Dissertations / Theses on the topic 'Coppie redox'

Il calore a bassa temperatura (LTH), inferiore a 100°C, è una forma di energia largamente disponibile che viene dispersa nell’ambiente, senza alcun utilizzo. La conversione di questo tipo di energia in elettricità aprirebbe le porte allo sfruttamento di fonti energetiche come il calore solare, geotermico e di scarto industriale. La conversione di LTH in elettricità non è però un processo efficiente a causa dei limiti posti dalla termodinamica, con la cosiddetta legge di Carnot, oltre che ai limiti tecnologici che riducono ulteriormente la conversione di questa forma di energia. I dispositivi preposti per convertire LTH in elettricità devono poter operare con alte efficienze e potenze, e devono essere facilmente scalabili ed economici. Purtroppo, attualmente nessun dispositivo è in grado di effettuare questa conversione con potenze ed efficienze abbastanza elevate da giustificare gli alti costi (materiali, operazionali e manutenzione) e la complessità dei dispositivi stessi ed è per questo motivo che LTH non trova tutt’ora alcuna applicazione Questo progetto di ricerca si è focalizzato sullo sviluppo di un dispositivo in grado di convertire LTH in maniera efficiente e con alte potenze. Tale dispositivo, chiamato Thermally Regnerable Redox-Flow Battery, TRB, è una batteria a flusso ricaricabile termicamente. Il dispositivo conta due diverse processi: la produzione energetica, che avviene in una cella elettrochimica in grado di produrre elettricità alle spese dell’energia libera di mescolamento di due soluzioni acquose dello stesso sale ma a diversa concentrazione. Quando le due soluzioni raggiungono la stessa concentrazione, la soluzione esausta viene mandata al secondo processo: un distillatore sottovuoto che rigenera il gradiente di concentrazione tra le due soluzioni sfruttando risorse di LTH. L’efficienza totale del dispositivo è quindi data dal prodotto tra l’efficienza della cella elettrochimica e l’efficienza del distillatore. Studi termodinamici dimostrano che per incrementare tale efficienza è fondamentale lavorare sull’efficienza del distillatore, il cui valore dipende dalla scelta del soluto e del solvente. In particolare, per questo lavoro di ricerca si è scelto di operare con soluzioni acquose di NaI/I2 e LiBr/Br2. I risultati raggiunti e le principali attività di ricerca vengono riportate brevemente in questo abstract: Con la determinazione dei coefficienti di attività, si è calcolato l’energia libera di mescolamento e il potenziale a circuito aperto per entrambi i set di soluzioni (NaI e LiBr). Le celle elettrochimiche sono state sviluppate specificamente per entrambi I sistemi studiati e test elettrochimici hanno permesso di valutare le performance dei due dispositivi, come potenza ed efficienza elettrochimica. La distillazione è stata modellizzata in modo da definire le condizioni ottimali di lavoro e determinare l’efficienza del processo.
Low-Temperature Heat (LTH), below of 100°C, has elicited great interest among the scientific community, as a source of energy since it does not see any form of utilization as it is currently simply released into the environment. Its conversion would open the doors to the exploitation of a huge amount of energy as well, such as geothermal, solar, and industrial waste heat. The conversion efficiencies of LTH are low because of the limitations imposed by Carnot law, as well as the existence of technological limits which further reduce the efficiency of the conversion of LTH. In order to be suitable for extensive industrial production, LTH converters should show high power densities, scalable and efficient whilst being cost-effective; to this point, the devices proposed for this afore mentioned application all failed to achieve suitable efficiencies and power density, making the LTH conversion unfeasible. This PhD project was focused on the design of a device called Thermally Regenerable Redox-Flow Battery (TRB) consisting of a redox-flow battery that can be recharged by a thermal process. The device is based upon a two-stages technology composed by a “power production” stage and a “thermal” stage: power production happens in an electrochemical cell which release electricity at the expenses of the mixing free energy of two water solutions of the same salt at different concentrations, referred to as a concentration cell. When the two solutions reach the same concentration, the exhausted fluid is sent to the second stage, the thermal process, which regenerates the initial mixing free energy, by exploiting LTH sources, through vacuum distillation. The efficiency of the technology is the product between the efficiencies of the units in the device where both stages happen: the electrochemical cell, engineered for power production, and a distillation unit, designed to be responsible for thermal conversion. NaI/I2 and LiBr/Br2 water solutions will be the most discussed redox couple in this thesis, as result of thermodynamic analysis that have shown the importance related to the solvent and salt choice to ensure high energy conversion efficiencies. The achieved results, as well as the main research activities, are briefly reported here: starting from the determination of the activity coefficients, mixing free energy of the initial solutions, and the open circuit voltage of the electrochemical are calculated. Electrochemical cells are specifically designed for both systems while electrochemical tests are performed to evaluate the main performances of the devices, such as power density and electrochemical efficiency. Modeling of the operational conditions of the thermal stage allows to determine the distillation efficiency for both the solutions. The initial experiments prove an unprecedented heat-to-electricity efficiency for both the systems: 3% for TRB-NaI and 4-5% for TRB based on LiBr, depending on the thickness of the membrane with a power density output of almost 10 W m-2 for both technologies, which opens various possibilities to implement further improvements into this new class of energy storage/converter devices.

In order to take on the challenge of the world energy issues, there is a necessity to identify alternative energy sources to the fossil fuels. The sun represents the most abundant source of energy, and one way to harvest it is by photovoltaic devices directly converting sunlight into electricity. Among all photovoltaic devices, the dye-sensitized solar cells have attracted much interest because of the potential to be commercialized thanks to the cheap materials and the low-cost production processes. However, there are still issues to overcome, mainly related to the stability of the devices relating to the electrolyte components. In this project, a new type of electrolyte systems based on copper complex redox couples were synthetized and applied to DSSCs. Different monodentate ligands were investigated, in particular 2-mpy, 3-mpy and 4-mpy were coordinated by the copper metal centre. Several experimental techniques were used to characterized the products of synthesis, such as 1H NMR spectroscopy, mass spectrometry, powder X-ray diffraction and elemental analysis. The electrolyte properties were studied by UV-Vis spectrophotometry and cyclic voltammetry. The performance of the resulting solar cells was investigated by photocurrent density/photovoltage and incident photon-to-current conversion efficiency measurements and the recombination loss processes were studied by impedance spectroscopy and electron lifetime determinations. The redox couples based on 2-mpy and 3-mpy as ligands gave DSSC devices with very high open-circuit voltage up to 0.94 V and overall conversion efficiency up to 9.1% at 1 sun illumination. This is one of the highest conversion efficiencies recorded for copper based DSSC electrolytes and much higher than the solar cells containing the reference [Co(bpy)3]2+/3+ redox system. The high photo voltage, was attributed to the large resistance to  electron  recombination losses, which lead to a higher charge in the conduction band of the TiO2 moving it to more negative energies. This was also confirmed by the longer electron lifetime in the presence of the copper redox couples than the reference cobalt one. The TBP Lewis base additive was replaced by the methylpyridine ligands to mitigate ligand exchange problems. The replacement was successful using 3-mpy as additive as well as ligand to the copper ions. In continuation of this work, the other components of the device and the assembly process should be optimized. Moreover, single crystals of the copper systems should be grown to determine the exact structure and thus offer a better understanding of the processes that might take place in the device. An interesting project would be to try a one-pot electrolyte formulation, i.e. where all the reactants, solvent and additives are mixed and directly injected into the device. This is a good strategy to avoid the pre-syntheses and all the problems related to those.
För att kunna ta sig an utmaningen med världens energiförsörjning, så måste alternativa energikällor till fossila bränslen identifieras. Ljus från solen utgör den mest tillgängliga källan till energi, och ett sätt att direkt omvandla denna energi till elektricitet är genom solceller. Bland olika typer av solceller, så har färgämnessensiterade solceller (DSSC) fått mycket uppmärksamhet pga deras kommersialiseringspotential med utgångspunkt i låg tillverkningskostnad. Det finns dock utmaningar som måste hanteras, huvudsakligen rörande stabilitet ssk avseende cellernas elektrolyt. Det här projektet omfattar studier av elektrolyter baserade på kopparkomplex som redoxsystem för DSSC. Särskilt kopparkomplex baserade på monodentata ligander, såsom 2- mpy, 3-mpy och 4-mpy, har studerats. Karaktärisering har baserats på flera olika tekniker, såsom 1H-NMR-spektroskopi, masspektrometri, pulverdiffraktion och elementaranalys. Elektroyuternas egenskaper har studerats genom UV-Vis-spektrofotometri och cyklisk voltametri. De resulterande solcellernas prestanda har undersökts genom fotoström/forospänningsstudier   och   IPCE-spektroskopi, samt rekombinationsförluster har kartlagts genom impedansspektroskopi och bestämning av fotoelektronernas livslängd. Redoxsystem baserade på 2-mpy och 3-mpy som ligander gav solceller som uppvisade mycket höga fotospänningar upp till 0,94 V och omvandlingseffektiviteter upp till 9,1% vis 1 sols bestrålning. Dessa prestanda är bland de högst uppmätta för DSSC baserade på kopparinnehållande elektrolyter och betydligt bättre än för referenssystem baserade på elektrolyter med [Co(bpy)3]2+/3+  som redoxpar. De höga fotospänningar som uppmätts tillskrivs en hög resistens mot rekombinationsförluster, vilket leder till högre laddning i ledningsbandet för TiO2 som i sin tur ger mer negativa energinivåer. Detta stöds även av de längre elektronlivslängder som uppmätts för system med kopparbaserade redoxsystem. Lewis-basen TBP, en vanlig additive till DSSC-elektrolyter, ersattes I dessa system med metylpyridinliganderna för att motverka problem med ligandutbyte. Detta utbyte var mest framgångsrikt för 3-mpy som additiv och samtidig ligand till kopparjonerna. Framtida studier bör omfatta en optimering av komponenter och konstruktion av DSSC baserade på kopparsystemen. Enkristaller av kopparsystemen bör syntetiseras för detaljerad strukturbestämning och därmed en bättre insikt i processer som sker i elektrolytsystemen. En intressant utveckling av projektet omfatta s k 'one-pot'-formulering av elektrolyter, där alla reaktander, lösningsmedel och additiver blandas och direkt injiceras i solcellen. Detta utgör en god startegi för att undvika för-synteser och alla problem relaterade till dessa.

