The focus of this thesis is the synthesis of organometallic complexes incorporating the η8-permethylpentalene titanium moiety (η⁸-Pn*Ti), their characterisation, and their reactivity with small molecules. <b>Chapter One</b> summarises the chemistry of the pentalene molecule, from its instability in the free state to the incorporation of the hydrocarbon into organometallic complexes. The chapter continues with a review of the coordination modes available to Pn and concludes with a brief discussion on the effects of permethylation of hydrocarbon ligands and the advent of permethylpentalene (Pn*). <b>Chapter Two</b> documents the improved synthesis of [Pn*TiCl(μ-Cl)]₂ utilising isomeric control imparted on the Pn* synthon, Pn*(SnMe₃)₂. This protocol permits access to a variety of methylated compounds through metathesis chemistry, of which five have been crystallographically elucidated, revealing the fold angle to be reliant on an interplay between steric and electronic factors. Mono-, bi- and trimetallic {Pn*TiMe₂, [Pn*TiMe(μ-Cl)]₂ and [Pn*Ti(μ-Me)]₂(μ-CH₂), and [Pn*TiMe(μ-Me)₂]₂Mg respectively} species were synthesised dependent on the methylating agent employed and they displayed varying thermal stabilities, with the dimeric nature of [Pn*TiMe(μ-Cl)]₂ proving crucial in the formation of [Pn*Ti(μ-Cl)]₂(μ-CH₂). <b>Chapter Three</b> describes the incorporation of classical organometallic ligands into the Pn*Ti moiety, including the first examples of benzyl, alkyl, aryl, allyl and η¹-Cp bound to a PnTi fragment. Seven complexes have been structurally characterised including the first ever crystal structure of a π-hydrocarbon bound Ti species bearing two CH₂^tBu groups, Pn*Ti(CH₂^tBu)₂, and the fluxional mixed hapticity complex Pn*Ti(η⁵-Cp)(η¹-Cp), whose η¹-Cp rearranges via a 1,2-sigmatropic shift. <b>Chapter Four</b> investigates the reactivity of the monomeric dialkyls, Pn*TiR₂ (R = Me, CH₂Ph, CH₂SiMe₃ and CH₂^tBu) with CO₂, CO and H₂. All four compounds demonstrate “normal” insertion of the CO₂ moiety into both Ti-R bonds, revealing a symmetrical bidentate coordination of the RCO₂ units. Computational studies have highlighted two competing pathways for their reaction with CO, dependent on the concentration of CO and size of R, which results either in formation of an enediolate or a titanoxirane. The reaction with H₂ yields the fascinating trimeric mixed valence, [Pn*Ti(μ₂-H)]₃(μ₃-H), the first structurally characterised example of a trimeric Ti-H species and the first to include a Ti-(μ₃-H) moiety. (Pn*TiCl)₂(μ-O) is formed by the action of adventitious H₂O and possesses a linear Ti-O-Ti bridge with a degree of Ti-O double bond character, supported by crystallographic data and DFT calculations. <b>Chapter Five</b> discusses ethylene polymerisation studies on the monomeric dialkyl complexes Pn*TiR₂ (R = Me, CH₂Ph, CH₂SiMe₃ and CH₂^tBu) using the activators [Ph₃C][B(C₆F₅)₄], [PhNMe₂H][B(C₆F₅)₄], AlⁱBu₃ and H₂. <b>Chapter Six</b> presents full experimental procedures for all of the syntheses and reactions outlined in Chapters Two to Five. <b>Chapter Seven</b> details characterising data for all novel compounds, and crystallographic data in the form of CIF files may be found in the electronic version.

As reações entre o íon pentacianoferrato(II) e os isômeros de acetilpiridina (py(CO)CH3) foram estudadas com o intuito de estabelecer o mecanismo da reação de ataque nucleofílico ao grupo nitrosilo coordenado. Estas reações de adição foram acompanhadas pela técnica stopped flow ll a 25,O&#186;C, em condições de pseudo primeira ordem, em meio alcalino com força iônica 0,10 M ajustada com LiC104 . Durante o processo, constatou-se que a formação dos produtos é precedida pelo aparecimento de intermediário azul com pequenos tempos de vida. A formação deste intermediário envolve o ataque da acetilpiridina na forma de carbânion, ao grupo nitrosilo coordenado, em competição com a adição do íon hidroxila. A lei da velocidade para o mecanismo proposto nesta etapa, tem a expressão abaixo para a constante de velocidade observada kobsl= KkL [py(CO)CH3] [OH-] + kOH [OH-] + k-L Os valores de KkL e k-L são respectivamente 1,91 &#177; 0,05 X 102M-2s-1 e 0,90&#177; 0,02 X 10-1 s-1</SUP para acetilpiridina com substituintes na posição para; 3,70&#177; 0,10X .. 10 M-2s-1 e 0,86 &#177; 0,02 X 10-1s-1 para o derivado na posição meta e 1 ,42 &#177; 0,04 X 10 M-2 s-1 e o 0,46 &#177; 0,01X10-1s-1para o derivado em orto. O kOH obtido nas condições experimentais é 0,302M-l s-1. o decaimento do intermediário ocorre devido a dissociação da espécie coordenada pelo NO cuja labilização pode ser provocada ou ocorrer em paralelo a isomerização do ligante. Esta reação também depende tanto da concentração do ligante como da concentração da hidroxila. A lei da velocidade resultante do mecanismo proposto, consistente com o comportamento cinético, leva à expressão [figura ver arquivo em PDF] Os valores de kd e KT determinados são respectivamente 8,3 X 10-2s-1 2,1 X 103 M-2 para derivados em para, 5,0 X 1º-2s s-1 e 3,90 X -10 M-2 Para o derivado em meta e 3,2 X 10-2s-1e 2,95 X 102 M-2 para o derivado em orto. A consistência do mecanismo proposto foi verificada através das constantes obtidas em experiências independentes acompanhando o decaimento dos intermediários sintetizados. O mecanismo foi ainda confirmado através dos estudos independentes das etapas propostas no mecanismo global. Esta adição das acetilpiridinas ao grupo NO coordenado foi aproveitada na obtenção de 1igantes carboni1-oximas correspondentes. Estes ligantes py(CO)CHNOH bem como as acetilpiridinas foram utilizados para sintetizar série de complexos Fe(CN)5L3- a partir do íon aquopentacianoferrato (II) , Fe(CN)5H2O3-. A caracterização dos 1igantes e complexos sintetizados foi feita na região de infravermelho, visível e ultra-violeta. Os espectros eletrônicos obtidos foram decompostos usando-se as funções Gaussianas simples e dupla e a 1ognormal. Os complexos apresentam-se fortemente coloridos, com bandas de absorção na região do visível e ultra-violeta próximo, cujas transições podem ser classificadas em; a. Transições de transferência de Carga Fe-L (CT); b. Transições de Campo Ligante (d-d); c. Transições Internas nos Ligantes (L-L); d. Transições de transferência de Carga Fe-CN (CT) Foram ainda verificados os efeitos de pH sobre as bandas de transferência de carga e as variações espectrais provenientes da oxidação do complexo. Os estudos de espectroscopia envolvendo os