本論文報導了幾個系列的新型鋅酞菁配合物以及氟硼二吡咯染料的合成與表徵。 這些精心設計的化合物可作為高效的和選擇性的光敏劑應用於靶向性光動力療法和細菌的光動力失活。 / 第一章概述了光動力療法，包括歷史發展、光物理和生物機制及其臨床應用現狀。 重點介紹了用於靶向性光動力療法的第三代光敏劑，其中包括基於靶向性配體、納米載體的光敏劑以及可激活的光敏劑。 另外，本章還簡單介紹了用於抗菌光動力療法的光敏劑。 / 第二章報導了一種新型的由細胞核定位的短肽共軛修飾的鋅酞菁配合物的合成與表徵。 此短肽分子的氨基酸序列為：Gly-Gly-Pro-Lys-Lys-Lys-Arg-Lys-Val。 我們研究了該化合物的光物理性質、聚集行為以及離體光動力活性，同時與其非肽共軛修飾的化合物進行了詳細的比較。 利用HT29人結腸腺癌細胞，研究發現此多肽共軛修飾的酞菁展示了較高的細胞吸收、更高的細胞內活性氧的產生效率和光毒性。 同時活體實驗證明此化合物增加了酞菁在裸鼠腫瘤的停留時間。 這些結果在本章中均進行了詳細的報導。 / 第三章敘述了另一種多肽共軛修飾的鋅酞菁化合物的製備和光物理性質。 這個多肽包含了一個環狀的氨基酸序列，即 Arg-Gly-Asp-D-Phe-Lys，此多肽被認為能以腫瘤相關的血管新生時的高表達的跨膜受體（如 α[subscript v]β₃ 整合素）為靶向。 利用 α[subscript v]β₃ 整合素高表達的 U87-MG 人惡性膠質瘤細胞，我們研究了這個化合物的細胞吸收、細胞內活性氧的產生、離體光動力活性以及亞細胞定位。 同時，用 α[subscript v]β₃ 整合素低表達的 MCF-7 人乳腺癌細胞作為對照。 / 通常，腫瘤細胞外的pH值比正常細胞組織的低，因此，我們合成一個由酸敏感的縮醛鍵連接的酞菁二聚體。 此二聚體會發生自身淬滅且對pH有響應。 通過電子吸收和熒光光譜， 我們詳細地研究了這個化合物在不同酸性條件下的光物理性質和斷開動力學。 由於酞菁環具有強的二聚化趨勢，這個二聚體能自身淬滅，因而呈現“失活狀態。 通過降低檸檬酸緩衝液的pH值，這個化合物的乙縮醛鍵能優先斷開，並且斷開的速率隨pH值的降低而增加。 兩個酞菁環的分開增強了熒光強度和單態氧的產生。 這個二聚光敏劑還能在 HT29 細胞內被激活，從而產生較強的細胞內熒光。 相比之下，由乙二醇鏈連接的類似物基本上沒有熒光發射。 同時，這個可斷開的二聚物對HT29細胞光毒性也比不可斷開的類似物高（半致死量：IC₅₀ = 0.35 vs. 0.59 μM）。 第四章對這些結果進行了詳細的報導。 / 在第五章中，我們報導了兩種以腫瘤靶向配體葉酸共軛修飾的二（苯乙烯基）－氟硼二吡咯衍生物的合成、光譜表徵以及光物理性質。 在這兩個化合物中，葉酸和二（苯乙烯基）－氟硼二吡咯是通過不同長度的乙二醇鏈連接的。 我們研究了這兩個化合物的鏈長對KB人鼻咽癌細胞和MCF-7細胞的吸收和離體光動力活性的影響。 前者能高表達葉酸受體，而後者作為低葉酸受體表達的一個對照。 與MCF-7細胞相比，兩個化合物都展示了對KB細胞較高的吸收和光毒性（半致死量：IC₅₀ = 0.062 vs. 2.56 μM 和0.177 vs. 0.995 μM）。 此外，具有較長鏈的化合物優先定位在溶酶體中，而較短鏈的那個化合物則較多停留在細胞的內質網。 / 第六章重點開發了一系列多胺以及不同長度的聚賴氨酸（包括2、4、8個賴氨酸）共軛修飾的鋅酞菁配合物，并用於抗菌光動力療法。 我們報導了它們的合成、光物理性質以及對甲氧西林青霉素敏感的格蘭陽性金黄色釀膿葡萄球菌和格蘭陰性綠膿桿菌的光動力抗菌活性。 其中，三-N-甲基化的酞菁顯示了特別高的效果，在濃度為16 nM時，能降低大於5 log10 的金黄色釀膿葡萄球菌。 / 第七章闡述了前面幾章的實驗部份。 論文的最後附上所有新化合物的核磁共振氫譜和碳譜。 / This thesis describes the synthesis and characterization of several series of novel zinc(II) phthalocyanines and boron dipyrromethenes (BODIPYs), which are carefully designed as efficient and selective photosensitizers for targeted photodynamic therapy (PDT) and photodynamic inactivation of bacteria. / Chapter 1 presents an overview of PDT, including its historical development, photophysial and biological mechanisms, and current research directions. Emphasis is placed on the third-generation photosensitizers for targeted PDT, including targeting ligand-based photosensitizers, nanoparticle-based photosensitizers, and activatable photosensitizers. A brief review of photosensitizers that can be used for antimicrobial PDT is also given. / Chapter 2 reports the synthesis and characterization of a novel zinc(II) phthalocyanine conjugated with a short peptide with a nuclear localization sequence, namely Gly-Gly-Pro-Lys-Lys-Lys-Arg-Lys-Val. The photophysical properties, aggregation behavior, and in vitro photodynamic activity of this compound have been investigated and compared with its non-peptide-conjugated analogue. It has been found that the peptide-conjugated phthalocyanine shows an enhanced cellular uptake, higher efficiency in generating intracellular reactive oxygen species (ROS), higher photocytotoxicity against HT29 human colorectal adenocarcinoma cells, and enhanced tumor-retention property in tumor-bearing nude mice. The results are reported in detail in this chapter. / Chapter 3 describes the preparation and photophysical properties of another analogue conjugated with a peptide containing the cyclic Arg-Gly-Asp-D-Phe-Lys sequence, which is known to target the upregulated transmembrane protein receptors such as α[subscript v]β₃ integrin during angiogenesis. The cellular uptake, intracellular ROS generation, in vitro photodynamic activity, and subcellular localization of this conjugate have been investigated against U87-MG human glioblastoma cells, which have a high expression of α[subscript v]β₃ integrin. MCF-7 human breast adenocarcinoma cells, which have a low expression of α[subscript v]β₃ integrin, have been used as a negative control. / On the base that the extracellular pH in tumors is generally lower than that in normal tissues, we have developed a pH-responsive self-quenched phthalocyanine dimer connected with an acid-sensitive ketal linker. The basic photophysical properties of this compound and its cleavage kinetics upon exposure to different acidic conditions have been extensively studied by electronic absorption and fluorescence spectroscopy. Owing to the strong dimerization tendency of the