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Post-transcriptional control of gene expression in Eukaryotes plays a pivotal role in determining intricated networks defining physiological and pathological conditions among each organism. RNA Binding Proteins (RBPs), by exploiting RNA-protein and protein-protein interactions, have been recognized as the main actors in modulating these processes. As a consequence, RBPs aberrant expression, modulation or mis-localization, leads to the insurgence of complex phenotypes and diseases. Therefore, targeting and modulating the activity of RBPs found associated to different pathologies represents a new promising therapeutic strategy. During my PhD I aimed at identify, characterize and refine inhibitors targeting the RNA binding protein HuR. HuR belongs to the ELAVL protein family, it is ubiquitously expressed in the cells and among tissues and highly conserved throughout mammalian evolution. By binding AU/U rich elements (ARE) in the 3’UTRs of mRNAs, HuR mainly stabilizes its target transcripts, enhancing their translation. ARE sequences are found in 7% of the human mRNAs, coding for protein involved in key cellular processes as: immune response and inflammation, cell division and proliferation, angiogenesis, senescence and apoptosis. Hence, dysregulation in HuR expression and in its subcellular localization have been associated with the insurgence of several pathologies, mostly cancers and inflammation diseases. Notably, malignant transformations and poor prognosis in patients have been found characterized by highly nuclear or cytosolic HuR expression in a significant number of human cancers. Indeed, the majority of HuR regulated transcripts encode for protein responsible for the appearance of several cancerogenic traits. In particular, critical crosstalk established between cancer cells and inflammation processes play a pivotal role in worsening and compromising cancers development and onset. Moreover, considering that 90% of mRNAs coding for cytokines and chemokines contains repeated AREs sites in the 3’UTR, HuR plays a strong regulatory role in immune system (innate and adaptive) development and homeostasis as well as in pathogenic mechanisms. The searching for HuR inhibitors represents a challenging area, in the drug discovery field, due to its pleiotropic functions and its intrinsic structural complexity, which presents unfolded regions and sequences prone to aggregation. HuR disruptors have been reported in the literature, but without systematic studies, thus the identification of a new class of small molecules is still at the beginning. Among the molecules discovered so far, in 2015 our group identified through a High-throughput Screening a natural compound, DHTS, as a bona fide HuR inhibitor. Following that finding, we, me included, ascribed to the molecule a well-defined mechanism of action, identifying the specific binding sites on which HuR:DHTS interaction is based, defining that upon the mRNA binding DHTS interplays with HuR maintaining the protein in a closed conformation, thus inhibiting its function. Furthermore, we demonstrated DHTS anti-cancer activity in vitro, in cellular context and in vivo, in an HuR-dependent manner. In this way, DHTS represented the molecular scaffold, for the generation of a new class of highly potent HuR inhibitors, called Tanshinone Mimics (TMs). A functional oriented approach was applied for the synthesis of new molecules harboring only DHTS chemical elements responsible for HuR targeting, leading to a completely new molecular scaffold, not previously described in the literature, with respect to the ancestor molecule. I have characterized and identified more potent molecules, describing their anticancer properties, through the evaluation of their capabilities of downregulating the total expression level of well-known HuR targets, coding for proteins involved in tumor insurgence and progression, as VEGF, ERBB2 and CTNNB1, and reducing cancer cell migration, cell cycle progression in a minor extent. On the other end, I have explored TMs anti-inflammatory properties, counteracting the inflammatory response mediated by macrophages, directly impairing the binding between HuR and its pro-inflammatory targets, diminishing their expression and related protein secretion. Moreover, I have put evidences on TMs activity in vivo in acute inflammation mouse models. Lastly, I have evaluated TMs activity in affecting T-cells proliferation, on which HuR it is known to play a regulatory role. In conclusion, we identified TMs with Structure-Activity Relationships (SARs) towards HuR inhibition and its biological implications, aimed at ameliorating their specificity and bioavailability suitable for in vivo therapeutic strategies.