complexos intermediários sintetizados foram feitos na tentativa de obter informações estruturais e propriedades para se estabelecer correlação com parâmetros cinéticos determinados. O comportamento eletroquímico dos complexos em estudo foi investigado através da voltametria cíclica. A partir destes dados obteve-se os parâmetros termodinâmicos bem como a correlação do Eo com a frequência da transição de transferência de carga vTC(Fe-L). Os complexos Fe(CN)5 py (CO)CHNOH3- apresentam comportamento fotoquímico típico, com deslocamento batocrômico das bandas de transferência de carga no decorrer da irradiação com luz visível e ultra-violeta. A fotosubstituição dos cianetos nos complexos Fe(CN)5L3- foi constatada pela primeira vez com o uso de ligantes que apresentam características quelantes ( como etilenodiamina e py(CO)CHNOH ) e estabilizam os complexos tetracianoferrato(II) correspondentes. A irradiação quase monocromática no complexo Fe(CN)5em3- mostra um rendimento quântico de 0,087 &#177; 0,003 para a saída do cianeto. A espécie formada fotoquimicamente foi isolada e a sua identidade foi \' confirmada espectroscopicamente e também, através da reação de oxidação com formação do tetracianoferrato com diimina. A análise do pentaciano(etilenodiamina) ferrato (II) consumido e a quantidade do complexo tetracianoferrrato correspondente formada mostra que a reação representada a seguir [figura ver arquivo em PDF] é o único processo fotoquímico efetivo que ocorre durante . o período de irradiação . / The reactions between the pentacyano(nitrosyl) ferrate(II) ion and the o-, m-, p-isomers of acetylpyridine (py(CO)CH3) were investigated by stopped flow technique, in order to evaluated the mechanisms of nucleophilic attack on the coordinated nitric oxide ligand. The kinetics of these addition reactions were followed spectrophotometrically, under pseudo first order conditions, at a temperature of 25°C, and &#181= 0,100 (lithium perchlorate and lithium hydroxide). A deep blue compound can be observed with a half-1ife of a few seconds. The formation of such an intermediate was described in terms of the attack of the carbanion of acetylpyridine to the coordinate nitric oxide ligand, in competition with the addition of the hydroxide ion. The experimental rate 1aw for the reaction can be expressed by a pseudo first order equation, consistent with our proposed mechanism; where kobsl= K.kL [py(CO)CH3] [OH- + kOH [OH-] + k-LThe rate constants kL and k-L refer to the nucleophilic attack step and the reversal reaction, respectively. The equilibrium constant K represents the formation of the carbanion, while kOH is associated with the parallel addition of the hydroxide ion to NO+. The values determined for KkL and k-L were, respectively , 196 M-2s-1, and 0.090 s-l for p-py(CO)CH3 ; 370 M-2s-1 and 0.080 s-l for m-py(CO)CH 3; and 14,2M-2s-1 and 0.046s-1 for o-py(CO)CH3 . The kOH value obtained under the experimental conditions is 0,302 M-1s-1 The decay of the intermediate yields the free carbonyloximes in solution. It may be associated with an intrinsic lability of the nitroso species, or even by an internal isomerization leading to a sterically hindered configuration of the ligand . The observed rate law was found to depend on the acetylpyridine and the hydroxide ion concentrations in the following way [see figure PDF file] where KT = K.kL/k-L, and . kd is the rate constant of dissociation of coordinated 1igand. The experimental values of KT and kd were, respectively, 2.1x103 M-2 and 0.082s-1 for p-py(CO)CH3; 390 M-2 and 0.050 s-1 for m-py (CO) CH3;and 295 M-2 and 0.032 s-1 for o-py(CO)CH3. Independent experiments using the intermediate species isolated as solids, allowed to confirm the consistency of our two step mechanism . From the pure carbonyl-oxime ligands obtained in this work we have synthesized the substituted complexes of pentacyanoferrate(II) coordinated by pyridine group. An extensive characterization of the ligands and of the complexes was carried out in this work, including the analysis of the electronic spectra in terms of Gaussians and log-normal functions, and the assignments of the vibrational spectra. Also examined were the pH effects on the charge transfer spectra, as well as the evaluation of the basicity constants of the coordinated cyanide and the heterocyclic ligands. We have also characterized the intermediates in terms of their electronic and vibrational spectra. Based on an electrochemical study, using mostly cyclic voltammetry, we have obtained the thermodynamic parameters of the several complexes. A linear correlation between the formal potentials and the energies of the charge transfer transitions was found in this work. The Fe (CN)5py (CO) CHNOH3- complexes were found to be photosensitive, turning slowly to a deep blue color under sun or ordinary light. The photolysis under controlled conditions, with a mercury lamp, in the visible - near uv region, produced neat spectral changes, with isosbestic points indicating a well behaved photochemical process. The product, in contrast to pentacyanoferrate(II) species, was found to be inert toward dimethyl sulfoxide. The same behavior has been observed for tetracyanoferrate(II) complexes with bidentate ligands. In analogy, the blue product was formulated as [see figure PDF file] Quantum yields were determined at several wavelengths however, it was not possible to distinguish , between the following photochemical processes, leading to the tetracyano species : [see figure PDF file] The second process taking place on the oxime isomer, which may be eventually present in very small amount, is expected to be highly effective because of the neighboring effect enhancing the formation of the 5 member ring. To clarify this point, we have investigated the photochemistry of the Fe(CN)5(en)3- complex. The results indicated that the formation of the Fe(CN)4en2- complex takes place with a quantum yield of 0,087&#177; 0,005 at 366nm, which is nearly 10 times the values obtained for carbonyl-oxime complexes. In this case, the photochemical process can be analysed quantitatively by determining the amount of the starting complex, or by isolating the tetracyano species by ionic exchange chromatography. Both ways gave comparable numbers, indicating that the measured quantum yields refer to the process [see figure PDF file] We therefore concluded that the labilization of the CN ligands in the carbonyl-oxime complexes should take place mostly according to the first route.

