During this project, photocatalytic material, nano sized titanium dioxide, was introduced into poly (lactic acid) to produce functional surface capable of self-cleaning property. Samples containing 0%, 5%, 10%, 15% and 20% titanium dioxide were prepared and etched with proteinase K to expose the nano particles on the surface. It was shown that the nano titanium dioxide could dispersed in the polymer matrix pretty well, it was also found that the nano particles affected the thermal and mechanical properties of the polymer matrix differently , due to difference in concentrations of nano filler. The self-cleaning property was evaluated by decolouration of stains caused by coffee and red wine, also by detecting degradation of methylene blue via a UV-vis spectrophotometer. By measuring changes in absorbance of light at 664nm wavelength after a maximum of 24h UV irradiation, it was possible to measure the degradation property of the samples. / Program: Masterutbildning i textilteknik

O objetivo do presente estudo, prospectivo e randomizado, é avaliar comparativamente as respostas hemodinâmicas, laboratoriais, imunomoleculares e clínicas, em dois grupos de pacientes submetidos a cirurgia de revascularização miocárdica com extracorpórea utilizando-se, em um deles infusão de azul de metileno durante o período intraoperatório. As variáveis hemodinâmicas estudadas foram: FC, PAE, PVC, DC, RVS, RVP, PAPM, PASS, PASD e PASM. Os dados laboratoriais avaliados foram: gasometria arterial, creatinina, leucócitos, bastões, neutrófilos, eosinífilos, basófilos, linfócitos, Ht, Hb, paquetas, Na+ e K+. Os marcadores imunomoleculares estudados foram: IL - 1ß, IL-6, IL-8, IL-10, IL-12 p40, TNF alfa e NO. Os dados clínicos avaliados foram: idade, sexo, raça, tabagismo, hipertensão, diabetes, angina estável, angina instável, infarto prévio, tempo de CEC, tempo de pinçamento aórtico, número de pontes realizadas, urina azulada, fezes azuladas, diarréia, náuseas, cefaléia, tontura, disúria, astenia e dispnéia. As variáveis citadas foram obtidas em todos ou em parte dos períodos seguintes: antes da indução, terceira hora, sexta hora, 24ª hora e 48ª hora após o término da CEC. Ocorreram diferenças estatisticamente significativas na resistência vascular sistêmica, na pressão arterial sistêmica diastólica, em parte das citocinas estudadas e no óxido nítrico. A análise dos resultados mostra que no grupo que utilizou azul de metileno houve resistência vascular sistêmica mais alta no período da sexta hora de pós-operátório, menor concentração de TNF alfa no período da terceira e 48ª hora e menores níveis de óxido nítrico no período da sexta hora. As medidas laboratoriais foram semelhantes em ambos os grupos exceto maior número de leucócitos e neutrófilos na 48ª hora após CEC no grupo contrôle. Verifica-se que o azul de metileno levou a melhores condições hemodinâmicas e menores valores e alguns marcadores de reposta inflamatória sistêmica após cirurgia de revascularização miocárdica com circulação extra-corpórea e não apresentou efeitos adversos importantes. / The objective of the present study, prospective and randomized, is to evaluate the hemodynamic, gasometric, immunomolecular and clinical response in two groups of patients submited to coronary artery surgery under cardiopulmonary bypass with the use, in one of them, of methylene blue infusion during the intraoperative period. The hemodynamic variable data evaluated were: heart rate, left atrial pressure, central venous pressure, cardiac output, systemic vascular resistance, pulmonary vascular resistance, mean pulmonary artery pressure, systolic systemic arterial pressure, dyastolic systemic arterial pressure and mean systemic arterial pressure. Laboratoryal data were: arterial gasimetry, urea, creatinine, leucocytes, neutrophils, eosinophils, basophils, lymphocytes, hematocrit, hemoglobin, platelets, sodium and potassium. The immunomolecular data were: IL-1ß, IL-6, IL-8, IL-10, IL-12p40, TNF alfa and NO. The clinical data evaluated were: age, gender, race, smoking, hypertension, diabetes, stable angina, unstable angina, previous infarction, cardiopulmonary bypass duration, aortic cross-clamp time, graft number, bluish urine, bluish feces, diarrhea, nausea, headache, dizziness, dysuria, tiredness and dyspnea. All the data were obtained, in all or part of the following periods: before the anesthesia and at the third, sixth, 24th and 48th hour after the end of the cardiopulmonary bypass. Statistically significant differences occurred in the systemic vascular resistance, diastolic systemic arterial pressure and in part of the evaluated cytokines, as well as with the nitric oxide. The analysis of the results show that, in the methylene blue patients group, the systemic vascular resistance was higher at the sixth hour, lower concentrations of TNF alfa at the third and at the 48th hour and lower levels of NO at the 6th hour. The laboratorial data were similar in the two groups, except for the number of leucocytes and neutrophils were higher in the control group at the 48th hour after the end of the cardiopulmonary bypass. The gasometric data showed no difference between the groups. It was verified that the methylene blue has induced better hemodynamic conditions and lower levels of part of markers of SIRS after coronary artery surgery under cardiopulmonary bypass and no siginifcant deleterious side effects.