phthalocyanine ring, this dimer is self-quenched and in the "OFF" state. By lowering the pH (< 6.5) in citrate buffer solutions, the linker is preferentially cleaved, and the rate of cleavage increases as the pH decreases. The separation of the phthalocyanine moieties leads to enhancement in fluorescence intensity and singlet oxygen production. This dimeric photosensitizer can also be activated inside HT29 cells causing strong intracellular fluorescence. By contrast, the fluorescence is hardly observed for the non-cleavable ethylene glycol-linked analogue. The photocytotoxicity of the cleavable dimer is also higher than that of the non-cleavable counterpart (IC₅₀ = 0.35 vs. 0.59 μM). The results are reported in detail in Chapter 4. / In Chapter 5, we describe the synthesis, characterization, and photophysical properties of two distyryl BODIPY derivatives conjugated with a folic acid as a tumor-targeting ligand via an ethylene glycol spacer with different chain length. The effects of the chain length on the cellular uptake and in vitro photodynamic activities of these compounds have been examined against KB human nasopharyngeal epidermal carcinoma cells and MCF-7 cells. The former are known to have a high expression of folate receptors, while the latter have been used as a negative control. Both compounds show enhanced cellular uptake and higher photocytotoxicity toward KB cells when compared with MCF-7 cells (IC₅₀ = 0.062 vs. 2.56 μM and 0.177 vs. 0.995 μM). The conjugate with a longer spacer shows preferential localization in the lysosomes, while the analogue with a shorter linker accumulates in the endoplasmic reticulum of the cells. / Chapter 6 focuses on the development of a series of zinc(II) phthalocyanines substituted with a polyamine moiety or a polylysine chain containing 2, 4, or 8 lysine units for antimicrobial PDT. Their synthesis, photophysical properties, and photodynamic antimicrobial activities against Gram (+) methicillin-sensitive Staphylococcus aureus and Gram (-) Pseudomonas aeruginosa are reported. The tri-N-methylated phthalocyanine is particularly potent showing a more than 5 log₁₀ reduction of the Staphylococcus aureus at 16 nM. / Chapter 7 gives the experimental details for the work described in the preceding chapters. ¹H and ¹³C{¹H} NMR 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. / Ke, Meirong. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 159-176). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese. / Abstract --- p.i / Abstract (in Chinese) --- p.v / Acknowledgment --- p.viii / Table of Contents --- p.xi / List of Figures --- p.xvi / List of Schemes --- p.xxiv / List of Tables --- p.xxv / Abbreviations --- p.xxvi / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- General Introduction of Photodynamic Therapy --- p.1 / Chapter 1.2 --- Mechanisms of Photodynamic Therapy --- p.2 / Chapter 1.2.1 --- Photophysical Mechanisms --- p.2 / Chapter 1.2.2 --- Biological Mechanisms --- p.4 / Chapter 1.3 --- Clinical Status of Photodynamic Therapy --- p.5 / Chapter 1.4 --- Overview of Photosensitizers --- p.7 / Chapter 1.5 --- Targeted Photodynamic Therapy --- p.13 / Chapter 1.5.1 --- Targeting Ligand-Based Photosensitizers --- p.13 / Chapter 1.5.1.1 --- Synthetic Peptides --- p.13 / Chapter 1.5.1.2 --- Proteins --- p.16 / Chapter 1.5.1.3 --- Aptamers --- p.18 / Chapter 1.5.1.4 --- Folic acid --- p.19 / Chapter 1.5.1.5 --- Other Biological Ligands --- p.20 / Chapter 1.5.2 --- Nanoparticle-Based Photosensitizers --- p.20 / Chapter 1.5.2.1 --- Biodegradable Nanoparticle-Based Photosensitizers --- p.21 / Chapter 1.5.2.2 --- Non-Biodegradable Nanoparticle-Based Photosensitizers --- p.23 / Chapter 1.5.3 --- Activatable Photosensitizers --- p.25 / Chapter 1.5.3.1 --- Environment-Activated Photosensitizers --- p.26 / Chapter 1.5.3.2 --- Enzyme-Activated Photosensitizers --- p.27 / Chapter 1.5.3.3 --- Nucleic Acid-Activated Photosensitizers --- p.29 / Chapter 1.6 --- Antimicrobial Photodynamic Therapy --- p.32 / Chapter 1.6.1 --- General Introduction --- p.32 / Chapter 1.6.2 --- Photosensitizers for Antimicrobial Photodynamic Therapy --- p.34 / Chapter Chapter 2 --- A Phthalocyanine-Peptide Conjugate with High in vitro Photodynamic Activity and Enhanced in vivo Tumor-Retention Property --- p.36 / Chapter 2.1 --- Introduction --- p.36 / Chapter 2.2 --- Results and Discussion --- p.37 / Chapter 2.2.1 --- Molecular Design and Synthesis --- p.37 / Chapter 2.2.2 --- Electronic Absorption and Photophysical Properties --- p.42 / Chapter 2.2.3 --- In Vitro Photodynamic Activities --- p.44 / Chapter 2.2.4 --- In Vivo Studies --- p.50 / Chapter 2.3 --- Conclusion --- p.52 / Chapter Chapter 3 --- Synthesis, Characterization, and Photodynamic Activity of a cylic RGD-Conjugated Phthalocyanine --- p.53 / Chapter 3.1 --- Introduction --- p.53 / Chapter 3.2 --- Results and Discussion --- p.54 / Chapter 3.2.1 --- Molecular Design and Synthesis --- p.54 / Chapter 3.2.2 --- Electronic Absorption and Photophysical Properties --- p.57 / Chapter 3.2.3 --- In Vitro Photodynamic Activities --- p.59 / Chapter 3.3 --- Conclusion --- p.67 / Chapter Chapter 4 --- A pH-Responsive Fluorescent Probe and Photosensitizer Based on the Dimerization Property of Phthalocyanines --- p.69 / Chapter 4.1 --- Introduction --- p.69 / Chapter 4.2 --- Results and Discussion --- p.70 / Chapter 4.2.1 --- Synthesis and Characterization --- p.70 / Chapter 4.2.2 --- Electronic Absorption and Photophysical Properties --- p.74 / Chapter 4.2.3 --- In Vitro Studies --- p.80 / Chapter 4.3 --- Conclusion --- p.84 / Chapter Chapter 5 --- Synthesis, Characterization, and Photodynamic Activities of BODIPY-Folate Conjugates --- p.86 / Chapter 5.1 --- Introduction --- p.86 / Chapter 5.2 --- Results and Discussion --- p.87 / Chapter 5.2.1 --- Synthesis and Characterization --- p.87 / Chapter 5.2.2 --- Electronic Absorption and Photophysical Properties --- p.92 / Chapter 5.2.3 --- In Vitro Studies --- p.94 / Chapter 5.3 --- Conclusion --- p.100 / Chapter Chapter 6 --- Synthesis, Characterization, and Antimicrobial Photodynamic Activities of Cationic Phthalocyanines --- p.102 / Chapter 6.1 --- Introduction --- p.102 / Chapter 6.2 --- Results and Discussion --- p.103 / Chapter 6.2.1 --- Synthesis and Characterization --- p.103 / Chapter 6.2.2 --- Electronic Absorption and Photophysical Properties --- p.108 / Chapter 6.2.3 --- In Vitro Photodynamic Antimicrobial Activities --- p.112 / Chapter 6.3 --- Conclusion --- p.114 / Chapter Chapter 7 --- Experimental Section --- p.115 / Chapter 7.1 --- General --- p.115 / Chapter 7.2 --- Synthesis --- p.119 / Chapter 7.2.1 --- Synthesis for Chapter 2 --- p.119 / Chapter 7.2.2 --- Synthesis for Chapter 3 --- p.125 / Chapter 7.2.3 --- Synthesis for Chapter 4 --- p.128 / Chapter 7.2.4 --- Synthesis for Chapter 5 --- p.132 / Chapter 7.2.5 --- Synthesis for Chapter 6 --- p.138 / Chapter 7.3 --- pH-Response Properties of 4.6 and 4.7 in Citrate Buffer Solutions --- p.143 / Chapter 7.4 --- In Vitro Studies --- p.144 / Chapter 7.4.1 --- Cell Lines and Culture Conditions --- p.144 / Chapter 7.4.2 --- Photocytotoxicity Assay --- p.145 / Chapter 7.4.3 --- Photodynamic Antimicrobial Inactivatoin Studies --- p.147 / Chapter 7.4.4 --- Intracellular ROS Measurements --- p.148 / Chapter 7.4.5 --- Cellular Uptake (Determined by Extraction Method) --- p.149 / Chapter 7.4.6 --- Cellular Uptake (Determined by Confocal Microscopy) --- p.150 / Chapter 7.4.7 --- Cellular Uptake (Determined by Flow Cytometry) --- p.152 / Chapter 7.4.8 --- Fluorescence Microscopic Studies --- p.153 / Chapter 7.4.9 --- Subcellular Localization Studies --- p.153 / Chapter 7.4.10 --- pH-Dependent Intracellular Fluorescence Studies --- p.155 / Chapter 7.5 --- In Vivo Imaging and Ex Vivo Organ Biodistribution --- p.156 / Chapter Chapter 8 --- Conclusion and Outlook --- p.157 / References --- p.159 / Chapter Appendix --- NMR Spectra of New Compounds --- p.177

