Thesis (Ph. D.)--University of Hong Kong, 1998. / Includes bibliographical references (leaves 198-208).

Thesis (M. Sc.)--Carleton University, 1992. / Also available in electronic format on the Internet.

Thesis (Ph.D.)--Bowling Green State University, 2005. / Document formatted into pages; contains xvii, 133 p. : ill. Includes bibliographical references.

A imobilização da MeP em suportes inorgânicos permite isolar o sítio de reação prevenindo a dimerização e/ou auto-destruição oxidativa da mesma, constituindo-se num catalisador biomimético. Neste projeto foi objetivo avaliar o comportamento biomimético de manganês porfirinas, comparando sistemas imobilizadas de diferentes maneiras em sílica funcionalizada em processos de oxigenação do cicloocteno ecicloexano, incluindo metabolismo de um fármaco. A primeira etapa do projeto consistiu na obtenção dos sistemas catalíticos contendo metaloporfirinas imobilizadas em sílicas modificadas. Para isso foi sintetizada a M(4-N-Py)TFPPH2 base livre, seguida da inserção de manganês (III) e metilação obtendo-se o catalisador Mn[{M(4-N-MePy)TFPP}]2+. Foi inserido manganês também nas porifinas base livre [T(4-N-MePy)P]Cl4 e [TFPP]H2 obtidas comercialmente obtendo-se os catalisadores Mn[T(4-N-MePy)P]5+ e Mn[TFPP]+. Realizou-se a funcionalização da sílica gel com (i) grupos sulfonatofenil e propilimidazol (SiSO3-IPG); (ii) grupos 3-aminopropil (APTES); (ii) grupos 3-(2-(2-aminoetilamino) etilamino) propil (AP(EA)2TS) e (iv) cloropropil e 1,6-diaminoexano (DA1,6Si). Essas sílicas foram imobilizadas nas manganêsporfirinas através de interações eletrostáticas ou via ligação covalente. Esses catalisadores foram usados na oxigenação de (Z)-cicloocteno e cicloexano e no estudo de metabolismo oxidativo do fármaco praziquantel (agente anti-helmíntico). Os catalisadores [Mn(TFPP)]- APTES, [Mn(TFPP)]- AP(EA)2TS, [Mn{M(4-N-MePy)TFPP}]-SiSO3, [Mn{M(4-N-MePy)TFPP}]- SiSO3(IPG), [Mn{M(4-N-MePy)TFPP}]-APTES, [Mn{M(4-N-MePy)TFPP}]- AP(EA)2TS, [Mn{M(4-N-MePy)TFPP}]- DA1,6Si foram usados em reações de epoxidação do (Z)-cicloocteno pelo PhIO e os resultados obtidos foram baixos. Já com H2O2 como oxidantes os resultados foram muito bons quando foi adicionado imidazol. Nas reações de hidroxilação do cicloexano os rendimentos obtidos foram altos quando a MnP foi imobilizada por interação eletrostática. Neste sistema as oxidações competitivas são minimizadas. Os sistemas com melhores resultados foram selecionados para estudos com o praziquantel (PZQ). Diferentemente dos resultados obtidos previamente com FeP, os sistemas com MnPs se revelaram bons catalisadores biomiméticos, uma vez que apresentaram quantidades expressivas do metabólito trans-4\'-OH, o principal metabólito produzido in vivo. As MnPs, em particular as piridis substituídas apresentaram boa conversão de PZQ sendo [Mn{T(4-N-MePy)P}]-SiSO3 o melhor, além de produzir 38 % do trans-4\'-OH, apresentou 87 % de conversão. Estes resultados preliminares indicam um sistema muito promissor com resultados inéditos. / The immobilization of metalloporphyrins in inorganic supports allows to isolate reaction site preventing dimerization and/or catalyst oxidative selfdestruction constituting in a biomimetic system. In this project the aim was evaluate the biomimetic behaviour of manganese porphyrins, comparing systems immobilized on sílica in different ways in oxygenations processes of (Z)- cyclooctene and cyclohexane, including a study of drug metabolism. Initially the catalytic systems containing metaloporphyrins immobilized on modified silica were obtained. The free base M(4-N-Py)TFPPH2 was firstly synthesized, then the MnIII was inserted, methylated obtaining the catalyst Mn[{M(4-N-MePy)TFPP}]2+. The MnIII also was inserted in the commercials free base [T(4-N-MePy)P]Cl4 e [TFPP]H2 obtaining the catalysts Mn[T(4-N-MePy)P]5+ e Mn[TFPP]+. The sílica gel were functionalizated with (i) sulfonatephenyl and propylimidazole groups (SiSO3-IPG); (ii) 3-aminopropil groups (APTES); (ii) 3-(2- (2-aminoethyilamine) ethilamine) propyl groups (AP(EA)2TS) and (iv) chloropropyl e 1,6-diaminehexane (DA1,6Si). Manganese porphyrins were immobilized on these sílica supports through electrostatic interactions or covalent bond. These catalysts were used in the (Z)-ciclooctene and cyclohexane oxigenationand in the oxidative metabolism of praziquantel (antihelmintic agent). 13 The catalysts [Mn(TFPP)]- APTES, [Mn(TFPP)]- AP(EA)2TS, [Mn{M(4-NMePy) TFPP}]-SiSO3, [Mn{M(4-N-MePy)TFPP}]- SiSO3(IPG), [Mn{M(4-NMePy) TFPP}]-APTES, [Mn{M(4-N-MePy)TFPP}]- AP(EA)2TS, [Mn{M(4-NMePy) TFPP}]- DA1,6Si were used in (Z)-ciclooctene epoxidation rendering low yields using PhIO as oxidant, contrasting the good yields when imidazole and H2O2 as oxidant were used. In the hydroxylation of cyclohexane the yields were high when the MnP were immobilized through electrostatic interaction. In this system the competitive oxidations are minimized. The best systems were selected for to study the praziquantel oxidation. Differently from FeP results previously obtained, the MnP systems revealed good biomimetic catalysts for PZQ, since high amount of trans-4\'-OH metabolite was obtained, the principal in vivo metabolites. The pyridil substituted MnP, particularly [Mn{T(4-N-MePy)P}]-SiSO3 showed the best results, besides the high yield of trans-4\'-OH (38%), the convertion attained 87%. These results are inedited and very promising biomimetic catalytic systems.

