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The primary aim was to validate and implement a urinary pharmacokinetic method for terbutaline to determine the relative lung and systemic bioavailability following inhalation and to measure the in-vitro characteristics of the emitted dose by these inhalation methods. Two new robust, accurate and sensitive high performance liquid chromatography methods for the determination of terbutaline in aqueous and urine samples were validated in accordance with the FDA and ICH guidelines. Terbutaline was extracted using solid phase extraction with salbutamol and bamethane as internal standards. The accuracy, precision, lower limit of detection and recovery for both methods were within recognized limits. The in-vitro characteristics of terbutaline sulphate inhalers were measured according to standard compendial methodology as well as adaptation of this methodology to simulate routine patient use. The dose emission of terbutaline sulphate from a Bricanyl Turbuhaler was determined using an inhalation volume of 4 L at inhalation flows of 10-60 L min-1. The particle size distribution was measured using an Anderson Cascade Impactor (ACI) with a mixing inlet valve to allow measurement at different flows. A steady increase in total emitted dose (TED) and the fine particle dose (FPD) was observed as the inhalation flow increased thereby highlighting the flow dependent dose emission characteristics of the Turbuhaler. The in-vitro dose emission characteristics of terbutaline sulphate from Bricanyl MDIs were measured according to the standard compendial methodology at a flow of 28.3 L min-1 using a 4 L inhalation volume. The TED and particle size distribution of terbutaline sulphate from the Bricanyl MDI were determined alone and with different spacers [AeroChamber Max (AMAX), AeroChamber Plus (APLUS), Fisonair and Nebuhaler]. The TED from the MDI alone was significantly higher than all MDI+spacers (p<0.001). The MDI with APLUS resulted in the smallest mass median aerodynamic diameter (MMAD) and the highest fine particle fraction (FPF). The MDI with AMAX resulted in the highest FPD. The in-vitro characteristics of terbutaline sulphate from Bricanyl respules using the Aeroneb Pro (vibrating mesh) and Sidestream jet nebulisers were determined by the CEN methodology and the Next Generation Impactor (NGI) methodology. The Aeroneb Pro was found to have significantly better aerodynamic properties than the Sidestream. The results from the NGI method were significantly different from the CEN method suggesting further evaluation of both methods. Cooling the NGI decreased the evaporation effect. Twelve healthy volunteers (6 females) completed in-vivo urinary terbutaline pharmacokinetic studies to determine the relative bioavailability following inhalation. The differences between the amounts excreted 0.5, 1, 2, 4, 6 and 24 hour post inhalation from a Bricanyl MDI (I) and oral (O) dosing of 500 µg terbutaline sulphate and with the co-administration of oral charcoal (IC and OC, respectively) were studied. No terbutaline was found in OC samples. The amount of terbutaline excreted 30 minutes post I and IC were significantly (p<0.001) higher than post O suggesting that the amount of terbutaline excreted 30 minutes post dosing can be used as an index of the lung deposition. The amount of terbutaline excreted 24 hour post I was significantly (p<0.01) higher than post O suggesting that the amount of terbutaline excreted 24 hour post dosing can be used as an index of the relative systemic bioavailability. The dose response relationships and the low inter and intra-subject variability studies confirm the feasibility of this method. To demonstrate the application of the method the effect of inhalation technique on the lung and systemic bioavailability following inhalation from a dry powder inhaler was evaluated. The effect of different spacers on the dose emitted from the Bricanyl MDI and the effect of different nebulisers on the dose emitted were also studied using twelve healthy volunteers (6 females) for each study. A fast inhalation flow using the Bricanyl Turbuhaler resulted in significantly higher amounts of terbutaline excreted 0.5 and 24 hour post dosing (2 doses of 500µg terbutaline sulphate from Bricanyl Turbuhaler) than slow inhalation flow (p<0.001). The Bricanyl MDI alone resulted in a significantly higher amount of terbutaline excreted 24 hour post dosing (2 doses of 250µg terbutaline sulphate from Bricanyl MDI) and significantly lower amounts excreted 30 minutes post dosing than the MDI+Spacers. The AMAX provided a greater amount of urinary terbutaline excreted 30 minutes post dosing than the APLUS and Nebuhaler. The Aeroneb Pro resulted in significantly higher amounts of terbutaline excreted 0.5 and 24 hour post dosing (1 dose of 5mg/2ml terbutaline sulphate from Bricanyl respule) than a Sidestream Jet nebuliser (p<0.001). Further application of the method was demonstrated by 12 (6 female) COPD non-invasive mechanically ventilated patients. One dose of 2mg in 0.8ml terbutaline sulphate respiratory solution from Aeroneb Pro and one dose of 5mg in 2ml terbutaline sulphate respiratory solution from Sidestream jet nebuliser resulted in a similar amounts of urinary terbutaline excreted 0.5 and 24 hour post dosing. The results were consistent with the results of the ex-vivo study performed on the same patients. The thesis highlights extension of the urinary pharmacokinetic method following inhalation to terbutaline and its application in volunteer and patient studies.