A Terapia Fotodinâmica (TFD) é uma modalidade terapêutica promissora que tem mostrado resultados clínicos efetivos, a lém de custo benefício favorável ao sistema de saúde. Embora a TFD esteja associada à indução de morte celular por necrose e, ou apoptose, pesquisas recentes comprovam a ativação da autofagia. Visando entender a relação entre a quantidade de espécies reativas de oxigênio (EROs), produzidas após fotoativação dos fotossensibilizadores (FSs), com a indução de morte autofágica, foram utilizados os FSs fenotiazínicos estruturalmente semelhantes, azul de metileno (MB) e 1,9-dimetil azul de metileno (DMMB); as linhagens celulares HeLa e HaCat, como modelos biológicos e LEDs emitindo em 633 nm, como fonte luminosa. Os ensaios de viabilidade em função da dose de luz e da concentração dos FSs verificaram que o aumento de morte celular está diretamente relacionado ao aumento da concentração e ao aumento da dose de luz, para ambos FSs. Verificou-se que nas condições de IC50 a concentração do DMMB (10 nmol/L) é menor que a do MB (2,0 µmol/L) em duas ordens de grandeza, e essa diferença também se reflete no grau de desbalanço oxidativo gerado após fotossensibilização. Foi verificado que para o MB, a elevada geração de EROs está fortemente correlacionada com a perda de viabilidade, enquanto que para o DMMB essa correlação é fraca, uma vez que há perda de sobrevida sem grandes gerações de EROs. No entanto, a diminuição de sobrevida causada pelo DMMB se correlaciona forte e significativamente ao aumento da autofagia, indicando ocorrência de morte celular autofágica tanto em células HaCaT quanto em células HeLa. As análises de dano em organelas indicaram que ambos FSs, após serem fotoativados, causam danos em lisossomas e em mitocôndrias de células HaCaT. E confirmou-se, por ensaio de localização subcelular, que ambos FSs estão nessas organelas. Uma vez que a localização subcelular do FS influencia no mecanismo de morte celular foto desenvolvido, verificou-se que o MB nas mesmas concentrações nanomolares do DMMB não induz autofagia, pois o mesmo encontra-se fotoquimicamente inativo nas mitocôndrias, devido à redução pelas coenzimas presentes nesta organela. O DMMB possui um potencial de redução menor que o MB, o que impede a redução deste FS nas mitocôndrias, e, mesmo em baixas concentrações, o DMMB é capaz de comprometer a integridade de mitocôndrias e lisossomas, e induz ir autofagia como um mecanismo de morte celular. As condições em que o MB não se encontra totalmente reduzido no ambiente celular são em concentrações mais elevadas, nas quais a geração do nível de estresse oxidativo é maior e não se observa resposta autofágica após fotossensibilização. Esses resultados mostram que a eficiência de morte celular causada por TFD não está necessariamente relacionada ao nível de estresse oxidativo gerado, uma vez que o DMMB induziu estresse oxidativo em menor extensão do que MB e, no entanto, induziu morte celular em maior extensão. Confirmou-se o conceito de que, fotossensibilizadores mais eficazes para a TFD devem resultar da melhoria