Introdução: A hipertensão arterial sistêmica (HAS) é uma condição clínica multifatorial caracterizada por níveis elevados e sustentados de pressão arterial. Nos últimos anos, estudos demonstraram o efeito cardiovascular de diversos metabólitos originados de várias espécies de plantas. O diterpeno é um exemplo, o qual age por meio de diversos mecanismos farmacológicos. Sabendo que o Manool pertence a esta classe de compostos, isso o torna uma substância com potencial uso no tratamento da HAS, motivo pelo qual se propôs o desenvolvimento deste trabalho. Objetivos: 1) Avaliar in vivo o possível efeito vasodilatador de diferentes doses do Manool e o efeito sobre os níveis plasmáticos de óxido nítrico (NO), em animais normotensos e hipertensos e; 2) Verificar in vitro os mecanismos endoteliais envolvidos na resposta de relaxamento, em anéis de aorta de ratos. Material e métodos: Os animais foram divididos aleatoriamente em dois grupos: hipertenso e normotenso. Os animais do grupo hipertenso foram submetidos ao procedimento cirúrgico 2R1C para indução de hipertensão, enquanto os animais do grupo normotenso foram sham-operados. A pressão arterial (PA) não-invasiva, foi mensurada utilizando-se um manguito, conectado a um sensor para registro de PA, colocado em torno da cauda do animal. Para identificar os efeitos in vivo do composto, três doses do composto foram aplicadas nos animais, a monitorização invasiva da PA foi realizada por meio do MP System 100 A. Para a medida do óxido nítrico (NO) plasmático, foi utilizada a técnica de quimiluminescência NO/ozônio (O3). Com intuito de observar os mecanismos envolvidos no relaxamento induzido pelo composto, curvas concentração-resposta para o Manool, foram obtidas em anéis de aorta com e sem endotélio, na presença e ausência de L-NAME e ODQ. Resultados: Os resultados sobre a ?PAS mostrou que o Manool, promoveu redução da PAS tanto em normotensos quanto hipertensos. Os resultados das curvas dose-resposta mostraram que o manool promoveu relaxamento Resumo dependente do endotélio e este foi inibido na presença de L-NAME e ODQ. Não foi observado diferença na dosagem de NOx. Conclusão: Em resposta aos objetivos propostos para a presente investigação pode-se concluir que o Manool é uma droga hipotensora, possivelmente dependente em grande parte da função endotelial via NO/cGMP. / Introduction: Systemic hypertension (SH) is a multifactorial clinical condition characterized by high and sustained levels of blood pressure. In recent years, studies have demonstrated the cardiovascular effect of various metabolites derived from many plant species. The diterpene is an example, which acts through different pharmacological mechanisms. The Manool belongs to this class of compounds, that makes a substance with potential use in the treatment of SH, which let us to propose the development of this work. Objectives: 1) To evaluate in vivo the possible vasodilator effect of different doses of Manool and the effect on the plasma levels of nitric oxide (NO) in normotensive and hypertensive animals; 2) Evaluate in vitro endothelial mechanisms involved in the relaxation response in rat aortic rings. Material and methods: The animals were randomly divided in two groups: normotensive and hypertensive. The animals of the hypertensive group underwent the surgical procedure 2K1C for hypertension induction, while the animals of the normotensive group were sham-operated. The blood pressure (BP) non-invasive, was measured using a cuff, connected to a sensor for registration BP, placed around the animal\'s tail. To identify the in vivo effects of the compound, three doses of the compound were applied in animals, invasive BP monitoring was performed using the System MP 100 A. For the measurement of NO plasma, we used the technique of chemiluminescence NO/ozone (O3). In order to observe the mechanisms involved in the relaxation induced by compound concentration-response curves for Manool were obtained in the aorta rings with and without endothelium in the presence and absence of L-NAME and ODQ. Results: The results on variation of systolic blood pressure (?SBP) showed that Manool, decreases the SBP in both normotensive as hypertensive. The results of the dose-response curves showed that the Manool promoted endothelium dependent relaxation and this was inhibited in the presence of L-NAME and ODQ. There was no difference in NOx dosage. Conclusion: In response to the proposed Abstract objectives for the present investigation may conclude that the Manool is a hypotensive drug, possibly dependent in large part on endothelial function NO / cGMP pathway.