Lung diseases such as asthma and chronic obstructive pulmonary disease (COPD) are major health burdens on the global population. To treat diseases of the lung, topical therapies using dry powder inhalers (DPIs) have been employed. However, a relatively small amount of dose (5.5 - 28 %) reaches the lung during DPI therapy leading to high inter-patient variability in therapy response and oropharyngeal deposition. Strategies were assessed to take patient variability in inhalation performance into account when developing devices to reduce throat deposition and to mitigate flow rate dependency of the emitted aerosol. A cyclone-spacer was manufactured and evaluated with marketed and in-house manufactured formulations. An in vivo study showed that a high resistance inhaler would produce longer inhalation times in lung disease patients and that a spacer with high resistance may prove a suitable approach to address inter-patient variability. Two spacer prototypes were evaluated with cohesively- and adhesively-balanced particle blends. The data suggested that the throat deposition dramatically decreased for the emitted particles when the spacers were used with the inhalers (e.g. 18.44 ± 2.79% for salbutamol sulphate, SS 4 kPa) due to high retention of the formulation within the spacer (87.61 ± 2.96%). Moreover, variation in fine particle fraction and dose was mitigated when increasing the flow rate (82.75 ± 7.34 %, 92.2 ± 7.7 % % and 77.0 ± 10.1 % at 30, 45 and 60 Lmin-1, respectively). The latter was an improvement over previous proposed DPI spacers, where variability in emitted dose due to airflow rate was a major issue. Due to the different physicochemical properties of the active pharmaceutical ingredients used in the formulation, throat deposition and respirable fraction for adhesively-balanced particles (e.g. SS) were double that of the cohesively- balanced particles (salmeterol xinafoate, SX) (e.g. 65.83 ± 8.99 % vs. 45.83 ± 5.04 % for SS:Coarse Lactose (CL) and SX:CL, respectively). Scanning electron microscopy revealed that surface-bound agglomerates were more freely removed from the carrier, but subject to decreased impaction-type deagglomeration forces in the spacer than for carrier-bound drug. An ex vivo study using breath profiles from healthy volunteers identified the minimization of differences between adhesively- and cohesively-balanced blends when full breath profiles were studied compared to square-wave airflow. Therefore the use of constant flow for in vitro testing should not be the sole flow regime to study aerosolization when developing new inhalation devices and formulations.

