酞菁是一種廣泛應用的多用途功能材料。本研究工作的目的是探索酞菁作為用於靶向光動力療法 (PDT) 的可激活的和高效光敏劑的潛力。就這研究課題，本論文描述了ー系列精心設計的酞菁光敏劑的合成、其光譜表徵、光物理屬性和體外光動力活性。 / 第一章概述了光動力療法，包括其歷史發展、光物理和生物機制及臨床應用現狀。本章介紹各種不同類型的光敏劑，其中重點介紹了酞菁，因它被視為最有前途的第二代光敏劑之一。為了提高療效，過往有不少努力都投放在去把光敏劑功能化，以實現它在化學療法和光動力雙效治療及靶向治療的作用。本章的結尾部分，我們更會引用相關的例子去討論和解釋這種先進治療方式的概念以及近期的發展。 / 含鉑藥物已作為臨床化療藥物廣泛應用於多種癌症的治療。我們設計了一種新型的酞菁鉑配合物共軛體系，以取得光動力和化學療法的雙重效果。第二章主要描述了由鋅(II)酞菁和具有抗癌性的奧沙利鉑衍生物構成的共軛體系的合成方法和光譜特性，同時對該共軛體系基本的光物理性能，聚合行為和體外光動力性能進行了考察，並與一些化合物模型進行了對比。該共軛體系展示出一種協同效應。在HT29 人結腸腺癌細胞內，奧沙利鉑的存在導致該共軛體系在黑暗裡產生暗毒性；在光照下，基於鋅(II)酞菁的存在，它產生了增强的細胞毒素效應。這種高效光動力行為也可以歸結為其較高的細胞攝取和活性氧 (ROS) 產生的功效。該共軛體系更傾向定位於細胞溶酶體並誘使主要通過細胞凋亡的細胞死亡。 / 多胺是普遍存在於細胞的陽離子，並在細胞的繁殖和分化中起着多重作用。許多腫瘤細胞表現出具有較高的多胺含量並且激活多胺載體以導入外源多胺來維持快速的細胞分裂活動。因此，與多胺類化合物的結合是提高光敏材料針對腫瘤細胞的方法之一。第三章描述了一系列多胺取代的鋅(II)酞菁的合成、光譜表徵和光物理特性，並考察了它們對於B16 黑色素瘤和中國倉鼠卵巢 CHO 細胞的光動力行為。同時對其細胞攝取率、亞細胞定位和細胞死亡機制進行了報導。 / 除了與這些腫瘤特異載體共軛連接，可被腫瘤相關刺激激活的光敏劑也是能提高腫瘤選擇性的一個好方法。谷胱甘肽 (GSH) 在細胞質中是最豐富的硫醇，也是在生物化學過程中主要的還原劑。細胞內的谷胱甘肽 (ca. 10 mM) 與細胞外部 (ca. 2 μM) 相比具有較高的濃度。 因此，我們可以利用以這個特性來啟動光敏劑。第四章報告了一種具有還原效應的矽(IV)酞菁。該化合物軸向由兩個二茂鐵基查爾酮衍生物通過二硫鍵取代，並易於在還原條件下快速斷裂。我們通過不同的光譜測試，對該化合物基本的光物理性能及其在還原試劑作用下的斷裂動力學進行了研究。我們也同時考察了存在和不存在外部還原試劑條件下，其對於MCF-7 人乳腺癌細胞的體外光動力行為，包括細胞毒素效應、細胞攝取和亞細胞定位。 / 為了進一步提高腫瘤的選擇性，發展一種可同時被兩種腫瘤相關刺激激活的光敏劑也是體現靶向治療的方法之一。 癌細胞除了比正常細胞含有較高的谷胱甘肽濃度外，它的另一種特性是其外區域的pH 值 (ca. 6.8) 比周圍正常組織(ca. 7.3) 相對較低。這種獨特的特徵也是一種機制來啟動光敏劑。第五章主要探討一種具有pH 和還原雙回應的矽(IV)酞菁。該化合物軸向分別由二茂鐵衍生物通過二硫鍵和腙鍵取代。由於連接鍵在生理的pH 值和低濃度還原試劑或其中一項的條件下不會斷裂，所以在二茂鐵的淬滅的影響下，光敏劑維持在光動力惰性的狀態。但是，在酸性和高濃度還原試劑的情況下，光敏劑會被激活。我們會在這一章探討這些外來刺激對光敏劑的光物理特性和體外光動力行為的影響。 / 第六章會就本項研究作出總結，而第七章則報導實驗程序。第八章列舉了本論文所引用的參考文獻。 / 論文的最後會附上所有新化合物的氫及碳核磁共振譜圖。 / Phthalocyanines are versatile functional materials for a wide range of applications. This research work aims to explore their potential as activatable and efficient photosensitizers for targeted photodynamic therapy (PDT). This thesis describes the synthesis, spectroscopic characterization, photophysical properties, and in vitro photodynamic activities of several series of carefully designed phthalocyanine-based photosensitizers. / Chapter 1 presents an overview of PDT, including its historical development, photophysical and biological mechanisms, and current clinical applications. Various classes of photosensitizers are introduced with emphasis put on phthalocyanines, which have emerged as a promising class of second-generation photosensitizers for PDT. In order to enhance the therapeutic efficacy, considerable effort has been expended to functionalize the photosensitizers with a view to achieving dual and targeted therapy. The concept and recent development of this advanced modality is discussed and illustrated with relevant examples at the end of this chapter. / Platinum-based drugs have been widely used as clinical chemotherapeutic drugs for the treatment of a variety of cancers. In order to bring about a dual photodynamic and chemotherapeutic effect, we have designed a novel phthalocyanine-platinum complex conjugate. Chapter 2 presents the synthesis and spectroscopic characterization of this conjugate, which comprises of a zinc(II) phthalocyanine and an oxaliplatin derivative that is known to have antitumor activity. The basic photophysical properties, aggregation behavior, and in vitro photodynamic activities of this conjugate have also been investigated and compared with those of some model compounds. This conjugate demonstrates a synergistic effect in which it shows