The Prion protein (PrP) is a cell surface glycoprotein that has been directly implicated in the pathogenesis of a range of neurological disorders referred to as the transmissible spongiform encephalopathies (TSE’s). The protein has been shown to bind copper within its unstructured N-terminus but the affinity and stoichiometry of the association is a matter of some debate. In addition, the functional significance of this copper binding has yet to be elucidated. This study aimed to determine accurate metal binding parameters for PrP through the use of calorimetry and to provide insight into the potential redox implications of metal once bound. A method of analysis for complex binding to proteins is thoroughly assessed and found to be suitable. The study also aimed to qualify the involvement of metals in the proteins remarkable ability to survive in the environment. This study confirms that PrP binds copper with an affinity relative to the amount of copper available to the protein. A high nanomolar affinity is reported within two regions on the protein, the octarepeat and the 5th site. Binding within the octarepeat region is found to be highest at low copper concentrations, reducing to micromolar affinity when copper levels exceed equivalents of 1. There is also strong evidence of a complex and cooperative binding mechanism. The 5th site also displays high nanomolar affinity for a single atom of copper. These two regions on the protein also interact in the coordination of copper (II). The copper bound protein is highly redox active and is capable of fully reversible cycling of electrons that are dependent mainly on the octarepeat. The protein does bind other divalent cations but none appear to be physiologically relevant considering the amount of these free metal ions in the body. When adsorbed to model clays, PrP is able to survive for long periods at room temperature. This longevity is increased significantly by the presence of metals in the soil, especially manganese. These data provide confirmation of the precise parameters of divalent cation binding to PrP. It also confirms that the copper bound protein is capable of a physiological redox role.

The main objectives of this project are the synthesis and redox- or photo-active modification and CO2 adsorption studies of metal-organic frameworks (MOFs) based on Cu3-pyrazolate secondary building units (SBUs). Trinuclear copper(II) complexes of the formula [Cu3(µ3-O)(µ-4-R-pz)3X3]z have been studied extensively due to their redox, magnetic and catalytic properties. In earlier work, we have shown that trinuclear copper(II) complexes of the formula [Cu3(µ3-O)(µ-4-R-pz)3X3]z pz = pyrazolato anion; R = H, CH(O), Cl, Br and NO2; X = Cl, NCS, CH3COO, CF3COO and pyridine – can be oxidized to the corresponding z+1, formally CuII2CuIII, species. In this project, fourteen (14) new copper-pyrazolate complexes of varying nuclearities (Cu3, Cu6, Cu7 and Cu12), terminal ligands (-NO2, py, -N3, -Cl) and bridging ligands (4-Cl-pzH and 4-Ph-pzH) have been synthesized. Efforts have been made to prepare MOFs based on the Cu3(µ3-O)-SBUs. While attempting to design the most suitable SBU for redox-active MOF construction, it was found that the one-electron oxidation of the all-CuII complex [Cu3(µ3-O)(µ-pz)3(NO2)3]2–, [8]2-, was achieved at redox potential more cathodic than any other Cu3(µ3-O)-complexes studied in our laboratory. The mixed-valent compound, [Cu3(µ3-O)(µ-pz)3(NO2)3]–, [8]-, the easiest accessible CuII2CuIII species known to date, was characterized spectroscopically. Compound [8] and analogous [11] release NO almost quantitatively upon the addition of PhSH or acetic acid. The system is catalytic in the presence of excess nitrite. Before embarking on the study of photo-active MOFs, a simpler model compound – a dimer of trimer [{Cu3(µ3-OH)(µ-4-Cl-pz)3(py)2}2(µ-abp)](ClO4)4 [21], where abp = 4,4’-azopyridine, was synthesized and its photochemistry was studied. The absorption spectra recorded before and after irradiation indicated a structural change. Two dimensional (2D) and three dimensional (3D) materials with {[Cu3(µ3-OH)(µ-4-R-pz)3]2+}n SBUs where R = Ph or Cl , which can potentially undergo cis/trans-isomerization, have been prepared during this project. A Phenyl substituent at 4-position on the pyrazole ligand leads to the formation of new class of 2D sheets. Three new 3D porous MOFs based on {[Cu3(µ3-OH)(µ-4-Cl-pz)3]2+}n SBUs have interpenetrated- lattice structures and are capable of adsorbing CO2 selectively. Compounds FIU-1 and FIU-3 also exhibit hysteretic sorption-desorption profiles indicating the flexibility of the MOFs upon adsorption. Compound FIU-1 demonstrates the usefulness of a hexanuclear CuII -pyrazolate moiety as an SBU for generating 3-fold interpenetrated 3D polymeric network. Complexes FIU-2 and FIU-3 have novel 3-fold interpenetrating 3D hexagonal framework structures. Compound FIU-2 crystallizes in the monoclinic crystal system with the P21/c space group, whereas FIU-3 crystallizes in triclinic space group P . Both structures contain Cu3-SBUs connected by the linkers through the Cu-termini.

Multiple myeloma (MM) is a prevalent B-cell neoplasm that remains incurable with currently available chemotherapeutic drugs. Existing drug regimens result in initial disease remission but MM often relapses with an aggressive, drug resistant phenotype with uniform mortality. Bortezomib (BTZ, proteasome inhibitor) is a frontline anti-MM drug that is used for treatment of newly diagnosed and relapsed MM. However both intrinsic and acquired BTZ resistance is observed. Hence, gaining a mechanistic understanding of BTZ-resistance can provide novel targets to increase and restore BTZ cytotoxicity in MM. Studies show that BTZ-mediated proteasome inhibition generates oxidative stress therefore, BTZ resistance can be caused by an increase in cellular antioxidant capacity of MM cells. Antioxidants like superoxide dismutases (SODs), glutathione (GSH), and glutathione peroxidases (GPxs) can maintain cellular redox homeostasis and confer resistance to oxidative stress. Additionally, an increased glucose metabolism can assist in maintaining low reactive oxygen species (ROS) levels formed as by-products of endogenous or therapy induced oxidative stress. This led us to test the hypothesis that BTZ resistance in MM is linked to redox regulation via the antioxidant network and generation of reducing equivalents. Retrospective analysis of clinically annotated MM dataset shows a correlation between SOD1 gene expression, MM progression, and poor overall and event free survival. In a MM cell line model with intrinsic or acquired BTZ resistance, our results show a correlation between half maximal inhibitory concentration (IC50) of BTZ and CuZnSOD activity. Upon inhibition of CuZnSOD activity with a clinically approved drug, disulfiram (DSF, Antabuse), BTZ cytotoxicity was increased. Furthermore, enforced overexpression of CuZnSOD conferred BTZ resistance in an otherwise BTZ sensitive MM cell line. MM cell lines with differential intrinsic BTZ cytotoxicity displayed a correlation between BTZ IC50 and GSH levels as well as GPx-1 activity. Gene expression profiling data from patients showed that poor prognosis associates with increased glycolytic gene expression in MM. Also, MM cell lines with intrinsic resistance toward BTZ exhibited increased glucose uptake, increased mRNA expression and activity of glucose-6-phosphate dehydrogenase (G6PD) with increased cytotoxicity with glucose deprivation or 2-deoxyglucose (2-DG) treatment. In conclusion, our results provide a rationale for utilizing redox-based combination protocols of clinically approved drugs (i.e. DSF and 2-DG) with BTZ to improve MM therapy responses.

Potable water can become contaminated with lead and copper due to the corrosion of pipes, faucets, and fixtures. The US Environmental Protection Agency Lead and Copper Rule (LCR) is intended to target sampling at high-risk sites to help protect public health by minimizing lead and copper levels in drinking water. The LCR is currently under revision with a goal of better crafting sampling protocols to protect public health. This study examined an array of factors that determine the location and timing of "high-risk" in the context of sampling site selection and consumer health risks. This was done using field studies and well-controlled laboratory experiments. A pilot-scale simulated distribution system (SDS) was used to examine the complex relationship between disinfectant type (free chlorine and chloramine), water age (0-10.2 days), and pipe main material (PVC, cement, and iron). Redox gradients developed in the distribution system as controlled by water age and pipe material, which affected the microbiology and chemistry of the water delivered to consumer homes. Free chlorine disinfectant was the most stable in the presence of PVC while chloramine was most stable in the presence of cement. At shorter water ages where disinfectant residuals were present, chlorine tended to cause as much as 4 times more iron corrosion when compared to chloramine. However, the worst localized attack on iron materials occurred at high water age in the system with chloramine. It was hypothesized that this was due to denitrification-a phenomenon relatively unexplored in drinking water distribution systems and documented in this study. Cumulative chemical and biological changes, such as those documented in the study described above, can create "high-risk" hotspots for elevated lead and copper, with associated concerns for consumer exposure and regulatory monitoring. In both laboratory and field studies, trends in lead and copper release were site-specific and ultimately determined by the plumbing material, microbiology and chemistry. In many cases, elevated levels of lead and copper did not co-occur suggesting that, in a revised LCR, these contaminants will have to be sampled separately in order to identify worst case conditions. Temperature was also examined as a potentially important factor in lead and copper corrosion. Several studies have attributed higher incidence of childhood lead poisoning during the summer to increased soil and dust exposure; however, drinking water may also be a significant contributing factor. In large-scale pipe rigs, total and dissolved lead release was 3-5 times higher during the summer compared to the winter. However, in bench scale studies, higher temperature could increase, decrease, or have no effect on lead release dependent on material and water chemistry. Similarly, in a distribution system served by a centralized treatment plant, lead release from pure lead service lines increased with temperature in some homes but had no correlation in other homes. It is possible that changes throughout the distribution system such as disinfectant residual, iron, or other factors can create scales on pipes at individual homes, which determines the temperature dependency of lead release. Consumer exposure to lead can also be adversely influenced by the presence of particulate iron. In the case of Providence, RI, a well-intentioned decrease in the finished water pH from 10.3 to 9.7, resulted in an epidemic of red water complaints due to the corrosion of iron mains and a concomitant increase in water lead levels. Complementary bench scale and field studies demonstrated that higher iron in water is sometimes linked to higher lead in water, due to sorption of lead onto the iron particulates. Finally, one of the most significant emerging challenges associated with evaluating corrosion control and consumer exposure, is the variability in lead and copper during sampling due to semi-random detachment of lead particles to water, which can pose an acute health concern. Well-controlled test rigs were used to characterize the variability in lead and copper release and compared to consumer sampling during the LCR. The variability due to semi-random particulate detachment, is equal to the typical variability observed in LCR sampling, suggesting that this inherent variability is much more important than other common sources including customer error, customer failure to follow sampling instructions or long stagnation times. While instructing consumers to collect samples are low flow rates reduces variability, it will fail to detect elevated lead from many hazardous taps. Moreover, collecting a single sample to characterize health risks from a given tap, are not adequately protective to consumers in homes with lead plumbing, in an era when corrosion control has reduced the presence of soluble lead in water. Future EPA monitoring and public education should be changed to address this concern.
Ph. D.