O concreto armado é um dos materiais de construção mais utilizados atualmente. Um dos fatores que levaram a essa preferência foi a maior durabilidade dos componentes, uma vez que o aço inserido no concreto se protege do ambiente externo e, consequentemente, de uma agressividade intensa pelo cobrimento de concreto empregado. Porém, mesmo considerando que um concreto adequadamente dosado, lançado e curado tende a ser durável, casos de deterioração prematura das estruturas de concreto podem ocorrer, trazendo à tona a importância do controle dos fatores responsáveis pela degradação natural da estrutura. Entre os fatores de deterioração, destaca-se a corrosão de armaduras, devido a sua elevada incidência e potencial de dano. Nas estruturas de concreto armado, são utilizados espaçadores para garantir o cobrimento especificado em projeto e o consequente confinamento do aço, garantindo assim o aumento da vida útil da estrutura. No entanto, a interface espaçador-concreto pode se tornar um ponto frágil para a entrada de agentes agressivos, como os íons cloreto. O objetivo deste trabalho foi avaliar a influência dessa interface utilizando espaçadores de argamassa industrializados e espaçadores de plástico, bem como a condição de exposição a que o concreto é submetido. Para a viabilização do estudo, foi utilizada a técnica de aceleração de corrosão, baseada no ensaio denominado Corrosão Acelerada por Imersão Modificada (CAIM) com aplicação de voltagem constante e corrente constante. Foram moldados corpos de prova em laboratório, com dimensões de 10 × 10 × 20 cm, estabelecidas pelo CAIM, com a utilização de dois tipos de espaçadores e cobrimentos estabelecidos de 25 mm e 50 mm, além de uma barra de aço com diâmetro de 12,5 mm, simulando uma situação real. Para a avaliação dos dados, as amostras passaram por análise microscópica, ensaio colorimétrico e de redimensionamento a laser, a fim de realizar análises qualitativas e quantitativas dos resultados. Este estudo verificou que tanto espaçadores de argamassa quanto de plástico contribuíram para uma maior degradação na região dos espaçadores, porém os de plástico apresentaram desempenho inferior quanto à ascensão de cloretos já na fase da iniciação. Além disso, a condição de exposição por ciclos de calor influencia claramente na interface entre espaçador e concreto, em especial nos espaçadores de plástico. / Reinforced concrete is one of the building materials most used today. One of the factors leading to this constructive choice was greater durability, since the steel is protected for the concrete cover from a strong aggressiveness of the external environment. However, even considering that an adequately dosed, cast and cured concrete, tends to be durable, cases of premature deterioration of concrete structures can occur, bringing to the fore the importance of control the factors responsible for the natural degradation of the structure. Among the deterioration factors, can be highlighted the rebars’ corrosion, because of the high incidence and potential damage. In reinforced concrete structures, spacers are used to ensure structural design specified cover depths and the steel confinement, which helps to increase the structure service life. However, the spacer-concrete interface can become a weak point for the entry of aggressive agents, such as chloride ions. This study aims to understand the influence of the spacer-concrete interface, analysing industrialized mortar spacers and plastic spacers, as well the concrete subjected to different curing condition. In order to make this work possible, a corrosion acceleration technique was used, based on corrosion acceleration test method, with application of constant voltage and constant current. Samples sizing 100 x 100 x 200 mm were cast in the laboratory. The samples were subjected to accelerated corrosion process stimulation, using two different spacers and cover depths (25 mm and 50 mm) and one rebar diameter (12.5 mm), simulating a real situation. The losses of cross section were measured by using microscopic analysis, colorimetric tests and 3D image reconstruction with laser, in order to perform qualitative and quantitative analysis. The results show that both, mortar spacers as plastic spacers, contributed to increase the transport in the contact region, but the plastic spacers produced the largest increase at the first stages. Furthermore, the increase of the temperature in the condition of exposure analysis by heat cycles influences in the interface between spacer and concrete, particularly with the plastic spacers.

