Cyclotech - contribution to solve the Technetium shortage by using low energy medical cyclotrons

This paper presents work in progress, to develop an efficient and economic way to directly produce Technetium 99metastable (99mTc) using low-energy cyclotrons. Its importance is well established and relates with the increased global trouble in delivering 99mTc to Nuclear Medicine Departments relying on this radioisotope. Since the present delivery strategy has clearly demonstrated its intrinsic limits, our group decided to follow a distinct approach that uses the broad distribution of the low energy cyclotrons and the accessibility of Molybdenum 100 (100Mo) as the Target material. This is indeed an important issue to consider, since the system here presented, named CYCLOTECH, it is not based on the use of Highly Enriched (or even Low Enriched) Uranium 235 (235U), so entirely complying with the actual international trends and directives concerning the use of this potential highly critical material. The production technique is based on the nuclear reaction 100Mo (p,2n) 99mTc whose production yields have already been documented. Until this moment two Patent requests have already been submitted (the first at the INPI, in Portugal, and the second at the USPTO, in the USA); others are being prepared for submission on a near future. The object of the CYCLOTECH system is to present 99mTc to Nuclear Medicine radiopharmacists in a routine, reliable and efficient manner that, remaining always flexible, entirely blends with established protocols. To facilitate workflow and Radiation Protection measures, it has been developed a Target Station that can be installed on most of the existing PET cyclotrons and that will tolerate up to 400 μA of beam by allowing the beam to strike the Target material at an adequately oblique angle. The Target Station permits the remote and automatic loading and discharge of the Targets from a carriage of 10 Target bodies. On other hand, several methods of Target material deposition and Target substrates are presented. The object was to create a cost effective means of depositing and intermediate the target material thickness (25 - 100μm) with a minimum of loss on a substrate that is able to easily transport the heat associated with high beam currents. Finally, the separation techniques presented are a combination of both physical and column chemistry. The object was to extract and deliver 99mTc in the identical form now in use in radiopharmacies worldwide. In addition, the Target material is recovered and can be recycled.

Reactores a tório: o futuro da energia nuclear de fissão

Dissertação para a obtenção do grau de mestre em Engenharia Electrotécnica Ramo de Energia

Oxo-molybdenum(VI) complexes containing chiral ligands: catalytic applications in selective epoxidations

Dissertation presented to obtain the Ph.D. degree in Chemistry

Periplasmic nitrate reductase revisited: a sulfur atom completes the sixth coordination of the catalytic molybdenum

J Biol Inorg Chem. 2008 Jun;13(5):737-53. doi: 10.1007/s00775-008-0359-6

PROX1 Promotes Metabolic Adaptation and Fuels Outgrowth of Wnt(high) Metastatic Colon Cancer Cells.

The Wnt pathway is abnormally activated in the majority of colorectal cancers, and significant knowledge has been gained in understanding its role in tumor initiation. However, the mechanisms of metastatic outgrowth in colorectal cancer remain a major challenge. We report that autophagy-dependent metabolic adaptation and survival of metastatic colorectal cancer cells is regulated by the target of oncogenic Wnt signaling, homeobox transcription factor PROX1, expressed by a subpopulation of colon cancer progenitor/stem cells. We identify direct PROX1 target genes and show that repression of a pro-apoptotic member of the BCL2 family, BCL2L15, is important for survival of PROX1(+) cells under metabolic stress. PROX1 inactivation after the establishment of metastases prevented further growth of lesions. Furthermore, autophagy inhibition efficiently targeted metastatic PROX1(+) cells, suggesting a potential therapeutic approach. These data identify PROX1 as a key regulator of the transcriptional network contributing to metastases outgrowth in colorectal cancer.

