Made available in DSpace on 2016-06-02T20:36:30Z (GMT). No. of bitstreams: 1 3525.pdf: 5204995 bytes, checksum: 3de0b93193d94cfce24d35cdc8277abc (MD5) Previous issue date: 2011-03-23 / Financiadora de Estudos e Projetos / Salen-type complexes are an important class of coordination compounds and are used as catalysts in various homogeneous and heterogeneous systems. Complexes of transition metals participate in many chemical processes, which make the study of these complexes very interesting. Research shows that the complexes of salen [salen = N, N'-ethylenebis (salicilidenoamina)] are efficient catalysts. Some compounds of this type have been investigated as catalysts for the oxidation of catechol. In this work three types of compounds the tetradentate ligands and symmetrical complexes, tridentate complexes and the asymmetric tetradentate complex, were synthesized. The series provided satisfactory yields. The compounds synthesized in this work were characterized by melting point, elemental analysis, vibrational spectroscopy in the IR region, absorption spectra in the UV-vis, conductivity measurements and solubility. The ligands were also characterized by nuclear magnetic resonance. From these characterizations, comparisons were made with respect to the effects of the substituents on the aromatic ring within the same series of compounds and also compared the results obtained for different lines of work. The kinetics was performed using a spectrophotometer, following the formation of the product derived from oxidation of 3,5-di-tert-butylcatechol at 400 nm. Among the complexes showed catalytic activity are the symmetrical complex [Cu (salen)], kcat = 2.6 x10-2 s-1, Vmax = 1.74 x10-7 mol L-1 s-1 and the complex asymmetric [Cu (3.5 Brsalen)]ass, kcat = 4.1 x10-2s-1, Vmax = 2.72 x10-7 mol L-1 s-1 and [Cu (3.5 Br4MeO-3, 5Br'salen) ]ass, kcat = 5.2 x10-2 s-1, Vmax = 3.39 x10-7 mol L-1 s-1. / Os complexos do tipo salen são uma classe importante dos compostos de coordenação e são utilizados como catalisadores em vários sistemas homogêneos e heterogêneos. Complexos de metais de transição têm participação em muitos processos químicos, o que torna o estudo desses muito interessantes. Pesquisas mostram que os complexos de salen [salen= N,N -etilenobis(salicilidenoamina)] são catalisadores eficientes. Alguns compostos deste tipo foram investigados como catalisadores na oxidação de catecol. Foram sintetizados nesse trabalho três tipos de compostos, os ligantes e complexos tetradentados simétricos; os complexos tridentados; e os complexos tetradentados assimétricos. As séries apresentaram rendimentos satisfatórios. Os compostos sintetizados nesse trabalho foram caracterizados por ponto de fusão, análise elementar, espectroscopia vibracional na região do IV, espectroscopia de absorção na região do UV-vis, medidas de condutividade e solubilidade. Os ligantes foram caracterizados também por Ressonância Magnética Nuclear. A partir dessas caracterizações, foram feitas comparações com respeito aos efeitos dos substituintes no anel aromático dentro de uma mesma série de compostos e também foram comparados os resultados obtidos para as diferentes séries do trabalho. A cinética foi realizada em um espectrofotômetro, acompanhando-se a formação do produto derivado da oxidação do 3,5-di-terc-Butilcatecol em 400 nm. Dentre os complexos que apresentaram atividade catalítica estão o complexo simétrico [Cu(salen)], kcat = 2,6x10-2 s-1, Vmax=1,74x10-7 mol L-1 s-1 e os complexos assimétricos, [Cu(3,5Brsalen)], kcat = 4,1x10-2s-1, Vmax=2,72x10-7mol-1 L-1 s-1 e [Cu(3,5Br4MeO-3,5Br salen)], kcat = 5,2x10-2 s-1, Vmax=3,39x10-7 mol L-1 s-1.

