四磺酸基酞菁锌的合成及其与牛血清白蛋白作用的研究

酞菁化合物及其金属配合物是一类光氧化还原反应的有效光敏剂,对恶性肿瘤具有荧光定位诊断和光动力治疗作用,并对金黄色葡萄球菌、链球菌以及某些寄生虫具有光灭活作用,已引起人们越来越多的兴趣[1].尤其是含不同数目磺酸取代基的酞菁金属配合物被认为是一种较有效的光动力治疗光敏剂.     

酞菁配合物的结构与其光动力抗癌活性

光动力治疗是一种正在发展中的治疗癌症的新方法.主要是利用抗癌光敏剂可优先在 肿瘤组织中富集的特性和随后在适当波长的光照下所引发的光敏化反应来杀死癌肿瘤.自198 5年以来,酞菁配合物作为抗癌光敏剂的研究越来越引人注目. 此文在总结51篇参考文献的 基础上,提出了酞菁配合物的结构与其光动力抗癌活性的某些相关性,着重讨论了中心离子 、环取代基、轴向配体对光动力活性和相关物化性质的影响.得出的一个主要的结论是两亲 性酞菁是极具潜力的光敏剂.     

卟啉、酞菁L-B膜中取代基的定向作用研究

由Π-A 曲线研究了五种具有不同取代基的卟啉、酞菁金属配合物不溶物膜的水/空气界面性质, 根据分子截面积和分子模型推断了单层膜中卟啉、酞菁环的可能取向及取代基的定向作用. 以偏振紫外测定了L-B 多层膜中大环的取向, 结果表明卟啉, 酞菁环以与它们在亚相表面相同的取向转移到固体基片上, 证明了取代基的性质和致目不同对分子大环的定向作用不同.     

含氮芳氧基取代酞菁金属配合物光敏产生1O2

采用以2,5-二甲基呋喃(DMFU)为探针,通过气相色谱内标法测定了4种中心金属(Zn(Ⅱ)、Cu(Ⅱ)、Ni(Ⅱ)、Co(Ⅱ))、4种取代基及α位或β位取代的28种含氮芳氧基取代酞菁金属配合物新物种光敏产生单线态氧(1O2)的速率常数。讨论了中心金属电子结构、取代基类型及取代位置对酞菁金属配合物光敏产生1O2能力的影响。结果表明,它们产生1O2的能力有很大差异:(1)相同取代基在相同位置取代情况下,中心金属为锌的酞菁配合物光敏产生1O2的能力均好于中心金属为铜、钴、镍的酞菁配合物;(2)氮杂芳氧基取代酞菁锌光敏产生1O2的速率常数显著大于相应位置氨基苯氧基取代酞菁锌的;(3)α位氮杂芳氧基取代酞菁锌光敏产生1O2的速率常数均大于相应取代基β位取代酞菁锌的。     

