Nitric oxide (NO) is an important biological molecule within the body, which over production of this molecule in response to different stimulations can cause various inflammatory diseases. Over production of this molecule is caused by the induction of the inducible nitric oxide synthase (iNOS) enzyme. This enzyme uses L-arginine as a substrate and therefore the presence and transport of this amino acid into the cells can be a key factor in regulating NO over production. Different signalling mechanisms have been implicated in the regulation of this pathway and one of which involves the Mitogen Activated Protein Kinases (MAPK). This family of proteins respond to inflammatory conditions and may mediate effects induced by inflammatory mediators. Of the MAPKs, the role of the c-Jun-N-terminal kinase (JNK) pathway in the induction of iNOS is still controversial. JNK and its downstream target, the transcription factor Activator Protein-1 (AP-1), have shown contradictory effects on iNOS induction leading to controversies over their role in regulating iNOS expression in different cell systems or with various stimuli. The studies described in this thesis have determined the role of JNK/AP-1 on iNOS expression, NO production, L-arginine uptake and also on the transporters responsible for L-arginine transport into the cells. The studies were carried out in two different cell types: rat aortic smooth muscle cells (RASMCs) and J774 macrophages which are both critically associated with the over production of NO in vascular inflammatory disease states. The first approach was to block the expression of the inducible L-arginine-NO pathway using SP600125 and JNK Inhibitor VIII which are both pharmacological inhibitors of JNK. The results from these studies showed that the pharmacological intervention was without effect in RASMCs, but inhibited iNOS, NO and L-arginine transport in J774 macrophages. In contrast, the molecular approach employed using two dominant negative constructs of AP-1 (TAM-67 and a-Fos) revealed a different profile of effects in RASMCs, where a-Fos caused an induction in iNOS and NO while TAM-67 had an inhibitory effect on iNOS, NO, L-arginine transport and CAT-2B mRNA expression. The latter was unaffected in RASMCs but suppressed in J774 macrophages by SP600125. Examination of JNK isoforms expression showed the presence of JNK1 and 2 in both cell systems. Moreover, stimulation with LPS/IFN- or LPS alone resulted in JNK phosphorylation which did not reveal any difference between smooth muscle cells and macrophages. In contrast, expression and activation of AP-1 subunits revealed differences between the two cell systems. Activation of cells with LPS and IFN- (RASMCs) or LPS alone (J774 macrophages) resulted in changes in the activated status of the different AP-1 subunit which was different for the two cell systems. In both cell types c-Jun, JunD and Fra-1 were increased and in macrophages, FosB activity was also enhanced. Inhibition of JNK with SP600125 caused down-regulation in c-Jun in both cell types. Interestingly this down-regulation was in parallel with increases in the subunits JunB, JunD, c-Fos and Fra-1 in RASMCs or JunB and Fra-1 in J774 macrophages. Since, SP600125 was able to exert inhibitory effects in the latter cell type but not in RASMCs, it is possible that the compensatory up-regulation of certain AP-1 subunits in the smooth muscle cells may compensate for c-Jun inhibition thereby preventing suppression of iNOS expression. This notion clearly needs to be confirmed but it is potentially likely that hetero-dimers formed between JunB, JunD, c-Fos and Fra-1 could sustain gene transcription in the absence of c-Jun. The precise dimer required has not been addressed but unlikely to exclusively involve JunB and Fra-1 as these are up-regulated in macrophages but did not sustain iNOS, NO or induced L-arginine transport in the presence of SP600125. To further support the argument above, the dominant negatives caused varied effects on the activation of the different subunits. a-Fos down-regulated c-Jun, c-Fos, FosB, Fra-1 whereas TAM-67 reduced c-Jun and c-Fos but marginally induced Fra-1 activity. Associated with these changes was an up-regulation of iNOS-NO by a-Fos and inhibition by TAM-67. Taken together, the data proposes a complex mechanism(s) that regulate the expression of the inducible L-arginine-NO pathway in different cell systems and the complexity may reflect diverse intracellular changes that may be different in each cell type and not always be apparent using one experimental approach especially where this is pharmacological. Moreover, these findings strongly suggest exercising caution when interpreting pure pharmacological findings in cell-based systems particularly where these are inconsistent or contradictory.