Made available in DSpace on 2016-06-02T20:36:46Z (GMT). No. of bitstreams: 1 5385.pdf: 2306216 bytes, checksum: daa1a7a640849ca4041dc0c6bf307073 (MD5) Previous issue date: 2011-08-02 / Universidade Federal de Sao Carlos / Salen-type complexes are an important class of coordination compounds, which have been used to catalyze a wide variety of reactions in various homogeneous and heterogeneous systems. Complexes of transition metals are very versatile and participate in many chemical processes, which make the study of these very interesting. Research shows that the complexes of salen [salen = N, N'-ethylenebis (salicilidenoamina)] are efficient catalysts, and some compounds of this type have been investigated as catalysts in the oxidation of catechol. In this work were synthesized three types of compounds, ligands, mononuclear complexes and binuclear complexes. The three series have satisfactory yields. The compounds synthesized in this work were characterized by melting point, elemental analysis, vibrational spectroscopy in the IR region, absorption spectra in the UV-vis, conductivity measurements and solubility. The ligands were also characterized by nuclear magnetic resonance. From these characterizations, comparisons were made between ligands, mononuclear and binuclear complexes, and also with respect to the effects of the substituents on the aromatic ring taking into account series with and without methoxy substituents at positions 3, 4 and 5. The kinetics was performed using a spectrophotometer, following the formation of the product derived from oxidation of 3,5-di-tertbutylcatechol at 400 nm. It was also observed, the proportion of conversion by gas chromatography. Among the complexes that showed catalytic activity are the cis and trans complex [Cu(Cu(salcn))Cl2], kcat = 0,037 s-1 e kcat = 0,035 s-1, respectively; and the cis and trans complex [Cu(Cu(5-MeOsalcn))Cl2], kcat = 0,040 s-1 e kcat = 0,060 s-1, respectively. / Salen complexos são uma importante classe de compostos de coordenação, os quais vêm sendo usados para catalisar uma larga variedade de reações em vários sistemas homogêneos e heterogêneos. Complexos de metais de transição são muito versáteis e tem participação em muitos processos químicos, o que torna o estudo desses muito interessantes. Pesquisas mostram que os complexos de salen [salen= N,N -etilenobis(salicilidenoamina)] são catalisadores eficientes, sendo que, alguns compostos deste tipo foram investigados como catalisadores na oxidação de catecol. Foram sintetizados nesse trabalho três tipos de compostos, ligantes, complexos mononucleares e complexos binucleares. As séries apresentaram rendimentos satisfatórios. Os compostos sintetizados nesse trabalho foram caracterizados por ponto de fusão, análise elementar, espectroscopia vibracional na região do IV, espectroscopia de absorção na região do UV-vis, medidas de condutividade e solubilidades, sendo que os ligantes também foram caracterizados por Ressonância Magnética Nuclear. A partir dessas caracterizações, foram feitas comparações entre ligantes, complexos mononucleares e binucleares, e também com respeito aos efeitos dos substituintes no anel aromático levando em consideração séries sem e com substituintes Metoxi nas posições 3, 4 e 5. As cinéticas foram estudadas por meio espectrofotométrico acompanhando-se a formação do produto derivado da oxidação do 3,5-di-terc-Butilcatecol em 400 nm. Também foi avaliada a porcentagem de conversão através de cromatografia gasosa. Dentre os complexos que apresentaram atividade catalítica estão os complexos cis e trans [Cu(Cu(salcn))Cl2], kcat = 0,037 s-1 e kcat = 0,035 s-1, respectivamente; e os complexos cis e trans [Cu(Cu(5-MeOsalcn))Cl2], kcat = 0,040 s-1 e kcat = 0,060 s-1, respectivamente.