Os objetivos do presente trabalho consistem na síntese de dois polímeros - poli(2,1,3-benzotiadiazol-4,7-ilenovinileno-alt-9,9-n-dioctil-2,7-fluorenilenovinileno) (PBTDV-alt-PDO27FV) e poli[4,7-(2,1,3-benzotiadiazolileno)-alt-(2,5-dioctilóxi-1,4- fenilenovinileno)] (PBTDV-alt-PDOPPV) - cinco oligômeros - 4,7-bis(2-(9,9-n-dioctil-9H-fluoren-2-il)vinil)2,1,3-benzotiadiazol (FBF); 2,7-bis(2-(2,1,3-benzotiadiazol-4-il)vinil)9,9-n-dioctil-9H-fluoreno (BFB); 4-(2-(9,9-n-dioctil-9H-fluoren-2-il)vinil)2,1,3-benzotiadiazol (FB); 1,2-bis(9,9-n-dioctil-9H-fluoren)2-vinileno (FF) e 2,2\'-(2,2\'-(9,9-n-dioctil-9H-fluoreno)2,7-bis(vinileno)bis(9,9-n-dioctil-9H-fluoreno) (FFF) - e três small molecules - 7,7\'-(4,4-bis(2-etil-hexil)-4H-silolo[3,2-b-:4,5-b\']ditiofen-2,6-diil)bis(6-fluoro-4-(5\'-hexil-[2\'-tiofeno-2\'-tiazol]-5-il)benzo[c][1,2,5]tiadiazol (G37FBT); 7,7\'-(4,4-bis(2-etil-hexil)-4H-silolo[3,2-b-:4,5-b\']ditiofen-2,6-diil)bis(6-fluoro-4-(2\'-isobutil-[5\',2\'-ditiazol])-5-il)benzo[c][1,2,5]tiadiazol (J1) e 7,7\'-(4,4-bis(2-etil-hexil)-4H-silolo[3,2-b-:4,5-b\']ditiofen-2,6-diil)bis(5\'-hexil-[2,2\'-bitiofeno]-5- bis(il)benzo[c][1,2,5]tiadiazol) (J2) - seguida da aplicação desses materiais em dispositivos fotovoltaicos e magnetorresistivos e em sensores de gás. Os polímeros e oligômeros preparados são derivados de poli(p-fenilenovinileno) e contêm unidades de fluoreno e/ou 2,1,3-benzotiadiazol, tendo sido empregada, na etapa final de cada síntese, reação de Wittig visando ao acoplamento e à formação das duplas vinilênicas. As small molecules, preparadas por meio de sucessivas formações de organo-estananas e reações de Stille, também foram sintetizadas com sucesso e em rendimentos apreciáveis. A espécie J2 não foi preparada com sucesso, obtendo-se, em contrapartida, um análogo dessa molécula, que foi devidamente isolado e caracterizado. No que tange à aplicação dos materiais em dispositivos fotovoltaicos, os resultados até então obtidos mostraram-se inconclusivos, sendo digno de nota, no entanto, que o estudo continua sendo conduzido por colaboradores. O trabalho de aplicação dos materiais em dispositivos magnetorresistivos apresentou resultados interessantes para os oligômeros FBF, BFB, FFF e FF, visto que dispositivos fabricados a partir das referidas espécies mostraram variação em seus valores de corrente elétrica quando submetidos a campo magnético de 200 mT. Por fim, foram desenvolvidos narizes eletrônicos com duas finalidades distintas: (a) identificação de diferentes espécies de madeira de interesse ambiental e (b) estudo da influência da atividade física no indivíduo por meio da análise do suor. Os sensores de gás foram preparados por meio da deposição de finos filmes de materiais orgânicos conjugados dopados sobre a superfície de eletrodos interdigitados. No estudo acerca da identificação de espécies de madeira, a análise de leave-one-out revelou 100 % de taxa de acerto na diferenciação entre as espécies angelim, cedro-rosa, imbuia e perobinha. O estudo da influência da atividade física no indivíduo também se mostrou promissor na medida em que identificou os diferentes estágios do exercício