Wu Yuen Sze. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1999. / Includes bibliographical references (leaves 98-107). / Abstracts in English and Chinese. / Table of contents --- p.i / Acknowledgements --- p.iv / Abstract --- p.v / List of compounds --- p.vi / Abbreviations --- p.x / Chapter Chapter 1 --- Synthesis and Structures of Low-valent Group14 Organometallic Compounds --- p.1 / Chapter 1.1 --- General apects of low-valent group 14 compounds --- p.1 / Chapter 1.2 --- Structures of germylenes and stannylenes --- p.3 / Chapter 1.3 --- Tetravalent group 14 Metal amides --- p.7 / Chapter 1.4 --- Objectives --- p.11 / Chapter 1.5 --- Results and Discussion --- p.12 / Chapter 1.5.1 --- Synthesis of germanium(II) compound [Ge{C(C5H4N- 2)C(Ph)N(SiMe3)2}{N(SiMe3)C(Ph)C(SiMe3)(C5H4N- 2)}] (29) --- p.12 / Chapter 1.5.2 --- Synthesis of tin(II) amide [Sn{N(SiMe3)C(Ph)C- (SiMe3)(C5H4N-2)}2] (30) --- p.14 / Chapter 1.5.3 --- Synthesis of tin(IV)(amide)dichloride [Sn{N(SiMe3)C- (Ph)C(SiMe3)(C5H4N-2)}2Cl2] (31) --- p.15 / Chapter 1.5.4 --- Spectroscopic Properties of Compounds 29-31 --- p.16 / Chapter 1.5.5 --- Molecular Structure of [Ge{C(C5H4N-2)C(Ph)N(Si- Me3)2}{N(SiMe3)C(Ph)C(SiMe3)C(C5H4N-2)}] (29) --- p.21 / Chapter 1.5.6 --- Molecular structure of [Sn{N(SiMe3)C(Ph)C(SiMe3)- (C5H4N-2)}2] (30) --- p.25 / Chapter 1.5.7 --- Molecular structure of [Sn{N(SiMe3)C(Ph)C(SiMe3)- (C5H4N-2)}2C12] (31) --- p.28 / Chapter Chapter 2 --- Synthesis and Structure of Group 14 Metal- Chalcogenones --- p.32 / Chapter 2.1 --- Multiple bond between group 14 metals and chalcogens --- p.32 / Chapter 2.2 --- Results and Discussion --- p.39 / Chapter 2.2.1 --- "Synthesis of germane- and stannane-chalcogenones [(RI)(R1.)Ge=E], [E = S 59, Se 60], [(R1)2Sn=S] (61)， [(R1)(R1.)Sn=Se] (62)" --- p.39 / Chapter 2.2.2 --- Spectroscopic properties of compounds 59-62 --- p.41 / Chapter 2.2.3 --- Molecular structure of [{N(SiMe3)C(Ph)C(SiMe3)- (C5H4N-2)}2Sn=S] (61) --- p.46 / Chapter 2.2.4 --- "Molecular structure of [{N(SiMe3)2C(Ph)C(C5H4N-2)}- {N(SiMe3)C(Ph)C(SiMe3)(C5H4N-2)}M=E] [M = Ge, E =S 59，Se 60; M = Sn,E = Se 62]" --- p.52 / Chapter Chapter 3 --- Reactivity of Low-valent Group 14 Organometallics Compounds --- p.59 / Chapter 3.1 --- Introduction --- p.59 / Chapter 3.1.1 --- Lewis-base behavior --- p.60 / Chapter 3.1.2 --- Lewis-acid behavior --- p.63 / Chapter 3.1.3 --- Oxidative-addition (or insertion) reactions --- p.65 / Chapter 3.2 --- Results and Discussion --- p.69 / Chapter 3.2.1 --- Lewis acid base behavior of [Sn(R2)2] (27) --- p.69 / Chapter 3.2.1.1 --- "Reaction of [Sn(R2)2] (27) with group 11 metal derivatives (M = Ag, X = Cl 91,I 92,SCN 93，CN94; M = Cu, X = Cl 95，I 96)-Synthesis of [(R2)2Sn→(μ- MX)]2" --- p.69 / Chapter 3.2.2 --- Oxidative-addition (or insertion) reaction of tin(II) compounds --- p.73 / Chapter 3.2.2.1 --- Reaction of AgNCO with [Sn(R2)2] (27) 一 Synthesis of [(R2)2Sn(NCO)2](97) --- p.73 / Chapter 3 .2.3 --- Spectroscopic properties of compounds 91-97 --- p.74 / Chapter 3.2.4 --- Molecular structure of [{CH(SiMe3)C9H6N-8}2Sn→(μ- AgCl)]2 (91) --- p.80 / Chapter 3.2.5 --- Molecular structure of [{CH(SiMe3)C9H6N-8}2Sn- (NCO)2] (97) --- p.85 / Appendix I / Chapter A. --- Experimental procedures for chapter 1 --- p.87 / Chapter B. --- Experimental procedures for chapter 2 --- p.90 / Chapter C. --- Experimental procedures for chapter 3 --- p.93 / Appendix II / Chapter A. --- References for chapter 1 --- p.98 / Chapter B. --- References for chapter 2 --- p.102 / Chapter C. --- References for chapter 3 --- p.104 / Appendix III / Chapter A. --- General procedures --- p.106 / Chapter B. --- Physical and analytical measurements --- p.106 / Appendix IV / Table A.l. Selected crystallographic data for compounds 29，30，31 --- p.109 / Table A.l. Selected crystallographic data for compounds 59，60，61 --- p.110 / "Table A.l. Selected crystallographic data for compounds 62, 91，97" --- p.111

Systematic Review - Recent studies have identified potential change within interpersonal relationships following mindfulness-based interventions such as MBSR and MBCT; however, few studies have explored this in a clinical sample, from the participants’ perspective. This study aimed to explore this phenomenon by synthesising qualitative studies to answer the following question: How do people with a mental health diagnosis experience interpersonal change following MBSR and MBCT. A systematic search strategy identified 117 studies, of which 12 met the final inclusion criteria. A thematic synthesis was conducted based on the protocol developed by Thomas and Harden (2008). The thematic synthesis revealed an overall theme of connection, with subthemes of ‘the group as a community’; ‘reconnecting with the self’; ‘skill development’ and ‘reconnecting with others’. These themes were further synthesised to consider the interconnections between them. This revealed two points of interest: the power of the group community and intra- to inter-personal development. These themes were explored in relation to existing literature. The results are discussed in relation to the limitations of the study, and future research recommendations are considered. Empirical Paper - Mindfulness-based cognitive therapy (MBCT) have been shown to be effective in reducing the impact of cognitive reactivity (CR) and improving outcomes for people with recurrent depression. It has been proposed that this effect may be mediated by the cultivation of self-compassion; however, there is limited research into this mechanism. This study aimed to explore the lived experience of a sad mood induction and compassionate repair in people with currently remitted recurrent depression, with and without experience of MBCT. Sixteen participants were recruited (10 MBCT, six non-MBCT). Participants underwent a two-phase mood manipulation, sad mood induction and loving-kindness meditation (directed to a loved one and the self) and completed self-report measures before and after each task. Following this, participants engaged in a semi-structured interview exploring their experiences. The results showed both mood manipulations were successful, and mood repair was apparent within all but one of the participants. The interviews were analysed using thematic analysis, identifying six key themes: vulnerability versus tolerance of depression; immersion versus transience of cognitive and emotional reactivity; avoidance versus tolerance of compassion; self-criticism versus self-acceptance; locus of control and mechanisms of repair. No differences were observed between the two groups in their qualitative or quantitative responses to the mood manipulations; however, those in the MBCT group with a greater level of current MBCT practice, appeared more able to transcend negative thinking and utilise the Loving Kindness Meditation (LKM) more effectively for both themselves and others. The results are discussed in relation to study limitations and their implication to clinical practice.