Nowadays the necessity for designing and synthesizing novel imaging agents increases rapidly. The long wavelength, and thus, low energy, of excitation and emission, and the good specificity and stability are examples of essential characteristics of ideal diagnostic and therapeutic agents. In this work, the synthesis and photophysical studies of metal complexes for biological applications were performed and evaluated, and it contained the development of (a) a porphyrin probe for imaging and treatment and (b) a tripodal thermal sensor for imaging. The research and study of the two cases of complex is analyzed in the second and third chapters, respectively, which follow the introduction or literature review to the diagnostic and/ or therapeutic agents which is given with examples in the first chapter. The scope of the main project, which is analysed in the second chapter, was the development and synthesis of a porphyrin-based bio-probe capable of bacterial fluorescence imaging. The porphyrin moiety of a complex is also able to generate singlet oxygen and this effect can be used for treatment purposes (PDT, Photodynamic Therapy). Thus, the complex can act as a diagnostic and therapeutic (anti-bacterial in this case) agent simultaneously. A probe with such a dual capability is known as theranostic agent. A theranostic agent is crucial for the enhancement and expansion of personalised medicine. The studies and physical measurements of the proposed, synthesised porphyrin complex have proved its capability to be used as a theranostic probe. Furthermore, after coupling the porphyrin moiety firstly with a small protein part (ampetoid: antimicrobial peptoid) and secondly with a radionuclide (Gallium-68), the in vitro and in vivo studies have to be performed. The aim of the project analysed in the third chapter was the development of a thermal sensor. Coordination of a tripodal ligand with a mixture of two lanthanides in various ratios was achieved and the photophysical measurements of the resulted complexes were evaluated. Lanthanide metals were chosen due to their unique photophysical properties that they offer when they are connected to an organic chomophoric ligand. Additionally, the preferred final luminophore product would obey a thermostable structure over a wide temperature range and it would be capable of effectively sensing the alterations in temperature. These properties were true for the ratio 99.5:0.5 for Terbium: Europium, and thus, the complex with such a consistency clarified the final product. Furthermore, the highly promising results after repeatedly photophysical (especially emission) measurements could conclude that the complex can be served as an ideal thermal sensor. Additional emission measurements at higher temperatures have to be done in order to confirm the ability of the proposed thermal sensor to be used for bio-imaging purposes. In conclusion, two-kind of metal complexes for biological applications were synthesized and their photophysical properties were assessed. Both the bulky porphyrin complex and the smaller tripodal ligand have shown promising results for their proposed applications. Of course, a more detailed assessment is required to verify their capability.