físico com taxa de acerto de 93 %, também definida pela técnica estatística de leave-one-out. / The present work consists on the synthesis of two polymers - poly(2,1,3- benzothiadiazole-4,7-ylenevinylene-alt-9,9-n-dioctyl-2,7-fluorenylenevinylene) (PBTDV-alt-PDO27FV) and poly[4,7-(2,1,3-benzothiadiazole-ylene)-alt-(2,5-dioctyloxy-1,4-phenylenevinylene)] (PBTDV-alt-PDOPPV) - five oligomers - 4,7-bis(2-(9,9-n-dioctyl- 9H-fluorene-2-yl)vinyl)2,1,3-benzothiadiazole (FBF); 2,7-bis(2-(2,1,3- benzothiadiazole-4-yl)vinyl)9,9-n-dioctyl-9H-fluorene (BFB); 4-(2-(9,9-n-dioctyl-9H-fluorene-2-yl)vinyl)2,1,3-benzothiadiazole (FB); 1,2-bis(9,9-n-dioctyl-9H-fluorene)2- vinylene (FF) and 2,2\'-(2,2\'-(9,9-n-dioctyl-9H-fluorene)2,7-bis(vinylene)bis(9,9-n-dioctyl-9H-fluorene) (FFF) - and three small molecules - 7,7\'-(4,4-bis(2-ethyl-hexyl)-4H-silolo[3,2-b-:4,5-b\']dithiophene-2,6-diyl)bis(6-fluoro-4-(5\'-hexyl-[2\'-thiophene-2\'- thiazole]-5-yl)benzo[c][1,2,5]thiadiazole (G37FBT); 7,7\'-(4,4-bis(2-ethyl-hexyl)-4H-silolo[3,2-b-:4,5-b\']dithiophene-2,6-diyl)bis(6-fluoro-4-(2\'-isobutyl-[5\',2\'-dithiazole]-5-yl)benzo[c][1,2,5]thiadiazole (J1) and 7,7\'-(4,4-bis(2-ethyl-hexyl)-4H-silolo[3,2-b-:4,5-b\']dithiophene-2,6-diyl)bis(5\'-hexyl-[2,2-bithiophene]-5-bis(yl)benzo[c][1,2,5]thiadiazole) (J2) - followed by the application of such materials in organic photovoltaics (OPV), magnetoresistive devices and gas sensors. The polymers and oligomers are all poli(p-phenylenevinylene)s derivatives containing 2,1,3-benzothiadiazole and/or substituted fluorene units in the main chain. Those materials\' preparation comprises a coupling Wittig reaction as the key step, through which the vinylenic bonds are formed. The small molecules mentioned above were synthesized by successive organostannane preparations followed by cross-coupling Stille reactions, leading to the target-compounds in considerably high yields. Although the route is a very useful methodology for synthesizing organic conjugated small molecules, J2 was not successfully prepared. The reaction led to a J2 analogue instead, that was properly isolated and characterized. The application of the cited materials in organic photovoltaics (OPVs) is still in progress, since the study has shown inconclusive results so far. The study of the organic magnetoresistive properties of the synthesized materials has led to interesting results for the oligomers FBF, BFB, FFF and FF. The devices containing those compounds in their active layers presented considerable variations in their electric current values when submitted to a magnetic field of 150 mT magnitude. Finally, electronic noses for two different applications were developed: (a) the identification of wood species that can be easily mistaken and (b) the study of exercise physiology through analyses of sweat samples. The gas sensors were prepared by the deposition of doped organic conjugated materials thin films onto the surface of intedigitated electrodes. The study on the differentiation of several species of wood showed 100 % rate of hits determined by leave-one-out statistics analysis. The study on the exercise physiology was also promising since it allowed the identification of the three different stages of the physical exercise with a 93 % rate of hits, also determined by leave-one-out methods. Thus, both studies suggest that the electronic nose can be a powerful tool to study many different targets in which the release of volatile compounds is involved