Bibliography: leaves 63-68.
This thesis is part of the greater study and looks into understanding the ferric leaching sub-process by establishing an effective way of measuring the rate of the chemical leach process.

It is important to optimize glass compositions for their specific purpose but also for the efficiency of the production process, the manufacturing of glass. This will be beneficial economically and environmentally. Today many processes and glass compositions are already optimized, but due to more strict legislation on toxic elements and substances there must be changes in many glass compositions. One of these elements is antimony; the oxide is used as fining agent to obtain a bubble free glass within a reasonable process time. One aim with this thesis is to obtain a deeper understanding of the fining mechanism in 20R2O-10MO-70SiO2 (R=Na and/or K, M = Ca and/or Ba, Mg, Sr) glasses in order to minimise the amount of Sb2O3. Another intention is to study the structure of 20R2O-10CaO-70SiO2 (R = Na, K) with Cu2+ as probe ion and thus get a deeper knowledge of the surrounding glass matrix.  The optical basicity scale is used to determine the acid/base character of the different glass compositions.   Fining efficiency results showed a remarkable increase of the number of remaining bubbles when the glass contains either approximately equal amounts of Na and K or Ca and Ba, Mg or Sr. The much higher number of bubbles in the potassium containing glasses compared to the sodium containing is explained by the increase in viscosity, the increase in optical basicity and thus lower oxygen activity. The differences in the fining efficiency when altering alkaline earth ions cannot be explained by the optical basicity values, it seems to be a more complicated situation.   This thesis also reports maximum in Vickers hardness and packing density as well as minimum in glass transition temperature for the mixed alkali glasses. The mixed alkaline earth glasses do not exhibit any clear nonlinear behaviour. Raman spectroscopy measurements showed a variation in the network connectivity which has a clear relation to the optical basicity of the different glass compositions. The combination of UV-Vis-NIR and X-ray absorption spectroscopy measurements showed that the coordination sphere for Cu(II) is a tetragonal distorted octahedron with two elongated Cu-O bonds along the z axis. There were no trends in the degree of tetragonal distortion, thus it was about the same for all the investigated glass compositions. Cu(I) is found to be coordinated by two oxygen ligands in mainly linear coordination sphere, evidenced from X-ray absorption spectroscopy.

In the copper smelting processes, the viscosity of the matte and the slag is an important factor for establishing efficiency. Impurities in the concentrates affect the viscosity not only by changing the melt structure but also by promoting precipitation of solid phase which sharply rises it. In this master thesis, a comprehensive methodology was established to study the MgO effects on the properties of a copper smelting slag. Thus, glassy samples were obtained and after confirmation of the composition and the glassy structure with EDS, SEM, and XRD analysis, they were examined through Ramanspectroscopy to study their glassy structure. Moreover, Mössbauer spectroscopy was used to determine the amount of Fe3+ in the samples. Models from the literature were compared to the experimental data. Coherence with the literature was found with the effect of MgO as a network modifier of the oxide melt structure and a promoter of high coordinated structures. Estimations through models were performed to study the iron redox equilibria of the melt and were compared with experimental data, but it was not possible to find the limit of Fe3+ at which precipitation of solid phase initiates.
I kopparsmältningsprocesserna är mattans och slaggens viskositet en viktig faktor för att uppnå effektivitet. Föroreningar i koncentraten påverkar viskositeten inte bara genom att ändra smältstrukturen utan också genom att främja utfällning av fast fas som kraftigt höjer den. I denna magisteruppsats fastställdes en omfattande metod för att studera MgO-effekterna på egenskaperna hos en kopparsmältningsslagg. Således erhölls glasiga prover och efter bekräftelse av kompositionen och den glasiga strukturen med EDS-, SEM- och XRD-analys undersöktes de genom Ramanspektroskopi för att studera deras glasstruktur. Dessutom användes Mössbauerspektroskopi för att bestämma mängden Fe3+ i proverna. Modeller från litteraturen jämfördes med experimentella data. Överensstämmelse med litteraturen hittades med effekten av MgO som ett nätverksmodifierare av oxidsmältstrukturen och en promotor för högkoordinerade strukturer. Uppskattningar genom modeller utfördes för att studera smältans järnredoxjämvikter och dessa jämfördes med experimentella data, men det var inte möjligt att hitta gränsen för Fe3+ vid vilken utfällning av fast fas initierades.

Les radicaux organiques tiennent une place de choix dans de nombreux domaines et il est établi que ceux-ci peuvent exister coordinés à des centres métalliques dans les métalloenzymes. La Galactose Oxydase par exemple contient une entité cuivre(II)-radical phénoxyle indispensable à sa réactivité pour l'oxydation aérobie d'alcools en aldéhydes. Ces travaux de thèse ont consisté en l'élaboration de complexes de métaux de transitions (cuivre, nickel, cobalt) à partir de ligands noninnocents. Les caractérisations des espèces sous divers degrés d'oxydation ont été réalisées par différentes techniques complémentaires d'analyse (l'électrochimie, la RPE, l'UV-visible-proche-IR, la resonance raman ainsi que la diffraction des rayons X) combinées à des études de chimie théorique. Nous avons synthétisé des complexes Ni(II)-salen symétriques et dissymétriques et montré que l'espèce oxydée radicalaire pouvait acquérir un caractère localisé (composé de classe II) ou délocalisé (composé de classe III selon Robin-Day) en fonction des substituants phénoliques. Dans des complexes Cu(II)-salophen nous avons mis en évidence une activité redox centrée sur le pont, conduisant à des espèces Cu(II)-radicaux π diaminobenzène. Dans le cas des complexes de cobalt, les orbitales redox actives du métal et du ligand sont si proches en énergie que l'espèce oxydée est un hybride de résonance entre les formes Co(III)-phénolate et Co(II)-phénoxyle. Nous avons évalué l'influence du remplacement des oxygènes du salen par des azotes sur la structure électronique des espèces oxydées. Enfin, des complexes ont été mis au point à partir d'un ligand bis(phénol)-dipyrrine et les espèces oxydées radicalaires ont été caractérisées structuralement. Elles ont un caractère mixte porphyrinyle-phénoxyle jamais mis en évidence au préalable
Organic radicals play key roles in various fields and it is established that they could coordinate metal centers in metalloenzymes. For example, Galactose Oxydase exhibits a copper-phenoxyl entity, essential for its reactivity (aerobic oxidation of alcohols to aldehydes). This thesis is focused on the design of transition metal complexes (copper, nickel, cobalt) from non innocent ligands. The characterization of species at various oxidation states has been performed by complementary analytical techniques (electrochemistry, EPR, UV-vis-NIR, raman resonance, X-ray crystallography) and theoretical chemistry. Several Ni-salen complexes were synthetized (symmetrical or not) and the resulting oxidized species could be either localized (class II compound) or delocalized (class III compound) radicals depending on the phenolic substituents. In Cu(II)-salophen complexes we successfully shed light on a bridge-centered redox activity, leading to Cu(II)-diaminobenzene π radical species. In the case of cobalt, both metal and ligand redox active orbitals are isoenergetic and the oxidized species is a resonance hybrid between the Co(III)-phenolate and the Co(II)-phenoxyl forms. We evaluated the influence of the replacement of the salen oxygen atoms by nitrogen ones on the electronic structure of the resulting oxidized species. Finally, original complexes were synthesized from a bis(phénol)-dipyrrine ligand and the radical oxidized species were structurally characterized. They exhibit a unprecedented mixed porphyrinyl-phenoxyl character