Monolayers of the cationic surfactant hexadecyltrimethylammonium halide (CTAX, where X = F¯, Cl¯, Br¯, and I¯) have been studied at the air-water and oilwater interfaces. At the air-water interface, the effects of the halide counterion and the addition of counterion were investigated. Sum-frequency spectroscopy (SFS), ellipsometry, and surface tensiometry indicated that the counterion changed the efficiency and effectiveness of the surfactant, both decreasing in the order of Br¯> Cl¯>F¯. The addition of salt in the form of 0.1 M KX was found to reduce the cmc but had little effect on the limiting area per molecule attained at the cmc, which increased from 44 Ų for CTAB to 65 Ų for CTAC and ca. 94 Ų for CTAF. Neither SFS nor ellipsometry provided any firm evidence for specific effects of the halide ions on the structure of the surfactant monolayers. For CTAB monolayers in the absence of excess electrolyte, the effect of area per molecule on the sum-frequency (SF) spectra was studied. Mixed monolayers of CTAB and tetradecane at the air-water interface exhibit a first-order phase transition from a conformationally disordered to a conformationally ordered state as the temperature is lowered. The phase transition occurs ca. 11 °C above the bulk melting point of tetradecane. A new experimental arrangement is described for acquiring SF spectra from surfactants at the oil-water interface. The key features of this approach are the stabilisation of a thin oil film between a sapphire prism and an aqueous phase, and the use of total internal reflection to enhance the total signal and discriminate against signals from other interfaces in the system. With this new methodology, the first SF vibrational spectra of surfactant monolayers at an alkane-water interface were obtained. Surface tensiometry was used to characterise the monolayers further. The structure of CTAB monolayers at the hexadecane-water interface was determined by SFS and compared with monolayers of CTAB at the air-water interface. At low concentrations, CTAB/hexadecane showed the expected features in the C-H stretching region, characteristic of a conformationally disordered monolayer. As the bulk concentration approached the critical micelle concentration, the spectra changed to one characteristic of a more ordered, upright conformation. Ellipsometric measurements supported this conclusion. This qualitative structural change is not observed in analogous monolayers at the air-water interface or CCl₄-water interface, or in surfactant solutions in contact with a hydrophobic solid surface.

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal.

Ce mémoire traite de la chimie des complexes pinceurs de nickel (II) cationiques ayant un ligand de type POCOP. Elle se divise en deux parties. La première traite de la synthèse, de la caractérisation et de la réactivité des complexes cationiques pinceurs de Ni(II) de type POCOP (POCOP = 1,3-bis(phosphinitobenzene), où C fait partie d’un cycle benzénique et est lié au métal, et P est un ligand phosphoré aussi lié au métal). Ces complexes ont un ligand acétonitrile coordonné au centre métallique et sont du type [(R-POCOPR’)Ni(NCMe)][OSO2CF3], où R est un substituant du cycle benzénique et R’ est un substituant sur le ligand phosphoré (R’ = iPr: R = H (1), p-Me(2), p-OMe(3), p-CO2Me(4), p-Br(5), m,m-tBu2(6), m-OMe(7), m-CO2Me(8); R’ = t-Bu : R = H (9), p-CO2Me(10)). Les complexes cationiques sont préparés en faisant réagir le dérivé Ni(II) neutre correspondant R-(POCOPR’)Ni-Br avec Ag(OSO2CF3¬) dans l’acétonitrile à température ambiante. L’impact des groupements R et R’ du ligand POCOP sur la structure et sur les propriétées électroniques du complexe a été étudié par spectroscopies RMN, UV-VIS et IR, analyse