Os objetivos do presente trabalho consistem na síntese de dois polímeros - poli(2,1,3-benzotiadiazol-4,7-ilenovinileno-alt-9,9-n-dioctil-2,7-fluorenilenovinileno) (PBTDV-alt-PDO27FV) e poli[4,7-(2,1,3-benzotiadiazolileno)-alt-(2,5-dioctilóxi-1,4- fenilenovinileno)] (PBTDV-alt-PDOPPV) - cinco oligômeros - 4,7-bis(2-(9,9-n-dioctil-9H-fluoren-2-il)vinil)2,1,3-benzotiadiazol (FBF); 2,7-bis(2-(2,1,3-benzotiadiazol-4-il)vinil)9,9-n-dioctil-9H-fluoreno (BFB); 4-(2-(9,9-n-dioctil-9H-fluoren-2-il)vinil)2,1,3-benzotiadiazol (FB); 1,2-bis(9,9-n-dioctil-9H-fluoren)2-vinileno (FF) e 2,2\'-(2,2\'-(9,9-n-dioctil-9H-fluoreno)2,7-bis(vinileno)bis(9,9-n-dioctil-9H-fluoreno) (FFF) - e três small molecules - 7,7\'-(4,4-bis(2-etil-hexil)-4H-silolo[3,2-b-:4,5-b\']ditiofen-2,6-diil)bis(6-fluoro-4-(5\'-hexil-[2\'-tiofeno-2\'-tiazol]-5-il)benzo[c][1,2,5]tiadiazol (G37FBT); 7,7\'-(4,4-bis(2-etil-hexil)-4H-silolo[3,2-b-:4,5-b\']ditiofen-2,6-diil)bis(6-fluoro-4-(2\'-isobutil-[5\',2\'-ditiazol])-5-il)benzo[c][1,2,5]tiadiazol (J1) e 7,7\'-(4,4-bis(2-etil-hexil)-4H-silolo[3,2-b-:4,5-b\']ditiofen-2,6-diil)bis(5\'-hexil-[2,2\'-bitiofeno]-5- bis(il)benzo[c][1,2,5]tiadiazol) (J2) - seguida da aplicação desses materiais em dispositivos fotovoltaicos e magnetorresistivos e em sensores de gás. Os polímeros e oligômeros preparados são derivados de poli(p-fenilenovinileno) e contêm unidades de fluoreno e/ou 2,1,3-benzotiadiazol, tendo sido empregada, na etapa final de cada síntese, reação de Wittig visando ao acoplamento e à formação das duplas vinilênicas. As small molecules, preparadas por meio de sucessivas formações de organo-estananas e reações de Stille, também foram sintetizadas com sucesso e em rendimentos apreciáveis. A espécie J2 não foi preparada com sucesso, obtendo-se, em contrapartida, um análogo dessa molécula, que foi devidamente isolado e caracterizado. No que tange à aplicação dos materiais em dispositivos fotovoltaicos, os resultados até então obtidos mostraram-se inconclusivos, sendo digno de nota, no entanto, que o estudo continua sendo conduzido por colaboradores. O trabalho de aplicação dos materiais em dispositivos magnetorresistivos apresentou resultados interessantes para os oligômeros FBF, BFB, FFF e FF, visto que dispositivos fabricados a partir das referidas espécies mostraram variação em seus valores de corrente elétrica quando submetidos a campo magnético de 200 mT. Por fim, foram desenvolvidos narizes eletrônicos com duas finalidades distintas: (a) identificação de diferentes espécies de madeira de interesse ambiental e (b) estudo da influência da atividade física no indivíduo por meio da análise do suor. Os sensores de gás foram preparados por meio da deposição de finos filmes de materiais orgânicos conjugados dopados sobre a superfície de eletrodos interdigitados. No estudo