A TFD está baseada no uso de um fármaco fotossensível que, uma vez ativado por luz visível e na presença do oxigênio, induz a produção de espécies reativas de oxigênio tais como o radical peroxila, o ânion radical superóxido e o radical hidroxila (Tipo I) ou oxigênio singlete (Tipo II), que atuam diretamente sobre os sistemas biológicos, induzindo a morte da célula por processo necrótico ou apoptótico. A maioria dos tipos de tumores responde ao tratamento e os resultados são promissores. Entretanto, órgãos altamente pigmentados e vísceras maciças (fígado, baço, rins e medula óssea) impedem a penetração da luz visível para o tratamento, o que representa um tipo de resistência aos protocolos da Terapia Fotodinâmica. Torna-se necessário, portanto, procurar por novos agentes fotossensibilizadores. Estudos mostraram que a ação fotodinâmica induz mudanças diretas na membrana celular que levam a um desequilíbrio na homeostase iônica celular (íons sódio, potássio e cálcio), o que certamente leva a um dano no transporte de proteínas da membrana plasmática e, em última análise, a um stress osmótico irreversível. Neste trabalho, procurou-se determinar a potencialidade do uso da 5,10,15,20-tetrakis[4-(1,4,7,10,13-pentaoxaciclopentadecane-2-aminometil)2,3,-5,6-tetrafluoro)fenil]-porfirina (H2C4P), e o Zn(II)5,10,15,20-tetrakis[4-(1,4,7,10,13-pentaoxaciclopentadecane-2-aminometil)2,3,5,6-(tetrafluoro)fenil]-porfirinato (ZnC4P) como fármaco fotossensível. Avaliou-se também a zinco ftalocianina associada ao éter de coroa onde, graças à presença do éter de coroa, pôde-se observar uma potencialização da ação fotodinâmica. Nos estudos fotofísicos e fotoquímicos, observou-se que os fármacos porfirínicos possuem importantes propriedades espectroscópicas para a TFD. O rendimento quântico de produção de oxigênio singlete foi medido e o valor encontrado para H2C4P ( = 0,62) foi maior que o valor encontrado para ZnC4P ( = 0,46). Os valores de rendimento quântico de produção dos estados excitado tripletes (T) para ZnC4P foi da ordem de 0,73 ± 0,06 e para H2C4P foi da ordem de 0,63 ± 0,05, mostrando que o mecanismos Tipo II para a porfirina base livre H2C4P é dominante e para o fotossensibilizador metalado ZnC4P tem-se Tipo I dominante. Ambos os sistemas apresentaram uma eficiente ação fotodinâmica nos estudos com a linhagem de células J774-A.1. Fez-se uso de sondas fluorescentes para monitorar a distribuição e alteração na homeostase de íons através da membrana plasmática. Esses estudos mostraram que a presença dos ligantes éter de coroa na estrutura da porfirina, atuando concomitantemente à ftalocianina, potencializa a ação fotodinâmica. Observou-se que o 18-crow-6 éter de coroa minimiza a diferença de potencial da mesma ordem de magnitude de quando está associado à ZnPc em uma formulação lipossomal (da ordem de 50%), o que mostra que a ZnPc não interfere na formação dos canais de íons potássio formados. Os resultados indicaram um grande potencial de aplicação do ligante éter de coroa associado ou ligado covalentemente ao fármaco no uso da TFD, visto que o éter de coroa não modificou as características fotofísicas e fotoquímicas dos fotossensibilizadores, uma nova perspectiva no que chamamos de Terapia Fotodinâmica Sinérgica. / Photodynamic Therapy (PDT) is based on the use of a photosensitive drug which, once activated by visible light and in the presence of oxygen, induces the production of several reactive species of oxygen, such as the peroxyl radical, superoxide anion and hydroxyl radical (Type I) or singlet oxygen (Type II), which act directly over the biological systems inducing the cell death, through a necrotic or apoptotic process. Most of the types of tumor respond to the treatment and the results are prosperous. However, highly pigmented organs and massive viscera (kidneys, spleen, liver and bone marrow) block the penetration of the visible light for the treatment, what represents a kind of resistance towards the Photodynamic Therapy protocols. Hence, it is necessary to look for new phosensitizing agents. Studies have shown that the photodynamic action induces direct changes in the cell membrane that lead to an unbalance in the cell ionic homeostasis (sodium, potassium and calcium ions), what certainly causes damage to the plasmatic membrane protein transport, and in a final analysis, irreversible osmotic stress. In this work, we aimed at determining the potentiality of the use of the 5,10,15,20-tetrakis[4-(1,4,7,10,13-pentaoxacyclopentadecane-2-aminometil)2,3,- 5,6-(tetrafluoro)phenyl] porphyrin (H2C4P), and the Zn(II)5,10,15,20-tetrakis[4- (1,4,7,10,13-pentaoxacyclopentadecane-2-aminomethyl)2,3,5,6-(tetrafluoro)- xvi phenyl]-porphyrinate (ZnC4P) as a photosensitive drug. We evaluated also the phytalocianine zinc associated to the crown ether where, due to the presence of the crown ether, we could observe a potentialization of the photodynamic action. In the photophysical and photochemical studies, we observed that the porphyirinic drugs present important spectroscopic properties to PDT protocol. The singlet oxygen production quantum yield was measured and the value found for H2C4P (FD = 0.62) was higher than that one found for ZnC4P (FD = 0.46). The value of the quantum yield of the production of the triplet excited states (FT) for ZnC4P was 0.73, and for H2C4P it was 0.63, showing that the mechanism Type II for the free-base porphyrin H2C4P is the dominant effect, and for the ZnC4P metallated photosensitizer, Type I process is the dominant one. Both systems present an efficient photodynamic action in the studies with the J774-A.1 cell strain. We used fluorescent probes to monitor the distribution and alteration of the ionic homeostasis through the plasmatic cell membrane. These studies showed that the presence of the crowned-ether ligants in the structure of the porphyrine, acting together with the dye structure, potentializes the photodynamic action. We observed that the 18-crow-6 crown ether decrease the difference in the transmembrane electrical potential in the same order of magnitude when it is associated to the ZnPC in a liposome formulation, (around 50%), what shows that the ZnPC does not interfere in the action of the potassium ion channels. xvii These results indicated a great potential of application of the crowned-ether ligant associated or covalently connected to the drug in the use of PDT, protocol once the crown ether structure did not modify the photophysical and photochemical characteristics of the photosensitizers, a new perspective in what we call Synergic Photodynamic Therapy.