The water-to-oxygen redox couple, H2O/O2, powers our aerobic life through the fundamental processes of natural photosynthesis and cellular respiration. Despite its vital role, any failure of this four-electron mechanism turns out to release O2-derived toxic radicals, inducing a severe oxidative damages of any synthetic and biological materials exposed to the aerobic risk. The aerobic formation of ROS is due to oxygen reduction in-vivo, generating the superoxide anion (O2•–), hydrogen peroxide (H2O2), and the hydroxyl radical (HO•). ROS give rise to fast, barrier-less, short-range and non-selective oxidation steps, being responsible for the “oxidative stress”, a key factor for cellular death, organ failure and aging diseases. In addition photo-oxidative stress is one key factor limiting plant productivity, i.e. bio-mass and food yield. Noteworthy, ROS-forming mechanisms are also lethal for the stability of bio-inspired materials designed for artificial photosynthesis in vitro. The biological defense against ROS-induced cellular damage stems from the combined action of “anti-oxidant” metallo-enzymes, as superoxide dismutase (SOD), and catalase (CAT). A detoxification cascade occurs via SOD-induced dismutation of O2•– into O2 and H2O2 which is then converted by CAT into H2O and O2 again. In this thesis will be presented the design of a set of novel anti-oxidant catalysts, based on different metal centers, that can emerge by the engineering of a synzyme with integrated SOD/CAT activity able to mimic both the enzymes activities and efficiently perform a complete ROS scavenging also in biological-like solution. The activity of the synzymes will be also tested in water splitting processes to perform both the water oxidation than the proton reduction reactions in water at neutral pH, a key feature to obtain sustainable energy sources from water. The obtained results will be divided in four main chapters: - Chapter 2: coupling of a polycationic Mn(III)-porphyrin, with a dinuclear Mn2(II,II)L2 core results in a dual Superoxide Dismutase (SOD) and Catalase (CAT) functional analog, Mn2L2Pn+, enabling a detoxification cascade of the superoxide anion and hydrogen peroxide into benign H2O and O2. The SOD/CAT artificial manifolds, joined in one asset, exhibit a peak catalytic performance under physiological conditions, with log kcat(O2•–) ≥ 7 and kcat(H2O2)/KM = 1890. The dual-enzyme (di-zyme) concept allows for a unique, built-in-self-protection, against the irreversible bleaching of the porphyrin unit, (> 75% protection), readily induced by H2O2 (200 μM, 20 equivalents, in buffer solution, pH=7.8). We show herein that incubation of the photosynthetic green algae, Chlamydomonas reinhardtii, with the synthetic di-zyme (as low as 0.1 μM), prevents H2O2 accumulation under high-light illumination conditions, thus providing an efficient anti-oxidant surveillance and photo-protection. - Chapter 3: dinuclear Cu(II)2L2 catalysts were synthesized and studied for their SOD/CAT activity. The goal of this study was to demonstrate that with a proper ligand set, is it possible tune the reactivity of an harmful metal like copper, turns it to a benign anti-oxidant system. The dinuclear copper complexes show SOD activity with logkcat up to 7.55 and CAT activity with rate of O2 production up to 4.4 μM/s. Kinetic studies of the process of hydrogen peroxide dismutation show also an evolution of the catalyst during the catalytic turnover. No evidence of oxidation of external substrates was also confirmed as consequence of the sacrificial internal scavenger. - Chapter 4: novel Fe(III)L, Fe(III)2L2 and Co2(II)L2 complexes have also been isolated. Preliminary results indicate that a multi-redox manifold is available for both species, however with scarce activity as ROS scavenger. These complexes show instead an interesting activity in the water oxidation process. In addition the anodic waves observed in reduction are promising for catalytic proton reduction processes performed by using directly water as proton source. - Chapter 5: application of oxygen evolving catalysts within functional materials has been explored in the field of porous membranes. This novel stimuli-responsive strategy against the irreversible fouling of porous materials and surfaces is based on the molecular design of catalytic pore walls that foster a chemo-mechanical, self-cleaning behaviour under neutral pH and mild conditions of pressure and temperature. To this aim, the catalase-like behaviour of the tetra-ruthenium substituted polyoxometalate, has been exploited for in-pore oxygen evolution so to induce an active fluid mixing and the displacement of foulant particles. The present study includes the fabrication of hybrid polymeric films with porous architecture embedding the tetra-ruthenium catalyst as artificial catalase to guarantee the material self-defence against pore occlusion and oxidative damage with aqueous H2O2 as mild chemical effector.
La coppia redox acqua-ossigeno, H2O/O2, alimenta la nostra vita aerobica attraverso i processi fondamentali della fotosintesi naturale e della respirazione cellulare. Nonostante il suo ruolo fondamentale, qualsiasi errore in questo meccanismo a quattro elettroni rilascia radicali O2-derivati tossici, inducendo gravi danni ossidativi ai materiali sintetici e biologici esposti. La formazione aerobica di ROS è dovuta alla riduzione dell'ossigeno in vivo, generando l'anione superossido (O2•-), perossido di idrogeno (H2O2) ed il radicale idrossile (HO•). I ROS danno origine ad una veloce ossidazione, senza barriere, a corto raggio e non selettiva, responsabile dello "stress ossidativo", un fattore chiave per la morte cellulare, insufficienza di organi e le malattie dell'invecchiamento. Inoltre lo stress foto-ossidativo è un fattore chiave che limita la produttività di piante, bio-masse e rese alimentari. Meccanismi ROS indotti sono anche letali per la stabilità dei materiali bio-ispirati progettati per fotosintesi artificiale in vitro. La difesa biologica contro i danni cellulari ROS indotti deriva dall'azione combinata di metallo-enzimi "anti-ossidanti", come la superossido dismutasi (SOD) e la catalasi (CAT). Il processo di disintossicazione avviene tramite la dismutazione SOD indotta di O2•- in O2 e H2O2 che viene poi convertita nuovamente da CAT in H2O e O2. In questa tesi verrà presentata la progettazione di una serie di nuovi catalizzatori antiossidanti, basati su differenti centri metallici, che possono derivare dalla progettazione di sinzimi con integrata attività SOD/CAT in grado di imitare entrambi gli enzimi ed eseguire efficientemente una completa rimozione di ROS in condizioni simili a quelle biologiche. L'attività dei sinzimi sarà testata inoltre nei processi di scissione dell'acqua per effettuare sia il processo di ossidazione dell'acqua che la riduzione di protoni in acqua a pH neutro, una caratteristica fondamentale per l’ottenimento fonti energetiche sostenibili dalla acqua. I risultati ottenuti saranno divisi in quattro capitoli principali: -Capitolo 2: l’unione di una porfirina policationica di Mn(III), con un sistema dinucleare Mn2(II,II)L2 risulta in un duplice analogo funzionale di superossido dismutasi (SOD) e catalasi (CAT), Mn2L2Pn+, consentendo una disintossicazione a cascata dell'anione superossido e del perossido di idrogeno in H2O e O2. I complessi SOD/CAT artificiali, uniti in un’unica struttura, mostrano un picco delle performance catalitiche in condizioni fisiologiche, con logkcat(O2•-) ≥ 7 e kcat(H2O2)/KM = 1890. Il concetto di doppio-enzima (di-zima) consente una autoprotezione unica, contro la degradazione irreversibile dell'unità porfirinica, (> protezione 75%), indotta rapidamente da H2O2 (200 μM, 20 equivalenti, in soluzione tampone, pH=7.8). Qui viene dimostrato che l'incubazione delle alghe verdi fotosintetiche, Chlamydomonas reinhardtii, con il di-zima sintetico (a concentrazioni fino a 0,1 μM), previene l'accumulo di H2O2 in condizioni di elevata illuminazione, fornendo così un efficiente azione anti-ossidante e foto-protettiva. -Capitolo 3: sono stati sintetizzati e studiati dei catalizzatori binucleari Cu(II)2L2 per la loro attività SOD/CAT. L'obiettivo di questo studio è stato quello di dimostrare che con una serie di leganti adeguati, è possibile regolare la reattività di un metallo dannoso come il rame, trasformandolo in un sistema anti-ossidante. I complessi binucleari di rame mostrano un’attività SOD con logkcat fino a 7,55 e un'attività CAT con velocità di produzione di O2 fino a 4,4 μM/s. Studi cinetici del processo di dismutazione dell’acqua ossigenata mostrano una evoluzione del catalizzatore durante il turnover catalitico. Nessuna evidenza dell’ossidazione di substrati esterni è stata osservata grazie alla presenza di una funzionalità interna sacrificale. - Capitolo 4: sono stati isolati dei nuovi complessi Fe(III)L, Fe(III)2L2 e Co2(II)L2. I risultati preliminari indicano che le specie sono in grado di sostenere processi multi-elettronici, ma con scarsa attività nell’eliminazione di ROS. Questi complessi mostrano invece un'attività interessante nel processo di ossidazione dell'acqua. Inoltre le onde anodiche osservate in riduzione sono promettenti nel processo di riduzione catalitica dei protoni eseguito utilizzando direttamente acqua come fonte di protoni. - Capitolo 5: è stata esplorata l’applicazione nel campo dei materiali funzionali di catalizzatori che sviluppano ossigeno all'interno di membrane porose. Questa nuova strategia stimolo-risposta contro l'incrostazione irreversibile di materiali porosi e superfici si basa sulla progettazione molecolare di pori con pareti catalitiche che esibiscono proprietà autopulenti chemo-meccaniche a pH neutro e in condizioni blande di temperatura e pressione. A questo scopo, l’attività di catalasi di un poliossometallato tetra-rutenio sostituito, è stata sfruttata per lo sviluppo di ossigeno dai pori in modo da indurre una miscelazione attiva del fluido e la rimozione delle particelle sporcanti. Il presente studio prevede la realizzazione di film polimerici ibridi con un’architettura porosa contenenti il catalizzatore di tetra-rutenio come catalasi artificiale per garantire al materiale un meccanismo di auto-difesa contro l’occlusione dei pori e i danni ossidativi, impiegando una soluzione acquosa di H2O2 come stimolo chimico.

Le cuivre est un métal essentiel, présent dans de nombreuses protéines de notre corps et joue un rôle crucial dans les processus biochimiques. Plus précisément, deux aspects ont fait du Cu un métal d’intérêt pour le traitement du cancer : le fait qu’il s’agisse d’un métal endogène, et qui devrait par conséquent avoir moins d’effets secondaires; et le couple redox Cu(II)/Cu(I) – rapporté comme pouvant générer des espèces réactives de l'oxygène (EROs). La première partie de la thèse est basée sur la synthèse, la caractérisation et l’étude de l’activité biologique d’un complexe dinucléaire de Cu(II) contenant un ligand de type salphène N,O-donneur (L1), conçu pour promouvoir une conversion rapide Cu(II)/Cu(I). Les tests cellulaires montrent une forte production d’EROs dans les lignées de cellules HeLa et plus de toxicité au sein des cellules cancéreuses que dans les saines. À partir de ce point de départ, L1 a été fonctionnalisé avec des groupes halogénés afin de moduler le potentiel rédox du couple Cu(II)/Cu(I). Cependant, tous les complexes correspondants présentent certains problèmes de solubilité. En ce sens, la deuxième partie de la thèse porte sur la dérivatisation du ligand L1 avec des groupes sulfonate, arginine et peptides avec capacité de pénetration intra cellulaire, afin d’améliorer sa biodisponibilité et penetrabilité en maintenant le même environnement de coordination autour du cuivre. La dernière partie de ce travail ouvre la porte à l’utilisation d’une plateforme dendritique multimodale pour être utilisé comme futur système d’administration de médicaments, en preuve de concept de ce système pour son utilisation dans de futures thérapies dirigées
Copper is an essential biometal, present in several proteins of our body and plays a crucial role in many biochemical processes. Two features make Cu attractive to be used in chemotherapy: its nature as an endogenous metal –which may imply fewer side effects than other exogenous metals- and its Cu(II)/Cu(I) redox pair –which can promote reactive oxygen species (ROS) generation. On the first part of this thesis work, we report the synthesis, characterization and biological evaluation of a dimeric Cu(II) complex bearing a N,O-donor salphen-like ligand (L1) specifically designed to promote a fast Cu(II)/Cu(I) redox interconversion. In vitro assays outline the high potentiality of the complex to undergo ROS generation inside HeLa cells, and that it shows higher cytotoxicity in cancer than in normal cell lines. From this promising starting point, L1 was functionalized with halogen groups to modulate the redox potential of the Cu(II)/Cu(I) redox pair. However, one of the main drawbacks faced with these complexes was their poor solubility. Therefore, the second part of the thesis was devoted to the functionalization of L1 with several groups/entities (sulfonate, arginine and/or Cell-Penetrating Peptides), in order to increase the solubility, bioavailability and the delivery of the complex inside the cell while maintaining the same Cu(II) coordination environment. Finally, the last part of our work opens the gate to the use of a multimodal dendritic platform as a promising drug carrier, in a proof-of-concept of the versatility of this system for future tailor-made anticancer targeted therapies