na especificidade das reações de fotossensibilização nos alvos celulares e não apenas em melhoria na eficiência de geração de ERO. / Photodynamic Therapy (PDT) is a promising therapeutic modality that has shown effective clinical outcomes and benefits in terms of costs to the national health system. Although PDT is associated with induction of cell death by necrosis or apoptosis, recent data suggest the activation of autophagy. In order to understand the relationship between reactive oxygen species (ROS), generated after light activation of photosensitizers (PSs), and the autophagic cell death induction, we have used two phenothiazines with similar structure - methylene blue (MB) and 1,9-dimethyl methylene blue (DMMB); HaCaT and HeLa cells were used as biological models and LEDs emitting at 633 nm were used as light source. Cell viability assays as function of light dose and PS concentration showed that the increase in cell death was directly proportional to the PS concentration and light dose, to the both PSs. At IC50 was verified that DMMB concentration (10 nmol/L) is lower than MB concentration (2,0 µmol/L) in two order of magnitude, and this difference is reflected in degree of oxidative stress promoted by photosensitizers . Only for MB the amount of detected ROS is highly correlated with loss of cell viability, while for DMMB this correlation is weak, because there is loss of viability without large generation of ROS. Nevertheless, the viability decreased for DMMB is highly correlated with the increase of autophagy, indicating occurrence of autophagic cell death in both HaCaT cells and in HeLa cells. The analyses of damaged cell organelles indicated that both PSs, after be photoactivated, induce lysosomal and mithochondrial damage in HaCaT cells. And the subcellular localization assay confirmed that DMMB and MB are localized in these organelles. Because the subcellular localization of PSs influences cell death mechanisms, this research identified that MB, in the same nanomolar concentration of DMMB, does not induce autophagy, because it is photochemically inactive in mitochondria due the reducing coenzymes present in this organelle. DMMB has a lower reduction potential than MB, which hinders PS reduction in mitochondria, and possibly generate a mild oxidative stress that compromise the integrity of mitochondria and lysosomes, and justify autophagy induction as a cell death mechanism. The conditions that MB is not fully reduced in the cellular environment are at higher concentrations, in which was detected high level of oxidative stress and autophagic cell death was not observed after photosensitization. These results show that the efficiency of cell death induced by PDT is not necessarily related with oxidative stress level, since the oxidative stress induced by DMMB was lesser than by MB, however, the cell death was greater. This research confirms the concept that more effective photosensitizers for PDT means greater specificity of photosensitization reactions, and not only improvement of the efficiency of ROS generation.