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Photodynamic therapy (PDT) and Magnetic resonance imaging (MRI) are two techniques used in therapeutic and diagnostic purpose respectively. PDT can selectively kill the cancer cells by utilizing light and photosensitizer, while MRI provides invasive imaging on our interior bodies. If these two techniques combine, the probe can act as both PDT and MRI agent at the same time. This theranostic agents can bring great efficiency in the cancer treatment. In this project, a porphyrin-cyclen gadolinium based dual functions bio-probe, PZnGdL, is designed for diagnostic and photodynamic therapeutic functions. PZnGdL demonstrated a great T1 signal enhancement for MRI, in which its T1 relaxivity is 15.06 mM-1s-1 (at 1.4T, 37oC). The T1 relaxivity is five-fold higher than the clinically approved MRI contrasting agent Gd-DOTA, (2.92 at 1.4T, 37oC). Furthermore, PZnGdL exhibits low dark toxicity and high photocytotoxicity. Therefore, its photodynamic therapeutic index (PDI) in HeLa cells is as high as 1348 upon 1 J/cm2 light irradiation. Results from the present study show that PZnGdL is an effective photodynamic therapy agent as well as a safe and promising MRI contrasting agent.

Research concentrated on the absorption, transformation, and storage of light energy is useful for the energy challenges faced by humanity. In particular, photocatalysis using solar energy to generate useful fuels has become a primary research goal in the drive to replace fossil fuels for the future. In this dissertation it is shown that poly-tetra(4-aminophenyl)porphyrin (pTAPP) can be oxidatively polymerized using a variety of methods, including electropolymerization, chemical oxidation, and interfacial polymerization and that pTAPP has photocatalytic ability to reduce O2 to H2O2 for a storable fuel. Organic conductive polymers such as pTAPP are attractive catalysts because of their high surface area and ability to coat electrodes. pTAPP in a mixed oxidation state is shown to have both its minimum charge transfer resistance as well as its minimum impedance to electronic conductivity in the film. The UV-vis-NIR absorption spectra of pTAPP with increased oxidative doping are similar to hyperporphyrin spectra, characteristic of a two-plus charge localized on a single porphyrin unit. This suggests the presence of a bipolaron on the individual porphyrin units, and thus a bipolaron conductivity mechanism has been proposed. pTAPP changes color depending on its oxidation state, and therefore is a promising material for electrochromic devices. A novel Pourbaix diagram was created as a means of illustrating the redox and protonation states of pTAPP as a function of changes in pH, applied potential, electrochromic behavior, and electronic conductivity. Both pTAPP and pCoTAPP were shown to be effective catalysts for the reduction of oxygen to hydrogen peroxide, with pCoTAPP a better catalyst than pTAPP. When pCoTAPP is irradiated, oxygen reduction occurs close to the thermodynamic potential, indicating a promising system for storage of solar energy.