This dissertation focuses on the development of cyclopentadienes as an emerging class of compounds for use in catalysis. Previous work in the Lambert group had established pentacarboxycyclopentadienes (PCCPs) as a promising class of Brønsted acids capable of being used as catalysts in acid-promoted reactions. The ease of their synthesis distinguished them from the comparable BINOL-derived phosphoric acids, and their unique mode of enantioinduction created opportunities for their use in enantioselective reactions. Initial efforts were focused on the synthesis of leading to the development of two complementary methods for their synthesis. Chapter 2 details the improvements made to the transesterification of penta(methoxycarbonyl)cyclopentadiene, which allowed for sterically encumbered alcohols to be used. Further, a new method for accessing the penta-acyl chloride intermediate was developed, leading to the ability for a wide array of electron-deficient PCCPs to be synthesized. The second half of the dissertation examines the use of electrophilic silicon reagents and their use as Lewis acids. Given our ability to access highly electron-deficient cyclopentadienes, the silyl cyclopentadienes were targeted as potential Lewis acids. Chapter 4 details the synthesis of these species, and their characterization. Having established a convenient route to silyl mono(carboxy)tetracyanocyclopentadienides, we examined their use as catalysts in halide abstraction reactions. Benzylic bromides could be activated and subsequently allylated, or arylated with a nucleophilic arene using allyltrimethylsilane as a sacrificial silyl source.

As reações entre o íon pentacianoferrato(II) e os isômeros de acetilpiridina (py(CO)CH3) foram estudadas com o intuito de estabelecer o mecanismo da reação de ataque nucleofílico ao grupo nitrosilo coordenado. Estas reações de adição foram acompanhadas pela técnica stopped flow ll a 25,O&#186;C, em condições de pseudo primeira ordem, em meio alcalino com força iônica 0,10 M ajustada com LiC104 . Durante o processo, constatou-se que a formação dos produtos é precedida pelo aparecimento de intermediário azul com pequenos tempos de vida. A formação deste intermediário envolve o ataque da acetilpiridina na forma de carbânion, ao grupo nitrosilo coordenado, em competição com a adição do íon hidroxila. A lei da velocidade para o mecanismo proposto nesta etapa, tem a expressão abaixo para a constante de velocidade observada kobsl= KkL [py(CO)CH3] [OH-] + kOH [OH-] + k-L Os valores de KkL e k-L são respectivamente 1,91 &#177; 0,05 X 102M-2s-1 e 0,90&#177; 0,02 X 10-1 s-1</SUP para acetilpiridina com substituintes na posição para; 3,70&#177; 0,10X .. 10 M-2s-1 e 0,86 &#177; 0,02 X 10-1s-1 para o derivado na posição meta e 1 ,42 &#177; 0,04 X 10 M-2 s-1 e o 0,46 &#177; 0,01X10-1s-1para o derivado em orto. O kOH obtido nas condições experimentais é 0,302M-l s-1. o decaimento do intermediário ocorre devido a dissociação da espécie coordenada pelo NO cuja labilização pode ser provocada ou ocorrer em paralelo a isomerização do ligante. Esta reação também depende tanto da concentração do ligante como da concentração da hidroxila. A lei da velocidade resultante do mecanismo proposto, consistente com o comportamento cinético, leva à expressão [figura ver arquivo em PDF] Os valores de kd e KT determinados são respectivamente 8,3 X 10-2s-1 2,1 X 103 M-2 para derivados em para, 5,0 X 1º-2s s-1 e 3,90 X -10 M-2 Para o derivado em meta e 3,2 X 10-2s-1e 2,95 X 102 M-2 para o derivado em orto. A consistência do mecanismo proposto foi verificada através das constantes obtidas em experiências independentes acompanhando o decaimento dos intermediários sintetizados. O mecanismo foi ainda confirmado através dos estudos independentes das etapas propostas no mecanismo global. Esta adição das acetilpiridinas ao grupo NO coordenado foi aproveitada na obtenção de 1igantes carboni1-oximas correspondentes. Estes ligantes py(CO)CHNOH bem como as acetilpiridinas foram utilizados para sintetizar série de complexos Fe(CN)5L3- a partir do íon aquopentacianoferrato (II) , Fe(CN)5H2O3-. A caracterização dos 1igantes e complexos sintetizados foi feita na região de infravermelho, visível e ultra-violeta. Os espectros eletrônicos obtidos foram decompostos usando-se as funções Gaussianas simples e dupla e a 1ognormal. Os complexos apresentam-se fortemente coloridos, com bandas de absorção na região do visível e ultra-violeta próximo, cujas transições podem ser classificadas em; a. Transições de transferência de Carga Fe-L (CT); b. Transições de Campo Ligante (d-d); c. Transições Internas nos Ligantes (L-L); d. Transições de transferência de Carga Fe-CN (CT) Foram ainda verificados os efeitos de pH sobre as bandas de transferência de carga e as variações espectrais provenientes da oxidação do complexo. Os estudos de espectroscopia envolvendo os complexos intermediários sintetizados foram feitos na tentativa de obter informações estruturais e propriedades para se estabelecer correlação com parâmetros cinéticos determinados. O comportamento eletroquímico dos complexos em estudo foi investigado através da voltametria cíclica. A partir destes dados obteve-se os parâmetros termodinâmicos bem como a correlação do Eo com a frequência da transição de transferência de carga vTC(Fe-L). Os complexos Fe(CN)5 py (CO)CHNOH3- apresentam comportamento fotoquímico típico, com deslocamento batocrômico das bandas de transferência de carga no decorrer da irradiação com luz visível e ultra-violeta. A fotosubstituição dos cianetos nos complexos Fe(CN)5L3- foi constatada pela primeira vez com o uso de ligantes que apresentam características quelantes ( como