INTRODUÇAO: O uso da epinefrina na ressuscitação cardiopulmonar (RCP) tem sido questionado devido aos efeitos adversos como dano miocárdico e cerebral. Fármacos como azul de metileno têm sido estudados como adjuvantes, objetivando reduzir essas lesões. OBJETIVOS: Neste estudo objetivou-se avaliar o efeito da administração do azul de metileno em bôlus durante a RCP, na lesão miocárdica e cerebral. MÉTODO: Quarenta e nove ratos Wistar machos submetidos a parada cardíaca por fibrilação ventricular foram distribuídos aleatoriamente em quatro grupos com 11 animais: azul de metileno (GA, 2mg/kg), solução salina (GC, salina 0,9% 0,1ml), epinefrina (GE, 20mcg/kg), epinefrina + azul de metileno (GM), além do grupo sham com 5 animais. A fibrilação ventricular foi induzida por estimulação elétrica direto no ventrículo direito por 3 minutos, sendo mantidos por mais 2 minutos em anóxia. As manobras de RCP foram iniciadas com o fármaco correspondente de cada grupo, massagem torácica, ventilação e desfibrilação. Após retorno a circulação espontânea (RCE), os animais foram observados durante quatro horas. Foram coletados sangue para gasometria e troponina, tecido cardíaco e cerebral para análise histológica, marcação de TUNEL, marcadores inflamatórios e de estresse oxidativo. Os grupos foram comparados por meio do teste não paramétrico de Kruskal-Wallis, com o teste de comparação múltipla com correção de Bonferroni quando adequado. RESULTADOS: Animais do grupo GE apresentaram 63% de RCE, enquanto o GC e GM obtiveram 40% e 45%, respectivamente, sem diferença estatística entre os grupos (p= 0,672). O grupo GA apresentou apenas 18% de RCE e foi excluído da análise. O tempo de RCP do GC foi maior comparado aos grupos GE e GM, mas sem diferença estatisticamente significativa. Os animais do grupo GM apresentaram PAM maior comparado ao grupo GC, no momento imediatamente após a RCE (P=0,007). Em todos os grupos os animais apresentaram acidose, queda da PaO2 e aumento do lactato após PCR e RCP. A mediana da troponina sérica foi maior no GC (130ng/ml) comparada ao grupo GE (3,8ng/ml), e GM (43,7ng/ml), porém sem diferença estatística. O grupo GC apresentou aumento significativo na expressão proteica dos marcadores BAX e TLR4. Não houve diferença estatística em relação a histologia e marcação de TUNEL entre os grupos submetidos a PCR. CONCLUSÃO: A utilização de azul de metileno em bolus na RCP de forma isolada apresentou resultados negativos em relação ao retorno da circulação espontânea. A utilização de azul de metileno associada a epinefrina não diminuiu a presença de lesões no cérebro e no coração decorrentes da parada cardíaca / INTRODUCTION: The use of epinephrine in cardiopulmonary resuscitation (CPR) has been questioned due to adverse effects such as myocardial and cerebral damage. Drugs such as methylene blue have been studied as adjuvants in order to reduce lesions. OBJECTIVES: The aim of this study was to evaluate the effect of methylene blue administration during CPR on myocardial and cerebral lesion. METHOD: Forty nine Wistar male rats submitted to ventricular fibrillation cardiac arrest (CA) were randomly assigned to four principal groups with 11 cases each one: methylene blue (MB, 2mg/kg), control (CTRL, 0.1ml saline 0.9%), epinephrine (EPI, 20?g/kg), epinephrine plus methylene blue (EPI+MB), and a sham group, wich have 5 cases. Ventricular fibrillation was induced by direct electrical stimulation in the right ventricle for 3 minutes and anoxia was maintained until a total of 5 minutes. CPR was initiated using the group drug, ventilation, chest compressions and defibrillation. The animals were observed for four hours after return of spontaneous circulation (ROSC). Blood samples were collected for blood gas and troponin measurements. Heart and brain tissues were harvested for the evaluation of oxidative stress, inflamation, histological and TUNEL staining. Groups were compared using the non-parametric Kruskal-Wallis test and Bonferroni post test. RESULTS: ROSC was achieved in 63% of the cases in EPI, 40% in CTRL, and 45% in EPI+MB (P=0.672). MB was excluded from analysis because of its low ROSC rate (18%). CPR duration was longer in CTRL compared to EPI and EPI+MB, without statistical significance. EPI+MB animals presented higher arterial pressure compared to the CTRL group, immediately after ROSC (P=0.007). All animals presented acidosis, decreased PaO2 and increased lactate after CA and CPR. Serum troponin was higher in CTRL (130ng/ml) compared with EPI (3.8ng/ml) and EPI+MB (43.7ng/ml), without statistical significance. CTRL presented higher BAX and TLR4 expression. There was no difference in TUNEL staining and histology among CA groups. CONCLUSION: Methylene blue in bolus during CPR did not improve outcome. Methylene blue combined with epinephrine did not decrease CA-related myocardial and cerebral lesions