1H and 13C{1H} NMR spectra of all the new compounds and crystallographic data are given in the Appendix. / Chapter 1 presents an overview of phthalocyanines including their general synthesis, properties, and applications. Special attention has been placed on the unsymmetrical analogues, and those which are efficient photosensitizers in photodynamic therapy. A brief account on BODIPYs as another versatile class of functional dyes is also given. / Chapter 2 describes the synthesis, spectroscopic characterization, photophysical properties, and in vitro photodynamic activities of three novel amphiphilic zinc(II) phthalocyanines substituted with one or two 3,4,5-tris(3,6,9-trioxadecoxy)benzoxy group(s). These compounds exhibit significantly higher photodynamic activities toward HepG2 and HT29 cell lines. The alpha-substituted analogue is particularly potent with IC50 values as low as 0.02 microM. The higher photodynamic activity of this compound can be attributed to its lower aggregation tendency in the culture media as shown by absorption spectroscopy and higher cellular uptake as suggested by the stronger intracellular fluorescence, resulting in a higher efficiency to generate reactive oxygen species inside the cells. / Chapter 4 focuses on a related series of 1,4-disubstituted zinc(II) phthalocyanines. These compounds possess two oligoethylene glycol methyl ether chains with various length at the 1,4-di-alpha-positions. The effects of the chain length on their aggregation, photophysical properties, cellular uptake, and in vitro photodynamic activities have been explored. / Chapter 5 presents the synthesis, characterization, and photophysical properties of another series of zinc(II) phthalocyanines conjugated with one, two or four isopropylidene protected glucofuranose unit(s) through a tetraethylene glycol linker. With these hydrophilic substituents, these macrocycles are highly soluble in common organic solvents and biological media. Their in vitro photodynamic activities toward HT29 and HepG2 cells have also been evaluated. Compared with the tetra-glucosylated phthalocyanines, which are almost nonphotocytotoxic, the mono- and di-glucosylated analogues exhibit a higher photodynamic activity. The di-alpha-substituted analogue is particularly potent with IC50 values as low as 0.03 microM. / Chapter 6 reports the synthesis, characterization, and photophysical properties of two novel conjugates of subphthalocyanine substituted axially with a BODIPY or distyryl-BODIPY moiety. Both systems absorb over a broad range in the visible region. They also exhibit a highly efficient photo-induced energy transfer process either from the excited BODIPY to the subphthalocyanine core or from the excited subphthalocyanine to the distyryl-BODIPY unit. The energy transfer quantum yields are close to unity for both of these conjugates. / Chapter 7 describes the preparation and photophysical properties of another two BODIPY and monostyryl-BODIPY conjugates which are linked to a silicon(IV) phthalocyanine core. These conjugates serve as excellent artificial photosynthetic models for the study of energy and electron transfer processes. Depending on the axial substituents, these conjugates exhibit predominantly a photo-induced energy or electron transfer process in toluene. / The related studies of a series of novel di-alpha-substituted zinc(II) phthalocyanines having two biocompatible triethylene glycol methyl ether chains or glycerol moieties are described in Chapter 3. Compared with the unsubstituted analogue, these compounds have a red-shifted Q band, and exhibit a relatively weaker fluorescence emission and higher efficiency to generate singlet oxygen. As a result, these compounds are promising candidates for photodynamic therapy. In vitro studies on HepG2 and HT29 cells have shown that they are highly photocytotoxic with IC50 values as low as 0.06 microM. / This thesis describes my synthetic studies on several series of functional zinc(II) phthalocyanines and boron dipyrromethenes (BODIPYs). Their applications as efficient photosensitizers in photodynamic therapy and light harvesting systems have also been explored. / Liu, Jianyong. / Adviser: Dennis Keepui Ng. / Source: Dissertation Abstracts International, Volume: 71-01, Section: B, page: 0326. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2009. / 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 Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese.