acerca da identificação de espécies de madeira, a análise de leave-one-out revelou 100 % de taxa de acerto na diferenciação entre as espécies angelim, cedro-rosa, imbuia e perobinha. O estudo da influência da atividade física no indivíduo também se mostrou promissor na medida em que identificou os diferentes estágios do exercício físico com taxa de acerto de 93 %, também definida pela técnica estatística de leave-one-out. / The present work consists on the synthesis of two polymers - poly(2,1,3- benzothiadiazole-4,7-ylenevinylene-alt-9,9-n-dioctyl-2,7-fluorenylenevinylene) (PBTDV-alt-PDO27FV) and poly[4,7-(2,1,3-benzothiadiazole-ylene)-alt-(2,5-dioctyloxy-1,4-phenylenevinylene)] (PBTDV-alt-PDOPPV) - five oligomers - 4,7-bis(2-(9,9-n-dioctyl- 9H-fluorene-2-yl)vinyl)2,1,3-benzothiadiazole (FBF); 2,7-bis(2-(2,1,3- benzothiadiazole-4-yl)vinyl)9,9-n-dioctyl-9H-fluorene (BFB); 4-(2-(9,9-n-dioctyl-9H-fluorene-2-yl)vinyl)2,1,3-benzothiadiazole (FB); 1,2-bis(9,9-n-dioctyl-9H-fluorene)2- vinylene (FF) and 2,2\'-(2,2\'-(9,9-n-dioctyl-9H-fluorene)2,7-bis(vinylene)bis(9,9-n-dioctyl-9H-fluorene) (FFF) - and three small molecules - 7,7\'-(4,4-bis(2-ethyl-hexyl)-4H-silolo[3,2-b-:4,5-b\']dithiophene-2,6-diyl)bis(6-fluoro-4-(5\'-hexyl-[2\'-thiophene-2\'- thiazole]-5-yl)benzo[c][1,2,5]thiadiazole (G37FBT); 7,7\'-(4,4-bis(2-ethyl-hexyl)-4H-silolo[3,2-b-:4,5-b\']dithiophene-2,6-diyl)bis(6-fluoro-4-(2\'-isobutyl-[5\',2\'-dithiazole]-5-yl)benzo[c][1,2,5]thiadiazole (J1) and 7,7\'-(4,4-bis(2-ethyl-hexyl)-4H-silolo[3,2-b-:4,5-b\']dithiophene-2,6-diyl)bis(5\'-hexyl-[2,2-bithiophene]-5-bis(yl)benzo[c][1,2,5]thiadiazole) (J2) - followed by the application of such materials in organic photovoltaics (OPV), magnetoresistive devices and gas sensors. The polymers and oligomers are all poli(p-phenylenevinylene)s derivatives containing 2,1,3-benzothiadiazole and/or substituted fluorene units in the main chain. Those materials\' preparation comprises a coupling Wittig reaction as the key step, through which the vinylenic bonds are formed. The small molecules mentioned above were synthesized by successive organostannane preparations followed by cross-coupling Stille reactions, leading to the target-compounds in considerably high yields. Although the route is a very useful methodology for synthesizing organic conjugated small molecules, J2 was not successfully prepared. The reaction led to a J2 analogue instead, that was properly isolated and characterized. The application of the cited materials in organic photovoltaics (OPVs) is still in progress, since the study has shown inconclusive results so far. The study of the organic magnetoresistive properties of the synthesized materials has led to interesting results for the oligomers FBF, BFB, FFF and FF. The devices containing those compounds in their active layers presented considerable variations in their electric current values when submitted to a magnetic field of 150 mT magnitude. Finally, electronic noses for two different applications were developed: (a) the identification of wood species that can be easily mistaken and (b) the study of exercise physiology through analyses of sweat