électrochimique, et diffraction des rayons X. Les valeurs de fréquence du lien C≡N (ν(C≡N)) augmentent avec le caractère électroattracteur du complexe, dans l’ordre 7 < 3 ~ 2 ~ 6 < 1 < 5 ~ 8 < 4 et 9 < 10. Ces résultats sont en accord avec le fait qu’une augmentation du caractère électrophile du centre métallique devrait résulter en une augmentation de la donation σ MeCN→Ni. De plus, les complexes cationiques montrent tous un potentiel d’oxydation Ni(II)/Ni(III) plus élevé que leurs analogues neutres Ni-Br. Ensuite, une étude d’équilibre entre un complexe neutre (R-POCOPR’)NiBr et un complexe cationique [(R-POCOPR’)Ni(NCMe)][OSO2CF3] démontre l’échange facile des ligands MeCN et Br. La deuxième partie de ce mémoire consiste en deux chapitres. Le premier (Chapitre 3) est une étude structurelle permettant une meilleure compréhension du mécanisme d’hydroamination des oléfines activées promue par les complexes présentés au chapitre 1, suivi de tentatives de synthèse de nouveaux composés POCOP cationiques comportant un ligand amine et nitrile, et de déplacement du groupement amine par un groupement nitrile. Le deuxième chapitre (4) décrit la réactivité et la cinétique de la réaction d’hydroamination et d’hydroalkoxylation d’oléfines activées, qui permet ainsi de mieux comprendre l’impact des différentes variables du système (groupements R et R’, température, substrats, solvent, etc.) sur la réactivité catalytique. / This thesis describes the chemistry of nickel (II) cationic pincer complexes bearing a POCOP ligand. The content is divided into two parts. The first part (chapter 2) concerns the synthesis, characterization and reactivities of nickel (II) cationic POCOP pincer complexes with an acetonitrile ligand coordinated to the metal center via the nitrile moiety, [(R-POCOPR’)Ni(NCMe)][OSO2CF3] where R is a ring substituent and R’ is a P-substituent (R’ = iPr : R = H (1), p-Me(2), p-OMe(3), p-CO2Me(4), p-Br(5), m,m-tBu2(6), m-OMe(7), m-CO2Me(8); R’ = t-Bu : R = H (9), p-CO2Me(10)). The cationic complexes are synthetized by reacting the neutral nickel (II) bromide derivatives R-(POCOPR’)Ni-Br with Ag(OSO2CF3) in acetonitrile at room temperature. The impact of R and R’ groups of the POCOP ligand on the structure and electronic proprieties of the complexes has been studied by NMR, UV-Vis and IR spectroscopy, as well as by single crystal x-ray diffraction studies and cyclic voltammetry measurements. The observed ν(C≡N) values were found to increase with the increasing electron-withdrawing nature of R, i.e., in the order 7 < 3 ~ 2 ~ 6 < 1 < 5 ~ 8 < 4 and 9 < 10. This trend is consistent with the anticipation that enhanced electrophilicity of the nickel center should result in an increase in net MeCN→Ni σ-donation. It is also interesting to note that all cationic complexes show a much higher Ni(II)/Ni(III) oxidation potential than their neutral Ni-Br analogues. Following this, an equilibrium study is presented that shows the facile exchange of the MeCN/Br ligands between the charge-neutral and cationic complexes (R-POCOPR’)NiBr and [(R-POCOPR’)Ni(NCMe)][OSO2CF3]. The second part of this thesis consists of two chapters describing, respectively, structural studies that are relevant to our understanding of the mechanism of hydroamination reactions promoted by the title complexes (chapter 3), and reactivity and kinetic studies aimed at understanding the impact of different variables (R and R’; temperature; substrates; solvent; etc.) on the Michael-type hydroamination and hydroalkoxylation of acrylonitrile and its substituted derivatives (chapter 4). Chapter 3 will also discuss the attempted synthesis of new amine and nitrile POCOP cationic and neutral complexes, as well as the facile displacement of the amine moiety by a nitrile.