La molécule X6TMPA, constituée d’une unité TMPA (tris(2-pyridylméthyl)amine) greffée de façon covalente à trois des six unités aromatiques du calix[6]arène, permet de coordiner et stabiliser un ion cuivre (Cu+ et Cu2+) dans un environnement mononucléaire. Ces composés possèdent des propriétés uniques en chimie hôte-invité ainsi qu’en réactivité redox. De tels systèmes présentent cependant des limitations car : – le macrocycle et les complexes métalliques associés ne sont solubles qu’en milieu organique ; – le complexe cuivreux obtenu avec un tel macrocycle n’est réactif vis-à-vis de l’oxygène qu’à l’état solide. Le présent travail de thèse décrit les modifications introduites dans la structure du composé X6TMPA pour faire face à ces restrictions, détaillant ainsi les études conduites afin d’évaluer l’impact des modifications sur les propriétés des molécules résultantes. Le chapitre 2 présente la stratégie synthétique de « trifonctionnalisation » du grand col du macrocycle. Elle a été employée pour l’introduction de groupements hydrophiles, qui rendent le calix[6]arène et les complexes métalliques associés solubles en milieu aqueux. Des études de reconnaissance moléculaire en solution aqueuse ont été ainsi menées. Une propriété très remarquable en chimie hôte-invité est la forte affinité du complexe cuivrique pour l’anion fluorure en milieu aqueux. Le chapitre 3 présente la stratégie synthétique de « hexafonctionnalisation » du grand col du macrocycle. Elle a permis d’obtenir des composés qui ont été utilisés pour des applications telles que l’immobilisation sur surface et la réaction de monoclick. Le chapitre 4 présente la stratégie synthétique de « trifonctionnalisation » du petit col du macrocycle. Elle a permis d’obtenir des systèmes réactifs en solution, notamment un composé contenant trois unités phénol qui donne un radical stable à température ambiante ainsi qu’un composé contenant trois unités quinone dans lequel la cavité est devenue une unité redox-active. Ainsi, des études concernant les macrocycles et leurs complexes monométalliques à base de Zn2+, Cu+ et Cu2+ sont exposées et discutées
The X6TMPA molecule is composed by a tris(2-pyridylmethyl)amine (TMPA) cap covalently linked to the small rim of the calix[6]arene. This compound can coordinate and stabilize a Cu(I)/Cu(II) ion in a mononuclear environment. These compounds possess unique properties in host-guest and redox chemistry.This PhD thesis work describes some synthetic strategies employed in order to modify the scaffold of the macrocycle, either at the large or the small rim. Moreover, the studies conducted in order to evaluate the impact of each structural modification on the reactivity of the resulting system are detailed. Chapter 2 describes the “large rim tri-functionalization” strategy. It has been employed to introduce three hydrophilic moieties on the calix[6]arene unit. These groups enable the water-solubilization of the molecule, as well as the Cu(I)/Cu(II) monometallic complexes. For these systems, host-guest chemistry in aqueous media has been explored: a remarkable property is the high affinity of the cupric complex for fluoride anion. Chapter 3 describes the “large rim hexa-functionalization” strategy. The obtained compounds have been employed for novel applications, as surface functionalization or “monoclick” reaction. Chapter 4 describes the “small rim tri-functionalization” strategy. The obtained compounds are reactive in solution. A phenol-containing macrocycle, that gives a stable radical species at room temperature, and a quinone-containing macrocycle, in which the calix[6]arene moiety is a redox-active unit, are presented. Moreover, the reactivity of the monometallic complexes (Zinc, Copper) has been explored and discussed

In perfect harmony with the "Year of Light (IYL 2015)", the thesis has been entirely centered on the concept of Light involving the development of transition metal complexes for both the conversion of light into electric energy through dye-sensitized solar cells and, conversely, the production of light starting from electricity by fabrication of electroluminescent devices. The main part of the thesis has been devoted to the sunlight-to-electricity conversion, a target that is well contextualized within the global commitment for the progressive increase of the percentage of electric energy produced by renewable resources. In this context dye-sensitized solar cells, DSSCs, are promising devices alternative to the well established technology of silicon photovoltaics for energy production from the abundant solar light. DSSCs are devices able to harvest solar light and convert it into electricity employing a sensitizer (adsorbed on a semiconductor) and a redox couple properly chosen and combined. The project have concerned the design, synthesis and characterization of both sensitizers and redox mediators constituted by ruthenium and copper-based complexes respectively, together with their final assembly into laboratory-type DSSCs to evaluate their performance. In this way an all-round study has been carried out, from molecules on paper to test benches, passing through laboratory counters. The second, minor part, of the thesis has been focused on the diametrically opposed task, the generation of light. In this context some luminescent heteroleptic complexes based on the cheap and quite abundant copper element have been proposed. The final aim has been the synthesis of efficient luminophores for fabrication of devices able to generate light applying an electric potential across two electrodes such as in organic light-emitting diodes, OLEDs, or in analogue light-emitting electrochemical cells, LECs. The light production in LED-type devices is very efficient especially compared with other traditional artificial light sources like incandescent or fluorescent lamps, and so in line with the international policy of reducing energy consumption. In conclusion the thesis project can be schematically depicted as a circular pathway that joints together two opposite but strictly interconnected concepts (i.e. light and electricity) mutually corresponding to the task and the mean, the start and the end.

The detection and potential treatment of oxidative stress in biological systems has been explored using isoindoline-based nitroxide radicals. A novel tetraethyl-fluorescein nitroxide was synthesised for its use as a profluorescent probe for redox processes in biological systems. This tetraethyl system, as well as a tetramethyl-fluorescein nitroxide, were shown to be sensitive and selective probes for superoxide in vitro. The redox environment of cellular systems was also explored using the tetramethylfluorescein species based on its reduction to the hydroxylamine. Flow cytometry was employed to assess the extent of nitroxide reduction, reflecting the overall cellular redox environment. Treatment of normal fibroblasts with rotenone and 2-deoxyglucose resulted in an oxidising cellular environment as shown by the lack of reduction of the fluorescein-nitroxide system. Assessment of the tetraethyl-fluorescein nitroxide system in the same way demonstrated its enhanced resistance to reduction and offers the potential to detect and image biologically relevant reactive oxygen species directly. Importantly, these profluorescent nitroxide compounds were shown to be more effective than the more widely used and commercially available probes for reactive oxygen species such as 2’,7’-dichlorodihydrofluorescein diacetate. Fluorescence imaging of the tetramethyl-fluorescein nitroxide and a number of other rhodamine-nitroxide derivatives was undertaken, revealing the differential cellular localisation of these systems and thus their potential for the detection of redox changes in specific cellular compartments. As well as developing novel methods for the detection of oxidative stress, a number of novel isoindoline nitroxides were synthesised for their potential application as small-molecule antioxidants. These compounds incorporated known pharmacophores into the isoindoline-nitroxide structure in an attempt to increase their efficacy in biological systems. A primary and a secondary amine nitroxide were synthesised which incorporated the phenethylamine backbone of the sympathomimetic amine class of drugs. Initial assessment of the novel primary amine derivative indicated a protective effect comparable to that of 5-carboxy-1,1,3,3- tetramethylisoindolin-2-yloxyl. Methoxy-substituted nitroxides were also synthesised as potential antioxidants for their structural similarity to some amphetamine type stimulants. A copper-catalysed methodology provided access to both the mono- and di-substituted methoxy-nitroxides. Deprotection of the ethers in these compounds using boron tribromide successfully produced a phenolnitroxide, however the catechol moiety in the disubstituted derivative appeared to undergo reaction with the nitroxide to produce quinone-like degradation products. A novel fluoran-nitroxide was also synthesised from the methoxy-substituted nitroxide, providing a pH-sensitive spin probe. An amino-acid precursor containing a nitroxide moiety was also synthesised for its application as a dual-action antioxidant. N-Acetyl protection of the nitroxide radical was necessary prior to the Erlenmeyer reaction with N-acetyl glycine. Hydrolysis and reduction of the azlactone intermediate produced a novel amino acid precursor with significant potential as an effective antioxidant.

Les conditions oxydantes de la surface terrestre actuelle sont dues à la teneur élevée en dioxygène de l’atmosphère. Au début de l’histoire de la Terre il y a 4.54 milliards d'années (Ga), l’oxygène n’était pas stable dans l’atmosphère. Il a fallu deux épisodes d’augmentation brutale de ce gaz atmosphérique pour qu’il atteigne son niveau actuel : l’un vers 2.4 Ga, nommé le Grand Evènement Oxydant (GOE) qui fait l’objet de ce projet, l’autre 2 milliards d’années plus tard, nommé l’Evènement Oxydant Néo-protérozoïque (NOE). Le GOE est vraisemblablement le résultat de l’émersion généralisée de larges continents dont l’érosion libère le phosphate dans l’océan, un nutriment nécessaire à la production biologique, qui a donc permis l’explosion de la photosynthèse oxygénée. Ces deux hausses d’oxygène atmosphérique coïncident avec deux évolutions majeures dans l’histoire de la vie : (i) peu après le GOE, les eucaryotes sont apparus, alors que (ii) le NOE correspond à l’apparition des métazoaires et à l’explosion cambrienne. L’étude de ces phénomènes atmosphériques primitifs peut avoir d’importantes répercussions sur notre compréhension de l’origine et de l’évolution de la vie, qu’on estime principalement marine à cet âge. Les seules archives de ces temps primitifs sur Terre sont les roches sédimentaires. Pour savoir comment l’oxygénation de l’atmosphère a pu être reliée à cette vie marine, il faut tout d’abord comprendre comment l’océan a interagi avec l’atmosphère lors de cet évènement d’oxygénation. Cette question est au coeur de ce projet : comment le GOE a-t-il affecté les cycles biogéochimiques océaniques dont la vie est dépendante ? Nous nous sommes intéressés aux formations ferrifères litées ou BIFs (Banded Iron Formations). La chimie de ces roches marines fait écho à celle de l’océan contemporain à leur formation. Déterminer quantitativement la composition de l’océan à partir de celles des sédiments, même chimiques, est un défi quasiment impossible à relever y compris dans l’océan moderne. C’est pourquoi nous avons proposé de déterminer le temps de résidence d’éléments sensibles aux conditions redox de la surface, le soufre, le fer et le cuivre dans l’océan pré-GOE. Nous avons obtenu, par des séries temporelles, le spectre des fluctuations isotopiques de ces éléments enregistrées dans des carottes de formations ferrifères litées. La limite inférieure du spectre donne le temps de résidence de ces éléments dans l’eau de mer et fournit donc une indication solide sur la teneur de ces éléments dans l’océan à cette période. Nous avons analysé des échantillons protérozoïques proches de la limite Archéen-Protérozoïque du Transvaal (Afrique du Sud) et d’Hamersley (Australie). Des échantillons eoarchéens de Nuvvuagittuq (Canada) ont été récoltés mais n'ont pas pu être analysés faute de temps
The present-day oxidizing conditions at Earth's surface are due to the high oxygen content of the atmosphere. However, oxygen was not always stable in the terrestrial atmosphere. Two distinct periods during which oxygen increased in a step-like manner were required to reach the current atmospheric oxygen level. The first, at about 2.4 Ga, is known as the Great Oxidation Event (GOE) and is at the core of this Ph.D. thesis. The other, occurring almost two billion years later, is called the Neo-Proterozoic Oxidation Event (NOE). The GOE likely is the result of the beginning widespread emergence of large continental expanses whose subsequent erosion gradually released phosphate into the ocean. Phosphate, a nutrient essential to organic production, in turn allowed the explosion of oxygenated photosynthesis. The GOE and NOE coincide with two major changes in the history of life. Shortly after the GOE, eukaryotes appeared, while the NOE corresponds to the appearance of metazoans and the Cambrian explosion. A better grasp of the GOE hence may have important implications for the understanding of the origin and evolution of life, which is thought to have been mainly marine at this stage in Earth history. The only records of the oxygen level during these ancient times are found in terrestrial sedimentary rocks. To understand how oxygenation of the atmosphere relates to marine life, we must first understand how the ocean was connected to the atmosphere during the GOE and how the GOE affected life-dependent ocean biogeochemical cycles. To this end we focused on banded iron formations (BIF). The chemistry of these sedimentary marine rocks directly reflects the chemistry of the contemporary ocean. Deriving quantitatively the composition of the ocean from a hydrogenous sediment is a challenge almost impossible to meet, even for the modern ocean. This is why we instead determined the residence time of redox-sensitive elements (in this case sulfur, iron, and copper) in the pre-GOE ocean. We specifically targeted the periods of isotopic fluctuations in these elements as recorded in BIF cores. The lower limit of the spectrum provides the residence time of these elements in seawater, hence giving a robust indication of their contents in the pre-GOE ocean. We sampled early Proterozoic BIF near the Archean-Proterozoic boundary in Transvaal (South Africa) and Hamersley (Australia), as well as Archean BIF from Nuvvuagittuq (Canada), though the latter were not analyzed during this thesis due to shortage of time

