Since the clinical success of platinum drugs (cisplatin and its derivatives) as anticancer agent, medicinal inorganic chemistry has become a field of growing interest because it offers an alternative for the design of therapeutic agents that are not readily available to organic compounds. Although cisplatin is one of the most widely used drugs in chemotherapy, it is not effective for all types of cancer. Moreover, platinum drugs are the cause of disabling side effects (neurotoxicity, nephrotoxicity, weight loss, nausea...) and their applicability is limited by innate or induced resistance to platinum in a narrow range of tumours. Therefore, this clinical success has promoted the search for cytotoxic compounds with enhanced activities and more acceptable toxicity profiles. This has stimulated interest in complexes containing other heavy metals of the platinum group such as ruthenium because these compounds show lower toxicity than drugs based on platinum. Some ruthenium compounds have already shown promising anticancer activity and two RuIII complexes trans-[RuCl4-(DMSO)(Im)]ImH (NAMI-A and trans-[RuCl4(Ind)2]IndH (KP1019) recently enter in clinical phase for their respectively antimetastatic and cytotoxic properties.In the essential aim of increasing activity and reducing side effects of anticancer agents, the Laboratoire de Synthèses Métallo-Induites has developed for several years organometallic ruthenium compounds RDC (Ruthenium Derivative Compound) in which one of the ligand is strongly bound to the metal via a strong σ C-Ru bond and stabilized by an intramolecular N-Ru bond. This thesis presents the recent advances of the laboratory in this field and the development of a second generation RDC in which the cylometallating ligand is stabilized by two N-Ru bonds. Thus, several complexes pass the symbolic barrier of the nanomolar range for their IC50 indicating a critical improvement. At the same time, we decided to focus our studies on osmium heavier congener, not only to complete the RDC chemical library, but also to verify the impact of exchanging the metal. An extensive chemical library ODC (Osmium Derivative Compound) of forty cyclometalated osmium complexes was synthesized and evaluated in vitro. Biological studies on these ODCs showed that osmium is another metal that deserves attention for the development of new effective antitumour drugs. The measurements of physicochemical properties such as red-ox potential and lipophylicity (log(Po/w)) allowed us to tentatively correlate these parameters to the level of activity, thus approaching a possible Property-Activity Relationship (P.A.R.). More insight into the role of the red-ox potential will probably become clearer as we progress into the mechanism of action of these species.

Este trabalho descreve estudos eletroquímicos e espectroscópicos da eletrooxidação de etanol, acetaldeído e ácido acético sobre uma superfície de platina monocristalina de baixo índice de Miller 110 modificada por ósmio (Os). O eletrodo monocristalino de Pt(110) foi modificado por Os espontaneamente e pela aplicação de potencial. Os eletrodos foram caracterizados eletroquimicamente, de forma que foram obtidos valores baixos, intermediários e altos de Os sobre a superfície de Pt(110). A eletrooxidação de etanol sobre Pt(110) e Pt(110)/Os, analisada pelas técnicas de voltametria cíclica e cronoamperometria, mostrou que as densidades de corrente para essa reação foram maiores nos graus de recobrimento entre 0,51 – 0,61 ML. A partir dos resultados de FTIR in situ, verificou-se que a reação de oxidação de etanol difere em seus caminhos de acordo com o grau de recobrimento de Os. O caminho um sugere a quebra da ligação C—C com maior intensidade em graus de recobrimento entre 0,36 – 0,80 ML, formando espécies como COlinear, CHx e, posteriormente, CO2. O caminho dois mostra a formação de acetaldeído a partir de 0,4 V sobre os eletrodos Pt(110) e Pt(110)/Os, e que pode haver ainda a produção de CO e ácido acético a partir desse orgânico sobre eletrodos com HOs > 0,80 ML, a baixos potenciais. O estudo realizado com acetaldeído mostrou que o desempenho na oxidação desse orgânico foi sutilmente maior para os eletrodos modificados por Os. O caminho três apresenta a produção de CO2 proveniente da oxidação de etanol diretamente a ácido acético sobre eletrodos com alto grau de recobrimento. Durante a oxidação ocorre a formação a baixos potenciais de COlinear em grandes quantidades. Além disso, há produção de ácido acético e posteriormente de CO2. Ainda nos eletrodos espessos, a produção de CO2 ocorre sem que se observe a presença de COlinear, indicando a possibilidade da oxidação de ácido acético a CO2. A eletrooxidação de ácido acético sobre os diversos eletrodos de Pt(110)/Os mostra que ocorre a quebra dessa molécula para formar CO2, embora de forma menos expressiva que as demais moléculas estudadas. Sendo que parte do CO2 produzido provavelmente tem sua origem no grupo COO- que está adsorvido sobre a superfície do eletrodo. / This work reports the electrochemical and spectroscopic results of ethanol, acetaldehyde and acetic acid electrooxidation onto low index platinum single crystal surface (110) modified by osmium (Os). The Pt(110) electrode was modified by spontaneous and electroless Os deposition and checked electrochemically in order to obtain low, intermediate and high Os coverages on Pt(110). The ethanol electrooxidation on Pt(110) and Pt(110)/Os, which used voltammetric cycle and cronoamperometric techniques, showed higher currents toward this reaction on Os coverage between 0.51-0.61 ML. The FTIR results reveal that ethanol oxidation has different pathways according to Os coverage. The step one suggests that the cleavage of ethanol C—C bond occurs with major intensity forming species such as COlinaer and CHx when the reached coverage is 0.36 – 0.80 ML and further producing CO2. At the step two, acetaldehyde formation is improved above 0.4 V on Pt(110) and Pt(110)/Os, and at low potentials on HOs > 0.80 ML, this molecule can oxidize and form CO and acetic acid. Studies on acetaldehyde showed that the catalytic activity is slightly higher on electrodes modified by Os. The step three presents the CO2 production through acetic acid onto electrodes with high Os coverage. During the oxidation of this molecule, COlinear is produced in large quantities at low potentials; there is formation of acetic acid and thereupon CO2. Onto Os thick electrode, CO2 production occurs without the presence of COlinear, indicating the possibility of acetic acid oxidation directly to CO2. The acetic acid oxidation on various electrodes modified by Os is possible with cleavage of C—C bond to form CO2, though this process is less significant than others organic molecules studied. Since the amount of CO2 produced can arise through the acetate group once this specie is adsorbed onto the electrode surface.