This thesis describes research carried out to investigate techniques for (i) rapidly assessing the reactivity of fly ash; and (ii) evaluating its interaction with air-entraining admixtures (AEAs), both with regard to use in concrete. The materials considered for the project included, 54 fly ashes from 8 UK sources, and an additional three materials from Bangladesh, covering a range of fineness, loss-on-ignition (LOI) and production conditions (run-of-station, carbon removed, air-classified, co-combustion, oxy-fuel technology); Portland Cements (PCs) from five UK sources with various properties (strength classes 32.5 R, 42.5 N and 52.5 N); laboratory grade hydrated and quick limes; and three commercial AEAs and a standard laboratory grade reagent (surfactant). The research examining fly ash reactivity considered activity index tests to BS EN 450 (BSI, 2005c) as the reference and investigated tests covering fly ash properties/providing measures of fly ash behaviour to rapidly assess this. These included (i) fly ash fineness (45 µm sieve residue, or LASER particle size distribution (PSD) parameters), LOI and flow properties; (ii) accelerated curing of PC and lime-based mortars (iii) lime consumption by fly ash when combined with PC in paste or suspension (Frattini) or from a saturated lime solution; (iv) various measures of fly ash chemical composition (based on oxide/mineralogical analysis); and (v) a quicklime slaking test. The test results were validated by strength tests with 100 mm concrete cube. Results of the above indicated good correlations between fly ash fineness, mortar flow/water requirement and (pozzolanic) activity index (standard or accelerated curing). However, fly ash reactivity and fresh properties appeared to be influenced by the properties of the test PC (e.g. chemical composition and fineness) and there is a need to take this into account during assessment. Generally, finer fly ashes gave better flow; however, there is an optimum fineness (d90 ~40 µm) for best performance, and which is similar to the fineness of the test PC. Strong correlations between the accelerated and standard cured PC-based mortar indicate the latter can be used to estimate the former taking account of the fly ash properties. In view of eliminating the effect of PC properties on reactivity, mortar tests with laboratory grade hydrated lime suggested potential for this. However, for better assessment, this approach requires further work to address issues relating to slower rates of strength gain and increased time requirements, although high temperature conditions were used for curing. Measuring Ca(OH)2 consumption from fly ash/PC paste or suspension agreed with the behaviour in mortar, but needs special instruments (e.g. TGA or XRF). A similar approach with saturated lime did not work well, despite several measures being taken to try and improve this. The oxide and mineralogical analysis results of fly ash did not give good correlations with activity index, but improved when a factor combining them with fineness was considered. The test results were validated in concrete and with air-classified fly ashes from single sources which gave clear trend/behaviour. The lime slaking test was found to be ineffective for identifying fly ash reactivity. The reactivity assessment results were validated by carrying out concrete strength tests. In general, more consistent trends were obtained for fly ash from single source as noted with mortar earlier. Methods adopted/developed to assess the interaction of fly ash with AEA included (i) the foam index test; (ii) acid blue 80 (AB80) dye adsorption test (spectroscopic method); and (iii) methylene blue test. High variability in foam index test results between different operators were noted, which reflected differences in the degree of shaking applied and difficulties in identification of the test end point. Adoption of an automatic shaker and determination of suitable test conditions reduced this by more than 50%. Reliable test procedures were also established for the AB80 dye adsorption method. The results obtained from these tests gave very good correlations with fly ash specific surface area and the AEA dose required (both with commercial AEAs and standard reagent) for achieving target air contents in mortar and concrete. The methylene blue dye test also gave good correlations with these parameters, but was less effective for low LOI fly ashes. Between laboratory tests were carried out at three UKQAA members and considered, LOI, fineness (45 µm sieve and LASER PSD), and activity index. The results gave good agreement with those obtained at the Concrete Technology Unit for this work and again emphasized the role of fly ash fineness on its reactivity. Overall, fly ash fineness was found to be the best means of rapidly assessing its reactivity. Some of the other methods considered gave promising behaviour but require further refinements. Therefore, it is suggested that in addition to 45 µm sieve residue, other types of fineness measurement (e.g. sub 10 µm quantities, d50 and d90) can be considered suitable alternatives to activity index. Similarly, foam index tests with the automatic shaker or the AB80 test method could both be used as fly ash physical requirement tests, or in production control for air-entrained concrete.