a cytotoxic effect in the dark due to the oxaliplatin moiety and an enhanced cytotoxicity upon illumination due to the phthalocyanine unit toward the HT29 human colon adenocarcinoma cells. The high photodynamic activity can also be attributed to its higher cellular uptake and reactive oxygen pecies (ROS) generation efficiency. This conjugate shows preferential localization in the lysosomes and induces cell death mainly through apoptosis. / Polyamines are ubiquitous cellular cations that play multifunctional roles in cell proliferation and differentiation. Many tumors cells have been shown to contain elevated polyamine levels and active polyamine transporters for importing exogenous polyamines in order to sustain rapid cell division. As a result, conjugation of polyamine analogues is one of the potential strategies to improve the tumor-targeting property of photosensitizers. Chapter 3 describes the synthesis, spectroscopic characterization, and photophysical properties of a series of polyamine-substituted zinc(II) phthalocyanines. Their photodynamic activities toward B16 melanoma and Chinese hamster ovary (CHO) cells have been investigated. Their cellular uptake, subcellular localization, and cell death mechanism are also reported herein. / Apart from conjugation to these tumor-specific vectors, the use of photosensitizers that can be activated by tumor-associated stimuli is also a promising approach to enhance the tumor selectivity. Glutathione (GSH) is the most abundant thiol in cytoplasm and the major reducing agent in many biochemical processes. The much higher intracellular GSH concentration (ca. 10 mM) compared with the extracellular levels (ca. 2 μM) provides a mechanism for activating photosensitizers. Chapter 4 reports the molecular design and development of a novel redox-responsive silicon(IV) phthalocyanine axially substituted with two ferrocenyl-chalcone derivatives via disulfide bonds, which are prone to rapid cleavage under a reducing environment. The basic photophysical properties of this compound and its cleavage kinetics upon exposure to a reductive stimulant have been studied by various spectroscopic methods. Its in vitro photodynamic activities including cytotoxicity, cellular uptake, and subcellular localization towa d MCF-7 human breast cancer cells, both in the absence and presence of an external reducing agent, have also been examined. / To further enhance the tumor specificity, development of activatable photosensitizers that can be activated concurrently by two different tumor-associated stimuli is also a promising strategy toward targeted PDT. Aside from the difference in GSH content between tumor and normal tissues, another unique feature of tumors is that their extracellular pH (ca. 6.8) is relatively lower as compared with that around the normal tissues (ca. 7.3). This characteristic offers another mechanism to trigger the response of photosensitizers. Chapter 5 focuses on the exploration of a dual pH- and redox-responsive silicon(IV) phthalocyanine in which the ferrocenyl quenchers are axially coordinated to the macrocycle through an acid-labile hydrazone bond and a reducible disulfide bond. At physiological pH and low level of reducing agent, or under one of these conditions, the linker(s) remain(s) intact and hence the photosensitizer remains photodynamically “inactive“ due to the quenching