O trabalho apresenta a síntese e a caracterização de novos compostos heterocíclicos benzazólicos dos tipos 2-(4’-aminofenil)-6-nitrobenzazóis fluorescentes por apresentar provável transferência de carga intramolecular no estado excitado (ICT) e iminas aromáticas basedas nos compostos 2-(4’-amino-2’- hidroxifenil)-6-nitrobenzazóis fluorescentes devido a mecanismo de transferência protônica intramolecular no estado excitado (ESIPT). Estes compostos foram caracterizados por espectroscopia de absorção na região do Infravermelho, ressonância magnética nuclear de hidrogênio (1H-RMN). Foram realizados estudos fotofísicos através das espectroscopia de absorção na região do ultravioleta-visível e de emissão de fluorescência, determinando assim, os prováveis estados eletrônicos excitados em solventes polares e apolares. / This work presents the synthesis and characterization of new fluorescent heterocyclic derivatives based on 2-(4'-aminophenyl)-6-nitrobenzazoles, as well as aromatic imines based on 2-(4'-amino-2'-hydroxyphenyl)-6-nitrobenzazoles. These molecules are photoactive due to an intramolecular proton transfer in the excited state (ESIPT) or a intramolecular charge transfer (ICT) mechanism. These compounds were characterized by infrared spectroscopy and nuclear magnetic resonance 1H-NMR. Photophysical studies were performed using the absorption spectroscopy in the ultraviolet-visible and fluorescence emission, thereby determining the excited electronic states in polar and nonpolar solvents.

Au-delà de son importance dans l’industrie nucléaire, la chimie d’oxydoréduction de l’uraniumretient de plus en plus l’attention des chercheurs. En effet, la capacité toute particulière descomplexes d’uranium à bas degré d’oxydation à promouvoir des réductions originales par desvoies inhabituelles suscite actuellement un grand intérêt, tout particulièrement leur aptitude àactiver dans des conditions douces des petites molécules telles CO, CO2, N2, ou encore descomposés aromatiques et des azotures. Les composés d’uranium, de part leurs propriétés decoordination tout à fait uniques pourraient offrir une alternative aux métaux de transitionclassiques pour la conception de catalyseurs. Cependant, comparativement aux métaux du bloc d,les processus polyélectroniques sont rares dans la chimie de l’uranium à bas degré d’oxidation quiest dominée par les transferts monoélectroniques. C’est pourquoi le développement de nouveauxcomplexes d’uranium capables de réaliser des réductions poly-électroniques est particulièrementintéressant. Le premier objectif de ce travail était d’associer à l’uranium des ligands non-innocentsservant de réservoir d’électrons. Ainsi nous avons utilisé des bases de Schiff p-conjuguées pourexplorer la chimie de cet élément à bas degree d’oxydation. Cela nous a permis d’isoler descomplexes riches en électrons dans lesquels des électrons sont stockés sur le ligand via laformation de liaisons C-C. Ces mêmes liaisons sont rompues en présence d’agent oxydant, et lesélectrons sont libérés pour réaliser des transformations polyélectroniques. Ce procédé a étéobservé pour plusieurs bases de Schiff, permettant de moduler les propriétés des composés. Dansune seconde approche, nous nous sommes intéressés à la synthèse et à l’étude de la réactivité denouveaux complexes d’uranium trivalent supportés par des ligands silanolates. De nouveauxcomposés dinucléaires d’uranium à basse valence ont été obtenus. Ces composés très réactifsdécomposent spontanément en clivant des groupements tertiobutyls des ligands, conduisant à laformation de complexes d’uranium(IV). En parallèle, un complexe monoanionique mononucléaired’U(III) a été isolé, nous permettant de comparer la réactivité de l’uranium trivalent dans différentsenvironnements stériques et électroniques. Ces études de réactivité ont permis de stabiliser unexemple rare de dimère d’uranium ponté par un groupement CS22- et ont mis en évidence lacapacité de l’uranium trivalent à promouvoir la dismutation de CO2 en carbonate et CO. La réactionde ces composés d’uranium trivalent vis-à-vis d’azotures organiques et inorganiques a produit denouveaux nitrures et nitrènes d’uranium originaux. Enfin, la