INTRODUÇÃO: O nervo facial (NF) desempenha um papel importante em diversas funções fisiológicas do organismo e controla a musculatura da mímica facial, responsável por transmitir sentimentos e emoções. O tratamento padrão-ouro para reconstrução do NF após trauma com secção é a anastomose término-terminal com cola de fibrina, que na maioria dos casos ainda produz resultados subótimos. Por isso, objetivou-se testar o efeito de uma nova técnica de reconstrução usando um protocolo de fusão axonal por polietilenoglicol (PEG), denominada sutura química, utilizando parâmetros eletrofisiológicos e histomorfométricos. MÉTODOS: Ratos Wistar foram divididos em 4 grupos. Após transecção do ramo mandibular do NF, o grupo controle foi submetido a anastomose dos cotos neurais com microssuturas. O grupo 2 foi tratado com microssuturas mais a sutura química. A sutura química consistiu de lavagem dos cotos neurais com solução de Krebs hipotônica contendo azul de metileno antes das microssuturas. Depois da sutura, seguiu-se a lavagem com solução de PEG e, por último, aplicação de solução de Krebs contendo cálcio. O grupo 3 recebeu microssuturas mais a solução com azul de metileno. E o grupo 4 foi tratado com microssuturas mais a solução de PEG. Os potenciais de ação musculares compostos (PAMCs) foram avaliados no pré-operatório e após 3 e 6 semanas das intervenções. A análise histomorfométrica foi realizada após 6 semanas. RESULTADOS: Os animais submetidos à sutura química apresentaram maior amplitude e menor duração dos PAMCs 3 e 6 semanas após a cirurgia em comparação com todos os demais grupos; na análise histológica, apresentaram maior contagem axonal e maior diâmetro axonal. CONCLUSÕES: A sutura química produziu recuperação mais intensa do NF após secção e sutura quando comparada à sutura isoladamente, pela avaliação eletrofisiológica e histomorfométrica, e pode ser útil em situações clinicas nas quais haja secção seguida de reparo neural imediato / BACKROUND: The gold standard treatment for traumatic transection of the FN continues to be end-to-end anastomosis using fibrin glue, which often yields unsatisfying results. OBJECTIVE: To test the outcome of a novel method of polyethylene glycol (PEG)-fusion on FN transection using electrophysiological and histophormometric parameters. METHODS: Wistar rats were divided into 4 groups. After FN transection, the control group was submitted to end-to-end anastomosis with microsutures. Group 2 was submitted to microsutures plus the PEG-fusion protocol. This protocol consisted in bathing nerve stumps with a calcium-free Krebs solution containing methylene blue (MB) before suturing. After suturing, the repaired nerve received a PEG solution followed by a calcium-containing Krebs solution. Group 3 received microsutures plus the MB solution and group 4 received microsutures plus the PEG solution. Compound muscle action potentials (CMAPs) were recorded before the intervention and 3 and 6 weeks afterwards. Histomorphometric analysis was done at 6 weeks time. RESULTS: The PEG-fusion protocol yielded larger CMAP amplitude, smaller CMAP duration at 3 and 6 weeks and a larger axon count and axon diameter. Between the other groups, no significant difference was seen. CONCLUSION: PEG-fusion produces better FN recovery after transection, when considering electrophysiological and histomorphometric analysis and may be of use in clinical scenarios of FN cut-severance followed by immediate repair

This work focuses on the design and synthesis of Au(I) and Ag(I) complexes from ligand systems that aim to combine both N-heterocyclic carbene (NHC) and phosphine ligand types. A number of synthetic approaches towards both the ligands and the prepared metal complexes have been developed, with a concerted effort on achieving the desired Au(I) or Ag(I) complexes with minimal reaction steps and synthetic style. The thesis body is divided into two main sections. The first section addresses the preparation of suitable ligand precursors of potential Au(I) and Ag(I) complexes in the form of halo- and phosphino-functionalised imidazolium salts. Several series of haloalkylimidazolium salts were prepared that encompass a range of halogens (Cl, Br, I), alkyl substituents (Me, i-Pr, t-Bu, n-Bu), differing alkyl linker length (n = 0-3), and a variety of organic spacers employed to bridge multi-imidazolium moieties. Novel bidentate and multidentate phosphinoalkylimidazolium salts were synthesised from the various haloalkylimidazolium salts, via the substitution of a halide with nucleophilic diphenylphosphide. A new approach towards rare methylene bridged phosphinomethylimidazolium salts was achieved from the reactions of