effect induced by the ferrocenyl unit(s). However, it becomes activated in an environment with low pH and high level of reducing agent, which is analogous to the conditions in tumor tissues. The effects of these external stimuli on the photophysical properties and in vitro photodynamic activities of this novel photosensitizer are examined in this chapter. / Chapter 6 concludes the present study while Chapter 7 reports the experimental procedures. All references adapted in this manuscript are presented in Chapter 8. / ¹H and ¹⁶C{¹H} NMR spectra of all the new compounds are given in the Appendix. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Lau, Ting Fong Janet. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 191-202). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese. / Table of Contents --- p.i / Acknowledgment --- p.vi / Abstract --- p.ix / Abstract (in Chinese) --- p.xii / Abbreviations --- p.xiv / List of Figures --- p.xviii / List of Tables --- p.xxvi / List of Schemes --- p.xxviii / Publication Related to This Thesis --- p.xxx / Chapter Chapter 1 --- Introduction / Chapter 1.1 --- Introduction --- p.1 / Chapter 1.1.1 --- History of Photodynamic Therapy --- p.1 / Chapter 1.1.2 --- Basic Principles of Photodynamic Therapy --- p.4 / Chapter 1.1.2.1 --- Photophysical Mechanisms --- p.4 / Chapter 1.1.2.2 --- Biological Mechanisms --- p.7 / Chapter 1.2 --- Photosensitizers of Photodynamic Therapy --- p.8 / Chapter 1.2.1 --- Characteristics of Ideal Photosensitizers --- p.10 / Chapter 1.2.2 --- First-Generation Photosensitizers --- p.11 / Chapter 1.2.3 --- Second-Generation Photosensitizers --- p.13 / Chapter 1.2.4 --- Phthalocyanine-Based Photosensitizers --- p.17 / Chapter 1.3 --- Toward Targeted Photodynamic Therapy --- p.23 / Chapter 1.3.1 --- Site-Specific Delivery of Photosensitizers --- p.23 / Chapter 1.3.1.1 --- Conjugation to Monoclonal Antibodies --- p.23 / Chapter 1.3.1.2 --- Conjugation to Tumor Vessel-Targeted Peptides --- p.24 / Chapter 1.3.1.3 --- Conjugation to Folic Acid --- p.26 / Chapter 1.3.2 --- Activatable Photosensitizers --- p.27 / Chapter 1.3.2.1 --- Environmental Activatable Photosensitizers --- p.27 / Chapter 1.3.2.2 --- Photodynamic Molecular Beacons --- p.30 / Chapter 1.4 --- Dual Chemo- and Photodynamic Therapy --- p.34 / Chapter 1.4.1 --- Covalent Conjugation --- p.34 / Chapter 1.4.2 --- Co-encapsulation in Polymeric Micelles --- p.36 / Chapter 1.4.3 --- Sequential Administration --- p.38 / Chapter 1.5 --- Objectives of This Study --- p.41 / Chapter Chapter 2 --- A Zinc(II) Phthalocyanine Conjugated with an Oxaliplatin Derivative for Dual Chemo- and Photodynamic Therapy / Chapter 2.1 --- Introduction --- p.42 / Chapter 2.2 --- Results and Discussion --- p.43 / Chapter 2.2.1 --- Molecular Design, Synthesis, and Characterization --- p.43 / Chapter 2.2.2 --- Electronic Absorption and Photophysical Properties --- p.46 / Chapter 2.2.3 --- In Vitro Photodynamic Activities --- p.49 / Chapter 2.3 --- Summary --- p.60 / Chapter Chapter 3 --- Zinc(II) Phthalocyanine-Polyamine Conjugates as Efficient Photosensitizers for Photodynamic Therapy / Chapter 3.1 --- Introduction --- p.62 / Chapter 3.2 --- Results and Discussion --- p.64 / Chapter 3.2.1 --- Preparation and Characterization --- p.64 / Chapter 3.2.2 --- Electronic Absorption and Photophysical Properties --- p.68 / Chapter 3.2.3 --- In Vitro Photodynamic Activities --- p.74 / Chapter 3.3 --- Summary --- p.84 / Chapter Chapter 4 --- A Redox-Responsive Silicon(IV) Phthalocyanine for Targeted Photodynamic Therapy / Chapter 4.1 --- Introduction --- p.85 / Chapter 4.2 --- Results and Discussion --- p.86 / Chapter 4.2.1 --- Preparation and Characterization --- p.86 / Chapter 4.2.2 --- Electronic Absorption and Photophysical Properties --- p.89 / Chapter 4.2.3 --- In Vitro Photodynamic Activities --- p.99 / Chapter 4.3 --- Summary --- p.104 / Chapter Chapter 5 --- A Dual pH- and Redox-Responsive Phthalocyanine-Based Photosensitizer for Targeted Photodynamic Therapy / Chapter 5.1 --- Introduction --- p.106 / Chapter 5.2 --- Results and Discussion --- p.107 / Chapter 5.2.1 --- Molecular Design, Synthesis, and Characterization --- p.107 / Chapter 5.2.2 --- Electronic Absorption and Photophysical Properties --- p.115 / Chapter 5.2.3 --- pH- and Redox-Responsive Properties --- p.118 / Chapter 5.2.4 --- In Vitro Photodynamic Activities --- p.130 / Chapter 5.3 --- Summary --- p.136 / Chapter Chapter 6 --- Conclusion and Future Outlook --- p.137 / Chapter Chapter 7 --- Experimental Section / Chapter 7.1 --- General --- p.138 / Chapter 7.1.1 --- Materials and Methods --- p.138 / Chapter 7.1.2 --- Photophysical Measurements --- p.139 / Chapter 7.1.3 --- Cell Lines and Culture Conditions --- p.140 / Chapter 7.1.4 --- Photocytotoxicity Assay --- p.141 / Chapter 7.1.5 --- ROS Measurements --- p.141 / Chapter 7.1.6 --- Intracellular Fluorescence Studies --- p.142 / Chapter 7.1.7 --- Cellular Uptake Determined by an Extraction Method --- p.142 / Chapter 7.1.8 --- Subcellular Localization Studies --- p.143 / Chapter 7.1.9 --- Flow Cytometric Studies --- p.144 / Chapter 7.2 --- Experiments Described in Chapter 2 --- p.145 / Chapter 7.2.1 --- Synthesis --- p.145 / Chapter 7.2.2 --- Photocytotoxicity Assay --- p.155 / Chapter 7.2.3 --- Intracellular Fluorescence Studies --- p.155 / Chapter 7.2.4 --- Cellular Uptake Determined by an Extraction Method --- p.155 / Chapter 7.2.5 --- Subcellular Localization Studies --- p.156 / Chapter 7.3 --- Experiments Described in Chapter 3 --- p.156 / Chapter 7.3.1 --- Synthesis --- p.156 / Chapter 7.3.2 --- Photocytotoxicity Assay --- p.171 / Chapter 7.3.3 --- Effect on Spermidine on the Cellular Uptake --- p.171 / Chapter 7.3.4 --- Intracellular Fluorescence Studies --- p.172 / Chapter 7.3.5 --- Subcellular Localization Studies --- p.172 / Chapter 7.4 --- Experiments Described in Chapter 4 --- p.173 / Chapter 7.4.1 --- Synthesis --- p.173 / Chapter 7.4.2 --- Redox-Responsive Fluorescence Emission Studies --- p.180 / Chapter 7.4.3 --- Redox-Responsive Singlet Oxygen Generation Studies --- p.180 / Chapter 7.4.4 --- Photocytotoxicity Assay --- p.180 / Chapter 7.4.5 --- Intracellular Fluorescence Studies --- p.181 / Chapter 7.4.6 --- Subcellular Localization Studies --- p.181 / Chapter 7.5 --- Experiments Described in Chapter 5 --- p.182 / Chapter 7.5.1 --- Synthesis --- p.182 / Chapter 7.5.2 --- pH- and Redox-Responsive Fluorescence Emission Studies --- p.189 / Chapter 7.5.3 --- pH- and Redox-Responsive Singlet Oxygen Generation Studies --- p.189 / Chapter 7.5.4 --- Intracellular Fluorescence Studies --- p.190 / Chapter Chapter 8 --- References --- p.191 / Chapter Appendix --- ¹H and ¹³C{¹H} NMR Spectra --- p.203

No description available.