No description available.

Background: Workers in a platinum group metals (PGMs) refinery are potentially exposed to various precious metals (iridium, osmium, palladium, platinum, rhodium and ruthenium) and their metal-salt compounds which may cause rhinitis, asthma, contact urticaria and conjunctivitis. Some cases revealed that sensitisation occurred in employees where it was not possible to detect any airborne soluble platinum or where the respiratory soluble platinum exposure was below the occupational exposure limit. It is unclear whether respiratory exposure or a combination of respiratory and dermal exposure may be involved in sensitisation and the possible elicitation of skin symptoms. Objectives: To determine if dermal exposure to PGMs took place during the refining process and in the administration area by using a removal method and to compare dermal exposure on the different anatomical areas and in two different working areas, Areas A and B for each of the PGMs. Methods: Dermal exposure samples were collected with a removal method using GhostwipesTM. The samples were collected from the palm of the hands, the wrists and the necks of the workers, before the shift started, before tea time, before lunch time and after the shift ended. The skin wipes were analysed for the PGMs (iridium, osmium, palladium, platinum, ruthenium and rhodium) according to Methods for the Determination of Hazardous Substances (MDHS) method 46/2, using Inductively Coupled Plasma-Mass Spectrometry. Results: No published data is available on occupational dermal exposure to PGMs in a precious metals refinery. This study proved that dermal exposure to PGMs in the refinery took place and was quantified. The PGM dermal exposure results in general, were very low (measured in nano grams), with platinum having the overall highest exposure. Exposure also occurred the most frequently during the last two intervals of the day, before lunch time and at the end of the shift. Exposure on all three the anatomical areas that were tested in the study, varied much with the palm of the hands having the highest exposure levels. There were also variations in exposure between areas A and B due to the fact that the processes in these two areas differ. Conclusions: It was confirmed that dermal exposure to PGMs took place at the precious metals refinery. The highest exposure took place before lunch time and towards the end of the shift. The metal to which the workers were exposed the most was platinum and the production area where the workers had the highest exposure to most of the metals was Area B. / MSc (Occupational Hygiene), North-West University, Potchefstroom Campus, 2015

