Nesta tese foram perseguidos novos avanços no campo das tetrapiridilporfirazinas supramoleculares polimetaladas, visando explorar a maior capacidade de conjugação eletrônica esperada para essa classe de compostos, e seus reflexos nas propriedades eletrônicas e eletroquímicas. Foram apresentadas novas rotas sintéticas para obtenção de tetra(3,4-piridil)porfirazinas centrometaladas coordenadas a complexos polipiridínicos de rutênio, MTRPyPz (M = Cu, Co). As propriedades espectroscópicas e eletroquímicas foram investigadas com o auxílio de técnicas de espectroscopia UV-Vis, Raman ressonante, voltametria cíclica, espectroeletroquímica e espectrometria de massas. Foram desenvolvidas aplicações em dispositivos amperométricos para determinação eletrocatalítica de substratos importantes nas indústrias, como nitrito, sulfito e ácido ascórbico. Os estudos também abrangeram a formação de compósitos das porfirazinas tetrarrutenadas com fullereno. Os nanomateriais híbridos apresentaram uma alta eficiência nos processos eletrocatalíticos com menor sobrepotencial no eletrodo, abrindo perspectivas interessantes de utilização em dispositivos moleculares / Research in supramolecular polymetallic tetrapyridylporphyrazines has been pursued in this Thesis, aiming the exploitation of the favorable electronic delocalization associated with conjugated aromatic rings, and its influence on the electronic and electrochemical properties. New synthetic routes have been developed for the preparation of tetra(3,4-pyridyl)porphyrazines containing Cu(II) and Co(II) ions in the center, and four chlorobis(2,2´bipyridine)ruthenium(II) complexes attached to the peripheral pyridyl groups. Their spectroscopic and electrochemical behaviors were investigated by means of UV-Vis and resonance Raman spectroscopy, cyclic voltammetry, spectroelectrochemistry and mass spectrometry. Applications in amperometric devices for determination of nitrite, sulfite and ascorbic acid were successfully developed. The thesis also focused on nanocomposites generated from the polymetallic porphyrazines and fullerene (C60). Such hybrid nanomaterials exhibited enhanced electrocatalytic activity associates with a significant decrease of overpotential, opening exciting perspectives of use in molecular devices

Nesta tese foram perseguidos novos avanços no campo das tetrapiridilporfirazinas supramoleculares polimetaladas, visando explorar a maior capacidade de conjugação eletrônica esperada para essa classe de compostos, e seus reflexos nas propriedades eletrônicas e eletroquímicas. Foram apresentadas novas rotas sintéticas para obtenção de tetra(3,4-piridil)porfirazinas centrometaladas coordenadas a complexos polipiridínicos de rutênio, MTRPyPz (M = Cu, Co). As propriedades espectroscópicas e eletroquímicas foram investigadas com o auxílio de técnicas de espectroscopia UV-Vis, Raman ressonante, voltametria cíclica, espectroeletroquímica e espectrometria de massas. Foram desenvolvidas aplicações em dispositivos amperométricos para determinação eletrocatalítica de substratos importantes nas indústrias, como nitrito, sulfito e ácido ascórbico. Os estudos também abrangeram a formação de compósitos das porfirazinas tetrarrutenadas com fullereno. Os nanomateriais híbridos apresentaram uma alta eficiência nos processos eletrocatalíticos com menor sobrepotencial no eletrodo, abrindo perspectivas interessantes de utilização em dispositivos moleculares / Research in supramolecular polymetallic tetrapyridylporphyrazines has been pursued in this Thesis, aiming the exploitation of the favorable electronic delocalization associated with conjugated aromatic rings, and its influence on the electronic and electrochemical properties. New synthetic routes have been developed for the preparation of tetra(3,4-pyridyl)porphyrazines containing Cu(II) and Co(II) ions in the center, and four chlorobis(2,2´bipyridine)ruthenium(II) complexes attached to the peripheral pyridyl groups. Their spectroscopic and electrochemical behaviors were investigated by means of UV-Vis and resonance Raman spectroscopy, cyclic voltammetry, spectroelectrochemistry and mass spectrometry. Applications in amperometric devices for determination of nitrite, sulfite and ascorbic acid were successfully developed. The thesis also focused on nanocomposites generated from the polymetallic porphyrazines and fullerene (C60). Such hybrid nanomaterials exhibited enhanced electrocatalytic activity associates with a significant decrease of overpotential, opening exciting perspectives of use in molecular devices