Ce travail est consacré à l'élaboration par voie humide (pontage, solvothermale et colloïdale) de photocatalyseur TiO2 supporté sur trois types de minéraux argileux d'origine marocaine: la stévensite, la beidellite et la palygorskite, à leurs caractérisations et finalement à l'évaluation de leurs activités photocatalytiques vis-à-vis de l'élimination en milieu aqueux du colorant anionique l'Orange G (OG) très utilisé en industrie textile. La stévensite et la beidellite sont toutes les deux des smectites de types magnésien trioctaédrique et aluminifère dioctaédrique respectivement. En revanche, la palygorskite est un minéral fibreux riche en Al doté d'un caractère dioctaédrique très marqué. Les matériaux photocatalyseurs supportés développés par le pontage de la stévensite ou de la beidellite ne révèlent pas de formation de piliers interlamellaires de TiO2, mais plutôt l'obtention dans les deux cas de matrice de TiO2 amorphe dans laquelle sont éparpillées quelques rares particules indemnes de phyllosilicates. De même, ceux à base de stévensite élaborés par la méthode solvothermale révèlent des particules du phyllosilicate désintégrées au sein d'une matrice de TiO2 toutefois cristallisée sous forme d'anatase. Néanmoins, la fonctionnalisation selon la voie colloïdale a permis d'immobiliser avec succès des nanoparticules d'anatase (10 nm) sur aussi bien des feuillets plus ou moins exfoliés de stévensite ou de beidellite que sur des fibres de palygorskite. L'anatase attachée aux particules de ces minéraux argileux demeure extraordinairement stable jusqu'à 900 °C alors que celle formée en absence de ces phyllosilicates se convertit complètement en rutile vers 650 °C. Cette stabilité remarquable de l'anatase supportée est due à l'empêchement de la croissance, par coalescence à haute température, de la taille de ses particules au-delà de la taille critique (30 nm) requise pour sa conversion en rutile relativement moins photoactive. Les essais de photocatalyse révèlent que l'activité catalytique des différents matériaux élaborés croit selon la méthode de fonctionnalisation: pontage - méthode solvothermale - voie colloïdale et aussi selon la nature du minéral argileux : stévensite - beidellite - palygorskite. En outre, les matériaux photocatalyseurs supportés, à base de beidellite ou de palygorskite, développés par la voie colloïdale, manifestent une activité deux fois supérieure à celle de la poudre commerciale TiO2 Degussa P25. Leurs particules floculent aisément, ce qui facilite leur élimination du milieu aqueux sans recourir à la microfilitration requise dans le cas de la Degussa P25. / This work was devoted to the elaboration by wet route (pillaring, solvothermal and colloidal) of TiO2 supported photocatalysts on three kinds of clay minerals (stevensite, beidellite and palygorskite) from Morocco, to their characterizations and finally to the evaluation of their photocatalytic activities towards the removal from aqueous media of anionic Orange G dye, widely used in textile industry. Stevensite and beidellite were magnesian trioctahedral and aluminiferous dioctahedral smectites respectively. Nevertheless, palygorskite was a fibrous Al-rich clay mineral with a predominant dioctahedral character. The photocatalyst materials elaborated by the pillaring of stevensite or beidellite did not reveal the formation of TiO2 interlayer pillars, but the observation of an amorphous matrix of Ti-rich phase within which were distributed some rare unaltered particles of phyllosilicates. Those based on stevensite elaborated according to solvothermal method also showed dissolved phyllosilicates particles, but within crystalline TiO2 anatase matrix. Nevertheless, the functionalized materials developed according to colloidal route exhibited successful immobilization of anatase nanoparticles (10 nm) onto as well as more or less exfoliated layers of stevensite or beidellite than on palygorskite fibers. Anatase remained remarkably stable up to 900 °C when attached to particles of clay minerals in comparison with that developed in their absence which underwent a complete transformation into rutile at around 650°C. This remarkable stability at high temperature of anatase supported on clay minerals particles was due to the hindrance of particles growth by sintering whose the sizes remained below the nucleus critical sizes (30 nm) required for its transition into less photoactive rutile. The photocatalysis tests revealed that the catalytic activity of different elaborated materials increased according to the synthesis route: pillaring process - solvothermal method - colloidal route and according to the nature of clay mineral: stevensite - beidellite - palygorskite. In addition, the supported photocatalysts based on beidellite or palygorskite prepared by colloidal route were found to be twice more active than the commercial TiO2 powder Degussa P25. Furthermore, their particles easily floculated so that they are readily removable from treated solutions without resorting to expensive microfiltration required upon the use of Degussa P25.