Existem evidências na literatura de que a administração de medicações, como corticosteróides inalatórios e broncodilatadores, utilizando inaladores pressurizados dosimetrados, é mais eficaz e segura do que com os nebulizadores convencionais. Entretanto, há evidências de que não só pacientes, mas também profissionais de saúde têm dificuldade no manejo dos inaladores pressurizados dosimetrados. A hipótese do presente estudo é que o conhecimento da técnica inalatória entre os profissionais da nossa Instituição é heterogêneo, sendo que não há informações sobre o nível deste conhecimento entre as diversas categorias profissionais. OBJETIVOS: Avaliar o conhecimento prático e teórico de profissionais da área médica, de enfermagem e fisioterapia sobre a utilização do inalador dosimetrado através de testes padronizados. MÉTODOS: Avaliações teóricas e práticas sobre o conhecimento do uso de inaladores pressurizados dosimetrados foram realizadas com médicos, fisioterapeutas, enfermeiras e auxiliares de enfermagem, atribuindo-se uma nota de 0 a 10 para cada avaliação. Calcularam-se as medianas das notas obtidas pelos profissionais de cada categoria, as questões com maiores e menores índices de erros e feita a comparação descritiva do desempenho das diversas categorias profissionais. Após as avaliações, instrução verbal e escrita sobre a utilização correta dos dispositivos foi fornecida a todos os participantes. A análise estatística foi feita através do método de Kruskal-Wallis de comparação de medianas. Também foi realizada a análise através de regressão logística múltipla seqüencial. RESULTADOS: foram avaliados 30 médicos residentes ou estagiários da pediatria, 23 médicos assistentes, 29 fisioterapeutas, 33 enfermeiras e 31 auxiliares de enfermagem, em um total de146 profissionais. Não foram entrevistados residentes ou assistentes do grupo de Pneumologia. Os médicos residentes, fisioterapeutas e os médicos assistentes obtiveram desempenho significativamente superior que os enfermeiros e auxiliares de enfermagem. Apenas os médicos residentes obtiveram mediana superior a seis. As questões práticas com maiores índices de erros foram as relativas à limpeza do espaçador. Questões relativas à agitação do inalador antes do uso e à limpeza da cavidade oral após a sua utilização também obtiveram alto índice de erros. A questão teórica mais errada foi a respeito do tempo necessário entre dois jatos em aplicações sucessivas do inalador pressurizado dosimetrado. CONCLUSÕES: O conhecimento teórico-prático dos profissionais de saúde da Instituição a respeito do uso de inaladores pressurizados dosimetrados é heterogêneo. Os médicos residentes, fisioterapeutas e médicos assistentes obtiveram desempenho significativamente melhor que os enfermeiros e auxiliares de enfermagem sendo que estes últimos estão diretamente envolvidos na aplicação prática destes dispositivos na rotina hospitalar. / There are data in the literature indicating that the administration of medications such as inhaled corticosteroids and bronchodilators, using metered-dose inhalers, is more effective and safer than its dispensation by conventional nebulizers. However, there is evidence that not only patients but also health care professionals have difficulty in dealing with pressurized dose inhalers. The hypothesis of the present study is that the knowledge of inhalation techniques among health professionals of our Institution is heterogeneous, and there is no information about this knowledge among the diverse categories of professionals. OBJECTIVE: To assess the practical and theoretical knowledge of medical professionals, nursing and physiotherapy on the use of metereddose inhalers by standardized testing. METHODS: Practical and written tests on the use of metered-dose inhalers were applied to physicians, physical therapists, nurses and nursing assistants. A score from 0 to 10 was assigned to each evaluation. Median scores were calculated for each professional category. Questions with higher and lower correct values were identified, and a descriptive comparison was made regarding the performance of the diverse professional categories. Following the examination, oral and written instructions on the correct use of the devices were provided for all participants. Statistical analysis was performed using the Kruskal-Wallis method for comparison of medians. A sequential logistic multiple regression analysis was also performed. RESULTS: A total of 146 professionals were assessed, including 30 fellows in pediatrics, 23 attending physicians, 29 physical therapists, 33 nurses and 31 nursing assistants. Fellows or attending physicians of the Pediatric Pulmonology Unit were not included in the study. Fellows, physical therapists and attending physicians performed significantly better than did nurses and nursing assistants. Only fellows had a median score greater than six. On the practical tests for infants and toddlers, the step most often missed was that related to cleaning the spacer. On practical tests, the steps related to shaking the inhaler and cleaning the mouth also presented high error indices. On the written tests, the question most often answered incorrectly was that related to the waiting time between puffs. CONCLUSIONS: The theoretical and practical knowledge of health professionals of our Institution on the use of metered-dose inhalers is heterogeneous. The performance of fellows, physical therapists and attending physicians was significantly better than that of nurses and nursing assistants who are directly involved in the practical application of these devices in the hospital routine.