密度泛函理论计算研究金属-N4大环化合物在酸性介质中的稳定性

质子交换膜燃料电池(PEMFCs)是一种能够有效地将化学能转换成电能的装置,其具有较高的效率及功率密度,还兼具环境友好的优点,因而在电动车和分布式电站等领域有广泛应用前景.然而,昂贵的价格及较差的耐久性阻碍了 PEMFCs的广泛应用.阴极氧还原反应(ORR)缓慢的动力学是限制 PEMFCs性能的主要因素.目前, Pt及其合金仍然是最有效的 ORR催化剂.有限的 Pt供应量是 PEMFC商业化的主要障碍之一.因此,具有较高 ORR活性的非贵金属催化剂越来越多的引起了人们的关注.在众多非贵金属 ORR催化剂中, Fe, Co等金属与氮共掺杂的碳材料最有望取代 Pt.一般认为,这类材料中起催化作用的活性中心是与金属酞菁(MPc)和卟啉(MP)等大环分子类似的金属-N4配位结构.无论是 MPc和 MP,还是掺杂碳材料催化剂,在酸性介质中的耐久性都不够好.具体原因至今仍没有定论.一些研究者认为中心金属离子与酸性介质中的质子交换引起的去金属中心是原因之一.我们通过密度泛函理论计算和热力学分析研究酸性介质(pH=1)中金属大环分子中金属离子和溶液中质子的交换反应,探讨去金属中心是否是造成金属大环类分子催化剂和金属与氮共掺杂碳基催化剂在酸性介质中不稳定的原因.
　　我们建立了研究金属大环化合物中心金属离子与溶液中质子的交换反应的热力学分析方法.在此基础上借助密度泛函理论计算获得各种金属酞菁和卟啉在强酸性介质中的金属离子平衡浓度,以确定相应金属大环分子的稳定性.研究结果表明,在酸性介质中铬、锰、锌类酞菁和卟啉分子很容易被质子化而形成相应的非金属酞菁和卟啉,原因可能是这三类金属的二价阳离子的3d轨道均为半充满或者全充满状态,使得它们与氮的配位能力下降;而铁、钴、镍、铜类酞菁和卟啉在酸性介质中金属化离子的平衡浓度几乎为零,表明它们基本上不发生金属离子与质子的交换反应,且稳定性趋势为 CoPc > NiPc > FePc > CuPc和 CoP > NiP > CuP > FeP,同时,相应的金属酞菁比金属卟啉更稳定.这表明具有氧还原活性的铁、钴类大环分子催化剂及铁、钴与氮共掺杂的碳材料在酸性溶液中的活性衰减并不是由于金属离子与质子的交换引起的.
　　我们还考察了取代基对大环分子中金属离子与质子交换反应的影响,结果发现,给电子取代基(甲基,氨基,叔丁基)会极大地增强酞菁铁和酞菁钴在酸性介质中的稳定性.对于酞菁铁而言,具有中等强度吸电子效应的四氯、四氟和十六氯取代后,其在酸性中稳定性有一定程度的增强,而具有强烈吸电子效应的四硝基及十六氟取代后,稳定性则降低.对于酞菁钴而言,上面提到的所有吸电子取代基都会使得其在酸性介质中变得更加不稳定,并且其不稳定程度随着取代基吸电子能力的增强而上升.     

密度泛函理论计算研究金属-N_4大环化合物在酸性介质中的稳定性（英文）

质子交换膜燃料电池(PEMFCs)是一种能够有效地将化学能转换成电能的装置,其具有较高的效率及功率密度,还兼具环境友好的优点,因而在电动车和分布式电站等领域有广泛应用前景.然而,昂贵的价格及较差的耐久性阻碍了PEMFCs的广泛应用.阴极氧还原反应(ORR)缓慢的动力学是限制PEMFCs性能的主要因素.目前,Pt及其合金仍然是最有效的ORR催化剂.有限的Pt供应量是PEMFC商业化的主要障碍之一.因此,具有较高ORR活性的非贵金属催化剂越来越多的引起了人们的关注.在众多非贵金属ORR催化剂中,Fe,Co等金属与氮共掺杂的碳材料最有望取代Pt.一般认为,这类材料中起催化作用的活性中心是与金属酞菁(MPc)和卟啉(MP)等大环分子类似的金属-N4配位结构.无论是MPc和MP,还是掺杂碳材料催化剂,在酸性介质中的耐久性都不够好.具体原因至今仍没有定论.一些研究者认为中心金属离子与酸性介质中的质子交换引起的去金属中心是原因之一.我们通过密度泛函理论计算和热力学分析研究酸性介质(pH=1)中金属大环分子中金属离子和溶液中质子的交换反应,探讨去金属中心是否是造成金属大环类分子催化剂和金属与氮共掺杂碳基催化剂在酸性介质中不稳定的原因.我们建立了研究金属大环化合物中心金属离子与溶液中质子的交换反应的热力学分析方法.在此基础上借助密度泛函理论计算获得各种金属酞菁和卟啉在强酸性介质中的金属离子平衡浓度,以确定相应金属大环分子的稳定性.研究结果表明,在酸性介质中铬、锰、锌类酞菁和卟啉分子很容易被质子化而形成相应的非金属酞菁和卟啉,原因可能是这三类金属的二价阳离子的3d轨道均为半充满或者全充满状态,使得它们与氮的配位能力下降;而铁、钴、镍、铜类酞菁和卟啉在酸性介质中金属化离子的平衡浓度几乎为零,表明它们基本上不发生金属离子与质子的交换反应,且稳定性趋势为Co PcNiPcFePcCuPc和Co PNiPCu PFeP,同时,相应的金属酞菁比金属卟啉更稳定.这表明具有氧还原活性的铁、钴类大环分子催化剂及铁、钴与氮共掺杂的碳材料在酸性溶液中的活性衰减并不是由于金属离子与质子的交换引起的.我们还考察了取代基对大环分子中金属离子与质子交换反应的影响,结果发现,给电子取代基(甲基,氨基,叔丁基)会极大地增强酞菁铁和酞菁钴在酸性介质中的稳定性.对于酞菁铁而言,具有中等强度吸电子效应的四氯、四氟和十六氯取代后,其在酸性中稳定性有一定程度的增强,而具有强烈吸电子效应的四硝基及十六氟取代后,稳定性则降低.对于酞菁钴而言,上面提到的所有吸电子取代基都会使得其在酸性介质中变得更加不稳定,并且其不稳定程度随着取代基吸电子能力的增强而上升.     