Le développement réactionnel est problème multidimensionnel complexe qui, dans un scénario représentatif, implique l’unique convergence de plusieurs paramètres à une réactivité désirée. Le choix incorrect d’un seul paramètre réactionnel tel que le pré-catalyseur, le ligand mais aussi le solvant ou encore l’acide/base peut complètement supprimer la réactivité du système. De ce fait, ce processus requiert souvent de nombreuses expérimentations pour obtenir un premier résultat probant. Pour éviter de tester toutes les combinaisons en parallèle, des approches créatives de criblage ont été développées ces dernières années mais le nombre important de reactions nécessaires à l’exploration de juste trois ou quatre paramètres est toujours un challenge pour les chimistes qui n’ont pas accès au criblage à haut debit. Afin de répondre à cette problèmatique, une stratégie combinatoire réaction-économique pour l’identification d’un lead hit dans une reaction spécifique est proposée. Des mélanges complexes de pré-catalyseurs et de ligands, choisis au préalable, sont testés avec un ou deux autres paramètres de reaction supplémentaires pour identifier de bonnes conditions de réaction dans un nombre minimum de manipulations. La déconvolution iterative permet ensuite d’identifier le catalyseur, généré in situ, le plus actif dans les conditions réactionnelles. L’application de cette approche est décrite sur une réaction de Friedel-Crafts, une arylation ortho-C–H sélective de composés benzamides, une alkylation C3 d’indole et en catalyse asymétrique sur une réaction d’hétéro Diels-Alder. / Reaction development is a complex multidimensional problem that, in a representative scenario, requires often the unique convergence of multiple parameters for a desired reactivity. The incorrect choice of a single parameter, such as the pre-catalyst, the ligand, the solvent or the acid/base, can completely eliminate the reactivity of the system. Thus, the process often requires extensive manipulations to obtain a lead hit. To avoid this time consuming process, many creative screening approaches have been developed but the large number of reactions necessary to explore the intersection of just three or four parameters is still a challenge for chemists who do not have access to high throughput experimentation. A reaction-economic combinatorial strategy is described for lead hit identification in catalyst discovery directed towards a specific transformation. Complex mixtures of rationally chosen pre-catalysts and ligands are screened against various reaction parameters to identify lead conditions in a small number of reactions. Iterative deconvolution of the resulting hits identifies which components contribute to the lead in situ generated catalyst. The application of this screening approach is described in the dehydrative Friedel-Crafts reaction, in the ortho-C–H arylation of benzamides, in the C3-indole alkylation and in the asymmetric hetero Diels-Alder cycloaddition.

Graphene has emerged as an appealing material for a variety of optoelectronic applications due to its unique electrical and optical characteristics. In this thesis, I will present recent advances in integrating graphene and graphene-boron nitride (BN) heterostructures with confined optical architectures, e.g. planar photonic crystal (PPC) nanocavities and silicon channel waveguides, to make this otherwise weakly absorbing material optically opaque. Based on these integrations, I will further demonstrate the resulting chip-integrated optoelectronic devices for optical interconnects. After transferring a layer of graphene onto PPC nanocavities, spectral selectivity at the resonance frequency and orders-of-magnitude enhancement of optical coupling with graphene have been observed in infrared spectrum. By applying electrostatic potential to graphene, electro-optic modulation of the cavity reflection is possible with contrast in excess of 10 dB. And furthermore, a novel and complex modulator device structure based on the cavity-coupled and BN-encapsulated dual-layer graphene capacitor is demonstrated to operate at a speed of 1.2 GHz. On the other hand, an enhanced broad-spectrum light-graphene interaction coupled with silicon channel waveguides is also demonstrated with ∼0.1 dB/μm transmission attenuation due to graphene absorption. A waveguide-integrated graphene photodetector is fabricated and shown 0.1 A/W photoresponsivity and 20 GHz operation speed. An improved version of a similar photodetector using graphene-BN heterostructure exhibits 0.36 A/W photoresponsivity and 42 GHz response speed. The integration of graphene and graphene-BN heterostructures with nanophotonic architectures promises a new generation of compact, energy-efficient, high-speed optoelectronic device concepts for on-chip optical communications that are not yet feasible or very difficult to realize using traditional bulk semiconductors.