etilenodiamina e py(CO)CHNOH ) e estabilizam os complexos tetracianoferrato(II) correspondentes. A irradiação quase monocromática no complexo Fe(CN)5em3- mostra um rendimento quântico de 0,087 &#177; 0,003 para a saída do cianeto. A espécie formada fotoquimicamente foi isolada e a sua identidade foi \' confirmada espectroscopicamente e também, através da reação de oxidação com formação do tetracianoferrato com diimina. A análise do pentaciano(etilenodiamina) ferrato (II) consumido e a quantidade do complexo tetracianoferrrato correspondente formada mostra que a reação representada a seguir [figura ver arquivo em PDF] é o único processo fotoquímico efetivo que ocorre durante . o período de irradiação . / The reactions between the pentacyano(nitrosyl) ferrate(II) ion and the o-, m-, p-isomers of acetylpyridine (py(CO)CH3) were investigated by stopped flow technique, in order to evaluated the mechanisms of nucleophilic attack on the coordinated nitric oxide ligand. The kinetics of these addition reactions were followed spectrophotometrically, under pseudo first order conditions, at a temperature of 25°C, and &#181= 0,100 (lithium perchlorate and lithium hydroxide). A deep blue compound can be observed with a half-1ife of a few seconds. The formation of such an intermediate was described in terms of the attack of the carbanion of acetylpyridine to the coordinate nitric oxide ligand, in competition with the addition of the hydroxide ion. The experimental rate 1aw for the reaction can be expressed by a pseudo first order equation, consistent with our proposed mechanism; where kobsl= K.kL [py(CO)CH3] [OH- + kOH [OH-] + k-LThe rate constants kL and k-L refer to the nucleophilic attack step and the reversal reaction, respectively. The equilibrium constant K represents the formation of the carbanion, while kOH is associated with the parallel addition of the hydroxide ion to NO+. The values determined for KkL and k-L were, respectively , 196 M-2s-1, and 0.090 s-l for p-py(CO)CH3 ; 370 M-2s-1 and 0.080 s-l for m-py(CO)CH 3; and 14,2M-2s-1 and 0.046s-1 for o-py(CO)CH3 . The kOH value obtained under the experimental conditions is 0,302 M-1s-1 The decay of the intermediate yields the free carbonyloximes in solution. It may be associated with an intrinsic lability of the nitroso species, or even by an internal isomerization leading to a sterically hindered configuration of the ligand . The observed rate law was found to depend on the acetylpyridine and the hydroxide ion concentrations in the following way [see figure PDF file] where KT = K.kL/k-L, and . kd is the rate constant of dissociation of coordinated 1igand. The experimental values of KT and kd were, respectively, 2.1x103 M-2 and 0.082s-1 for p-py(CO)CH3; 390 M-2 and 0.050 s-1 for m-py (CO) CH3;and 295 M-2 and 0.032 s-1 for o-py(CO)CH3. Independent experiments using the intermediate species isolated as solids, allowed to confirm the consistency of our two step mechanism . From the pure carbonyl-oxime ligands obtained in this work we have synthesized the substituted complexes of pentacyanoferrate(II) coordinated by pyridine group. An extensive characterization of the ligands and of the complexes was carried out in this work, including the analysis of the electronic spectra in terms of Gaussians and log-normal functions, and the assignments of the vibrational spectra. Also examined were the pH effects on the charge transfer spectra, as well as the evaluation of the basicity constants of the coordinated cyanide and the heterocyclic ligands. We have also characterized the intermediates in terms of their electronic and vibrational spectra. Based on an electrochemical study, using mostly cyclic voltammetry, we have obtained the thermodynamic parameters of the several complexes. A linear correlation between the formal potentials and the energies of the charge transfer transitions was found in this work. The Fe (CN)5py (CO) CHNOH3- complexes were found to be photosensitive, turning slowly to a deep blue color under sun or ordinary light. The photolysis under controlled conditions, with a mercury lamp, in the visible - near uv region, produced neat spectral changes, with isosbestic points indicating a well behaved photochemical process. The product, in contrast to pentacyanoferrate(II) species, was found to be inert toward dimethyl sulfoxide. The same behavior has been observed for tetracyanoferrate(II) complexes with bidentate ligands. In analogy, the blue product was formulated as [see figure PDF file] Quantum yields were determined at several wavelengths however, it was not possible to distinguish , between the following photochemical processes, leading to the tetracyano species : [see figure PDF file] The second process taking place on the oxime isomer, which may be eventually present in very small amount, is expected to be highly effective because of the neighboring effect enhancing the formation of the 5 member ring. To clarify this point, we have investigated the photochemistry of the Fe(CN)5(en)3- complex. The results indicated that the formation of the Fe(CN)4en2- complex takes place with a quantum yield of 0,087&#177; 0,005 at 366nm, which is nearly 10 times the values obtained for carbonyl-oxime complexes. In this case, the photochemical process can be analysed quantitatively by determining the amount of the starting complex, or by isolating the tetracyano species by ionic exchange chromatography. Both ways gave comparable numbers, indicating that the measured quantum yields refer to the process [see figure PDF file] We therefore concluded that the labilization of the CN ligands in the carbonyl-oxime complexes should take place mostly according to the first route.