Background: Workers in a platinum group metals (PGMs) refinery are potentially exposed to various precious metals (iridium, osmium, palladium, platinum, rhodium and ruthenium) and their metal-salt compounds which may cause rhinitis, asthma, contact urticaria and conjunctivitis. Some cases revealed that sensitisation occurred in employees where it was not possible to detect any airborne soluble platinum or where the respiratory soluble platinum exposure was below the occupational exposure limit. It is unclear whether respiratory exposure or a combination of respiratory and dermal exposure may be involved in sensitisation and the possible elicitation of skin symptoms. Objectives: To determine if dermal exposure to PGMs took place during the refining process and in the administration area by using a removal method and to compare dermal exposure on the different anatomical areas and in two different working areas, Areas A and B for each of the PGMs. Methods: Dermal exposure samples were collected with a removal method using GhostwipesTM. The samples were collected from the palm of the hands, the wrists and the necks of the workers, before the shift started, before tea time, before lunch time and after the shift ended. The skin wipes were analysed for the PGMs (iridium, osmium, palladium, platinum, ruthenium and rhodium) according to Methods for the Determination of Hazardous Substances (MDHS) method 46/2, using Inductively Coupled Plasma-Mass Spectrometry. Results: No published data is available on occupational dermal exposure to PGMs in a precious metals refinery. This study proved that dermal exposure to PGMs in the refinery took place and was quantified. The PGM dermal exposure results in general, were very low (measured in nano grams), with platinum having the overall highest exposure. Exposure also occurred the most frequently during the last two intervals of the day, before lunch time and at the end of the shift. Exposure on all three the anatomical areas that were tested in the study, varied much with the palm of the hands having the highest exposure levels. There were also variations in exposure between areas A and B due to the fact that the processes in these two areas differ. Conclusions: It was confirmed that dermal exposure to PGMs took place at the precious metals refinery. The highest exposure took place before lunch time and towards the end of the shift. The metal to which the workers were exposed the most was platinum and the production area where the workers had the highest exposure to most of the metals was Area B. / MSc (Occupational Hygiene), North-West University, Potchefstroom Campus, 2015

trans-2,5-Disubstituted-tetrahydrofurans (THFs) are a common structural motif in many biologically active natural products, particularly in the Annonaceous acetogenins. This thesis develops a new route for their synthesis and applies it to the total synthesis of the Annonaceous acetogenin sylvaticin. Chapter 1: Introduction – Synthetic routes to trans-2,5-substituted tetrahydrofurans This chapter reviews methods for the synthesis of trans-2,5-THFs that have been applied to natural products synthesis. Chapter 2: Results & Discussion – A Novel Route to trans-THFs The rearrangement of activated 2,5-disubstituted cis-THFs is reviewed and is developed into a new synthetic method for the synthesis of trans-THFs. The reaction proceeds via a hydride shift mechanism to form an oxonium ion. Intramolecular reduction by a tethered hydrosilane stereoselectively forms the trans-THF. The mechanism of the rearrangement is investigated with the use of different stereoisomers and a deuterium labelling study. A cross-over study is carried out which confirms the reaction occurs via the proposed hydride shift mechanism. Chapter 3: Introduction – The Annonaceous Acetogenins This chapter introduces the Annonaceous acetogenins, a biologically active class of natural products often found with THF rings in their structure. The three key areas for their synthesis are explored- the synthesis of the THF core, the synthesis of the butenolide ring, and their coupling. Chapter 4: Results & Discussion – The Synthesis of Sylvaticin The Annonaceous acetogenin sylvaticin is introduced, and its isolation in nature and biological activity reviewed. With the aid of a model system study to extend the scope of the reaction, the methodology developed in Chapter 2 is then applied to the synthesis of sylvaticin. The synthesis, the first to be reported, is completed in a total of 19 linear steps starting from commercially available tetradecatetraene. In order to prove the obtained structure is that found in nature, a comprehensive investigation is undertaken using Mosher ester derivatives and the synthesis of its bis-epimer, 4,36-epi,epi sylvaticin. Chapter 5: Experimental Full experimental procedures and characterisation of compounds are reported.

No description available.