capacité de ces agents réducteurspuissants à transférer des électrons au toluène a permis d’isoler une famille de complexessandwiches inversés où deux cations uranium sont liés de part et d’autre d’un cycle aromatique. / Beyond its importance in nuclear industry the redox chemistry uranium is attracting increasinginterest because complexes of low-valent uranium can promote unusual reductive chemistrythrough unusual reaction pathways, including attractive examples of CO, CO2, N2, arenes andazides activation in mild condition. Due to the unique coordination and bonding properties ofuranium, its compounds could provide an attractive alternative to transition metals for thecatalytic transformation of small molecules. However, metal-based multi-electron processesremain uncommon in uranium chemistry especially in comparison with the d-block metals, thechemistry of low-valent uranium being dominated by single-electron transfers. In this context, thefirst aim of this project was to investigate the association of low-valent uranium to a non-innocentligand acting as an independent electron reservoir at a same molecule. Accordingly, weinterrogated the use of highly p-delocalized Schiff bases ligands for supporting low-valent uraniumchemistry. This led to the isolation of electron-rich complexes which are stabilized by storingelectrons on the ligands through the formation of C-C bonds. Interestingly, these C-C bonds can becleaved by oxidizing agents and the electrons released to participate in multi-electron redoxreactions. This process was observed within different Schiff-base ligand scaffolds, allowing atuning of the properties of the compounds. The second part of this work was dedicated to thesynthesis of novel trivalent uranium complexes supported by siloxy ligands and the study of theirredox reactivity and coordination properties. Novel dinuclear highly-reactive low-valent uraniumassemblies were developed. The study of their limited stability revealed that these compounds arespontaneously decomposing through the cleavage of tBu groups from the supporting ligandsresulting in the formation of U(IV) species. In parallel, a mononuclear trivalent uranium atecomplex was obtained, allowing to compare the reactivity of U(III) in different steric and electronicenvironements. Hence we became interested in studying the redox reactivity of these compoundswith different substrates including CO2, CS2, azides and arenes. These investigations led to thestabilization of a rare CS22- sandwich complex of uranium, and highlited the ability of U(III) topromote reductive disproportionation of CO2 to carbonate and CO. The reaction of these trivalenturanium siloxide species with organic and inorganic azides produced original uranium imidos andnitridos compounds with original topologies. Finally the capacity of these strongly reducing agentsto transfer electrons to the toluene fragment lead to the isolation of a family of arenes invertedsandwich complexes.

Made available in DSpace on 2014-06-11T19:29:06Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-04-19Bitstream added on 2014-06-13T18:38:45Z : No. of bitstreams: 1 martin_cs_me_sjrp.pdf: 1815881 bytes, checksum: f4bcade9143b72e80d41d79ebd336a65 (MD5) / A presente dissertação de mestrado apresenta o estudo da eletropolimerização de monômeros à base de Schiff na ausência de cátions metálicos (N,N’-bis(5-aminosalicilidenoimina) – NH2 -salen) e do monômero a base de Schiff contendo níquel como cátion metálico no centro ligante tetradentado (N,N’,N’’,N’’’-tetrabis(salicilideno)3,3’,4,4’-bifenileno tetramino de níquel (II)) – Ni2 (Bisalphen). A obtenção do monômero NH 2 -salen foi realizada pela redução metálica em meio ácido do monômero NO 2 -salen (N,N’-bis(5-nitrosalicilidenoimina)), sendo confirmada pela técnica de espectroscopia no infravermelho (FTIR), espectrofotometria na região de UV-vís e por espectroscopia de massa (MS-EI). As análises dos voltamogramas de eletropolimerização, e dos perfis voltamétricos em solução aquosa, demonstram um mecanismo de por acoplamento C–N. O mecanismo foi confirmado pelo estudo de velocidade de varredura e número de ciclos de potenciais, como também