MoS2, among many other transition metal dichalcogenides (TMDCs), holds great promise for future applications in nano-electronics, opto-electronics and mechanical devices due to its ultra-thin nature, flexibility, sizable band-gap, and unique spin-valley coupled physics. However, there are two main challenges that hinder careful study of this material. Firstly, it is hard to achieve Ohmic contacts to mono-layer MoS2, particularly at low temperatures (T) and low carrier densities. Secondly, materials' low quality and impurities introduced during the fabrication significantly limit the electron mobility of mono- and few-layer MoS2 to be substantially below theoretically predicted limits, which has hampered efforts to observe its novel quantum transport behaviours. Traditional low work function metals doesn't necessary provide good electron injection to thin MoS2 due to metal oxidation, Fermi level pinning, etc. To address the first challenge, we tried multiple contact schemes and found that mono-layer hexagonal boron nitride (h-BN) and cobalt (Co) provide robust Ohmic contact. The mono-layer spacer serves two advantageous purposes: it strongly interacts with the transition metal, reducing its work function by over 1 eV; and breaks the metal-TMDCs interaction to eliminate the interfacial states that cause Fermi level pinning. We measure a flat-band Schottky barrier of 16 meV, which makes thin tunnel barriers upon doping the channels, and thus achieve low-T contact resistance of 3 kohm.um at a carrier density of 5.3x10^12/cm^2. Similar to graphene, eliminating all potential sources of disorder and scattering is the key to achieving high performance in MoS2 devices. We developed a van der Waals heterostructure device platform where MoS2 layers are fully encapsulated within h-BN and electrically contacted in a multi-terminal geometry using gate-tunable graphene electrodes. The h-BN-encapsulation provides excellent protection from environmental factors, resulting in highly stable device performance, even at elevated temperatures. Both optical and electrical characterization confirms our high quality devices, including an ultra-clean interface, a record-high Hall mobility reaching 34,000 cm^2/Vs, and first observation of Shubnikov–de Haas oscillations. The development of Ohmic contact and fabrication of high quality devices are critical to MoS2 application and studying its intrinsic properties. Therefore, the progress made in this work will facilitate efforts to study novel physical phenomena of MoS2 that were not accessible before.

A caracterização ex situ e in situ de eletrodos constituídos de IrO2-Nb2O5 revelou que a morfologia, a atividade eletrocatalítica para a reação de desprendimento de O2 (RDO) e a performance para a reação de formação de O3 (RFO) são fortemente dependentes da composição nominal da camada ativa. Baseados em estudos preliminares, escolheu-se a composição IrO2-Nb2O5 (45:55 % mol) para uma extensiva investigação da RDO/RFO, avaliando a influência das variáveis de preparo do eletrodo, da temperatura e da composição do eletrólito. Propôs-se um mecanismo eletródico para RDO/RFO, considerando a influência da composição do eletrólito e dos sítios ativos superficiais. Demonstrou-se que a introdução de PF6- no eletrólito de suporte aumenta significativamente o rendimento da RFO através da inibição da RDO no domínio dos elevados sobrepotenciais. O segundo material eletródico investigado foi o eletrodo de diamante dopado com boro (DDB) de origem comercial. Este material apresenta área superficial e rugosidade sensivelmente maiores que os reportados na literatura, sendo que as diversas análises demonstram um filme de boa qualidade. O pré-tratamento da superfície de DDB resulta na remoção de impurezas e na oxidação da superfície, alterando o caráter hidrofóbico do eletrodo. Sua condutividade e comportamento eletroquímico são dependentes da concentração superficial de transportadores de carga, relacionado diretamente ao potencial aplicado. Desta forma, este eletrodo de DDB altamente dopado apresenta comportamento próximo ao de um metal em potenciais mais anódicos. Os estudos cinéticos em diversos eletrólitos e temperaturas demonstram que o eletrodo de DDB caracteriza-se pela quase ausência de sítios de adsorção ? causa dos elevados sobrepotenciais e energias de ativação para a RDO. De forma surpreendente, a introdução de flúor-ânions no eletrólito resulta na diminuição da energia de ativação para a RDO e da eficiência de corrente para a RFO. Este último parâmetro é função direta da ?eletronegatividade absoluta? dos flúor-ânions. Altas concentrações de NaF alteram a condutividade do eletrólito e a hidrofobicidade do eletrodo, afetando o comportamento cinético do ânodo. Em eletrólitos contendo KPF6, entretanto, a entropia de ativação eletroquímica parece exercer um pronunciado efeito sobre a energia de ativação da RDO. No mecanismo proposto para o eletrodo de DDB, destaca-se a importância da interação entre o principal intermediário da RDO/RFO, HO·, e a superfície do filme. / Ex situ and in situ characterisation of IrO2-Nb2O5 electrodes reveal morphology, electrocatalytical activity for the oxygen evolution reaction (OER) and electrochemical ozone production (EOP) performance are strongly dependent on nominal composition of the oxide film. Based on preliminary studies, the electrode IrO2-Nb2O5 (45:55 mol%) composition was chosen to conduct an extensive OER/EOP investigation, analysing the influence of: electrode preparation procedure, temperature and electrolyte composition. An electrode mechanism for OER/EOP is proposed taking into account the influence of the electrolyte composition and the active surface sites. It is demonstrated that the introduction of PF6- into the electrolyte increases significantly the EOP performance due to inhibition of the OER in the high overpotential domain. The second electrode material investigated is a commercial sample of the boron doped diamond electrode (BDD). This material presents surface area and roughness considerably higher than those reported in literature, however several analyses demonstrate the good quality of the film. The pre-treatment of the BDD surface results in the removal of impurities and surface oxidation, which alters the hydrophobic character of the film. Its conductivity and electrochemical behaviour depend on the surface charge carriers concentration that is directly related to the applied potential. Therefore, this heavily doped BDD sample presents a behaviour resembling a metal at more anodic potentials. Kinetic investigations of several electrolytes and temperatures show BDD electrode is characterised by the almost absence of adsorption sites ? the main cause of the high overpotentials and activation energies for OER. Surprisingly, the introduction of fluoro-anions into the electrolyte results in lower activation energies for OER and lower EOP current efficiency. The latter parameter is directly related to the ?absolute electronegativity? of the fluoro-anions. High NaF concentrations modify the electrolyte conductivity and electrode hydrophobicity. However, in electrolytes containing PF6-, the electrochemical activation entropy seems to exert a pronounced effect on the activation energy for OER. In the proposed OER/EOP mechanism at BDD electrode, a key parameter is the interaction between the main intermediate, HO·, and the electrode surface.