Des complexes salen et dipyrrophénolate de fer comportant des unités phénolatesenrichies en électron (substituants tert-butyl ou methoxy) ont été préparés. Leur chimieoxydative conduit à des espèces radicalaires dont une a été caractérisée par diffraction desRX. Les complexes dipyrrophénolate de manganèse et cuivre ont été également étésynthétisés et oxydés, engendrant des espèces radicalaires. Le premier s’est avéré efficace entermes d’oxygénation d’oléfines, le second pour l’oxydation d’alcools.La fonctionnalisation des phénols par des chaînes alkylimidazolium rend les complexeshydrosolubles. Les salophen de nickel ainsi préparés interagissent fortement avec l’ADN Gquadruplexe(KD < 1-2 mM) en s’empilant sur le dernier quartet de guanine. Ils stabilisent lesG-quadruplexes contre la dénaturation thermique et bloquent l’activité de la télomérase avecdes IC50 < 3 mM
We prepared salen and dipyrrophenolate iron complexes involving electron rich (tertbutyland methoxy substituents) phenolate moieties. Their oxidative chemistry leads to radicalspecies, one of them being characterized by X-Ray diffraction. The manganese and copperdipyrrophenolate complexes were also synthesized and oxidized, affording radical species.The first ones are efficient catalysts for the oxygenation of olefins, while the second ones areactive towards alcohol oxidation.Functionnalization of the phenols by alkylimidazolium chains makes the compoundshydrosoluble. The so-prepared nickel salophen complexes interact strongly with GquadruplexDNA (KD < 1-2 mM), mainly through p-stacking interactions over the lastguanine quartet. They stabilize the G-quadruplex structures against thermal denaturation andinhibit telomerase activity with IC50 < 3 mM

Oxygen and nitric oxide reductases are enzymes found in aerobic and anaerobic respiration, respectively. Both enzyme groups belong to the superfamily of Heme-Copper Oxidases, which is further divided into several subgroups: oxygen-reducing enzymes into A-, B- and C-type and nitric oxide reductases into qNORs and cNORs. Oxygen reducing enzymes use the energy released from oxygen reduction to take up electrons and protons from different sides of the membrane. Additionally, protons are pumped. These processes produce a membrane potential, which is used by the ATP-synthase to produce ATP, the universal energy currency of the cell. Nitric oxide reductases are not known to conserve the energy from nitric oxide reduction, although the reaction is highly exergonic. Here, the detailed mechanism of a B-type oxidase is studied with special interest in an element involved in proton pumping (proton loading site, PLS). The study supports the hypothesis that the PLS is protonated in one and deprotonated in the consecutive step of the oxidative catalytic cycle, and that a proton is pumped during the final oxidation phase. It further strengthens the previous suggestion that the PLS is a cluster instead of a single residue or heme propionate. Additionally, it is proposed that the residue Asp372, which is in vicinity of the heme a3 propionates previously suggested as PLS, is part of this cluster. In another study, we show that the Glu15II at the entry of the proton pathway in the B-type oxidase is the only crucial residue for proton uptake, while Tyr248 is or is close to the internal proton donor responsible for coupling proton pumping to oxygen reduction. The thesis also includes studies on the mechanism and electrogenicity of qNOR. We show that there is a difference in the proton-uptake reaction between qNOR and the non-electrogenic homolog cNOR, hinting at a different reaction mechanism. Further, studies on a qNOR from a different host showed that qNOR is indeed electrogenic. This surprising result opens up new discussions on the evolution of oxygen and nitric oxide reductases, and about how energy conservation can be achieved.

At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 4: Manuscript.

Les dérèglements dans l'homéostasie du cuivre (Cu) ont été liés à la maladie d'Alzheimer (MA) et au cancer. Dans la MA le Cu se lie au peptide Aβ dans les plaques amyloïdes, impactant sur la production d'espèces oxygénées réactives (ROS). L'augmentation de la présence de Cu a également été impliquée dans la croissance tumorale. Ceci a conduit au développement de thérapies à base de Cu. L'utilisation de complexes de Cu pro-oxydants semble être une stratégie prometteuse pour le cancer. Dans la MA, des chélateurs qui bloquent l’activité redox du Cu sont nécessaires. Dans un environnement biologique, la stabilité d’un complex de Cu par rapport à ses concurrents physiologiques, est un aspect essentiel à considerer. Spécialement, le rôle des biomolécules liant/réductrices de Cu (telles que les métallothioneines, le glutathion et la cystéine) est très important. Cette thèse vise à étudier l’impact de ces molécules sur l’activité redox/stabilité de complexes de Cu médicinaux. Les études montrent que ces molécules sont des acteurs essentiels, car elles peuvent conduire à des réactions de dissociation, transmétallation, supprimant ainsi la production de ROS
Defects in copper (Cu) homeostasis have been linked to Alzheimer’s disease (AD) and Cancer. In AD, Cu has been found to bind to Aβ-peptides in extracellular amyloid-plaques, likely impacting the production of reactive oxygen species (ROS). Increased Cu levels have also been implicated in tumor growth. This has led to the development of Cu-based drugs. Particularly, the use of pro-oxidant Cu-complexes appears to be a promising strategy in cancer. Contrarily, in AD, redox silencing chelators are warranted. In a biological environment, the kinetic/thermodynamic stability of a Cu-complex against physiological competitors, is a key aspect to consider. In particular, the role of Cu-binding and reducing biomolecules (including metallothioneins, gluathione and cystein) is of pivotal importance. Within this context, this thesis aims to investigate the impact of these molecules on the redox-activity and stability of medicinal Cu-complexes. The studies carried out show that these molecules are key players for the fate of a Cu-complex, as they could lead to reactions of dissociation or transmetallation, abolishing the Cu-dependent ROS production

Une attention croissante est portée aux cascades multi enzymatiques pour l’élaboration de procédés de synthèse plus efficaces. Cependant, le contrôle de l’expression hétérologue de plusieurs gènes dans un même hôte s’avère difficile et peut mener à un déséquilibre du flux réactionnel. Pour exploiter au mieux les avantages d’une cascade in vivo, il est nécessaire d’ajuster les activités de chaque étape, et de construire des catalyseurs cellulaires capables de programmer la stœchiométrie des enzymes. Nous avons développé dans ce projet une approche originale pour moduler le ratio de deux enzymes in cellulo en jouant sur le nombre de copies de plasmides par cellule (PCN). Nous avons choisi comme modèle un système autosuffisant associant une Alcool Déshydrogénase (ADH) et une Baeyer-Villiger MonoOxygenase (BVMO), NADP(H)-dépendantes. Plusieurs plasmides recombinants portant les deux gènes ont été conçus et combinés dans E. coli. Les souches de co-expression construites ont été comparées en termes de PCN, de production d’enzymes et d’activité. Nous avons montré l’importance d’un choix judicieux de la combinaison de plasmides ainsi que l’existence d’une corrélation entre ratios d’enzymes et activité. Nos biocatalyseurs s’étendent sur une gamme allant du système inactif à un système affichant un TTN d’environ 6000. Ce système a permis la synthèse de lactones d’intérêt industriel, la dihydrocoumarine et la caprolactone, à partir d’indanol et de cyclohexanol. Enfin, sur ce modèle de combinaison de plasmides, trois nouveaux biocatalyseurs cellulaires, associant l’ADH à diverses BVMOs, ont été créés afin d’élargir la gamme d’esters et de lactones synthétisables à partir d’alcools
Growing attention is paid to multienzymatic cascades to develop more efficient synthetic processes. However, in in cellulo process, the control of the simultaneous heterologous expression of several genes in the same host is often difficult and can lead to imbalances in the reaction flow. To exploit the benefits of cascades, activities of each step have to be adjusted and thus, cellular biocatalysts capable of programming enzymes stoichiometry have to be constructed. In this work, to modulate the stoichiometry of two enzymes in vivo, we developed an original approach based on the copy number per cell of plasmids (PCN) used as vectors. The PCN is regulated in bacteria by three main mechanisms leading, according to the replicon, to low, medium or high PCN. As proof of concept, we chose a self-sufficient system combining an Alcohol Dehydrogenase (ADH) and a Baeyer-Villiger MonoOxygenase (BVMO), both NADP(H)-dependent. Several recombinant plasmids harboring both genes were designed and combined in E. coli. Coexpression strains constructed were compared in terms of PCN, enzyme production and activity. We showed the importance of a judicious choice of plasmids combination and the existence of a correlation between enzymes ratios and activity. Our biocatalysts ranged from an inactive system to a system with a TTN of about 6000. This system allowed the synthesis of lactones of industrial interest, dihydrocoumarin and caprolactone, via double oxidation of indanol and cyclohexanol. Finally, based on this plasmids combination model, three new cellular biocatalysts combining ADH with various BVMOs were designed to broaden the range of esters and lactones synthesizable from alcohols