Existem evidências na literatura de que a administração de medicações, como corticosteróides inalatórios e broncodilatadores, utilizando inaladores pressurizados dosimetrados, é mais eficaz e segura do que com os nebulizadores convencionais. Entretanto, há evidências de que não só pacientes, mas também profissionais de saúde têm dificuldade no manejo dos inaladores pressurizados dosimetrados. A hipótese do presente estudo é que o conhecimento da técnica inalatória entre os profissionais da nossa Instituição é heterogêneo, sendo que não há informações sobre o nível deste conhecimento entre as diversas categorias profissionais. OBJETIVOS: Avaliar o conhecimento prático e teórico de profissionais da área médica, de enfermagem e fisioterapia sobre a utilização do inalador dosimetrado através de testes padronizados. MÉTODOS: Avaliações teóricas e práticas sobre o conhecimento do uso de inaladores pressurizados dosimetrados foram realizadas com médicos, fisioterapeutas, enfermeiras e auxiliares de enfermagem, atribuindo-se uma nota de 0 a 10 para cada avaliação. Calcularam-se as medianas das notas obtidas pelos profissionais de cada categoria, as questões com maiores e menores índices de erros e feita a comparação descritiva do desempenho das diversas categorias profissionais. Após as avaliações, instrução verbal e escrita sobre a utilização correta dos dispositivos foi fornecida a todos os participantes. A análise estatística foi feita através do método de Kruskal-Wallis de comparação de medianas. Também foi realizada a análise através de regressão logística múltipla seqüencial. RESULTADOS: foram avaliados 30 médicos residentes ou estagiários da pediatria, 23 médicos assistentes, 29 fisioterapeutas, 33 enfermeiras e 31 auxiliares de enfermagem, em um total de146 profissionais. Não foram entrevistados residentes ou assistentes do grupo de Pneumologia. Os médicos residentes, fisioterapeutas e os médicos assistentes obtiveram desempenho significativamente superior que os enfermeiros e auxiliares de enfermagem. Apenas os médicos residentes obtiveram mediana superior a seis. As questões práticas com maiores índices de erros foram as relativas à limpeza do espaçador. Questões relativas à agitação do inalador antes do uso e à limpeza da cavidade oral após a sua utilização também obtiveram alto índice de erros. A questão teórica mais errada foi a respeito do tempo necessário entre dois jatos em aplicações sucessivas do inalador pressurizado dosimetrado. CONCLUSÕES: O conhecimento teórico-prático dos profissionais de saúde da Instituição a respeito do uso de inaladores pressurizados dosimetrados é heterogêneo. Os médicos residentes, fisioterapeutas e médicos assistentes obtiveram desempenho significativamente melhor que os enfermeiros e auxiliares de enfermagem sendo que estes últimos estão diretamente envolvidos na aplicação prática destes dispositivos na rotina hospitalar. / There are data in the literature indicating that the administration of medications such as inhaled corticosteroids and bronchodilators, using metered-dose inhalers, is more effective and safer than its dispensation by conventional nebulizers. However, there is evidence that not only patients but also health care professionals have difficulty in dealing with pressurized dose inhalers. The hypothesis of the present study is that the knowledge of inhalation techniques among health professionals of our Institution is heterogeneous, and there is no information about this knowledge among the diverse categories of professionals. OBJECTIVE: To assess the practical and theoretical knowledge of medical professionals, nursing and physiotherapy on the use of metereddose inhalers by standardized testing. METHODS: Practical and written tests on the use of metered-dose inhalers were applied to physicians, physical therapists, nurses and nursing assistants. A score from 0 to 10 was assigned to each evaluation. Median scores were calculated for each professional category. Questions with higher and lower correct values were identified, and a descriptive comparison was made regarding the performance of the diverse professional categories. Following the examination, oral and written instructions on the correct use of the devices were provided for all participants. Statistical analysis was performed using the Kruskal-Wallis method for comparison of medians. A sequential logistic multiple regression analysis was also performed. RESULTS: A total of 146 professionals were assessed, including 30 fellows in pediatrics, 23 attending physicians, 29 physical therapists, 33 nurses and 31 nursing assistants. Fellows or attending physicians of the Pediatric Pulmonology Unit were not included in the study. Fellows, physical therapists and attending physicians performed significantly better than did nurses and nursing assistants. Only fellows had a median score greater than six. On the practical tests for infants and toddlers, the step most often missed was that related to cleaning the spacer. On practical tests, the steps related to shaking the inhaler and cleaning the mouth also presented high error indices. On the written tests, the question most often answered incorrectly was that related to the waiting time between puffs. CONCLUSIONS: The theoretical and practical knowledge of health professionals of our Institution on the use of metered-dose inhalers is heterogeneous. The performance of fellows, physical therapists and attending physicians was significantly better than that of nurses and nursing assistants who are directly involved in the practical application of these devices in the hospital routine.