At the end of this thesis, the 1H and 13C {1H} NMR spectra of all the new compounds are listed in the Appendix. / Chapter 1 presents an overview of BODIPYs, including their general synthesis, properties, reactivities, and applications. The use of these compounds as photosensitizers for photodynamic therapy and fluorescent sensors for metal ions is highlighted. / Chapter 2 reports the synthesis, spectroscopic characterization, photophysical propreties, and in vitro photodynamic activities of a series of symmetrical distyryl BODIPYs substituted with one to five hydrophilic oligoethylene glycol monomethyl ether chain(s). In general, these compounds are essentially non-aggregated in DMF, resulting in a strong fluorescence emission and relatively high efficiency in generating singlet oxygen. Being formulated with 0.05% Tween 80, these compounds act as efficient photosensitizers. The compound which contains five triethylene glycol monomethyl ether chains exhibits the highest photocytotoxicity with an IC50 value as low as 7 nM toward HT29 human colorectal carcinoma cells. The high photodynamic activity of this compound can be attributed to its high efficiency in generating singlet oxygen, low aggregation tendency, and high cellular uptake. In addition, this compound also has a strong and selective affinity to the endoplasmic reticulum of the cells, causing cell death mainly through apoptosis. / Chapter 3 reports a related study on a series of unsymmetrical distyryl BODIPYs. These compounds possess three triethylene glycol monomethyl ether chains and another substituent at the other styryl group. The effects of this substituent on the photophysical properties, aggregation behavior, cellular uptake, and subcellular localization have been explored. Furthermore, their in vitro photodynamic activities have also been evaluated and compared with those of symmetrical analogues reported in Chapter 2. / Chapter 4 describes a novel ratiometric near-infrared fluorescent dye based on distyryl BODIPY with a 4-dimethylaminophenylethynyl group at the 2- and 6-positions. This compound exhibits a remarkable blue-shift in its absorption and fluorescence emission positions upon protonation with trifluoroacetic acid in organic solvents or HC1 in water in the presence of 0.05% Tween 80. These changes can be made reversible upon addition of a base. / Chapter 5 describes two monostyryl BODIPYs which contain two or four water-soluble amide chains as the metal chelators. The photophysical properties of these compounds and their spectral response to various metal ions have been investigated. The results show that the compound with two amide chains can detect Zn2+ ion in MeCN. They bind in a 1:1 stoichiometry with a binding constant of 2.2 x 104 M-1 . The fluorescence emission increases remarkably in intensity and shifts substantially to the blue from 620 to 572 nm due to the inhibition of the intramolecular charge transfer. The compound which contains four amide chains can detect Cd2+ ion with a high selectivity in phosphate buffered saline. / Chapter 6 reports the synthesis and spectral properties of a silicon(IV) phthalocyanine with two axial bis(2-picolyl)amine moieties which act as the binding sites for metal ions. The effects of various metal ions on its absorption and fluorescence spectra have been examined. The results indicate that this compound shows a relatively high sensitivity to Zn 2+ ion. Moreover, the proposed binding mode and the sensing mechanism are also discussed. / This thesis describes the synthesis and characterization of several series of functional boron dipyrromethenes (BODIPYs) and a silicon(IV) phthalocyanine. Their applications as efficient photosensitizers in photodynamic therapy and selective fluorescent sensors for metal ions are also reported herein. / He, Hui. / Adviser: Dennis Kee Pui Ng. / Source: Dissertation Abstracts International, Volume: 73-02, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / 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, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Yuen Yung Hui. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2002. / 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. / Mode of access: World Wide Web. / Abstracts in English and Chinese. / Yuen Yung Hui.