Geology of the Sand Creek porphyry molybdenum prospect /

The Sand Creek Prospect is located within the eastern exposed margin of the Coast Plutonic Complex. The occurrence is a plug and dyke porphyry molybdenum deposit. The rock types, listed in decreasing age: 1) metamorphlc schists and gneisses; 2) diorite suite rocks - diorite, quartz diorite, tonalite; 3) rocks of andesitic composition; 4) granodiorites, coarse porphyritic granodiorite, quartzfeldspar porphyry, feldspar porphyry; and 5) lamprophyre. Hydrothermal alteration is known to have resulted from emplacement of the hornblende-feldspar porphyry through to the quartz-feldspar porphyry. Molybdenum mineralization is chiefly associated with the quartz-feldspar porphyry. Ore mineralogy is dominated by pyrite with subordinate molybdenite, chalcopyrite, covelline, sphalerite, galena, scheelite, cassiterite and wolframite. Molybdenite exhibits a textural gradation outward from the quartz-feldspar porphyry. That is, disseminated rosettes and rosettes in quartz veins to fine-grained molybdenite in quartz veins and potassic altered fractures to fine-grained molybdenite paint or 6mears in the peripheral zones. The quartz-feldspar porphyry dykes were emplaced in an inhomogeneous stress field. The trend of dykes, faults and shear zones is 0^1° to 063° and dips between 58° NW and 86* SE. Joint Pole distribution reflects this fault orientation. These late deformatior maxima are probably superimposed upon annuli representing diapiric emplacement of the plutons. A model of emplacement involving two magmatic pulses is given in the following sequence: Diorite pulse (i) dioritequartz diorite, (ii) tonalites; granodiorite pulse (iii) hornblende-fildspar microporphyry, hornblende/biotite porphyry, (iv) coarse grained granodiorite, (v) quartz-feldspar porphyry, (vi) feldspar porphyry, and (vii) lamprophyre. The combination of plutonic and coarse porphyritic textures, extensive propylitic overprinting of potassic alteration assemblages suggests that the. prospect represents the lower reaches of a porphyry system.

Kinetic and mechanistic studies for the molybdenum- catalyzed oxidation of organic sulfides and olefins by t- DuO2H

This research was focussed on the effects of light, solvent and substituents in the molybdenum-catalyzed oxidation of phenylmethyl sulfides with t-Bu02H and on the effect of light in the molybdenum-catalyzed epoxidation of l-octene with t-Bu02H. It was shown that the Mo(CO)6-catalyzed oxidation of phenylmethyl sulfide with t-Bu02H~ at 35°C, proceeds 278 times faster underUV light than under laboratory lighting, whereas the Mo02(acac)2-catalyzed oxidation proceeds only 1.7 times faster under UV light than under normal laboratory lighting. The difference between the activities of both catalysts was explained by the formation of the catalytically active species, Mo(VI). The formation of the Mo(VI) species, from Mo(CO)6 was observed from the IR spectrum of Mo(CO)6 in the carbonyl region. The Mo(CO)6-catalyzed epoxidation of l-octene with t-Bu02H showed that the reaction proceeded 4.6 times faster under UV light than in the dark or under normal laboratory lighting; the rates of epoxidations were found to be the same in the dark and under normal laboratory lighting. The kinetics of the epoxidations of l-octene with t-Bu02H, catalyzed by Mo02(acac)2 were found to be complicated; after fast initial rates, the epoxidation rates decreased with time. The effect of phenylmethyl sulfide on the Mo(CO)6-catalyzed epoxidation of l-octene waS studied. It was shown that instead of phenylmethyl sulfide, phenylmethyl sulfone, which formed rapidly at 85°C, lowered the reaction rate. The epoxidation of l-octene was found to be 2.5 times faster in benzene than in ethanol. The substituent effect on the Mo02(acac)2-catalyzed oxidations of p-OH, p-CHgO, P-CH3' p-H, p-Cl, p-Br, p-CHgCO, p-HCO and P-N02 substituted phenylmethyl sulfides were studied. The oxidations followed second order kinetics for each case; first order dependency on catalyst concentration was also observed in the oxidation of p-CHgOPhSMeand PhSMe. It was found that electron-donating groups on the para position of phenylmethyl sulfide increased the rate of reaction, while electronwithdrawing groups caused the reaction rate to decrease. The reaction constants 0 were determined by using 0, 0- and 0* constants. The rate effects were paralleled by the activation energies for oxidation. The decomposition of t-Bu02H in the presence of M.o (CO)6, Mo02 (acac)2 and VO(acac)2 was studied. The rates of decomposition were found to be very small compared to the oxidation rates at high concentration of catalysis. The relative rates of the Mo02(acac)2-catalyzed oxidation of p-N02PhSMe by t-Bu02H in the presence of either p-CH30PhSMe or PhSMe clearly show that PhSMe and p-CHgOPhSMe act as co-catalysts in the oxidation of p-N02PhSMe. Benzene, mesity1ene and cyclohexane were used to determine the effect of solvent in the Mo02 (acac)2 and Mo(CO)6-catalyzed oxidation of phenylmethyl sulfide. The results showed that in the absence of hydroxylic solvent, a second molecule of t-Bu02H was involved in the transition state. The complexation of the solvent with the catalyst could not be explained.The oxidations of diphenyl sulfoxide catalyzed by VO(acac)2, Mo(CO)6 and Mo02(acac)2 showed that VO(acac)2 catalyzed the oxidation faster than Mo(CO)6 and Mo02 (acac)2_ Moreover, the Mo(CO)6-catalyzed oxidation of diphenyl sulfoxide proceeded under UV light at 35°C.