Os peptídeos antimicrobianos desempenham papéis protetores críticos em uma gama de doenças humanas, incluindo o câncer. Vários estudos demonstraram funções - tais como proliferação, angiogênese, apoptose e imunomodulação - desses peptídeos em vias cancerígenas cruciais. Investigamos o papel do Peptídeo antimicrobiano LL-37 sobre stemness em câncer de mama (SKBR3) e células de melanoma (A375). Análise por PCR array da expressão diferencial de genes em SKBR3 e A375 com knockdown por siRNA para o mRNA de LL-37 revelou uma regulação negativa de genes relacionados com stemness, incluindo transcriptase reversa da telomerase, forkhead box D3 e para o fator indiferenciado de transcrição de células embrionárias 1, notavelmente em células de câncer de mama.Além disso, as células SKBR3 com knockdown para a expressão de LL-37 mostraram uma diminuição da produção de oncosferas em comparação com controles negativos, enquanto as células A375 exibiram uma produção aumentada. Tomados em conjunto, nossos achados indicam um papel para LL- 37 em stemness, dependendo do tipo de celular analisado / Antimicrobial peptides play critical protective roles in a range of human diseases, including cancer. Multiple studies have demonstrated functions -- such as proliferation, angiogenesis, apoptosis and immunomodulation -- of these peptides in crucial cancer pathways. We investigated the role of the antimicrobial peptide LL-37 on stemness in breast cancer (SKBR3) and melanoma cells (A375). PCR array analysis of differential gene expression in SKBR3 and A375 cancer cell lines downregulated for LL-37 expression by siRNA revealed downregulation of genes related to stemness, including telomerase reverse transcriptase, forkhead box D3 and undifferentiated embryonic cell transcription factor 1, remarkably in breast cancer cells. Furthermore, SKBR3 cells knocked down for LL-37 expression showed a decreased production of oncospheres in comparison with negative controls, while A375 cells exhibited increased production. Taken collectively, our findings indicate a role for LL-37 in cancer cell stemness depending on the cell type

Os peptídeos antimicrobianos desempenham papéis protetores críticos em uma gama de doenças humanas, incluindo o câncer. Vários estudos demonstraram funções - tais como proliferação, angiogênese, apoptose e imunomodulação - desses peptídeos em vias cancerígenas cruciais. Investigamos o papel do Peptídeo antimicrobiano LL-37 sobre stemness em câncer de mama (SKBR3) e células de melanoma (A375). Análise por PCR array da expressão diferencial de genes em SKBR3 e A375 com knockdown por siRNA para o mRNA de LL-37 revelou uma regulação negativa de genes relacionados com stemness, incluindo transcriptase reversa da telomerase, forkhead box D3 e para o fator indiferenciado de transcrição de células embrionárias 1, notavelmente em células de câncer de mama.Além disso, as células SKBR3 com knockdown para a expressão de LL-37 mostraram uma diminuição da produção de oncosferas em comparação com controles negativos, enquanto as células A375 exibiram uma produção aumentada. Tomados em conjunto, nossos achados indicam um papel para LL- 37 em stemness, dependendo do tipo de celular analisado / Antimicrobial peptides play critical protective roles in a range of human diseases, including cancer. Multiple studies have demonstrated functions -- such as proliferation, angiogenesis, apoptosis and immunomodulation -- of these peptides in crucial cancer pathways. We investigated the role of the antimicrobial peptide LL-37 on stemness in breast cancer (SKBR3) and melanoma cells (A375). PCR array analysis of differential gene expression in SKBR3 and A375 cancer cell lines downregulated for LL-37 expression by siRNA revealed downregulation of genes related to stemness, including telomerase reverse transcriptase, forkhead box D3 and undifferentiated embryonic cell transcription factor 1, remarkably in breast cancer cells. Furthermore, SKBR3 cells knocked down for LL-37 expression showed a decreased production of oncospheres in comparison with negative controls, while A375 cells exhibited increased production. Taken collectively, our findings indicate a role for LL-37 in cancer cell stemness depending on the cell type

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal

Les oxydes La2Mo2-yWyO9 (1,0 ≤y ≤ 2,0) ont été obtenus par voie de synthèse solide-solide et caractérisés par diffraction des rayons X (température ambiante et en température) ainsi que par analyse thermique différentielle. Un diagramme de phase de ce système est proposé. Les phases thermodynamiquement stables à température ambiante sont : pour 1,0≤ y ≤1,2 une solution solide de type β-La2Mo2O9 (cubique); pour 1,3≤ y ≤1,575 un domaine biphasique de phases de type β-La2Mo2O9+ α-La2W2O9 et pour 1,6≤ y ≤2,0 une solution solide de type α-La2W2O9. Dans le domaine biphasique, une distribution inhomogène du tungstène est suspectée. Il est clair que les composés à teneur en tungstène supérieure à y=1,2 ne conviennent pas pour utilisation en piles à combustibles à oxydes solides.Des études de diffusion cationiques par SIMS ont été menées sur des couples La2Mo2O9 (LMO)/La0.8Sr0.2MnO3-δ (LSM) après leurs recuits à haute température. Des cristaux de LaMnO3 en forme de barreau ont été observés sur les pastilles de LMO et la croissance d’une phase de type SrMoO4 a été constatée sur la pastille LSM. Des hypothèses expliquant les mécanismes possibles de diffusion sont présentés. Les coefficients de diffusion en volume du strontium et du manganèse dans LMO et du molybdène dans LSM sont estimés proches respectivement de 1x10-20 cm2.s-1 et 1x10-15 cm2.s-1 à 800°C. Des études similaires de diffusion ont été menées par dépôts de solutions riches en cations manganèse et strontium sur des pastilles de LMO et d’une solution riche en cation molybdène sur une pastille de LSM. Après recuit, la formation de cristaux de LaMnO3 au niveau de la zone de dépôt de la solution de manganèse a été observée. Les coefficients de diffusion du molybdène dans LSM et du strontium dans LMO semblent être beaucoup plus importants -proches de 1-2x10-10cm2.s-1 à 1150°C- que ceux obtenus lors des mesures sur couple LMO/LSM. De par leur réactivité, le couple LMO/LSM ne semble pas adapté pour une application dans le domaine des piles à combustible, sauf si une couche tampon appropriée les sépare.Les stabilités de LMO et de LMO dopé tungstène ont été étudiées sous atmosphères réductrices. Suivant le taux de perte en oxygène, des changements structuraux successifs ont été observés : de phase LMO à La7Mo7O30(7730), phase amorphe réduite La2Mo2O7-δ et décomposition partielle sous forme de molybdène métallique. Le domaine de stabilité de La2Mo2-yWyO9 sous faible pression de O2 ne semble pas dépendant du taux de tungstène alors que la cinétique de réduction, elle, évolue avec y. En revanche, la limite de stabilité de la phase 7730 apparait dépendante du taux de tungstène. La phase réduite amorphe existe sur un large domaine de stoechiométrie en oxygène (7-δ de 6,69 à 6,20), cependant sa stabilité vs. PO2 reste à démontrer. Les mesures de résistivité conduites sur un échantillon amorphe de La2Mo2O7-δ de faible compacité et sans fissure ont montré une augmentation significative de la conductivité (> 1 S.cm-1 à 1000 K) vis-à-vis de La2Mo2O9, avec une pseudo-énergie d’activation de 0.255eV. Il a été supposé qu’une conductivité électronique de type n résulte de la réduction partielle des cations Mo6+ en Mo3+ et Mo4+. / La2Mo2-yWyO9 (y = 1.0 to 2.0) oxides were synthesized by conventional solid state route and studied by XRD, TC-XRD and DTA. A phase diagram of the series was proposed. The thermodynamically stable phases at room temperature are: for 1.0≤ y ≤1.2 a cubic β-La2Mo2O9 type solid solution, for 1.3≤ y ≤1.575 a biphasic mixture of β-La2Mo2O9 type + α-La2W2O9 type phases, and for 1.6≤ y ≤2.0 a triclinic α-La2W2O9 type solid solution. Inhomogeneous distribution of W is suspected in the biphasic samples. It is clear that the compounds above y =1.2 are not suitable for SOFC applications.Cationic diffusion studies were performed using SIMS on La2Mo2O9 (LMO)/La0.8Sr0.2MnO3-δ (LSM) annealed couples. Rod shaped LaMnO3 grains were observed on LMO pellet and SrMoO4 type phases were seen to be growing on LSM pellet. Hypotheses for possible reaction mechanisms are presented. Bulk diffusion coefficients of Sr and Mn in LMO and of Mo in LSM are extrapolated to be around 1x10-20 cm2.s-1 and 1x10-15 cm2.s-1, respectively, at 800oC. Similar diffusion studies were performed by depositing Mn and Sr cation rich solutions on LMO pellets and Mo rich solution on LSM pellet. Mn solution was observed to be forming, upon annealing, LaMnO3 single crystals on the surface of the LMO pellet. Mo in LSM and Sr in LMO diffusion coefficients appear to be much higher than in LMO/LSM couple experiments, namely around 1-2x10-10cm2.s-1 at 1150°C. Because of the reactivity, LMO/LSM couple is not desirable for SOFC applications, unless an appropriate buffer layer separates them.The stability of LMO and W-LMO was studied under reductive atmospheres. Successive structural changes from LMO to La7Mo7O30 (7730), an amorphous reduced phase La2Mo2O7-δ, and partial decomposition to metallic Mo were observed as a function of oxygen loss. The pO2 stability domain of La2Mo2-yWyO9 did not appear to change with W content, but the reduction kinetics varied with y. At reverse, the stability limit of the 7730 phase was found to be dependent on W content. The amorphous reduced phase can accommodate a wide range of oxygen stoichiometry (7-δ from 6.69 to 6.20), but its stability vs. pO2 is questioned. Resistivity measurements performed on a low compacity crack-free amorphous La2Mo2O7-δ sample showed significant increase in the conductivity (> 1 S.cm-1 at 1000 K) relative to La2Mo2O9, with a pseudo activation energy 0.255eV. It is postulated that n-type electronic conductivity arises from partial reduction of hexavalent Mo6+ to a mixture of Mo3+ and Mo4+.