Submitted by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2016-09-13T19:07:13Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) PATRICIA MEDEIROS SCHMIDT.pdf: 1364423 bytes, checksum: 44d4424176381aef09781de156ac940d (MD5) / Approved for entry into archive by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2016-09-13T19:10:12Z (GMT) No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) PATRICIA MEDEIROS SCHMIDT.pdf: 1364423 bytes, checksum: 44d4424176381aef09781de156ac940d (MD5) / Made available in DSpace on 2016-09-13T19:10:12Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) PATRICIA MEDEIROS SCHMIDT.pdf: 1364423 bytes, checksum: 44d4424176381aef09781de156ac940d (MD5) Previous issue date: 2015-07-31 / O alumínio (Al) é o metal mais comum da crosta terrestre, e sua elevada biodisponibilidade o torna um importante contaminante ambiental. O Al pode se acumular em vários órgãos e tem sido associado a diversas doenças, principalmente neurodegenerativas. Entretanto, pouco ainda se sabe sobre seus efeitos no sistema cardiovascular. Assim, este estudo investigou os efeitos da exposição aguda ao cloreto de alumínio (AlCl3) sobre a pressão arterial, o estresse oxidativo e a reatividade vascular de ratos. Para tal, ratos Wistar foram divididos nos grupos: Untreated: veículo (água ultrapura, ip) e AlCl3: dose única de AlCl3 (100 mg/kg ip). A pressão arterial sistólica e diastólica foi avaliada em ratos anestesiados por meio de canulação da artéria carótida imediatamente antes a administração do AlCl3 e após 1h. A reatividade de aorta foi realizada em banho de órgãos e curvas concentração resposta para acetilcolina, nitroprussiato de sódio e fenilefrina foram obtidas na presença e ausência de endotélio, L-NAME (inibidor da óxido nítrico sintase), apocinina (inibidor da NADPH oxidase), TEA (bloqueador dos canais de potássio) e SOD (scavenger de ânion superóxido). A produção de óxido nítrico (NO) foi mensurada em artérias; espécies reativas de oxigênio (EROs), malondialdeído (MDA) e níveis de tióis não-proteicos foram avaliados no plasma, assim como as atividades da superóxido dismutase (SOD), catalase, glutationa-peroxidase e glutationa-S-transferase (GST). A concentração sérica de alumínio após uma única injeção intraperitoneal de AlCl3 atingiu 147,7 ± 25,0 μg/L; esta exposição não alterou a pressão arterial, contudo induziu aos seguintes efeitos: 1) diminuição da resposta vasoconstritora à fenilefrina; 2) aumento da modulação endotelial negativa e biodisponibilidade de NO, bem como a produção de EROs vascular pela NADPH oxidase, principalmente ânions superóxido; 3) aumento dos níveis de MDA e tióis; 4) 8 maior atividade da catalase e GST 5) diminuição da atividade da SOD. Portanto, a exposição aguda ao AlCl3 promove alterações vasculares, e este efeito parece estar associado ao aumento da biodisponibilidade de NO e sua ação sobre os canais de K+, provavelmente atuando como um mecanismo compensatório sobre o estresse oxidativo. Estes resultados sugerem que o Al pode ser considerado como um agente tóxico vascular. / Aluminum (Al) is the most common metal and its high bioavailability points this as an important environmental contaminant. Aluminum can be accumulated in several organs and has been associated with several diseases, mainly neurological disorders. At cardiovascular system, there are not enough evidences of Al-induced dysfunction. We investigated the effects of acute exposure to aluminum chloride (AlCl3) on blood pressure, oxidative stress and vascular reactivity. Male Wistar rats were divided into groups: Untreated: vehicle (ultrapure water, ip) and AlCl3: single dose of AlCl3 (100 mg/kg ip). Systolic and diastolic blood pressure were assessed in anesthetized rats by cannulation of carotid artery immediately before and after one hour of aluminum administration. Aortic rings reactivity was investigated in isolated organ bath and concentration-response curves to acetylcholine, sodium nitroprusside and phenylephrine were performed in the presence and absence of endothelium, the nitric oxide synthase inhibitor L-NAME, the NADPH oxidase inhibitor apocynin, the K+ channels blocker TEA and the superoxide anion scavenger SOD. Nitric oxide (NO) released was studied in arteries; reactive oxygen species, malondialdehyde and nonprotein thiol levels were measured in plasma, as well as superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase activities. Serum aluminum concentration after a single intraperitoneal injection of AlCl3 reaches 147.7 ± 25.0 μg/L. This treatment did not change blood pressure, although inducing the following effects: 1) decreased vasoconstrictor response to phenylephrine; 2) increased negative endothelial modulation and nitric oxide released as well as vascular reactive oxygen species production from NADPH oxidase, mainly superoxide anions; 3) increased malondialdehyde and thiol levels; 4) enhanced catalase and glutathione-S-transferase activities and 5) decreased SOD activity. Therefore, AlCl3-acute exposure promotes vascular changes. This effect seems to be 10 associated with increased nitric oxide bioavailability, possibly acting on K+ channels, seems to occur probably as a compensatory mechanism on oxidative stress. These results suggest that this metal might be considered as a cardiovascular toxic agent.