Molybdenum (IV) imido silylamido and hydride complexes : stoichiometric and catalytic reactivity, mechanistic aspects of hydrosilation reactions

This thesis describes the synthesis, structural studies, and stoichiometric and catalytic reactivity of novel Mo(IV) imido silylamide (R'N)Mo(R2)(173_RIN-SiR32-H)(PMe3)n (1: Rl = tBu, Ar', Ar; R2 = Cl; R32 = Me2, MePh, MeCl, Ph2, HPh; n = 2; 2: R' = Ar, R2 = SiH2Ph, n = 1) and hydride complexes (ArN)Mo(H)(R)(PMe3)3 (R = Cl (3), SiH2Ph (4». Compounds of type 1 were generated from (R'N)Mo(PMe3)n(L) (5: R' = tBu, Ar', Ar; L = PMe3, r/- C2H4) and chlorohydrosilanes by the imido/silane coupling approach, recently discovered in our group. The mechanism of the reaction of 5 with HSiCh to give (ArN)MoClz(PMe3)3 (8) was studied by VT NMR, which revealed the intermediacy of (ArN)MCh(172 -ArN=SiHCl)(PMe3)z (9). The imido/silyl coupling methodology was transferred to the reactions of 5 with chlorine-free hydrosilanes. This approach allowed for the isolation of a novel ,B-agostic compound (ArN)Mo(SiHzPh)(173 -NAr-SiHPhH)(PMe3) (10). The latter was found to be active in a variety of hydrosilation processes, including the rare monoaddition of PhSiH3 to benzonitrile. Stoichiometric reactions of 11 with unsaturated compounds appear to proceed via the silanimine intermediate (ArN)M(17z-ArN=SiHPh)(PMe3) (12) and, in the case of olefins and nitriles, give products of Si-C coupling, such as (ArN)Mo(R)(173 -NAr-SiHPh-CH=CHR')(PMe3) (13: R = Et, R' = H; 14: R = H, R' = Ph) and (ArN)Mo(172-NAr-SiHPh-CHR=N)(PMe3) (15). Compound 13 was also subjected to catalysis showing much improved activity in the hydrosilation of carbonyls and alkenes. Hydride complexes 3 and 4 were prepared starting from (ArN)MoCh(PMe3)3 (8). Both hydride species catalyze a diversity of hydrosilation processes that proceed via initial substrate activation but not silane addition. The proposed mechanism is supported by stoichiometric reactions of 3 and 4, kinetic NMR studies, and DFf calculations for the hydrosilation of benzaldehyde and acetone mediated by 4.

Hydrosilylation and hydroboration catalyzed by imido-hydride complexes of molybdenum (IV)