This PhD project has explored the use of novel nitroxide annulated porphyrinic macrocycles as photosensitisers (PSs) for photodynamic therapy (PDT). The PSs have been synthesised, structurally, photophysically and photochemically characterised and investigated biologically through cell assays to determine their potential as photoactivated anticancer drugs. Tetra-nitroxide annulated phthalocyanines (Pcs) were initially investigated. Each of these compounds exhibit four annulated nitroxide-containing rings in a rigid, planar arrangement with fixed distance and geometry with respect to the macrocycle core, which is a novel structural motif in Pc chemistry. The presence of the nitroxides purportedly has two effects: to quench fluorescence and to increase photochemical singlet oxygen production by the compound. While nitroxides, as paramagnetic compounds, are non-fluorescent, their reduction to diamagnetic hydroxylamines results in an increased fluorescence yield. In this way, the nitroxide Pcs can potentially be used as probes for metabolic activity in biological systems, where the primary fate of the nitroxide moiety is reduction. Here, the fluorescence properties of the nitroxide-annulated Pcs were investigated through reduction of the nitroxide moieties by biologically significant reductants and calculation of fluorescence quantum yields. The singlet oxygen quantum yields of the Pcs were determined by two methods, the chemical trapping of singlet oxygen and the direct observation of singlet oxygen luminescence. While the quantum yields of the Pcs were promising when compared to clinically relevant PSs, the tetra-nitroxide Pcs did not exhibit increased quantum yields with respect to their nitroxide-free analogues. Additionally, there was minimal photodynamic action in cell assays. Subsequent fluorescence microscopy confirmed that this was most probably due to the fact that the Pcs were not localising within the cells. To improve the photodynamic action of the Pcs, two polymer-based delivery strategies were employed to enhance their delivery in biological environments. Firstly, the nitroxide Pcs were coupled to linear polymers to create polymer Pc hybrids. The second method involved the encapsulation of the nitroxide Pcs within polymer-based micelles. The synthesis of the polymer Pc hybrids was via a fast and efficient Atom Transfer Nitroxide Radical Coupling (ATNRC) reaction. The hybrids were synthesised as Mg, Zn or free-base (2H) Pc complexes, with either hydrophobic or hydrophilic polymer arms. The hybrids displayed high fluorescence quantum yields and reasonable singlet oxygen quantum yields. Again, these attributes this did not extend to any cell growth inhibition, even for the hydrophilic derivatives. Micellisation of the Pcs with a poly(styrene)-poly(acrylic acid) (PSty-PAA) star diblock copolymer afforded micelles with a range of concentrations of Pcs encapsulated within the glassy PSty core. Fluorescence studies showed that the micelles protected the nitroxide moieties from reduction by ascorbate, a result that could find application in EPR imaging and oximetry. During singlet oxygen experiments, the micelles were found to perform as nanoreactors, supramolecular assemblies which provide a reaction volume for other reagents. Pcs in the micelle cores effectively generated singlet oxygen and while this failed to escape the micelles, it was very effective in the oxidation of a hydrophobic model compound. Although there are potential applications for the micelle systems in waste-water remediation, these systems were ineffective in the PDT assays. With the difficulties associated with the biological delivery of the nitroxide Pcs in mind, hydrophilic mono-nitroxide annulated porphyrazine (Pz) macrocycles were designed and synthesised. Pzs exhibit many of the favourable optical properties of the Pcs. Synthesis of these compounds proceeded via Linstead macrocyclisation to give the target MgPz with A3B type substitution. A nitroxide-free A4 Pz was also isolated as a side-product. Transmetallation and/or hydrolysis gave access to Mg and Zn A3B and A4 carboxylate Pzs. These compounds were structurally characterised and their fluorescence characteristics investigated. The 1O2 quantum yields of the Pzs were also studied. Significantly, nitroxide annulation was found to enhance 1O2 generation of the Pzs relative to nitroxide-free analogues. The Zn carboxylate Pzs were shown to effectively inhibit the growth of tumour cell lines in PDT assay and the MgA4 carboxylate displayed strong 2-photon fluorescence within the cytoplasm of NFF cells. Experiments on freshly excised skin showed the carboxylate Pzs to be highly effective 2-photon PSs for PDT. In conclusion, we have identified several carboxylate Pzs which should be tested further in in vivo PDT experiments.