手性过渡金属(Mn,Co,Ni)-Salen配合物催化NaOCl不对称环氧化苯乙烯的反应研究

本文论述了由手性1,2-二苯基乙二胺与适当取代的邻羟基苯甲醛生成的希佛碱作为过渡金属Co(Ⅱ)、Ni(Ⅲ)、Mn(Ⅲ)的配体合成的6种过渡金属-Salen配合物在NaOCl下均相催化苯乙烯不对称环氧化反应的效果。对环氧化反应进行控制性研究,我们发现环氧化反应与中心金属离子的相关性可能主要源于配体结构、金属离子的选择及二者结合而形成的配合物的空间构型。好的不对称环氧化反应催化剂要求中心金属离子具有适当的氧化还原电位,对底物烯烃因其取代基的大小,催化剂结构的空间构型应有好坏之分,我们得到的循环伏安数据及实验结果部分说明这一点。同时对手性镍(Ⅱ)-Salen及手性锰(Ⅲ)-Salen配合物的催化反应机理配合实验现象分别作出假设,都经过自由基历程,但却是截然不同的活性氧化物种,同时,由于起主要作用的不对称诱导因素不同,不对称诱导方向有异。对同一催化剂在不同pH值下起作用的活性氧化物种类别也可能不同。     

手性过渡金属(Mn, Co, Ni)-Salen配合物催化NaOCl不对称环氧化苯乙烯的反应研究

本文论述了由手性1, 2-二苯基乙二胺与适当取代的邻羟基苯甲醛生成的希佛碱作为过渡金属Co(II)、Ni(II)、Mn(II)的配体合成的6种过渡金属-Salen配合物在NaOCl下均相催化苯乙烯不对称环氧化反应的效果。对环氧化反应进行控制性研究, 我们发现环氧化反应与中心金属离子的相关性可能主要源于配体结构、金属离子的选择及二者结合形成的配合物的空间构型。好的不对称环氧化反应催化剂要求中心金属离子具有适当的氧化还原电位, 对底物烯烃因其取代基的大小, 催化剂结构的空间构型应有好坏之分, 我们得到的循环伏安数据及实验结果部分说明这一点。同时对手性镍(II)-Salen及手性锰(III)-Salen配合物的催化反应机理配合实验现象分别作出假设, 都经过自由基历程, 但却是截然不同的活性氧化物种, 同时, 由于起主要作用的不对称诱导因素不同, 不对称诱导方向有异。对同一催化剂在不同pH值下起作用的活性氧化物种类别也可能不同。     

双核金属酞菁类化合物催化脱硫机理研究Ⅲ──M（Ⅱ）Pc－PcM（Ⅱ）的电子结构及M（Ⅱ）与Pc间的键合方式

采用ＩＮＤＯ／Ｓ方法研究了双核金属酞菁类化合物Ｍ（Ⅱ）Ｐｃ－ＰｃＭ（Ⅱ）（Ｍ＝Ｃｒ、Ｍｎ、Ｆｅ、Ｃｏ、Ｎｉ、Ｃｕ、Ｚｎ）的电子结构．结果表明当金属离子Ｍ（Ⅱ）与酞菁环键合后，其价电子重新布居，从而导致在Ｍ＝Ｃｒ、Ｍｎ、Ｆｅ、Ｚｎ时中心金属离子从酞菁环得到电子；而当Ｍ＝Ｃｏ、Ｎｉ、Ｃｕ时却是中心金属离子向酞菁环转移电子．键合方式的研究结果表明在Ｍ（Ⅱ）Ｐｃ－ＰｃＭ（Ⅱ）分子中，中心金属离子与酞菁环间存在着σ配键、反馈π键和离域π键三种化学键形成，从而在中心金属离子与酞菁环间产生灵活的“电荷呼吸”作用，构成了双核金属酞菁类化合物氧化还原作用的基础．     