The present thesis deals with different aspects of the chemistry of oxovanadium(IV) complexes, their interaction with double stranded DNA, photo-induced DNA cleavage, photo-enhanced cytotoxicity in visible light and red light and localisation and cellular uptake to understand the mechanism of cell death. Chapter I presents a general introduction on potential of transition metal complexes as photochemotherapeutic agents. A brief introduction about Photodynamic Therapy (PDT) as a new alternative to chemotherapy for treating cancer has been made. Various modes of interaction of small molecules with duplex DNA are described. Recent reports on metal-based photocytotoxicity, photo-induced DNA cleavage activity and cellular localization are presented in detail. Objective of the present investigation is also dealt in this Chapter. Chapter II of the thesis deals with the synthesis, characterization, DNA binding and photo-induced DNA cleavage activity of ternary oxovanadium(IV) complexes of ONO-donor 2-(2-hydroxybenzylideneamino)phenol (salamp) and phenanthroline bases to explore the photo-induced DNA cleavage activity in UV-A light of 365 nm and photocytotoxicity in visible light. Chapter III deals with the photo-induced DNA cleavage and photocytotoxicity of ternary oxovanadium(IV) complexes containing ONN-donor N-2-pyridylmethylidine-2-hydroxyphenylamine (Hpyamp) Schiff bases and phenanthroline bases. The objective of this work is to investigate the photo-induced DNA cleavage activity in near-IR light. Photocytotoxicity and cell cycle arrest have been studied in HeLa cancer cells. Chapter IV deals serendipitous discovery of planar triazinuim cationic species by vanadyl-assisted novel ring cyclization reaction. The compounds are synthesised, characterized and their DNA binding and anaerobic photoinduced DNA cleavage activity are presented. The importance of the thiazole moiety in the triazinuim species in cellular uptake has been investigated. Photocytotoxicity, localization and cell death mechanism have been studied in HeLa and MCF-7 cells. Chapter V describes the synthesis, characterization, DNA binding, photo-induced DNA cleavage activity and photocytotoxicity of oxovanadium(IV) complexes containing 2-(1H-benzimidazol-2-yl)-N-(pyridin-2-ylmethylene)ethaneamine (Hpy-aebmz) and curcumin as photosensitizer. The effect of conjugating naphthalimide on Hpy-aebmz on photoinduced DNA cleavage and photocytotoxicity has been studied. Cellular uptake, localization and mechanism of cell death induced by complexes have been investigated. Chapter VI presents ternary oxovanadium(IV) complexes having, 2-((1H-benzimidazol-2-yl)methylimino-methyl)phenol (Hsal-ambmz) and phenanthroline bases. The complexes were synthesized, characterized and their DNA binding property studied. Photo-induced DNA cleavage activity and photocytotoxicity in red light has been discussed. Anthracene has been conjugated to a tridentate ligand to investigate cellular uptake, localization and cell death mechanism. Mitochondria targeting property of the complexes having dipeptide has been studied and compared with clinically used drug Photofrin®. The references have been compiled at the end of each chapter and indicated as superscript numbers in the text. The complexes presented in this thesis are represented by bold-faced numbers. Crystallographic data of the complexes, characterized structurally by single crystal X-ray crystallography, are given in CIF format in the enclosed CD (Appendix-I). Due acknowledgements have been made wherever the work described is based on the findings of other investigators. Any unintentional omission that might have happened due to oversight or mistake is regretted.