halomethylimidazolium salts with diphenylphosphine. The second section investigates the preparation of Au(I) and Ag(I) complexes from the halo- and phosphino-functionalised imidazolium salts. A series of dicationic 10, 12, and 14-membered metallacyclic Ag(I) complexes were prepared from the bidentate phosphinoalkylimidazolium salts. The dinuclear Ag(I) metallacycles combine two phosphino-functionalised NHC ligands that are bridged by two coordinated Ag(I) ions in an exclusively head-to-head arrangement. A dinuclear Ag(I) metallacycle was investigated for transmetallation potential to a Au(I) complex and found to selectively transmetallate at the Ag(I) coordinated to the NHC ligands to form a bimetallic metallacycle. Unexpected phosphine oxidation of a 10-membered dinuclear Ag(I) metallacycle resulted in complex disproportionation to an isolable and rare silver(I) trimer. Metal-NHC complexes from haloalkylimidazolium salts have not been reported previously, a novel approach to the synthesis of a series of Au(I) complexes from haloalkylimidazolium salts and a respective gold source was developed and is reported herein. Different synthetic approaches towards Au(I) complexes with the phosphinoalkylimidazolium salts explored a variety of ways to generate the NHC from an imidazolium in the presence of the phosphine. A one-pot, high yielding synthesis of a dinuclear Au(I) complex from PPh3 was also devised, with controlled assembly of the complex resulting in a similar head-to-head ligand arrangement to the dinuclear Ag(I) metallacycles. As an aside, a family of mononuclear [Au(R2NHC)2]+ complexes (R = Me, i-Pr, t- Bu, n-Bu, Cy) prepared previously in our research group, was expanded because of the promising antimitochondrial activity shown by [Au(i-Pr2NHC)2]+. Two new [Au(R2NHC)2]+ complexes with simple alkyl chain functionality were prepared with fine-tuned lipophilicity in close proximity to that of [Au(i-Pr2NHC)2]+.

Although survival rates are increasing, brain injury continues to be a leading cause of death after cardiac arrest (CA). Permanent brain damage after CA is determined by limited tolerance to ischemia from CA and cardiopulmonary resuscitation (CPR), as well as the unique cerebral response to reperfusion after return of spontaneous circulation (ROSC). A major pathway leading to neurotoxic cascade and neuronal injury after CA involves the increased presence of reactive oxygen and nitrogen species generated during ischemia and reperfusion. The magnitude of cerebral oxidative injury induced by free radicals increased with the duration of CA (Paper I). Nitric oxide (NO), a free radical responsible for the formation of reactive nitrogen species, is increased during global ischemia from CA and reperfusion (Paper IV). Hypothetically, the administration of a drug that counteracts the overproduction of NO and also acts as a scavenger of oxygen free radicals might be warranted in order to reduce the damage caused by nitrosative and oxidative stress. For these purposes we used methylene blue (MB), an old dye that has been used in medicine for almost half a century, and an experimental pig model of 20 min of ventricular fibrillation (VF) to reflect a clinical scenario of ischemia/reperfusion injury. Administration of MB added to a hypertonic-hyperoncotic solution (MBHSD) that was started during CPR and continued for 50 min after ROSC increased short-term survival by decreasing myocardial damage, as well as cerebral peroxidation and inflammatory injury (Paper II). Immunostaining of cerebral tissue collected at different time points after CA and ROSC (Paper IV) provided experimental evidence that cortical blood-brain barrier (BBB) disruption begins as early as  during the initial phase of untreated as well as treated CA. The results indicated that MB administration reduced the neurologic injury and BBB disruption considerably, but did not reverse the ongoing detrimental processes. The demonstrated positive effects of MB were related to a decrease of nitrite/nitrate tissue content, and thus to a decrease of excess NO due to the MB inhibitory effects on NOS isoforms. A mixture of MB in hypertonic sodium lactate (MBL) was investigated to facilitate administration of MB in “the field.” Based on findings that MBL cardio- and neuroprotective properties were similar to those of MBHSD, there is reason to believe that the use of MBL might be extended during ongoing CPR and after ROSC (Paper III). It would therefore make sense to try using MB as a pharmacological neuroprotectant during or after clinical CPR in order to expand the temporal therapeutic window before other measures for neuroprotection such as hypothermia are available.