磺化2,3-萘酞菁锌(Ⅱ)、钴(Ⅱ)的电子吸收光谱和荧光光谱的研究

研究了磺化2，3-萘酞菁锌(Ⅱ)、钴(Ⅱ)在DMF(N，N-二甲基甲酰胺)、DMSO(二甲基亚砜)、乙醇、水等溶剂中的电子吸收光谱和荧光光谱．萘酞菁配合物的Q带与相应的酞菁配合物Q带相比，电子吸收光谱红移80～90nm，荧光光谱红移约100nm，荧光强度也显增加．在金属萘酞菁中引入磺酸基，配合物的电子吸收光谱Q带发生红移，但是影响不大、对于相同中心金属的配合物，改变溶剂的种类对配合物的电子吸收光谱的Q带影响较大．在金属萘酞菁环上引入一个磺酸基时，在相同溶剂中与无取代萘酞菁相比发生荧光光谱Q带红移，荧光强度增大．但在萘酞菁环上继续引入磺酸基时，荧光强度反而减少．磺化萘酞菁钴比磺化萘酞菁锌有较大的荧光强度．不同浓度下的电子吸收光谱和荧光光谱说明金属萘酞菁有集聚倾向、能形成基激缔合物．     

Synthesis and properties of photo-activable phthalocyanines: a brief overview

Phthalocyanines (Pcs) can very well satisfy the different demands of photosensitizer in photodynamic therapy (PDT) such as absorption, amphiphilicity and most importantly, high photochemical reactivity, depending on the subtle interplay of structure?Cfunction relationships. They have been shown to be phototoxic against a number of tumor cells. Certain criteria of ideal photosensitizers for PDT were described. A brief summary of the synthesis and some properties of photo-activable Pcs have been presented and an outlook for future photocytotoxic Pcs given. These Pcs are classified into three groups: (1) Pcs with different peripheral and/or non-peripheral substitution; (2) Pcs with different axial substitution; (3) Pcs with different metal center.     

A TDDFT investigation of bay substituted perylenediimides: Absorption and intersystem crossing

The conformational structure and electronic spectra properties of a series of bay substituted perylenediimides (PDI) derivatives have been investigated by means of density functional theory (DFT) and time‐dependent DFT. The B3LYP and PBE0 hybrid exchange‐correlation functionals were applied in conjunction with the double‐ζ quality SVP basis set. These compounds are interesting for organic materials science and as photosensitizers in cancer phototherapy (PDT), because of their intense absorption in the visible region. Results show that the substitution at the bay position of the PDI parent molecule with N‐alkyl groups shifts the absorption maxima towards the red part of the visible spectrum (around 650–700 nm) as required for the applications in PDT. The main PDT action mechanisms have been investigated by computing of electron affinities, ionization potentials, triplet energies and spin‐orbit matrix elements between singlet and triplet excited states. © 2012 Wiley Periodicals, Inc.     

Immobilized phthalocyanines of magnesium,aluminum, and zinc in photodynamic treatment of mesenchymal stromal cells

Phthalocyanines of magnesium, aluminum, and zinc immobilized on nano-sized silica and poly-N-vinylpyrrolidone in aqueous solutions were synthesized. Photochemical activity of the immobilized metal complexes was assessed by generation of singlet oxygen. Nontoxic concentrations of the new photosensitizers were determined in vitro. A comparative analysis of the efficiency of photodynamic therapy (PDT) was performed for immobilized phthalocyanines using mesenchymal stromal cells as a cell model. Aluminum phthalocyanine immobilized on nano-sized silica displayed the highest cell tropism. Irradiation of phthalocyanine-loaded cells resulted in generation of active singlet oxygen and subsequent apoptotic cell death. The use of immobilized phthalocyanines allowed decreasing the effective concentration (dose) of photosensitizer and enhancing the PDT cytotoxicity.     

Iodine substituted phosphorus corrole complexes as possible photosensitizers in photodynamic therapy: Insights from theory

The search for new dyes to be used as photosensitizers in photodynamic therapy (PDT) is a field of great interest from both experimental and theoretical viewpoints. In this study, the main photophysical properties (excitation energies, singlet-triplet energy gap, and spin orbit coupling matrix elements) of some unsubstituted and iodine substituted phosphorus corrole complexes have been determined by using density functional theory and its time-dependent formulation. Results show that these compounds can be proposed as photosensitizers in PDT. The heavy atom effects have been rationalized on the basis of El-Sayed rules.     