Thesis (M.S.)--Rochester Institute of Technology, 1990. / Includes bibliographical references.

No description available.

Thesis (Ph.D.)--York University, 2005. Graduate Programme in Chemistry. / Typescript. Includes bibliographical references (leaves 160-178). Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://wwwlib.umi.com/cr/yorku/fullcit?pNR11543

Syntheses of various octasubstituted open-shell (Ni(II), Pd(II) and Pt(II)) metallophthalocyanines and their metal-free analogues have been carried out. Spectroscopic characterizations, photophysical and photochemical studies were carried out to determine the effects of these metals on the molecules using the metal-free phthalocyanine analogues as benchmark. Metal-binding studies of few thio-derivatised phthalocyanines were done to increase the number of palladium metal on the phthalocyanine ligands and determine the effect of increasing number of this metal on phthalocyanine properties. Palladium (PdPc) and platinum phthalocyanines (PtPc) gave good triplet and singlet oxygen quantum yields making them suitable for further investigation in application as photosensitisers. Using 4-nitrophenol as model pollutant, photosensitization reactions were carried out under homogenous and heterogeneous conditions. The reactions were monitored using UV-vis spectroscopy. The MPcs were adsorbed on functionalized single wall carbon nanotube (SWCNT-COOH) to form heterogeneous photosensitizers with PtPc failing to adsorb on the SWCNT-COOH. Under the heterogeneous condition, all the PdPcs photosensitization kinetics was consistent with Langmuir-Hinshelwood reaction model. The best photosenstiser, β-palladium dodecylthio phthalocyanine was also deployed in sensitization of oxidation of 4-chlorophenol and pentachlorophenol under homogenous and heterogeneous conditions to establish the ability of the molecules to sensitize oxidation of wide range of phenolic pollutants. Identifications of the products of the reactions were conducted using gas chromatography and high pressure liquid chromatography (HPLC) hyphenated with mass analyzer (LC-MS). Mechanisms of all the reactions were investigated and all the complexes, in spite of reduced lifetime resulting from open-shell nature of the metals, sensitized the reactions through singlet oxygen mediated pathway. All the heterogeneous sensitisers were recyclable in the 4- nitrophenol oxidation but β-palladium dodecylthio phthalocyanine proved unrecyclable in the oxidation of pentachlorophenol.

This work focuses on the development of red light-activated porphycene-based photosensitizers for anti-tumor photodynamic therapy (PDT) under both normoxic and hypoxic conditions. A total of seven water-soluble porphycenes have been designed, synthesized and evaluated as potential PDT agents in terms of their photophysical and photobiological properties using principally the human nasopharyngeal carcinoma (HK-1) cells. Among the porphycenes synthesized, two were neutral amphiphilic aryl porphycenes, TDEGPPo and Zn(II) TDEGPPo, with relatively weak photo-cytotoxic activities even under normoxic condition. Two cationic porphycenes, TPyBPo and TriPyPPo, exhibited strong photo-cytotoxic activities, with LD50 of 0.3 mM at a light dose of 3 J/cm2, under normoxic condition. However, much lower photo-cytotoxicity was observed under hypoxic condition for TPyBPo and TriPyPPo, with LD50 of 3 mM and 3.5 mM, respectively, obtained at high light doses (>10 J/cm2). Two alkyl porphycenes with one and two sulfonoamide diglycol functionalities, TBPoS-OH and TBPoS-2OH, were synthesized and shown to exhibit very potent photo-cytotoxic activities, with respective LD50 of 53 nM and 20 nM (light dose 8 J/cm2) under normoxic conditions. Most importantly, comparably potent photo-cytotoxicity was also observed for these porphycenes under hypoxic conditions, with respective LD50 of 65 nM and 50 nM (light dose 8 J/cm2). In addition, these porphycenes were taken up by the HK-1 cells very rapidly, with >90% accumulated inside the cells after only 1 h of incubation. Confocal microscopy revealed that these porphycenes were localized at the lysosomes, mitochondria as well as endoplasmic reticulum. Furthermore, the predominant mode of cell death caused by the PDT action of these porphycenes was shown to be apoptosis. In an attempt to effect mitochondria localization to enhance apoptotic cell death for these porphycenes, TBPoS-OH was conjugated with rhodamine B to produce the TBPoS-Rh B conjugate. This porphycene-Rh B conjugate also displayed very potent photo-cytotoxicity under both normoxic and hypoxic conditions, with LD50 of 52 nM and 85 nM, respectively, at a light dose of 8 J/cm2. However, confocal microscopy revealed its principal subcellular localization was at the lysosomes, not the mitochondria. The PDT activities of these porphycenes were compared to a well-known patented PDT agent, EtNBS, which is active under both normoxic and hypoxic conditions, with LD50 of 58 nM and large than 1000 nM, respectively, towards the HK-1 cells. This comparison clearly shows that our sulfonoamido-porphycenes, TBPoS-OH, TBPoS-2OH and TBPoS-Rh B conjugate, display a 15- to 25-fold stronger hypoxic PDT activity relative to EtNBS, thus making these porphycenes excellent candidates for hypoxic anti-tumor photodynamic therapy.