The synthesis of metal-redox active ligand complexes is described, along with reactivity studies aimed at facilitating novel C-N bond forming reactions. A copper bis(iminosemiquinone) structure is characterized, analyzed and its reduction series are characterized and the reactivity of the Cu(II) bis(amidophenolate) analog is investigated with tosyl azide. The identification of the major reaction product and its characterization is detailed, with reaction sensitivities and heavily distorted x-ray diffraction single crystal structure generating a complex data set. The characterization of the isolated product is ongoing, with EPR studies aimed at identifying the radical nature of the complex. Unusual solvent effects and solubility issues have been noted with these initial EPR studies and more data is necessary before analysis can be properly attempted. An ytterbium bis(amidophenolate) complex was synthesized and its reactivity studied with aryl azides. Initial reactivities generate the first documented lanthanide tetrazenes in-lieu of the targeted ytterbium imido. Reactivities and characterization of these complexes support a stable, heavily ionic tetrazene-metal complex with no observed redox nature, UV light sensitivities, or imido azide-tetrazene equilibrium observed in various tetrazene transition metal complexes. Synthesis of a sterically blocked ytterbium imido was attempted, utilizing DMAP. Initial isolation was achieved with characterization and reactivity studies supporting the imido nature of the complex. The weak coordinating of the DMAP provided instability that proved in opposition to crystallization, however, so the imido could not be confirmed. Initial reactions using alternative steric hinderance from triphenylphosphine oxide and pyridine N-oxide prove promising to increasing the stability of the presumed ytterbium imido. Organic synthesis was performed generating a potential antibacterial agent. The synthesis of cyclopropenes was initiated as antagonists for ETR proteins in fruits and plants. The intermediates proved highly sensitive to harsh chemical conditions, which was overcome utilizing a tin-mediated Barbier allylation. The cyclopropene alcohol synthon was synthesized, though protecting group optimization is necessary.

Three Cu complexes varying in oxidation state from +1 to +3 were prepared from CuII starting materials and the hexafluoro-α-cumyl alkoxide ligand. These species include a targeted CuII tris-alkoxide, K[Cu(OC(C6H5)(CF3)2)3] (3); a trimeric Cu(I) complex, {K(18C6)}[K2{Cu(OC(C6H5)(CF3)2)2}3] (4); and a rare organocuprate CuIII complex, {K(18C6)}[Cu(OC(C6H4)(CF3)2)2] (5), which is stable at RT and has formed via ortho¬ metalation of two C-H bonds present. The three complexes have been structurally characterized, and 4 and 5 were studied using NMR spectroscopy to gain insight into the mechanism of formation. Using the bidentate perfluoropinacolate ligand (pinF)2-, four CuI complexes of the form K[(R3P)Cu(pinF)] or {K(18C6)}[(R3P)Cu(pinF)], with PR3 = PPh3 (9, 11) or PCy3 (10, 12) have been synthesized, and structurally and spectroscopically characterized. Complexes 9-12 reduce O2 at -78°C to form a symmetric trinuclear {Cu3O2} species, SyTpinF, which has been characterized by EPR, cryo-MS, and stopped-flow spectroscopy. Kinetic formation and decay constants in conjunction with DFT calculations revealed evidence for an asymmetric, trimeric, intermediate species, AsTpinF, which forms prior to SyTpinF. The trimeric core catalytically oxidizes para-hydroquinone to benzoquinone as a form of oxidase chemistry. The CuII complex, K2[Cu(pinF)2] (14), has been evaluated for stability at reducing potentials in organic and aqueous media by cyclic voltammetry and UV-vis. The electrochemical reactivity of 14 was examined in basic conditions, which showed that 14 is a precatalyst for the reduction of the NOx substrates NO3- and NO2-. The catalytic onset potential of NOx reduction coincides with the reduction of a transient CuI species to Cu0 on the glassy carbon based electrode. Controlled potential electrolysis with concomitant 15N-NMR studies have shown near quantitative reduction of NO3- to NO2- and NH4+ products or reduction of NO2- to NH4+.

In several oxidoreductase metalloenzymes, organic cofactors are transiently converted to radicals in order to achieve efficient catalytic turnover. This is, for example, the case of a tyrosine residue in galactose oxidase. Similarly, small-molecule catalysis can be improved when a transient radical ligand is involved. The present work aims at tailoring the structure of three classic ligands to make them redox-active, i.e. active participants in the electronic structure and reactivity of their complexes upon oxidation. The approach is to render an aromatic moiety on the ligand electron-rich by addition of NMe2 substituents. The first chapter describes a neutral Ni(II) complex with 1. This complex undergoes two reversible oxidations that were characterized by electrochemistry, electron paramagnetic resonance spectroscopy, optical spectroscopy and density functional theory. These oxidations are ligand-based, producing a radical ligand and a diiminoquinone successively. The second chapter investigates Cu(II) complexes of 1 and 2, for the bio-relevance of Cu in several oxidoreductases. Both ligands oxidize to a radical that is ferromagnetically coupled to the unpaired electron of Cu(II). Spectroscopic characterization and theoretical calculations provide a description of the electronic structure of the oxidized complexes. The third chapter looks at a Co(III) complex of 3, which is electron-rich and undergoes redox processes at low potentials. The optical absorption behaviour of the oxidized products is similar to that of the free ligand, suggesting ligand-based oxidation. As a whole, this thesis describes the effect of strongly electron-donating ligand substituents on the redox and electronic properties of a metal complex. The design leads to an easy strategy by which to tune the electronic structure of a complex by controlling the redox properties of its ligand.

碩士
淡江大學
化學學系
81
Binuclear Copper(II) complexes containing .alpha.-dimmine and azide ligand had been synthesised. The starting material complex G prepared by cupric acetate with binucleating ligand PPA in methanol. A series of complexes was prepared by reaction of complex G with sodium azide in different acidic condition( Hydrochloric acid, Acetic acid, Perchloric acid, Fluoroboric acid, Hexafluorophosphoric acid). The crystal and molecular structures complex A and complex C had been determined from X- ray diffraction data. The crystal structure of complex A was triclinic, space group Pi; a=8.586(5), b=9.099(7), c=13.770(9), .alpha.= 84.24(6), .bata.=84.44(6),.gamma.=76.18(5); Z=2. The copper(II) was coordinated by square pyramidal N3OCl environment . Teh crystal structure of complex C was orthorhombic; space group Pccn; a=27.791(4),b=12.4163(2), c=14.479(3), Z=8. The copper(II0 was coordinated by square pyramidal N3O2 environment. Infrared and electronic spectra ha been used to characterize these complexes. The infrared spectra showed that acetate ion was monodentate ligand and the azide was bridged ligand in general. There were one special case in which azide was monodentate ligand. The electronic spectra showed LMCT band at 372nm which was assigned to .pi.azide. .arrr. Cu(II) transition. The d-d band was observed at new 625nm. Cyclic Voltammetry was employed to study the electrochemical properties. In general, these complexes were reduced in successive, quasi-reversible one-electron one step at 0.14V and -0.17V. The first step was assigned to the reduction of Cu(II,II) to Cu(II,I); and teh second step was assigned to the reduction of Cu(II,I) to Cu(I,I) complex; and there was a stripping peak at +0.2V. It corresponds to two successive mondelectronic steps from the bis Cu(II,II) to the bis Cu(I,I) species. The catalystic oxidation reaction was defined by cyclic voltammetry adn electronic spectra. The result showed that this was a irreversible reacion as it reacted with oxygen.

The mechanism of the copper(II)-catalysed oxidation of thiosulfate ion by iron(III) in aqueous solutions is poorly understood, but is of interest because of its analytical applications, and its relevance to the disposal of waste solutions of thiosulfate and sulfoxyanions in general. The aim of this study was to determine or confirm the mechanisms of the reactions between copper(H) and thiosulfate, iron(III) and thiosulfate, and the reaction of aqueous mixtures of both metal ions with thiosulfate. This was done with a view to assessing the application of these reactions in both existing and proposed analytical procedures for the determination of copper and/or iron in aqueous media, with techniques such as flow-injection analysis. Stopped-flow and continuous flow methods were employed both to characterise the short-lived, coloured complexes of copper(II) and iron(III) with thiosulfate and to record kinetic data for the study of their rapid decomposition reactions. In addition, Raman spectra of frozen solutions of the iron (III)-thiosulfate complex were recorded for the first time.

碩士
國立臺灣大學
化學研究所
93
Potentiometric titrations of the copper centers in the particulate methane monooxygenase (pMMO) from Methylococcus capsulatus (Bath) are described. The reduction potentials of the various copper centers were measured by poising the enzyme in pMMO-enriched membranes in the presence of different redox mediators in an electrochemical cell, and quickly freezing the sample to record their low temperature EPR signals. Measurements of the low temperature EPR intensities of the type 2 sites and trinuclear Cu(II) centers yielded [Cu(I)]/[Cu(II)] for the various copper centers at the various different potentials, and the mid-point potentials were determined from the Nernst equation. The measurements were performed on two different forms of the enzyme in pMMO-enriched membranes: (i) the enzyme as isolated aerobically, but in the absence of hydrocarbon substrate; and (ii) the same preparation oxidized under air in the presence of acetylene or other hydrocarbon substrates. While the E-cluster copper sites exhibited essentially the same high reduction potential of +490 mV, substantially different results were obtained for the redox behavior of the C-cluster copper ions between the two forms. The reduction potentials of the oxidized C-cluster copper sites observed in the EPR were found to be substantially lower compared to that of the E-clusters. Accordingly, the redox potential of the oxidized bis(μ–oxo)dicopper(III) and bis(μ–peroxo)dicopper (II) dimer associated with the isolated type 2 site of the same cluster must be considerably higher than +490 mV, and there must be a kinetic barrier for transfer of electrons from the E-clusters to this site. This “splitting” of the redox potential of the trinuclear copper cluster is artifactual of the non-physiological state of enzyme created from the oxidation of the six copper ions by eight oxidizing equivalents from two dioxygen molecules. When the enzyme is turning over in the presence of hydrocarbon substrate, the dioxygen chemistry is tightly linked to the hydroxylation chemistry to achieve kinetic competence, and the redox potentials of the C-cluster copper ions were found to be substantially higher. The results of the present study add a significant chapter to our understanding of the structure and function of pMMO. First, the potentiometric titrations confirmed without any further question the existence of C-cluster and E-cluster copper ions, the number of distinct C-clusters, as well as the functional role they play in the methane hydroxylation chemistry, as the various copper centers are distinguished by distinct redox behaviors in the EPR, as manifested by their different appearance in the EPR spectrum at different potentials. Second, the different redox behavior of the C-clusters copper ions between the “as-isolated” enzyme and during turnover in the presence of hydrocarbon substrate has led to important insights into the details of how electron transport, dioxygen chemistry and hydrocarbon oxidation are linked in this complex system.