by Lim Che Lau. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1996. / Includes bibliographical references (leaves 79-84). / Title Page --- p.i / Table of Contents --- p.ii / List of Tables --- p.iv / List of Figures --- p.v / List of Schemes --- p.vii / Acknowledgments --- p.viii / Abstract --- p.ix / Chapter CHAPTER 1: --- INTRODUCTION / Chapter 1.1. --- Historical Background --- p.1 / Chapter 1.2. --- FTICR with External Ion Source --- p.2 / Chapter 1.3. --- High Mass Analysis in FTICR --- p.4 / Chapter 1.4. --- Outline of Present Work --- p.7 / Chapter CHAPTER 2: --- INSTRUMENTATION AND EXPERIMENTAL / Chapter 2.1. --- Instrumentation --- p.8 / Chapter 2.1.1 --- Ion Source --- p.10 / Chapter 2.1.1.1. --- Liquid Secondary Ion Mass Spectrometry --- p.11 / Chapter 2.1.1.2. --- Electrospray Ionization --- p.12 / Chapter 2.1.2. --- Electrostatic Ion Focusing System --- p.15 / Chapter 2.1.3. --- ICR Analyzer Cell and Magnet --- p.18 / Chapter 2.1.4. --- Data Acquisition and Handling System --- p.22 / Chapter 2.2. --- Experimental --- p.22 / Chapter 2.2.1. --- Liquid Secondary Ion Mass Spectrometry --- p.22 / Chapter 2.2.2. --- Electrospray Ionization --- p.23 / Chapter 2.2.3. --- Nozzle-Skimmer Dissociation --- p.24 / Chapter 2.2.4. --- Sustained Off-Resonance Irradiation Collision- Induced Dissociation --- p.24 / Chapter 2.2.5. --- Data Acquisition and Processing --- p.27 / Chapter 2.2.6. --- Mass Calibration --- p.27 / Chapter CHAPTER 3: --- STRUCTURAL CHARACTERIZATION OF TERPYRIDINE-BASED POLYETHER DENDRIMERS AND THEIR IRON(II) METALLOCOMPLEXES BY LIQUID SECONDARY ION MASS SPECTROMETRY AND ELECTROSPRAY IONIZATION MASS SPECTROMETRY / Chapter 3.1. --- Introduction --- p.28 / Chapter 3.2. --- Sample Preparation --- p.29 / Chapter 3.3. --- Results and Discussion --- p.30 / Chapter 3.3.1. --- Liquid Secondary Ion Mass Spectrometry Studies --- p.30 / Chapter 3.3.1.1. --- Dendrimers --- p.30 / Chapter 3.3.1.2. --- Metallodendrimers --- p.41 / Chapter 3.3.2. --- Electrospray Ionization Mass Spectrometry Studies --- p.47 / Chapter 3.4. --- Conclusions --- p.53 / Chapter CHAPTER 4: --- STUDIES OF LANTHANIDE(III) PORPHYRIN- PHTHALOCYANINE HETEROLEPTIC SANDWICH COMPLEXES USING ELECTROSPRAY IONIZATION / Chapter 4.1. --- Introduction --- p.54 / Chapter 4.2. --- Results and Discussion --- p.55 / Chapter 4.2.1. --- Molecular Weight Determination --- p.57 / Chapter 4.2.2. --- Structural Elucidation --- p.65 / Chapter 4.2.3. --- Charge-Transfer Processes --- p.72 / Chapter 4.3. --- Conclusions --- p.76 / Chapter CHAPTER 5: --- CONCLUSIONS --- p.77 / References --- p.79

Thesis (M.Sc. (Chemistry)) - Rhodes University, 2009.

Thesis (Ph.D.(Chemistry))--University of Pretoria, 2009. / Includes abstract in English. Includes bibliographical references. Also available online.

Thesis (Ph.D.) - University of Queensland, 2004. / Includes bibliography.