The aim of this study was to obtain the molecular marker of Taiwania cryptomerioides Hayata based on DNA sequence data of PCR- sequencing and inter-simple sequence repeat (ISSR), and to evaluate the genetic diversity of populations of Taiwania cryptomerioides Hayata and molecular phylogeny of T. cryptomerioides and Taiwania flousiana Gaussen. The sequence data based on the internal transcribed spacer (ITS) of a total of 108 samples of T. cryptomerioides were determined. Eight different populations of T. cryptomerioides and 12 samples of T. flousiana from Yunnan, China were analyzed. The finding of the study showed that heterogeneity of ITS region within individuals of T. cryptomerioides was high by showing high nucleotide diversity among ITS sequences both in T. cryptomerioides ( £k = 0.18153) and T. flousiana ( £k = 0.19751). The findings fit in Tajima¡¦s D test of neutrality based on DNA sequence variation in the ITS region of T. cryptomerioides and T. flousiana. It is not obvious to incorporate into different population through clustering analysis based on data of the ITS region of T. cryptomerioides and T. flousiana. However, slightly genetic differentiation between T. cryptomerioides and T. flousiana was found, which figured of Fst (Fst = 0.0441~ 0.0856, an average value = 0.0611). On the other hand, the samples were studied by using ISSR markers. Of the 100 primers screened, 4 produced highly reproducible ISSR bands, and 24 discernible DNA fragments were generated with 17 being polymorphic. Based on cluster analysis of molecular data, the cluster is not clear among populations of T. cryptomerioides and T. flousiana. The analysis of AMOVA revealed that the variance component between species of T. cryptomerioides and T. flousiana was 38.54¢H (P < 0.001); however, the variance component within species is 61.46 (P < 0.001). The variation within population of T. cryptomerioides was 84.74¢H (P < 0.001) and the variance between populations is 15.26¢H (P < 0.001), indicating that the genetic diversity of individuals within population was high. The aforementioned data suggest that gene flow among different populations of T. cryptomerioides was high, indicating that the genetic diversity was high among individuals of T. cryptomerioides but was low between populations. Furthermore, it is concluded both species are genetically closer and could be grouped into the same species.

This thesis concerns the design and implementation of novel auto-immolative spacers for use in probes for enzymatic activity in vivo.The first part relates the development and in vitro validation of cyclisation spacers which couple the action of an aminopeptidase to the release of a phenol. The modular three-component fluorogenic probes based on these 1,2-diamine spacers are very robust (halflife > 560 h), but are also rapidly enzymatically processed, and quickly (halftime ~3 min) release an exceptionally photostable, insoluble ESIPT fluorophore. The probes have excellent detection sensitivity relative to current methods (signal to control ratio > 3000:1), and provide the first demonstration of a macroscopically binary off-ON system for phenol-releasing probes of aminopeptidase activity. The probe system may allow the exceptionally sensitive, ESIPT-based molecular imaging of a range of exopeptidases. The spacers may also be applied in off ON peptidase probes of other phenolic fluorophores, to peptidase-specific phenol/alcohol prodrugs for targeted therapy, or more generally in chemical adapter technologies.In the second part, two novel families of auto-immolative elimination/tautomerisation spacers were designed for use in three-component off ON magnetogenic probes sensing glycosidase activity. The first known substrate-spacer designs based on 2-hydroxyfurans and on carbimidates were explored. Notably, 2 furanol glycosides were synthesised in pursuit of high-energy alternatives to quinone methides, and a general method for preparing model carbimidate-bearing ligands for pro-magnetic probes was elaborated.