Zinc(II), copper(II), and copper(I) complexes of the pentadentate ligand, ((5-MeimidH)$\sb2$DAP) were prepared and studied as their (BF$\sb4$)$\sp-$ salts. The divalent compounds, (M$\sp{\rm II}$((5-MeimidH)$\sb2$DAP)) (BF$\sb4$)$\sb2$ (M = Zn, Cu), were found to have intermediate geometries between idealized trigonal bipyramidal and square pyramidal structures by x-ray crystallography. It is assumed that (Cu$\sp{\rm I}$((5-MeimidH)$\sb2$DAP)) (BF$\sb4$) is also pentacoordinate as is its parent compound, (Cu$\sp{\rm I}$((imidH)$\sb2$DAP)) (BF$\sb4$). In addition to the x-ray structures, the new compounds have been fully characterized, where appropriate, by a battery of techniques for both the solid and solution states. These studies all suggest that the pentacoordinate structures of the solid state are also retained in solution. Variable-temperature proton NMR studies in non-aqueous solvents were used to extensively probe the intramolecular conformational dynamics of (M((5-MeimidH)$\sb2$DAP)) $\sp{\rm n+}$ (M = Zn(II), Cu(I)) and two related pentacoordinate systems ((M((imidH)$\sb2$DAP)) $\sp{\rm n+}$ and (M((py)$\sb2$DAP)) $\sp{\rm {n+}}$). Computer simulation of the temperature-dependent methylene proton regions were used to observe $\lambda$ and $\delta$ chelate ring conformations. Coalesence rate constants were obtained in four of the six cases. The electron self-exchange rate of the (Cu((5-MeimidH)$\sb2$DAP)) $\sp{+/2+}$ couple was measured in CD$\sb3$CN, as a function of temperature, by dynamic NMR line-broadening techniques. Under controlled conditions ($\mu$ = 25 mM), the observed rate constant ranged from 0.9($\pm$0.1) $\times$ 10$\sp4$ M$\sp{-1}$ s$\sp{-1}$ (243 K) to 3.9($\pm$0.4) $\times$ 10$\sp4$ M$\sp{-1}$ s$\sp{-1}$ (293 K) with activation parameters of $\Delta$H$\sp\ddagger$ = 12.5 kJ mol$\sp{-1}$ and $\Delta$S$\sp\ddagger$ = $-$116 J mol$\sp{-1}$ K$\sp{-1}$. The present electron self-exchange rate constant, together with those for two related Cu(I/II) couples ((Cu((imidH)$\sb2$DAP)) $\sp{+/2+}$ and (Cu((py)$\sb2$DAP)) $\sp{+/2+}$) indicate a possible relationship between intramolecular dynamics of the Cu(I) species and the electron self-exchange rates of the Cu(I/II) couples. Finally, the reactivity of (Cu$\sp{\rm I}$((5-MeimidH)$\sb2$DAP)) $\sp+$ towards O$\sb2$ was investigated and found to be something other than a reversible process. Although an initial uptake stoichiometry of 2Cu:O$\sb2$ was obtained by manometry, a Toepler pump experiment showed that regeneration of Cu(I) proceeded without significant release of O$\sb2$.

The thesis entitled “Design and Development of Synthetic Methods using Metal-mediated and Metal-free Redox Reactions: Novel C-H Activations, Reductions and Oxidative Transformations” is presented in 4 chapters Chapter 1; Iodine catalyzed amination of benzoxazoles: efficient metal free route to 2-aminobenzoxazoles under mild conditions. The Chapter 1 of this thesis describes iodine catalyzed C-H activation of benzoxazole with primary and secondary amines to form oxidative aminated products. Selective C-H oxidation is a frontline area of modern chemical research as it offers the opportunities to new avenues and more direct synthetic strategies for the synthesis of complex organic molecules.1 In this context, transition metals such as palladium copper, nickel etc, are used extensively for the functional group directed C-H activation, and thus provides new, rapid, low-cost, and environmentally benign protocols for the construction of new chemical bonds.2 During the past two decades iodine and hypervalent iodine have been focus of great attention as they provide mild, chemoselective and environmentally benign strategies in contrast to toxic metal oxidants.3 In this chapter, a facile metal-free route of oxidative amination of benzoxazole with secondary or primary amines in the presence of catalytic amount of iodine (5 mol%) in aq tert-butyl hydroperoxide (1equiv) and AcOH (1.1 equiv) at ambient temperature, under the solvent-free reaction condition is presented. This user-friendly method to form C-N bonds produces tert-butanol and water as the by-products, which are environmentally benign. A wide range of benzoxazole derivatives containing electron-donating and electron-withdrawing groups were coupled with both primary and secondary amines (Scheme 1). Application of this methodology is demonstrated by synthesizing therapeutically active benzoxazoles by reacting 5-chloro-7-methylbenzoxazole with N-methylpiperazine and N-ethylhomopiperazine to obtain corresponding N-aminatedbenzaxozoles, which exhibit antidiarrhetic activity (Scheme 2).4 Scheme 2 Chapter 2: NIS catalyzed reactions. amidation of acetophenones and oxidative amination of propiophenones Chapter 2 is divided in to 2 parts. Part 1 describes the synthesis of α-ketoamides by using acetophenone and secondary amine in the presence of N-iodosuccinamide and TBHP in acetonitrile at room temperature, whereas Part 2 reveals the synthesis of 2-aminoketones by reacting aryl alkyl ketones and suitable secondary amine in the presence of NIS and TBHP. Part 1: Oxidative amidation, synthesis of α-ketoamide: Alpha α-ketoamides are important intermediates in organic synthesis that are present in a variety of natural products, and pharmaceutically active compounds. Herein, a mild and efficient conversion of acetophenones to α-ketoamide is documented by using aq.TBHP and N-iodosuccinamide (NIS) as a catalyst, at ambient temperature. This amidation reaction was found to be versatile as several aetophenone derivitives containing electron-withdrawing and electron-donating substituents underwent a facile amidation. It was also found that acetyl derivatives of heterocylic compounds could be easily converted to their corresponding ketoamides (few examples are shown in Scheme 3).5 Scheme3 Part 2 of Chapter 2 narrates a novel amination of propiophenone and its derivatives catalysed by NIS in the presence of TBHP to furnish their corresponding 2-aminoketone derivatives (Scheme 4). These derivatives are ubiquitous scaffolds that are present in a wide variety of therapeutic agents. Some of these compounds are used in the treatment of depression, smoking cessation, as monoamine uptake inhibitors, rugs for cancer. They are photoinitiators, precursors to β-aminoalcohols, such as pseudoephedrine analogues. 2-Aminoacetophenone analogues are also important intermediates for the formation of several heterocyclic compounds and are active moieties in several important drugs such as ifenprodil, Scheme 4. Chapter 3: Efficient oxidation of primary azides to nitriles This Chapter is divided in to 2 parts, which presents the oxidation of primary azides to their corresponding nitriles. Part 1: An Efficient oxidation of primary azides catalyzed by copper iodide: a convenient method for the synthesis of nitriles In Part 1, an efficient oxidation of primary azides catalyzed by copper iodide to their corresponding nitriles is reported. Herein, the oxidation of primary azide to nitrile is performed using catalytic amount of copper iodide, and aq TBHP in water at 100 ° C. This methodology is compatible with a wide range of primary benzylic azides that contain electron-donating and electron-withdrawing functional groups. The oxidation was found to be selective and a number of oxidizable functional groups were well-tolerated during the reaction conditions (few examples are shown in Scheme 5).6 Scheme 6 Furthermore, oxidation of secondary azides furnished the corresponding ketones in excellent yields (Scheme 6).6 In the Part 2 of Chapter 3, a non-metal catalysed oxidation of primary azides to nitriles at ambient temperature is reported. This part reveals the oxidation of primary azides to nitriles by employing catalytic amounts of KI (25 mol%), DABCO (25 mol%) and aq. TBHP (3 equiv., 70% solution in water). This reaction provides a good selectivity, as double and triple bonds were not oxidized under the reaction conditions. Additionally, chemoselective oxidation of benzylicazides against aliphatic azides increases the potential application of the present method (Scheme 7).7 Chapter 4: Chemoeselective reduction of olefins Part 1: Iron chloride catalysed aerobic reduction of olefins using aqueous hydrazine at ambient temperature Chapter 4 describes the reduction olefins and acetylenes, which is presented in two Parts. Part 1 documents utility of hydrazine (1.5 equiv) for the chemoselective reduction of nonpolarised carbon-carbon bond using iron catalysts. In this part, a chemoselective reduction of alkenes and alkynes in the presence of a variety of reducible functional groups is demonstrated (Scheme 8). The highlight of the present method is that the reduction proceeds well at room temperature and requires only 1.5 equiv of hydrazine hydrate. The olefin reduction by hydrazine depends upon the controlled release of diimide during the reduction. Generally, metal catalyzed reduction of olefins employ a large excess of hydrazine (10-20 equiv), which might be attributed to uncontrolled release of diimide during the reduction.8 Scheme 8 Part 2: Guanidine catalyzed aerobic reduction: a selective aerobic hydrogenation of olefins using aqueous hydrazine In Chapter 4, part 2, organocatalytic generation of diimide and its utility to reduce the double bonds is presented. Generation of diimide in situ by using organo catalysts and its use for the reduction of carbon-carbon double bond is one of the interesting topics in organic chemistry. It has been shown in this part of the thesis that the reduction of olefin at room temperature can be efficiently performed by using 10 mol% of guanidine nitrate, 2 equiv of aqueous hydrazine in oxygen atmosphere. This method tolerates a variety of reducible functional groups such as nitro, azido, and bromo and protective groups such as methyl ethers, benzyl ethers, and Cbz groups. It is also shown that terminal olefin can be selectively reduced in the presence of internal olefin (Scheme 9). Unlike other methods that employ diimide strategy, the present method is shown to be efficient in reducing substrates those contain internal double bonds such as cinnamyl alcohol and its derivatives