定位剂和诊治药物得到了广泛而深入的研究,受到化学、医学及生物学界的广泛关注。     

萘基卟啉的合成与性能研究

以萘基醛类化合物为原料与吡咯在丙酸中回流合成了3种含萘基的新型卟啉化合物,其中2种化合物尚未见文献报道,其结构通过1H NMR,IR和UV-V is确定。与四苯基卟啉相比,萘基的引入增大了卟啉环的共轭性,使得光学吸收波长与荧光发射波长均发生不同程度的红移,Q带吸收峰形改变且激发波长增长。结合卟啉光谱四轨道理论对该变化进行了讨论。     

吡啶基卟啉的合成及表征

卟啉类的化合物将广泛应用于我们的日常生活中。卟啉化合物是由于其特殊的生物学意义和能够应用于人工光合作用,非线性光学零件及传感器等而产生的。人们正在广泛研究它的优化合成及应用方面,如新型手性卟啉结合锌等金属元素后,具有对半胱氨酸的特殊识别作用。本文合成了一种吡啶基卟啉化合物1,并通过核磁共振谱、荧光光谱和紫外光谱等手段对其进行了表征。     

新型β-取代卟啉光敏剂的合成及其抗肿瘤活性

合成了新型β-取代卟啉光敏剂2-氢醌-5,10,15,20-四(4-羟基苯基)卟啉锌(Ⅱ)[Zn(Ⅱ)P],并初步研究了其体外抗肿瘤活性.用目前抗癌效果最好的第二代光敏剂m-THPC与Zn(Ⅱ)P、Cu(Ⅱ)P对肺癌细胞系A-549进行对比实验,结果表明Zn(Ⅱ)P的抗癌细胞活性比m-THPC更好.     

光动力治疗中提高光敏剂靶向性的研究进展

由于具有微创、时空选择性高、重复应用不产生耐药性等优点,光动力治疗被认为是一种极具前景的新型癌症治疗方法。但是,传统的光敏剂靶向性有限,会对正常组织产生毒副作用,极大地限制了光动力治疗的临床应用。构建靶标型光敏剂和可激活光敏剂是提高光敏剂肿瘤靶向性的有效途径。本文按靶标型光敏剂和可激活型光敏剂进行分类,对目前的研究进展进行总结概述,并对未来光动力治疗所面临的挑战进行了展望。     

D-A型卟啉衍生物作为光敏剂的影响因素

近年来,染料敏化太阳能电池(Dye-sensitized solar cell,DSSC)作为一种新型模拟自然界光合成原理的光伏电池得到了迅速发展,光敏剂的性能决定DSSC对光的利用。概述了卟啉衍生物作为光敏剂所具有的独到的结构优势,卟啉环上有多个可修饰的位点,且对光的利用率高,同时讨论了D-A型卟啉衍生物作为光敏剂的影响因素。     

卟啉类物质的基本合成方法

卟啉类化合物由于其独特的结构及性能,在抗癌、分析化学、模拟光合成、光电材料、催化氧化等方面具有广阔的应用前景。作者以典型物质四苯基卟啉的合成方法为例,对卟啉类物质的基本合成方法进行了比较、总结。     

葡萄糖键联卟啉的新合成方法

由5－（对溴丁氧基苯基）－10，15，20－三－（对甲氧基苯基）卟啉 或5，10，15，20－四－（对溴丁氧苯基）卟啉与α－D－葡萄糖经一步反应，得到相应的葡萄糖键联卟啉。该合成方法操作简便，反应条件温和，总产率高。     

金属卟啉光敏剂对染料亚甲基橙的光降解的研究

卟啉是一种具有良好光敏性的特殊大环共轭芳香化合物。文章利用活性自由基聚合的方法,以不对称羟基金属卟啉为原料,合成出具有温度响应性聚合物修饰的金属卟啉光敏剂,并通过核磁谱图分析证实了目标产物的结构。又以其作为光催化降解光敏剂,降解有机污染物亚甲基橙。考察不同光降解反应条件下,卟啉聚合物在氧化剂H_2O_2存在下,可见光照射下降解率最佳。同时也考察了不同温度、分子量、pH对光催化降解的影响。     