pela caracterização por espectroscopia Raman. Em solução aquosa o filme de poli(NH-salen) apresentou um único par redox na ausência de oxigênio molecular, atribuído ao par redox R 1 -NH-C-R 2 /R 1 -N=C-R 2 , onde um aumento da concentração de espécie eletroativa foi obtida em função do aumento da razão [carga do íon]/[raio iônico] dos ânions presentes em solução, que pode ser atribuído a necessidade da difusão dos ânions no processo de transferência eletrônica. Para comparação dos mecanismos de formação, a obtenção do filme polimérico do complexo metálico Ni 2 (Bisalphen) foi realizada de modo semelhante, modificando apenas o solvente e eletrólito suporte utilizado. Na etapa de eletropolimerização, os resultados foram satisfatórios somente em solvente THF contendo... / This dissertation presents the study of electropolymerization of monomers to the Schiff base in the absence of metal cations (N, N'-bis (5-amine-salicylideneimine) - NH2 -salen) and the Schiff base monomer containing nickel as metallic cation in the tetradentate center (N,N',N'',N'''-tetrabis(salicylidene) 3,3',4,4'-biphenylene-tetramine of nickel (II) - Ni2 (Bisalphen)). The NH 2 -salen monomer synthesis was realized by metallic reduction in acid medium from NO2 -salen (N,N'-bis(5-nitro-salicylideneimine)), being confirmed by the infrared spectroscopy (FTIR), UV-Vis spectrophotometry, and mass spectroscopy of electronic impact (MS-EI). The voltammetric profiles obtained on electropolymerization stage and in aqueous solution show the mechanism formation based on C-N coupling. This mechanism was confirmed by scan rate, potential cycle number study, and by the Raman characterization. In aqueous solution the poli(NH-salen) film showed one redox couple in absence of molecular oxygen, which was ascribed to R 1 -NH-C-R 2 /R 1 -N=C-R 2 redox couple. The increase of surface coverage was obtained in function of [ion charge]/[ionic radius] ratio of the anions present in aqueous solution, which can be ascribed to necessity of anion diffusion on electronic transfer. In order to compare the electropolymerization mechanism, the polymeric film of Ni2 (Bisalphen) was also obtained by electropolymerization technique. However, the solvent and supporting electrolyte were different. In the electropolymerization stage, the results were satisfactory only in THF solvent using the TBAP as supporting electrolyte, which can be ascribed to low solubility of complex in other solvents, as well as the low dipole value, necessary to propagation of the reaction. Due to presence of the metallic cation on monomer structure, the electropolymerizatiom... (Complete abstract click electronic access below)

O trabalho apresenta a síntese e a caracterização de novos compostos heterocíclicos benzazólicos dos tipos 2-(4’-aminofenil)-6-nitrobenzazóis fluorescentes por apresentar provável transferência de carga intramolecular no estado excitado (ICT) e iminas aromáticas basedas nos compostos 2-(4’-amino-2’- hidroxifenil)-6-nitrobenzazóis fluorescentes devido a mecanismo de transferência protônica intramolecular no estado excitado (ESIPT). Estes compostos foram caracterizados por espectroscopia de absorção na região do Infravermelho, ressonância magnética nuclear de hidrogênio (1H-RMN). Foram realizados estudos fotofísicos através das espectroscopia de absorção na região do ultravioleta-visível e de emissão de fluorescência, determinando assim, os prováveis estados eletrônicos excitados em solventes polares e apolares. / This work presents the synthesis and characterization of new fluorescent heterocyclic derivatives based on 2-(4'-aminophenyl)-6-nitrobenzazoles, as well as aromatic imines based on 2-(4'-amino-2'-hydroxyphenyl)-6-nitrobenzazoles. These molecules are photoactive due to an intramolecular proton transfer in the excited state (ESIPT) or a intramolecular charge transfer (ICT) mechanism. These compounds were characterized by infrared spectroscopy and nuclear magnetic resonance 1H-NMR. Photophysical studies were performed using the absorption spectroscopy in the ultraviolet-visible and fluorescence emission, thereby determining the excited electronic states in polar and nonpolar solvents.