published_or_final_version / abstract / Chemistry / Doctoral / Doctor of Philosophy

At the end of this thesis, the 1H and 13C{ 1H} NMR spectra for all the new compounds and the crystallographic data are given as an Appendix. / Chapter 1 presents an overview of phthalocyanines and subphthalocyanines, including their general synthesis, properties, photosensitizing applications, and supramolecular chemistry. / Chapter 2 describes the synthesis and spectroscopic characterization of a series of subphthalocyanines axially substituted with an oligoethylene glycol chain [SPcB(OCH2CH2)nOH] (n = 3, 4) or a p-phenoxy oligoethylene glycol methyl ether chain [SPcBOC 6H4(OCH2CH2)nOCH3] (n = 2, 3). Their in vitro photodynamic activities toward HT29 human colorectal adenocarcinoma and HepG2 human hepatocarcinoma cells have also been investigated. In general, these compounds are essentially non-aggregated, resulting in a strong fluorescence emission and high efficiency to generate singlet oxygen. Being formulated with Cremophor EL, these subphthalocyanines function as efficient photosensitizers and exhibit a high photocytotoxicity. The phenoxy analogues show a relatively high photostability and are particularly potent toward these cell lines. / Chapter 3 reports the synthesis, spectroscopic characterization, and in vitro photodynamic activities of a new series of water-soluble subphthalocyanines. The photodynamic activities of these compounds against HepG2 and HT29 cells have also been evaluated. They exhibit high singlet oxygen quantum yields, but different degree of photostability, which greatly affects their photocytotoxicity. The relatively high photostability of the carboxy subphthalocyanine and its salts renders them highly photocytotoxic. / Chapter 4 describes the axial coordination of two subphthalocyanines having an axial pyridyl group with several tetrapyrrole derivatives, including zinc(II) and ruthenium(II) porphyrins and phthalocyanines. By using various spectroscopic methods and X-ray diffraction analyses, the formation of 1:1 hetero-dyads has been confirmed. The binding constants between the pyridyl subphthalocyanines and these metallotetrapyrrole derivatives have also been determined by a fluorescence titration method. / Chapter 5 presents the synthesis and spectroscopic characterization of a covalently linked subphthalocyanine-cyclodextrin conjugate. The host-guest interactions between this compound and a tetra-sulfonated porphyrin in aqueous medium have been investigated by various spectroscopic methods. This supramolecular system exhibits an efficient photo-induced energy transfer process from the excited subphthalocyanine core to the porphyrin moiety. This host-guest approach provides a new strategy to construct mixed subphthalocyanine and porphyrin systems, which have not been explored so far. / Chapter 6 reports the use of a series of zinc(II) and silicon(IV) phthalocyanines as photocatalysts for the photooxidation of olefins and 1-naphthol. These compounds are efficient photosensitizers producing singlet oxygen to form the oxidized products in high yields. The only exceptions are two dendritic silicon(IV) phthalocyanines which have a relatively low efficiency to generate singlet oxygen. Three photosensitizers have also been examined for their recyclability in the photooxidation of alpha-terpinene and furan-2-carboxylic acid. All of them can be recycled at least four times without a significant loss of catalytic activity. / This thesis reports our investigation of two versatile classes of functional dyes, namely phthalocyanines and subphthalocyanines, focusing on their photosensitizing applications and supramolecular chemistry. / Xu, Hu. / Adviser: Dennis K. P. Ng. / Source: Dissertation Abstracts International, Volume: 70-06, Section: B, page: 3506. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references. / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