La nitrate réductase périplasmique de Rhodobacter sphaeroides possède, un cofacteur à Mo (site actif), un centre [4Fe-4S] et deux hèmes de type c formant une chaîne de transfert électronique intramoléculaire. Ce travail est centré sur deux aspects moléculaires de la catalyse de cette enzyme : la réactivité au niveau du site actif de l’enzyme et les processus de transfert d’électrons intramoléculaires. Ces questions sont abordées en s’appuyant parallèlement sur des approches de mutagénèse dirigée, d’activités enzymatiques, de spectroscopie de résonance paramagnétique électronique (RPE) en onde continue et impulsionnelle et sur des mesures de potentiels redox associés aux cofacteurs de l’enzyme. La première partie de ce travail est consacrée à la caractérisation spectroscopique et physico-chimique d’intermédiaires Mo(V) du site actif afin de déterminer leur structure et leur positionnement possible dans le cycle catalytique. Nous avons ainsi étudiée de manière détaillée deux intermédiaires Mo(V) en présence de nitrate dont nous montrons qu’ils présentent des différences structurales au-delà de la première sphère de coordination du Mo. Dans la seconde partie, nous mettons en évidence le rôle d'un acide aminé très conservé (Lys) dans le transfert d'électrons intramoléculaire. Cet acide aminé chargé positivement est situé dans la seconde sphère de coordination du centre [4Fe-4S] et joue un rôle majeur dans la modulation des propriétés rédox du centre [4Fe-4S], ce qui affecte fortement les propriétés catalytiques de l'enzyme. L’ensemble de nos résultats permettent ainsi d’identifier dans l’environnement du Mo des éléments déterminants dans la réactivité de l’enzyme. / The periplasmic nitrate reductase from Rhodobacter sphaeroides contains, in addition to the Mo-cofactor, a [4Fe-4S] center and two c-type hemes defining an intramolecular electron transfer chain. This work focuses on two molecular aspects of the catalysis: the reactivity of the Mo-cofactor, and the intramolecular electron transfer step. These issues are dealt by combining approaches as site-directed mutagenesis, enzymatic activities, continuous-waves (CW) and pulse electron paramagnetic resonance spectroscopy (EPR), UV-Vis spectroscopy and redox titration of metal cofactors of the enzyme. A first part of this work is devoted to the spectroscopic and physicochemical characterization (thermodynamic and kinetic properties) of Mo (V) intermediates of the active site in order to determine their structure and their catalytic relevance. We have undertaken a detailed characterization of two Mo(V) intermediates generated in presence of nitrate, which display some structural differences beyond the first coordination sphere of the Mo(V) ion. In a second part, we highlight the role of a highly conserved amino acid (Lys) in intramolecular electron transfer. This positively-charged amino acid is located in the second coordination sphere of the [4Fe-4S] center and plays a major role in the redox properties tuning of the [4Fe-4S] center thus strongly affecting the catalytic properties of the enzyme. All together, these data provide some structural insights on the enzyme reactivity beyond the first coordination sphere of the Mo-cofactor.

Keggin-based aluminum nanoclusters have been noted to be efficient sorbents for the adsorption of arsenic, copper, lead, and zinc from water. Obtaining a molecular-level understanding of the adsorption processes associated with these molecules is of fundamental importance and could pave the way for rational design strategies for water treatment. Furthermore, due to their size and the availability of experimental crystal structures, Al nanoclusters are computationally tractable at the atomistic modeling level. The adsorption of contaminants onto metal-oxide surfaces with nanoscale Keggin-type structural topologies has been established, but identification of the reactive sites and the exact binding mechanism are lacking. In more common surface studies the two main factors that affect reactivity have been found to be charge and functional group identity. Since Al nanoclusters each have a distinct shape we introduce the effects of shape as a third factor. In all the work presented in this dissertation, it is extremely apparent that the shape of the aluminum particle plays the most important role in nanoparticle reactivity studies. We first focus on the reactivity of three aluminum polycations: [Al13O4(OH)24(H2O)12]7+ (Al13), [Al30O8(OH)56(H2O)26]18+ (Al30), and [Al32O8(OH)60(H2O)30]20+ (Al32). Using outer-sphere adsorption of sulfate and chloride as probe adsorbents, density functional theory (DFT) calculations determined that the reactivity can be represented as a function of particle topology, and not functional group identity or charge. Further exploring the shape-reactivity relationship of Al30 we reveal that cations and anions have opposing trends and ion reactivity can be generalized. It is determined that all cations favor the adsorption sites on the caps of Al30 and all anions favor adsorption in the beltway (middle) region. This result is supported by the visualization of the electrostatic potential of Al30 and three-dimensional induced charge density maps. The middle of the cluster is more positive than the caps, and this promotes anion adsorption in the beltway and cation adsorption on the caps. Next we explore the reactivity of co-adsorption (outer-sphere anions and inner-sphere cations) onto Al30 through a collaborative approach. Al30 with two surface-bound Cu2+ cations (Cu2Al30-S) was experimentally crystallized in the presence of disulfonate anions; however, in the Cu2Al30-S structure the cations bind to the beltway region of the cluster. Using DFT we determined that the counter anions play a key (and governing) role in the crystallization of Cu2Al30-S. This result that outer-sphere adsorption dictates inner-sphere adsorption does not appear in surface calculations, it is unique to Keggin studies. Seeing that all anions favor adsorption to the beltway region and all cations favor adsorption to the cap region we set out to determine if any reactivity patterns can be reversed. In order to do this inner-sphere As(V) and P(V) adsorption is modeled onto Al30 through another collaborative approach. The experimental crystal structure of (TBP)2[Al2(μ4-O8)(Al28(μ2-OH)56(H2O)26)]14+ (where TBP = t-butylphosphonate (CH3)3CPO3) has been synthesized, and using DFT calculations we can alter the R-group of P(V) or the DFT As(V) analogue to see if the inner-sphere anion ever prefers to bind to the cap region instead of the beltway. We observe that no matter the intrinsic properties of the R-group the anion always prefers to bind to the beltway region, which once again shows that the shape-reactivity relationship plays a major role in Keggin based structure reactivity. Since As(V) is such a harmful ion we extend our As(V) adsorption studies to aluminum surfaces. As(V) has been experimentally shown to bind to aluminum surfaces in a bidentate binuclear configuration. By modeling a variety of configurations we can confirm and explain that the bidentate binuclear configuration is most stable due to the least amount of strain on the As(V) atom. Aluminum surfaces are common DFT models to study but are computationally expensive, due to this fact some people choose to model small Al octahedral cluster models instead. Comparing the reactivity of both systems we see a significant difference in energy magnitudes and ranges and can conclude that small Al octahedral cluster models cannot take place of aluminum surfaces. All in all, the work presented in this dissertation provides an important contribution in our understanding of Keggin based Al compounds. Keggin based compounds are very sparsely studied computationally and this work helps to fill a knowledge gap. Hopefully the insights obtained from this work can help guide future Keggin based studies.