Neste trabalho inicialmente foi feita uma breve apresentação sobre a utilização de compostos de bases de Schiff e Cobre(II) como catalisadores na reação de oxidação de sulfetos. Foi feita a determinação das estruturas cristalinas dos compostos: N,N\'-bis(3-etoxisalicilideno)-(1,2etileno- diamina) Cu(II), sistema cristalino ortorrômbico grupo espacial Pbcn a = 7.639(5); b= 12.760(5); c= 19.733(5)Å; V = 1923.4(15) (3)Å3; Dcalc = 1.505 Mg/m3; MM = 435.96; e m = 1.170 mm-1, N,N\'-bis (4-dietilaminasalicilideno) - (1,2etilenodiamina) Cu(II), sistema monoclínico, C2/c, a = 19.571(2); b=9.8514(2)=; c=12.4552(4) Å; Beta = 93.705(9)o; V =2396.4(5) Å3; Dcalc=1.358 Mg.m-3; MM= 490.10; e m = 0.944 mm-1, N,N\'-bis(3-metoxisalicilideno)-(1,2etilenodiamina)Cu(II), sistema ortorrômbico, Pna21, a = 7.5140(6); b= 9.2629(9); c= 24.721(3)Å; V =1720.6(3) Å3; Dcalc = 1.575 Mg,m-1; MM = 407.91; e m = 1.302 mm1 e (SALAHE)Cu(II), monoclínico, P21/C, a = 18.3216(2) Å; b=4.804(3) Å; c=19.801(2)Å; Beta = 98.908(6)o; V =2396.4(5) Å3; Dcalc=1.358 Mg.m-3; MM= 490.10; e m = 0.944 mm-1. Os cálculos teóricos para as quatro moléculas foram efetuados partindo-se das coordenadas atômicas cristalográficas. Foram modeladas, para posterior estudo teórico, as moléculas de vinte e seis compostos de bases de Schiff e Cobre(II) análogos. Foram calculadas 104 variáveis para cada composto, e realizado o estudo de correlação estrutura-atividade catalítica através de métodos de Quimiometria. Foi obtido um modelo de correlação utilizando a classe de compostos de atividade catalítica pré-definida. Finalmente foi realizada a tentativa de previsão de atividade dos vinte e quatro compostos com atividade não conhecida, obtendo-se como resultado a probabilidade de vinte deles serem ativos como catalisadores da conversão sulfeto-sulfóxido . / Initially, in this work, a brief presentation about Schiff bases and their applications as catalysist. The crystalline structure determination was made for the compounds: N,N\'-bis(3-etoxysalicylidene)- (1,2ethylenediamine) Cu(II), crystal system orthorhombic spatial group Pbcn a = 7.639(5); b= 12.760(5); c= 19.733(5)Å; V = 1923.4(15) (3)Å3; Dcalc = 1.505 Mg/m3; MM = 435.96; e m = 1.170 mm-1, N,N\'-bis (4- diethylaminesalicilidene) - (1,2ethylenediamine) Cu(II), monoclinic, C2/c, a = 19.571(2); b=9.8514(2)=; c=12.4552(4) Å; B= 93.705(9)o; V =2396.4(5) Å3; Dcalc=1.358 Mg.m-3; MM= 490.10; e m = 0.944 mm-1, N,N\'-bis(3-metoxysalicilidene)- (1,2ethylenediamine) Cu(II), orthorhombic, Pna21, a = 7.5140(6); b= 9.2629(9); c= 24.721(3)Å; V =1720.6(3) Å3; Dcalc = 1.575 Mg,m-1; MM = 407.91; e m = 1.302 mm1 e (SALAHE)Cu(II), monoclinic, P21/C, a = 18.3216(2) Å; b=4.804(3) Å; c=19.801(2)Å; B= 98.908(6)o; V =2396.4(5) Å3; Dcalc=1.358 Mg.m-3; MM= 490.10; e m = 0.944 mm-1. The theoretical calculations for the four molecules had been effected starting of the crystallographic atomic coordinates. Twenty-six molecules without determined crystallographic structure had been shaped for theoretical study. 104 variables for each compound had been calculated, and carried through the correlation study structure-catalyst activity through chemometric methods. A separation model was gotten in one single class. Finally the attempt of forecast of activity of twenty four compounds with activity unknown was carried through, getting itself as resulted the probability of twenty in all to be able to become active.