Le dessalement de l’eau de mer par osmose inverse connait un intérêt croissant depuis une vingtaine d’années afin de répondre aux besoins en eau potable et en eau d’irrigation dans de nombreuses régions dans le monde. Cependant, le bore contenu dans l’eau de mer est incomplètement éliminé par osmose inverse et des concentrations supérieures à la valeur limite de 0,3 mg/ sont obtenues. Dans cette étude, nous présentons des résultats sur l'élimination du bore de l'eau de mer en utilisant une technique hybride de résine échangeuse d'ions/microfiltration sans addition continue de résine. Une membrane de microfiltration en céramique a été utilisée pour retenir la résine échangeuse d'ions dans le réservoir d'alimentation et la boucle de circulation tandis que la solution modèle de bore ou l’eau de mer était continuellement ajoutée. Tout d'abord, des résines fines de taille moyenne 40 - 60 µm ont été obtenues par broyage et tamisage de résines commerciales (Amberlite IRA743, Diaion CRB05 et Purolite S108). Les résines ont ensuite été testées en système batch pour obtenir les cinétiques de sorption et par la technique hybride de sorption/microfiltration pour mesurer les courbes de perçage et le flux de perméat. L'effet de la dose de résine, de la concentration initiale en bore, de la pression transmembranaire et de la taille des pores de la membrane a été étudié. Dans une deuxième partie, l’effet de la taille des particules de résine sur les courbes de perçage en sortie d’une colonne a été déterminé et une comparaison entre les performances d’une colonne et d’un système hybride a été proposée. Dans une dernière partie, les isothermes et cinétiques de sorption expérimentales sont comparées à des équations classiques, et les courbes de perçage en colonne et en système hybride sont modélisées. En conclusion, il est suggéré que le procédé hybride de résine échangeuse d'ions et microfiltration sans ajout continu de résines peut être une technique possible pour l'élimination du bore / The maximum concentration suggested by the World Health Organization is 0.3 mg/L. In this study, we investigated a hybrid process for boron removal from water which associates sorption on ion exchange resin and microfiltration, without continuous resin addition. First, fine resins were obtained by grounding and sieving at 40 and 60 µm commercial resins (Amberlite IRA743, Diaion CRB05 and Purolite S108). The resins were then tested in batch to obtain the kinetics and in the hybrid sorption/microfiltration process to measure breakthrough curves and permeate flux. A ceramic microfiltration membrane was used to retain the ion exchange resin in the feed tank and the circulation loop while the boron solution was continuously added and the permeate collected for analysis. The effect of resin dosage, boron initial concentration, transmembrane pressure and membrane pore size was studied. In a second part, the effect of the size of the resin particles on the breakthrough curves measured at the outlet of a column was determined and a comparison between the performances of a column and a hybrid system are proposed. For the Amberlite IRA743 resin, the overall process was tested: reverse osmosis followed by hybrid sorption/microfiltration. The hybrid process was able to re-duce concentration of bacterial and phytoplankton cells thanks to the steric rejection by the microfiltration membrane, suggesting that the same membrane can be used as a pretreatment before reverse osmosis in a desalination plant. In a final part, the experimental isotherms and kinetics are compared with classical models, and the breakthrough curves obtained with a column and with the hybrid sys-tem are modelised. Overall, it is suggested that the hybrid process of ion exchange resin and microfiltration without continuous addition of resin may be a possible technique for boron removal

Superfícies funcionais dependem do controle das características das superfícies de um material para obter-se um desempenho funcional desejado. Essas superfícies têm importância em diversas áreas na engenharia, como: eletrônica, ótica, energia e tribologia. No campo da tribologia, uma aplicação é em virabrequins. A funcionalização da superfície adiciona micro cavidades que diminuem o atrito e aumentam as forças de sustentação do virabrequim. Para isso, essas cavidades possuem uma geometria específica, uma microrampa. Devido a essa forma especial, a fabricação dessas microrampas é complexa, já tendo sido alcançada empregando a metodologia de texturização com rebolos padronizados. Essa metodologia consiste na inscrição de padrões geométricos no rebolo durante a dressagem, posteriormente transferidos para a peça. Como a indústria moderna utiliza rebolos de CBN de ligante vitrificado para a retificação de virabrequins, a metodologia de texturização supracitada deve ser aplicável a esse ferramental. Esse trabalho descreve o desenvolvimento de uma unidade de dressagem capaz de inscrever padrões geométricos em rebolos de CBN vitrificados, sendo seu projeto baseado em análise modal. O trabalho apresenta as restrições de projeto, conceitos de solução, simulações dinâmicas e modelagem do processo de texturização. Para maximizar a resposta dinâmica, a unidade foi projetada para operar próxima de sua frequência natural. A unidade projetada é capaz de inscrever padrões geométricos no rebolo utilizando um disco dressador rotativo, e as texturas das peças produzidas com esse rebolo padronizado apresentam boa precisão geométrica para a aplicação em virabrequins. / Engineered surfaces rely on the control of the surface characteristics of a material to achieve a desired functional performance. These functional surfaces are important in several areas of engineering, such as: electronics, optics, energy and tribology. On tribology field, an application is in crankshafts. The surface functionalization is achieved by adding micro-cavities that reduce friction and increase crankshaft lift forces. These cavities have a specific geometry, called microramp. Due to this special geometry, manufacturing microramps is a complex process, having been achieved using the methodology of texturizing via grinding. This methodology consists in the inscription of geometric patterns in the grinding wheel during the dressing operation, later transferred to the piece. As the modern industry uses vitrified CBN grinding wheels for crankshaft grinding, the texturing methodology should be applicable to this tool. This work describes the development of a dressing unit capable of inscribing geometric patterns in vitrified CBN grinding wheels, having its design based on modal analysis. The work presents the design constraints, solution concepts, dynamic simulations and modeling of the texturing process. To maximize dynamic response, the unit is designed to operate near its natural frequency. The designed unit can inscribe geometric patterns on the grinding wheel using a rotating dressing disc, and the textures of the parts produced have good geometric precision for crankshaft applications.