This thesis describes the synthesis, structural studies, stoichiometric and catalytic reactivity of novel Mo(IV) imido hydride complexes (Cp)(ArN)Mo(H)(PMe3) (1) and (Tp )(ArN)Mo(H)(PMe3) (2). Both 1 and 2 catalyze hydrosilylation of a variety of carbonyls. Detailed kinetic and DFT studies found that 1 reacts by an unexpected associative mechanism, which does not involve Si-H addition either to the imido group or the metal. Despite 1 being a d2 complex, its reaction with PhSiH3 proceeds via a a-bond metathesis mechanism giving the silyl derivative (Cp )(ArN)Mo(SiH2Ph)(PMe3). In the presence of BPh3 reaction of 1 with PhSiH3 results in formation of (Cp)(ArN)Mo(SiH2Ph)(H)2 and (Cp)(ArN)Mo(SiH2Ph)2(H), the first examples ofMo(VI) silyl hydrides. AI: 1 : 1 reaction between 2, PhSiD3 and carbonyl substrate established that hydrosilylation is not accompanied by deuterium incorporation into the hydride position of the catalyst, thus ruling out the conventional mechanism based on carbonyl insertion carbonyl. As 2 is nomeactive to both the silane and ketone, the only mechanistic alternative we are left with is that the metal center activates the carbonyl as a Lewis acid. The analogous nonhydride mechanism was observed for the catalysis by (ArN)Mo(H)(CI)(PMe3), (Ph3P)2(I)(O)Re(H)(OSiMe2Ph) and (PPh3CuH)6. Complex 2 also catalyzes hydroboration of carbonyls and nitriles. We report the first case of metal-catalyzed hydroboration of nitriles as well as hydroboration of carbonyls at very mild conditions. Conversion of carbonyl functions can be performed with high selectivities in the presence of nitrile groups. This thesis also reports the first case of the HlH exchange between H2 and Si-H of silanes mediated by Lewis acids such as Mo(IV) , Re(V) , Cu(I) , Zn(II) complexes, B(C6Fs)3 and BPh3.

Uranium à Sept-Îles : ethnographie d'un refus. Essai de résistance populaire.

Ce mémoire de maîtrise traite d’un phénomène social critique qui a gagné en importance au Québec : la montée des groupes de résistance populaire contre des projets d’exploitation des ressources naturelles. À partir d’une étude de cas, l’auteur tâche ici d’approfondir les questions relatives à ces luttes collectives tout en mettant en lumière les diverses modalités d’engagement qui, par leurs registres et leurs compositions en « systèmes-experts », se répercutent dans l’espace public tout en transformant, d’une certaine manière, l’arène politique. Ces dynamiques des mouvements de résistance tendent également à s’infléchir en amont des projets de développement, pour se matérialiser en aval, soit dès les premières phases d’appropriation territoriale, c’est-à-dire les premiers travaux exploratoires comme tels. Cette enquête de terrain se focalise sur ces enjeux. En prenant comme observatoire le projet de Terra Ventures à Sept-Îles, en région nord-côtière, concernant un projet d’exploration uranifère, l’auteur insiste sur les multiples références collectives qui sont autant de perspectives pour comprendre ce phénomène. À travers l’étude de cette résistance populaire qui s’est profilée contre ce projet d’exploration, c’est l’industrie minière au Québec, son histoire, ses mythes, et sa mémoire qui est, enfin, en trame de fond.

Synergistic solvent extraction of Thorium(IV) and Uranium(VI) with β-diketones in presence of oxo-donors

The thesis entitled “Synergistic solvent extraction of Thorium(IV) and Uranium(VI) with β-diketones in presence of oxo-donors” embodies the results of the investigations carried out on the extraction of thorium(IV) an uranium(VI) with heterocyclic β-diketones in the presence and absence of various macrocyclic ligands and neutral organophosphorus extractants. The objective of this work is to generate the knowledge base to achieve better selectivity between thorium(IV) and uranium(VI) by understanding the interactions of crown ethers or neutral organophosphorus extractants with metal-heterocyclic β-diketonate complexes. Para-substituted 1-phenyl-3-methyl-4-aroyl-5-pyrazolones, namely,1-phenyl-3-methyl-4-(4-fluorobenzoyl)-5-pyrazolone (HPMFBP) and 1-phenyl-3-methyl-4-(4-toluoyl)-5-pyrazolone (HPMTP) were synthesized and characterized by elemental analysis, IR and H NMR spectral data. The synthesized ligands have been utilized for the extraction of thorium(IV) and uranium(VI) from nitric acid solutions in the presence and absence of various crown ethers. Thorium(IV) and uranium(VI) complexes with HPMPP(1-Phenyl-3-methyl-4-pivaloyl-5-pyrazolone) and neutral organophosphorus extractants were synthesized and characterized by IR and P NMR spectral data to further understand the interactions of neutral organophosphorus extractants with metal-chelates. Solid complexes of thorium(IV) and uranium(VI) with para-substituted 4-aroyl-5-isoxazolones and crown ethers were isolated and characterized by various spectroscopic techniques to further clarify the nature of the extracted complexes.