新型卟啉光敏剂:同分异构体空间结构与光敏活性

以2-硝基四苯基卟啉及其Cu（Ⅱ）、Ni（Ⅱ）配合物为原料,分别与1-萘酚、2-萘酚反应,合成了4对β-萘酚基四苯基卟啉同分异构体,并通过1HNMR、UV、IR、MS对新化合物进行了结构表征。比较了两类卟啉同分异构体作为光动力治疗光敏剂在光敏抗菌及光敏切割DNA方面的活性差异,并利用Chem3D软件的MM2分子力场计算方法确定了卟啉同分异构体的空间优势结构。结果表明,β-萘酚基四苯基卟啉同分异构体空间结构的非平面程度相当,光敏活性差异也不明显,卟啉的非平面性与光敏活性具有一定的一致性。     

间-四对甲氧基苯基卟啉的合成

采用Ｖ（吡咯）∶Ｖ（对甲氧基苯甲醛）＝１∶１．７６的混合物为原料,在二甲苯溶剂中,以２％（ｗ）的氯乙酸为催化剂,在常压和１４２℃下合成了间 四对甲氧基苯基卟啉。经重结晶和Ａｌ２Ｏ３柱层析,得紫红色结晶产品,产率２３．６％。经可见吸收光谱分析知,在氯仿介质中有６个大的吸收峰,波长分别为４２１．３、４８７．２、５１８．１、５５５．２、５９３．６和６５０．３ｎｍ,证明该卟啉是一种较四苯基卟啉更有效的光吸收剂。     

Low-Dose Near-Infrared Light-Activated Mitochondria-Targeting Photosensitizers for PDT Cancer Therapy

Phthalocyanines (Pcs) are promising candidates for photodynamic therapy (PDT) due to their absorption in the phototherapeutic window. However, the highly aromatic Pc core leads to undesired aggregation and decreased reactive oxygen species (ROS) production. Therefore, short PEG chain functionalized A₃B type asymmetric Pc photosensitizers (PSs) were designed in order to decrease aggregation and increase the aqueous solubility. Here we report the synthesis, characterization, optical properties, cellular localization, and cytotoxicity of three novel Pc-based agents (LC31, MLC31, and DMLC31Pt). The stepwise functionalization of the peripheral moieties has a strong effect on the distribution coefficient (logP), cellular uptake, and localization, as well as photocytotoxicity. Additional experiments have revealed that the presence of the malonic ester moiety in the reported agent series is indispensable in order to induce photocytotoxicity. The best-performing agent, MLC31, showed mitochondrial targeting and an impressive phototoxic index (p.i.) of 748 in the cisplatin-resistant A2780/CP70 cell line, after a low-dose irradiation of 6.95 J/cm². This is the result of a high photocytotoxicity (IC₅₀ = 157 nM) upon irradiation with near-infrared (NIR) light, and virtually no toxicity in the dark (IC₅₀ = 117 μM). Photocytotoxicity was subsequently determined under hypoxic conditions. Additionally, a preliminarily pathway investigation of the mitochondrial membrane potential (MMP) disruption and induction of apoptosis by MLC31 was carried out. Our results underline how agent design involving both hydrophilic and lipophilic peripheral groups may serve as an effective way to improve the PDT efficiency of highly aromatic PSs for NIR light-mediated cancer therapy.     