At the end of this thesis, 1H and 13C{ 1H} NMR spectra for all the new compounds and the crystallographic details for the X-ray structure are given as Appendices. / Chapter 1 presents an overview of photodynamic therapy, including its historical development, photophysial and biological mechanisms, and current clinical situation. A brief review of second-generation photosensitizers and the different approaches for targeted photodynamic therapy are also given. / Chapter 2 reports the synthesis and characterization of a silicon(IV) phthalocyanine which is substituted axially with two diamino moieties, together with its di- and tetramethylated derivatives. The non-methylated analogue shows a high photocytotoxicity toward HT29 human colorectal adenocarcinoma and HepG2 human hepatocarcinoma cells with IC50 values down to 0.01 muM. Interestingly, this compound also exhibits a pH-dependent behavior. The fluorescence quantum yield increases by four folds and the singlet oxygen quantum yield increases by three folds in water when the pH decreases from 7.0 to 5.0. The preliminary results suggest that this compound is a promising photosensitizer of which the photodynamic activity can be modulated by changing the pH of the environment. Furthermore, this compound can be used as a near-infrared fluorescence probe for optical imaging of intracellular acidic level. / Chapter 3 reports a novel series of aminophenyl-substituted silicon(IV) phthalocyanines. The aminophenyl moieties in these conjugates can also modulate the photophysical and photosensitizing properties of the phthalocyanine core through changing the pH of the environment. These phthalocyanines exhibit a low photocytotoxicity under physiological conditions (pH 7.4). It is likely that the amino groups, in the free amine form, can quench the singlet excited state of phthalocyanine by a photoinduced electron transfer (PET) mechanism, and reduce the chance of intersystem crossing and the efficiency in generating singlet oxygen. The strong aggregation tendency of these compounds in this pH environment is another major reason for the low photocytotoxicity. When the pH is lower to 6.4-6.9, the amino groups are protonated so that they are no longer electron donors, and the compounds become less aggregated. These changes lead to an increase in photocytotoxicity. The results of this study are reported in this Chapter. / Chapter 4 describes a new series of silicon(IV) phthalocyanines conjugated axially with various polyamine derivatives. Polyamines are naturally occurring compounds which are involved in a number of cell processes including cell proliferation and differentiation. Their biosynthetic activity and polyamine levels in some tumor cells are significantly higher than those in normal cells. Conjugation of polyamine analogues is therefore one of the promising approaches to improve the tumor-targeting property of photosensitizers. This Chapter describes the synthesis, spectroscopic characterization, and photophysical properties of these compounds. Their photodynamic activities toward HT29 and Chinese hamster ovary (CHO) cells have also been studied in detail. Their cellular uptake, subcellular localization, cell death mechanism, and in vivo photocytotoxicity have also been studied. / In Chapter 5, we report a series of silicon(IV) phthalocyanines containing one or two cholesterol unit(s) at the axial position(s), including their synthesis, spectroscopic characterization, photophysical properties, and in vitro photodynamic activities. These cholesterol-containing photosensitizers can form stable conjugates with low-density lipoprotein (LDL), which is the major lipoprotein carrier for cholesterol in human plasma. On the basis that cancer cells generally express significantly more LDL receptors than normal cells, these cholesterol-conjugated phthalocyanines are designed with a view to enhancing their selectivity toward tumor. Unfortunately, conjugation of cholesterol reduces the photodynamic activity of the silicon(IV) phthalocyanines as a result of their higher aggregation tendency. / This thesis reports the synthesis, spectroscopic characterization, and photophysical and biological properties of several series of novel silicon(IV) phthalocyanines which are specially designed as efficient and selective photosensitizers for photodynamic therapy. / Jiang, Xiongjie. / Source: Dissertation Abstracts International, Volume: 72-01, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references and index. / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.