姜黄素桥连卟啉光敏剂的合成及表征

为了开发新的高效光动力治疗光敏剂, 以2-(2-羟基萘基)-5,10,15,20-四苯基卟啉及其Cu(Ⅱ), Ni(Ⅱ), Zn(Ⅱ)配合物为原料, 利用1,6-二溴己烷桥连具有抗癌活性的小分子姜黄素, 设计合成4个新型的天然产物桥连卟啉化合物. 通过UV, ¹H NMR, IR, MS及元素分析等手段对该新型光敏药剂进行了结构表征; 在此基础上, 采用凝胶电泳法考察了化合物在光照和无光照条件下对pBR322质粒DNA的切割能力. 作为潜在光敏剂与DNA相互作用的初步研究表明, 其与DNA结合能力较强, 具有明显的光敏切割效果.     

Tailoring photosensitive ROS for advanced photodynamic therapy

Photodynamic therapy (PDT) has been considered a noninvasive and cost-effective modality for tumor treatment. However, the complexity of tumor microenvironments poses challenges to the implementation of traditional PDT. Here, we review recent advances in PDT to resolve the current problems. Major breakthroughs in PDTs are enabling significant progress in molecular medicine and are interconnected with innovative strategies based on smart bio/nanomaterials or therapeutic insights. We focus on newly developed PDT strategies designed by tailoring photosensitive reactive oxygen species generation, which include the use of proteinaceous photosensitizers, self-illumination, or oxygen-independent approaches. While these updated PDT platforms are expected to enable major advances in cancer treatment, addressing future challenges related to biosafety and target specificity is discussed throughout as a necessary goal to expand the usefulness of PDT.Subject terms: Biological therapy, Biosensors     

Computational design of chlorin based photosensitizers with enhanced absorption properties

The porphyrin and chlorin parent compounds constitute the base of many potent photosensitizers aimed to be utilized in photodynamic therapy (PDT). However, the photosensitizers available on the market today are not ideal for use in PDT; many of them suffering from drawbacks such as long-lasting photosensitization or absorption at wavelengths below the optimal tissue penetration. This has emphasized the need of new photosensitizers with improved photodynamic properties. In the present study we have used density functional theory based methods to design new chlorin compounds with conjugated substituents such as vinyl groups and carboxylic acids, aiming for strong absorption in the therapeutic window of PDT. The specific substituent positions were found to have a significant effect on the spectra. A chlorin with four propenoic acids was able to red-shift the absorption the most compared with non-substituted chlorin, generating the red-most absorption at 755 nm, and with significantly enhanced oscillator strengths. The results from the present study constitute a useful starting point for further design of tetrapyrrole derivatives as improved photosensitizers.     

Effect of Axial Ligands on the Molecular Configurations,Stability, Reactivity,and Photodynamic Activities of Silicon Phthalocyanines

To demonstrate the effect of axial ligands on the structure–activity relationship, a series of axially substituted silicon phthalocyanines (SiPcs) have been synthesized with changes to the axial ligands. The reactivity of the axial ligand upon shielding by the phthalocyanine ring current, along with their stability, photophysical, and photodynamic therapy (PDT) activities were compared and evaluated for the first time. As revealed by single‐crystal XRD analysis, rotation of the axial ? OMe ligands was observed in SiPc 3 , which resulted in two molecular configurations coexisting synchronously in both the solid and solution states and causing a split of the phthalocyanine α protons in the ¹H NMR spectra that is significantly different from all SiPcs reported so far. The remarkable photostability, good singlet oxygen quantum yield, and efficient in vitro photodynamic activity synergistically show that compound 3 is one of the most promising photosensitizers for PDT.     

The role of photosensitizer molecular charge and structure on the efficacy of photodynamic therapy against Leishmania parasites

Photodynamic therapy (PDT) is emerging as a potential therapeutic modality in the clinical management of cutaneous leishmaniasis (CL). In order to establish a rationale for effective PDT of CL, we investigated the impact of the molecular charge and structure of photosensitizers on the parasitic phototoxic response. Two photosensitizers from the benzophenoxazine family that bear an overall cationic charge and two anionic porphyrinoid molecules were evaluated. The photodynamic activity of the photosensitizers decreases in the following order: EtNBSe > EtNBS > BpD > PpIX. The studies suggest that compared to hydrophobic anionic photosensitizers, the hydrophilic cationic benzophenoxazine analogs provide high effectiveness of PDT possibly due to (1) their strong attraction to the negatively charged parasitic membrane, (2) their hydrophilicity, (3) their high singlet oxygen quantum yield, and (4) their efficacy in targeting intracellular organelles.