An environmental friendly and simple approach to synthesis of Platinum (Pt), Palladium (Pd), Rhodium (Rh) and Osmium (Os) nanoparticles via gamma radiolysis is demonstrated. Herein, we report on the effect of gamma rays radiation on Platinum (Pt), Osmium (Os), Rhodium (Rh) and Palladium (Pd) salts solutions for synthesis of nanoparticles. Pt, Os, Rh and Pd salts solutions of different concentrations were exposed to intense gamma rays irradiation with doses varying from 70 to 120 kGy. The metal ion salt solutions were easily converted into metal nanoparticles (MNP) using radiolysis method. The radiolytic conversion effect produced MNP suspended in the solution. For Pt, Pd and Rh a metal coating on the edges of the polypropylene tube used as a container, was unexpectedly observed but not for the Os solution. Physical/chemical properties of γ-ray produced nanoparticles were reported. UV-Vis spectroscopy, X-ray diffraction (XRD) and High resolution transmission electron microscopy (HRTEM) analyses confirmed that both the coating and the MNP correspond to the pure metal coming from the reduction of the initial salt. HRTEM analysis shows the particles size and particle distribution of the produced nanoparticles. Quantitative analysis of the XRD patterns shows information about the size and stress of the converted metals. The functional groups in the solvent are analysed by Fourier Transform Infrared spectroscopy (FTIR). The production of a metal coating on polypropylene plastic tubes by gamma-rays irradiation is presenting an interesting alternative to conventional techniques of metal deposition especially for coating the inner part of a tube. / Physics / D. Lit. et Phil. (Physics)

A extratibilidade de sais de fosfônio foi aproveitada para elaborar método de separação Ir-Rh, mediante a extração do sal de trifenil n-propil fosfônio do cloro-complexo de Ir(IV,) em clorofórmio. O coeficiente de extração de 99,2%, permite retirar o irídio do meio aquoso com grande eficiência. O irídio assim separado é determinado diretamente, por via espectrofotométrica, em 494 mµ, em faixa de concentração de 5,0 a 50,0 µg/ml. Pd(II), Pt(IV) e Os(IV) interferem e são eliminados previamente, assim como Au(III). Os ânions interferentes, I-, Br- e SCN- são também eliminados previamente. Muitos íons podem estar presentes, tais como Co(II),Cu(II), Mn(II), Fe(III), Ni(II), As(V), Sb(V), NO3-, ClO4- e SO4--. Após a separação do Ir (IV), o Rh(III) que permanece, na solução é complexado com íons azoteto e extraído em clorofórmio depois de precipitado com íons trifenil n-propil fosfônio, sendo o coeficiente de extração de 98,3%. A determinação ê também feita no próprio solvente, mediante medida espectrofotométrica em 404-408 mµ, para um intervalo de concentração de . 10,0 a 70,0 µg/ml. Uma separação envolvendo Os(IV), Pd(II)e Pt(IV) foi elaborada, eliminando-se Pd(II) e Pt(IV) por extração de ambos em metil n-butil cetona a partir de uma solução contendo SCN-. O Os(IV) é determinado na solução aquosa na forma de OsC16-- por medida espectrofotométrica em 370 mµ, válida para a faixa de concentração de 2,0 a 20,0 µg/m1. / Abstract not available.

Notre travail de thèse a été dédié à la synthèse et à la caractérisation bio-physicochimique de complexes osmium nitrosyle, qui pourraient relarguer l'oxyde nitrique (NO) au sein des cellules tumorales pour conjuguer les propriétés anticancéreuses souvent associés aux complexes du groupe du platine avec la toxicité de l'oxyde nitrique. Le premier chapitre de notre mémoire de thèse présente l'état de l'art dans le domaine des composés anticancéreux et le rôle de l'oxyde nitrique dans l'apoptose cellulaire. Le deuxième chapitre concerne la synthèse et la caractérisation de complexes d'azole (C)[Os(NO)Cl4(A)] (C = Bu4N+, Na+, HA+; A = indazole, pyrazole, benzimidazole, imidazole), où le plus cytotoxique est H2ind[cis-Os(NO)Cl4(indazole)]. Le troisième chapitre est consacré à l'étude cinétique et thermodynamique par RMN de l'isomérisation trans ↔ cis du complexe (Bu4N)[Os(NO)Cl4(indazole)] qui met en évidence un processus d'isomérisation de type dissociatif. Le quatrième chapitre concerne la synthèse et la caractérisation de complexes d'aminoacides (Bu4N)[Os(NO)Cl4(L)] (L = gly, picolinate, L-, D-pro) qui ont une très faible activité antiproliférative. Le dernier chapitre est consacré à la synthèse et à la caractérisation de clusters hétérométalliques [{Os(NO)Cl3(Ox)}4Ln] (Ln = Gd, Tb, Dy, Y ; Ox=oxalate) dans lesquels la coordinance 8 ou 9 du lanthanide dépend de son rayon ionique. Le précurseur {Os(NO)Cl3(Ox)} a l'activité antiproliférative la plus élevée de tous les complexes osmium nitrosyle connus