7-二芳氨基香豆素类光敏染料的合成及光谱性能

以7-二芳氨基香豆素为电子给体,联噻吩或联苯噻吩为π桥,氰乙酸为电子受体设计合成了两个"D-π-A"型香豆素类光敏染料(Ⅴ1和Ⅴ2),通过核磁共振氢谱及高分辨质谱测定,确认其化学结构,测定了其紫外-可见吸收光谱、荧光发射光谱。采用密度泛函理论-高斯密度泛函〔DFT-B3LYP/6-31G(d)〕对化合物进行几何优化,并进一步用TD-DFT方法计算得到吸收光谱和发射光谱,分析了构效关系。结果表明,与7-二苯氨基香豆素光敏染料(Ⅴ_3和Ⅴ_4)相比,7-二芴氨基香豆素光敏染料(Ⅴ_1和Ⅴ_2)的基态能级差分别由2.49 eV和2.62 eV减小至2.31 eV和2.49 eV;激发态能级差也相应减小了0.52 eV和0.42 eV;与以联苯噻吩为π桥的光敏染料(Ⅴ_2和Ⅴ_4)相比,以联噻吩为π桥的光敏染料(Ⅴ_1和Ⅴ_3)具有更好的分子平面性,最大吸收波长分别红移4nm和19 nm,发射波长则分别红移9 nm和16 nm。     

Mitochondria-Targeting Selenophene-Modified BODIPY-Based Photosensitizers for the Treatment of Hypoxic Cancer Cells

Two red-absorbing, water-soluble and mitochondria (MT)-targeting selenophene-substituted BODIPY-based photosensitizers (PSs) were realized ( BOD − Se , BOD − Se − I ), and their potential as photodynamic therapy (PDT) agents were evaluated. BOD − Se − I showed higher ¹O₂ generation yield thanks to the enhanced heavy-atom effect, and this derivative was further tested in detail in cell culture studies under both normoxic and hypoxic conditions. BOD − Se − I not only effectively functioned under hypoxic conditions, but also showed highly selective photocytotoxicity towards cancer cells. The selectivity is believed to arise from differences in mitochondrial membrane potentials of healthy and cancerous cells. To the best of our knowledge, this marks the first example of a MT-targeted BODIPY PS that functions under hypoxic conditions. Remarkably, thanks to the design strategy, all these properties where realized by a compound that was synthesized in only five steps with 32 % overall yield. Hence, this material holds great promise for the realization of next-generation PDT drugs for the treatment of hypoxic solid tumors.     

Synthesis of Red-Light-Responsive Pheophorbide-a Tryptamine Conjugated Photosensitizers for Photodynamic Therapy

Six methyl pheophorbide-a derivatives were prepared by linking a tryptamine side chain at the C-13 ¹ , C-15 ² and C-17 ³ positions of pheophorbide-a. P repared conjugates were characterized and evaluated for their photocytotoxicity against A549 cells. The conjugate 6 a with strong absorption at 413 nm (Soret band), 663–671 nm (Q bands) and comparable fluorescence quantum yield (0.26) was found to exhibit significant cytotoxicity (659 nM). Molecular integration of pheophorbide-a and tryptamines showed synergistic effects as the most potent conjugate 6 a was identified with enhanced photocytotoxicity when compared to methyl pheophorbide-a. T he conjugate 6 a was smoothly taken up by A549 cells and exhibited intracellular localization predominantly to lysosome in the cytoplasm. Upon photoirradiation 6 a generated singlet oxygen to show potent cytotoxicity toward A549 cells.     

Synthesis and Characterization of Novel Purpurinimides as Photosensitizers for Photodynamic Therapy

A series of novel purpurinimides with long wavelength absorption were designed and synthesized to develop novel and potential photosensitizers. These compounds were investigated through reduction, oxidation, rearrangement reaction and amidation reactions of methyl pheophorbide a. They demonstrated a considerable bathochromic shift of the major absorption band in the red region of the optical spectrum (695–704 nm). Newly synthesized purpurinimides were screened for their antitumor activities, and showed higher photodynamic efficiency against A549 cell lines as compared to purpurin-18 methyl ester. The results revealed the novel purpurinimides could be potential photosensitizers.