Neste trabalho foi realizada a síntese de amidas, bem como de ácidos e ésteres borônicos, derivados dos aminoácidos L-cistina e L-cisteína, através de rota sintética simples, curta e de baixo custo, com o intuito de busca e a identificação de novo(s) inibidor(es) do proteassomo 20S. Esta classe de compostos possui estrutura que permite a inserção de diversos grupos funcionais, o que confere versatilidade e a construção de biblioteca de compostos que contém partes hidrofílicas e hidrofóbicas importantes para posterior avaliação inibitória. Para tanto, empregou-se rota sintética química convencional e rota biocatalisada para a formação da ligação amida. Os compostos derivados de L-cisteína foram obtidos via síntese clássica de peptídeos a qual forneceu os compostos desejados em rendimentos de até 85%. Por outro lado, tentativas de obtenção das amidas via biocatálise não se mostraram efetivas. Já amidas derivadas de L-cistina foram obtidas em rendimentos de até 79%, via síntese tradicional e até 100% de conversão através de rota biocatalítica. A inserção do átomo de boro nas estruturas se deu utilizando-se metodologias sintéticas já bem estabelecidas na literatura. Os ésteres borônicos derivados de L-cisteína foram obtidos em bons rendimentos (até 78%), enquanto que não foi possível obter-se compostos de boro derivados de L-cistina. Por sua vez, os compostos contendo ácido borônico na estrutura foram sintetizados via reação de hidrólise dos respectivos ésteres borônicos, em rendimentos moderados (até 34%). Após a obtenção dos compostos contendo grupamentos organoboro realizou-se avaliação inibitória dos mesmos frente ao proteassomo 20S. Valores de IC50 iguais a 52 &#181;M foram obtidos para composto derivado de L-cisteína contendo grupamento éster borônico, que se mostraram inibidores moderados e reversíveis. Ácidos borônicos se mostraram sem capacidade de inibir o proteassomo 20S. Adicionalmente, realizaram-se estudos de modelagem molecular com a finalidade de elucidar os resultados obtidos experimentalmente. Inicialmente realizaram-se cálculos de modelagem molecular através da realização de docking de alguns compostos e após geração de modelo farmacofórico. De maneira geral observou-se que os inibidores derivados da L-cisteína não ocupam a mesma cavidade que o fármaco bortezomibe, o que pode explicar a diferença na atividade dos compostos frente à inibição do proteassomo 20S. Também se observou que, tendo-se a interação dos inibidores com a enzima, a vizinhança do átomo de boro tem grande influência na capacidade inibitória, uma vez que estes grupamentos determinam qual a região da cavidade do proteassomo 20S será ocupada pelo inibidor. / In our study, amides, boronic acids and esters derivatives from L-cysteine and L-cysteine were synthesized by simple, short and inexpensive synthetic route, in order to search for new inhibitor(s) of the 20S proteasome. This class of compounds has a structure that allows inclusion of various functional groups, giving it versatility and allowing the construction of library compounds containing hydrophilic and hydrophobic moieties, important for further evaluation. To this end, we used conventional chemical synthetic route and biocatalysis for peptide bond formation. The compounds derived from L-cysteine were obtained by classical synthesis of peptides which provided the desired compounds up to 85% yields. On the other hand, attempts to obtain the amides via biocatalysis were not effective. However, amides derived from L-cystine were obtained with up to 79% yields via chemical synthesis and conversion up to 100% using biocatalytic route. The insertion of the boron atom in the structures was possible using synthetic methodologies well established in literature. Boronic esters derived from L-cysteine were obtained in good yields (up to 78%), whereas it was not possible to obtain boron compounds derived from L-cystine. In turn, compounds containing boronic acids in the structure were synthesized by hydrolysis reaction of the respective boronic esters in moderate yields (up to 34%). With organoboron compounds in hand, we turned our attention to inhibitory assessment against the 20S proteasome. IC50 up to 52 &#181;M were obtained when L-cysteine boronic ester derivatives were evaluated. These compounds are moderate and reversible inhibitors. L-cysteine boronic acids derivatives have shown not ability to inhibit the 20S proteasome. Additionally, molecular modeling studies were carried out in order to elucidate the results obtained experimentally. Initially molecular modeling calculations were carried out by performing docking experiments of some compounds. Generation of pharmacophoric model calculations was also executed. In general, it was observed that inhibitors derived from L-cysteine do not occupy the same cavity that drug bortezomib, which may explain the difference in the activity of compounds against the inhibition of 20S proteasome. We also observed that, with the interaction of inhibitors and enzyme, the side chains around boron atom has a great influence on inhibitory capacity, since these groups determine which region of the 20S proteasome cavity is occupied by the inhibitor.