Thesis (Ph. D.)--Georgia State University, 2006. / Title from title screen. Dabne White Dixon, committee chair; Kathryn Betty Grant, Markus W. Germann, committee members. Electronic text (252 p. : ill., charts (some col.)) : digital, PDF file. Description based on contents viewed June 18, 2007. Includes bibliographical references.

Low dimensional nanostructures have defined the frontier of the research in material science for the last two decades. Presented here are the results of experimental research on growth, device fabrication and application of quasi-one dimensional phthalocyanines and metal oxides to gas-sensing. The possibility of rational tuning of the growth conditions, in order to control composition, morphology, size, orientation and alignment of the grown low-dimensional nanostructures was investigated. Employing custom designed heating stages coupled with optical microscope the in situ approach of monitoring the growth of nanostructures has been realized. Using this method, the growth of VO2 nanowires and nanoplatelets have been investigated and two novel growth mechanisms were discovered and explained. A variety of phthalocyanine and metal-oxide nanowire-based chemical sensors have been proposed, fabricated and tested. The focus of our research was on the development of new sensing principles and the improvement of existing ones. In particular, nanowires of tin and titanium dioxide were proposed to be used as self-heated chemiresistors capable of operating in the absence of an external heater, thus paving the way for ultra-low power consumption sensors. For the first time VO2 nanowires were used to create a nano-Pirani gauge and a gas sensor employing a sharp temperature-driven metal-insulator transition in this material. The sensor is sensitive to both chemically active and inert gases. Its performance is modeled and optimization parameters are presented.

In this work the interaction between peripherally (b) substituted nickel tetrahydroxyphthalocyanines (b-NiPc(OH)4 and poly-b-Ni(O)Pc(OH)4) with 4-chlorophenol is theoretically rationalized by performing calculations at the B3LYP/6-31G(d) level. Density functional theory (DFT) and molecular orbital theory are used to calculate the condensed Fukui function for phthalocyanine derivatives and 4-chlorophenol, in order to determine the reactive sites involved when 4-chlorophenol is oxidized, and to compare theoretically predicted reactivity to experimentally determined electrocatalytic activity. Electrocatalytic activities of adsorbed NiPc derivatives: OPGE-α-NiPc(OH)8 (OPGE = ordinary pyrolytic graphite electrode, α = nonperipheral substitution), OPGE-a-NiPc(OH)4 and OPGE-β- NiPc(OH)4 are compared with those of the polymerized counterparts: OPGE-poly-α-Ni(O)Pc(OH)8, OPGE poly-a-NiPc(OH)4 and OPGE-poly-β-NiPc(OH)4, respectively. β-NiPc(NH2)4, β-NiPc(OH)4, α-NiPc(OH)4, α-NiPc(OH)8, α-NiPc(C10H21)8 are adsorbed on singled walled carbon nanotube (SWCNT) and β-NiPc(NH2)4-SWCNT (linked to SWCNT), are used to modify glassy carbon electrode (GCE) and employed for the electro oxidation of chlorophenols. The β-NiPc(NH2)4-SWCNT gave the best current response for the oxidation of 4-chlorophenol. α-NiPc(OH)8-SWCNT and α-NiPc(C10H21)8 gave the best resistance to electrode fouling due to oxidation by product of 4-chlorophenol. The synthesis of conjugates of cadmium telluride quantum dots (CdTe-QDs) capped with thioglycolic acid and peripherally substituted nickel tetraamino phthalocyanine (β-NiPc(NH2)4) complex were also employed for the oxidation of chlorophenols. Separation of one of the diastereomers of 1, 2-subnaphthalocyanine (SubNPc) was achieved as well as separation of the enantiomers. The absorption and magnetic circular dichroism spectra, together with theoretical calculations, reveal rather small variations in the frontier molecular orbitals of the SubNPc compared to conventional subphthalocyanine (SubPc), except for the destabilization of the highest occupied molecular orbital (HOMO), which results in a characteristic absorption in the Soret band region. The chirality of SubNPc, including the cyclic dichroism (CD) signs and intensities, are discussed in detail.

The purpose of this review is to compile preclinical and clinical results on phthalocyanines (Pcs) as photosensitizers (PS) for Photodynamic Therapy (PDT) and contrast agents for fluorescence imaging. Indeed, Pcs are excellent candidates in these fields due to their strong absorbance in the NIR region and high chemical and photo-stability. In particular, this is mostly relevant for their in vivo activation in deeper tissular regions. However, most Pcs present two major limitations, i.e., a strong tendency to aggregate and a low water-solubility. In order to overcome these issues, both chemical tuning and pharmaceutical formulation combined with tumor targeting strategies were applied. These aspects will be developed in this review for the most extensively studied Pcs during the last 25 years, i.e., aluminium-, zinc- and silicon-based Pcs.