Expansive clay mineral contamination of road aggregate materials in Texas is a persistent problem. Hydrous layer silicate minerals - particularly smectites - in concretes are associated with decreased strength and durability in Portland cement and asphalt concretes. The Texas Department of Transportation (TXDOT) and Texas A&M Transportation Institute (TTI) evaluated the methylene blue adsorption test for its potential to identify and estimate quantities of expansive clays in aggregate stockpiles. Clay mineral quantification was completed for 27 geologically-diverse aggregate materials from Texas, Oklahoma, and Arkansas. X-ray diffraction analysis (XRD) of separated clays on glass was conducted, and NEWMOD was utilized to model the resulting diffraction patterns. Methylene blue adsorption (MBA) and cation exchange capacity (CEC) of clay fractions (< 2µm) and -40 mesh screenings (< 400 µm) were determined for most aggregates. Many of the aggregates exhibited significant quantities of expansive clay minerals such as smectite, which are linked to deleterious performance properties in concretes. While the majority of aggregates were derived from crushed limestone or calcareous river gravel parent materials, severalexhibited uncommon origins and unusual clay mineralogy. Due to the relatively low number of aggregates tested and diverse geological origins of the different aggregates,it proved difficult to formalize any conclusions abouttrendsbetweenthedifferent aggregate performance properties.

N-heterocyclic carbenes (NHCs) have become a very popular class of ligands, which has found uses in numerous catalytic applications. The use of such compounds in combination with phosphorus-based ligands within metal complexes has enabled the design of very active yet robust catalytic systems. The following chapters will describe the design of novel well-defined palladium- and ruthenium-based pre-catalysts featuring a NHC and a phosphorus-based ligand, referred at as mixed ligand systems. Such species were employed in catalysis where their properties appeared highly beneficial, uses at low catalysts loading and under harsh conditions were then envisioned. The preparation of a series of well-defined palladium mixed NHC/phosphine species is presented in chapter 2. Their catalytic activity in the aqueous Suzuki-Miyaura reaction of aryl chlorides and boronic acids, using low catalyst loadings, is described. The observation of catalytic activity of the latter systems in the hydration of nitriles prompted us to further investigate this reactivity. This reaction appeared to be operative in the absence of palladium species and could be performed under base-catalysed conditions, which was studied in detail and depicted in chapter 3. The combination of a NHC and a phosphite ligand in ruthenium olefin metathesis pre-catalysts has been underexplored. Preliminary results showed that such species could be readily prepared and presented an unusual geometry and a high catalytic activity. Variations in phosphite-containing ruthenium olefin metathesis pre-catalysts are presented. Chapter 4 describes the investigation of various Schrock carbene moieties in such architectures, as well as their implications in structure and catalysis. Chapter 5 depicts attempts to design olefin metathesis Z-selective pre-catalysts by inserting a chelating NHC moiety within phosphite-containing ruthenium species. This dissertation concludes on the potential of such mixed species in catalysis, and armed with the new knowledge provided by this work, proposes potential developments of such chemistry in the design of always more robust and active catalytic systems.