This thesis concerns the design and implementation of novel auto-immolative spacers for use in probes for enzymatic activity in vivo.The first part relates the development and in vitro validation of cyclisation spacers which couple the action of an aminopeptidase to the release of a phenol. The modular three-component fluorogenic probes based on these 1,2-diamine spacers are very robust (halflife > 560 h), but are also rapidly enzymatically processed, and quickly (halftime ~3 min) release an exceptionally photostable, insoluble ESIPT fluorophore. The probes have excellent detection sensitivity relative to current methods (signal to control ratio > 3000:1), and provide the first demonstration of a macroscopically binary off-ON system for phenol-releasing probes of aminopeptidase activity. The probe system may allow the exceptionally sensitive, ESIPT-based molecular imaging of a range of exopeptidases. The spacers may also be applied in off ON peptidase probes of other phenolic fluorophores, to peptidase-specific phenol/alcohol prodrugs for targeted therapy, or more generally in chemical adapter technologies.In the second part, two novel families of auto-immolative elimination/tautomerisation spacers were designed for use in three-component off ON magnetogenic probes sensing glycosidase activity. The first known substrate-spacer designs based on 2-hydroxyfurans and on carbimidates were explored. Notably, 2 furanol glycosides were synthesised in pursuit of high-energy alternatives to quinone methides, and a general method for preparing model carbimidate-bearing ligands for pro-magnetic probes was elaborated.

A espessura de cobrimento das armaduras, que se interpõe entre as barras de aço e o ambiente proporcionando proteção contra os agentes agressivos, é fator determinante na durabilidade das estruturas de concreto armado. Embora o emprego do espaçador para assegurar o cobrimento especificado seja normatizado, a regulamentação brasileira não dispõe nenhum método de fixação e distribuição dos dispositivos. Levantamentos in loco efetuados durante esta pesquisa, em obras localizadas em Porto Alegre/RS e Cuiabá/MT, mostraram através de medições em elementos estruturais já executados, que as espessuras de cobrimento estão não conformes com as especificações de projeto. Dentro deste levantamento, os resultados mais preocupantes estão relacionados ao fundo de viga e lajes. Para lajes de concreto armado, notou-se durante a execução, que alguns fatores poderiam influenciar na obtenção deste requisito proposto em norma. Sendo assim, buscou-se testar através de simulação computacional diferentes combinações de variáveis, como por exemplo, a distribuição de espaçadores, as características da armadura e o carregamento acidental presente durante a concretagem. Diante dos resultados apresentados pelo estudo computacional, onde um grande percentual de combinações apresenta a plastificação total das barras de aço, testou-se em laboratório alguns conjuntos de variáveis, a fim de mensurar a deformação permanente na malha de armadura. Foi possível constatar que armaduras compostas com diâmetros de 4,2 mm e 5,0 mm, apresentam resultados críticos na obtenção da espessura de cobrimento, independentemente da distribuição dos espaçadores, deformando permanentemente a armadura chegando a um valor de 17,31 mm, e assim, prejudicando diretamente a durabilidade da estrutura de concreto armado. / The cover to reinforcement ensures durability, it is responsible for protecting the armor front the environment aggressive agents. The use of spacers is a recommendation standard, however the regulation does not provide sufficiente methodology of use subsidies. Thus, cover to reinforcement just barely achieved during the structural element execution as show in this research, through surveys conducted in the cities of Porto Alegre/RS and Cuiabá/MT. With that, by computer and experimental simulation, some variables observed during the solid slabs execution, such as armor characteristics, overlays thickness and spacers distribution were tested in different configurations. The results shows that the smaller diameter reinforcements (4,2 and 5,0 mm) create critical situations in relation to overlays obtainment, independent of the configuration, all the reinforcements suffer permanent deformation, reaching 17,31 mm, affecting the performance of the reinforced concrete structure.