Neste trabalho estudamos propriedades estruturais, magnéticas e eletrônicas de complexos de cobre em duas classes de ligantes semelhantes com potenciais aplicações nas áreas de nanotecnologia e farmacologia. A primeira classe de ligantes é do tipo bases de Schiff, conhecidas por sua vasta gama de aplicações em química e biologia, aqui estudadas como miméticos de sítios de proteínas e também como potenciais metalo-fármacos. Procuramos investigar as características estruturais e eletrônicas buscando correlacionar as informações obtidas experimentalmente com as obtidas através de cálculos de estrutura eletrônica. Em especial, no estudo da competição pelo íon Cu entre as bases de Schiff e a proteína albumina, mostramos a influência de diversos fatores como, por exemplo, a geometria dos ligantes e a sua estrutura eletrônica. A segunda classe estudada é constituída de bases modificadas de DNA com a habilidade de complexar metais (espécie [M-DNA]) e formar estruturas com acoplamento ferromagnético. Observamos para as espécies [M-DNA] que o acoplamento ferromagnético é estabilizado através de dois efeitos: a) diferentes estados de carga que podem gerar distorções na coordenação quadrado planar; b) a adição do backbone do DNA. Utilizamos neste estudo o método Projector Augmented Wave (PAW) e também bases locais dentro da Teoria do Funcional da Densidade, atrav´es dos c´odigos computacionais CP-PAW e Gaussian03. / We studied structural, electronic and magnetic properties of copper complexes with two similar classes of ligands with potential applications in nanotechnology or pharmacology. The first class of compounds consists of Schiff bases and corresponding copper complexes. We investigated structural and electronic properties of these complexes searching for correlations among the information obtained experimentally and by electronic structure calculations. In special, in the study of the competition for the Cu ion between Schiff bases and the albumin protein, we show the influence of different factors such as the geometry of the ligands and their electronic structure. The second class of ligands focused in our studies are modified DNA bases coordinated to copper, where EPR studies have shown ferromagnetic interactions among the metal centers. We studied in this case the influence of the charge state and of the backbone in the magnetization of the Cu chain. In all cases presented here, we used ab-initio electronic structure calculations in the framework of the Density Functional Theory (DFT). This has been done using the CP-PAW code and the Gaussian03 code.

Il y a de nos jours un besoin urgent de découvrir de nouveaux médicaments pour relever le défi de la multirésistance dans le traitement des infections bactériennes et le cancer. Dans cette perspective, des bases de Schiff dérivées de dithiocarbazates et leurs complexes métalliques correspondants sont des candidats intéressants puisqu'ils peuvent être facilement synthétisés et permettent une grande diversité de coordination. Dans cette étude, des complexes tetradentes et bidente ont été préparés. Les ligands et complexes synthétisés ont été entièrement caractérisés par différentes méthodes spectroscopiques et physico-chimiques dans le solide et en solution. L'activité antibactérienne de ces complexes a ensuite été étudiée et a permis de sélectionner un complexe " leader " (plus efficace, stable et fonctionnalisable). Ce complexe a alors été modifié afin d'augmenter sa stabilité en milieux biologique, sa solubilité dans l'eau ainsi que son activité. Il a été conjugué avec différentes entités : des peptides pénétrants, un polyéthylène glycol (PEG) et un peptide inhibiteur des pompes d'efflux bactériennes. Ces complexes ont montré une remarquable activité antibactérienne sur neuf souches de bactéries Gram-positives et Gram-négatives et en particulier, ils se sont avérés très efficaces contre S.aureus. L'activité anti-cancéreuse des complexes non-conjugués a également été étudiée et les complexes de cuivre sélectionnés et testés sur des cellules de cancer du sein ont montré une cytotoxicité élevée. Ceci met en évidence la pertinence d'utiliser les complexes métalliques, pour à la fois stabiliser les ligands et générer des composés plus actifs. / There is an urgent need to discover new drugs with novel mechanisms of action, higher activity and improved selectivity to address the severe challenge of multidrug resistance in treating bacterial infections and cancer. In view of this, Schiff bases derived from S-substituted dithiocarbazate and their corresponding metal complexes with a plethora of potentially exciting biological activities and coordination chemistry are attractive candidates. Metal complexes of tetradentate NNSS and bidentate NS ligands have been prepared. The compounds were fully characterized with various physico-chemical and spectroscopic methods in solution and solid state. Conjugation of the most promising antimicrobial compound to various moities (polyarginine, polyethylene glycol (PEG) and an bacterial efflux pump inhibitor) was achieved to prepare improved therapeutic agents. The nanoarginines (R9) derivatives showed the most encouraging synergistic effect upon conjugation and complexation to copper ion with enhanced water solubility, bacteria cell membrane permeability and bioactivity. The Cu(II) R9 derivatives possess remarkable antibacterial activity against a wide spectrum of bacteria and in particular, highly efficacious against S. aureus. This show that the conjugation of polyarginine to dithiocarbazate compounds can greatly influence their therapeutic potential. Cytotoxic assay was also carried out for selected non-conjugated compounds. All the selected Cu(II) complexes assayed against breast cancer cells lines exhibited good cytotoxicity. This work highlights the relevance of the strategy that consists of using metal complexes to stabilize the ligands and improve their bioactivity.

A series of 31 sulfur-nitrogen donor ligands and 64 metal(II) complexes have been investigated. The thiomethylated aniline ligands 2–(methylthiomethyl)aniline 2MT and 2–(methylthio)aniline 2MA were synthesized with their substituted derivatives (-Me, -MeO, -Cl, -Br, -NO2) to serve as chelating agents. These ligands behave as bidentate ligands with SN donor group with Co(II), Ni(II) and Cu(II). The Co(II) and Ni(II) complexes have the ML2Cl2 molecular formula while the Cu(II) complexes formed with MLCl2 stoichiometry where L is the bidentate ligand. The ligands and their metal(II) complexes have been characterized by elemental analysis and with spectroscopic techniques. The trend observed in the NMR spectra and IR frequencies of the thiomethylated compounds shows there is a significant difference between the 2MT and 2MA series as a result of sulfur lone pairs extending the conjugation of the aromatic ring in the case of the latter. The effect of the position and electronic nature of ring substituent on the NMR shifts of the amine protons is discussed. The 6- and 5-membered chelate complexes formed by the 2MT and 2MA ligands respectively do not show significant diversity in their spectroscopic properties. From the elemental analysis for the Co(II) and Ni(II) complexes, their compositions reveal 1:2 M:L stoichiometry with 2 chlorine atoms from the respective metal salts. In addition, the spectroscopic data are largely indicative of tetragonally distorted structures for these solid complexes. The X-ray crystallography data reveal the Cu(II) complexes exist as square pyramidal dimers and with long Cu–Cl equitorial bonds fit into the tetragonally distorted octahedral structure. The electrolytic nature of Co(II) and Cu(II) complexes in DMF were found to be similar, they behave as non electrolytes in contrast to Ni(II) complexes which are 1:1 electrolytes. The electronic spectra of these metal(II) complexes were found to be different for both their solid forms and in solutions of DMF and DMSO and this has been discussed. The thiomethylated aniline ligands possess the amine and thioether groups which are present in many known biologically active compounds, hence the biological activity of the ligands and their metal complexes were tested against three strains of bacteria and one fungus. The methoxy-substituted derivatives were found to possess better inhibitory activity and this was similarly reflected in the metal(II) complexes. The activity of the complexes can be said to be in the order, Cu(II) > Co(II) > Ni(II). The Schiff-base derivatives were prepared from the ligands and para-methoxysalicylaldehyde and their Cu(II) complexes were synthesized in order to determine their biological activity. The Schiff-base ligands were found to be less active than their parent ligands. The Cu(II) complexes are not soluble in water, DMSO or DMF, as a result and could not be evaluated for their biological activity. Based on the good results from the antimicrobial evaluation, the antiplasmodial activity of some of the Co(II), Ni(II) and Cu(II) complexes of the thiomethylated ligands against Plasmodium falciparum (FCR-3) was determined. At 50 μM concentration level, the Cu(II) complexes show activity equal or better than the prophylactic chloroquine. The Cu(II) complexes with the methoxy-substituted demonstrated exceptional activity but their Co(II) and Ni(II) analogues did not show any activity. The cytotoxicity of the active Cu(II) complexes at 50 μM concentration was determined against the breast cancer cell line (MDA-MB-231). The compounds destroyed the cancer cell in the range of 28–40%, thus showing their preferred activity against the parasitic cell instead of the cancer cell. The selectivity demonstrated by these compounds have shown them to be potential antimalarial agents and this could be further investigated.