samples. The gas sensors were prepared by the deposition of doped organic conjugated materials thin films onto the surface of intedigitated electrodes. The study on the differentiation of several species of wood showed 100 % rate of hits determined by leave-one-out statistics analysis. The study on the exercise physiology was also promising since it allowed the identification of the three different stages of the physical exercise with a 93 % rate of hits, also determined by leave-one-out methods. Thus, both studies suggest that the electronic nose can be a powerful tool to study many different targets in which the release of volatile compounds is involved

No Capítulo 1, os fundamentos da cristalografia de raios X estão sucintamente descritos. No Capítulo 2, seis estruturas de pequenas moléculas contendo átomos pesados em sua constituição foram determinadas. As quais são resumidas a seguir: 1)[Ru2Cl5(CO)(PPh3)3], Mr = 1194,21, cristaliza-se no sistema monoclínico, grupo espacial P21/c com a =14,618(4)&#197, b=18,043(7)&#197, c=20,31(3)&#197; &#946=99,81(5)&#176; V=5277(8)&#1973; Z=4; Dcalç =1,503g/cm-3; &#955(MoK&#945) = 0,71073&#197; &#956 = 0,954 mm-1; F(000) = 2404; R=0,538 para 9281 reflexões independentes e 487 parâmetros refinados. Os átomos de Ru estão ligados em ponte através de três ânions Cl. Um átomo de Ru é coordenado a dois outros átomos de Cl e a um ligante PPh3, o outro átomo de Ru está coordenado a dois ligantes PPh3 e a uma molécula de CO. 2)[RuCl3(dppb)H2O], Mr = 651,88, cristaliza-se no sistema ortorrômbico, grupo espacial Pbca; com a=14,932(1) &#197, b=18,133 (3)&#197, c=20,59(3)&#197; V=5576,0(1)&#1973; Z=8; Dcalc =1,553g/cm-3; &#955(MoK&#945) = 0,71073&#197; &#956 = 0,985 mm-1; F(000)=2648; R=0,0461 para 4892 reflexões independentes e 316 parâmetros refinados. O complexo é hexacoordenado. Os átomos P encontram-se em posição cis, um em relação ao outro, formando um complexo próximo de uma estrutura octaédrica. Esta estrutura apresentou interação intermolecular Cl...H. A distância entre o H de uma molécula e o Cl é de 2,48(2)&#197. 3) FeC19H1919N19S19], Mr=377,28, cristaliza-se no sistema monoclínico, grupo espacial P21/n; com a=11,715(2)&#197, b=7,830(2)&#197, c=18,728(3)&#197; &#946=91,570(1)&#176; V=1717,1(6)&#1973; Z=4; Dcalc =1,459g/cm-3; &#955(MoK&#945) = 0,71073&#197; &#956 = 1,004 mm-1; F(000)=784; R=0,0453 para 3018 reflexões independentes e 218 parâmetros refinados. O complexo é formado por um átomo de ferro decacoordenado em uma extremidade e na outra existe um anel aromático, indicando que os radicais genéricos mostrados na Seção (2.5) são R\'=C\'H IND. 3\', X=S1 e R\"=fenil. 4)[pyH][RuCl4(dmso)(py)].(CH2Cl2)1/2, Mr=562,11 cristaliza-se no sistema triclínico, grupo espacial P1; com a= 7,7608(1)&#197, b=85451(1)&#197, c=15,095(5)&#197; &#945=88,27(2)&#186; &#946=79,33(2)&#186; &#947,=88,77(1)&#186; V=983,2(4)&#1973; Z=2; Dcalc=1,899gcm-3; &#955(CuK&#945)=1,54184 &#197; &#956=15,001 mm-1; F(000)=556; R=0,0886 para 2909 reflexões independentes e 204 parâmetros refinados. O Ru está octaedricamente coordenado a quatro átomos Cl coplanares, a um N do anel de uma piridina e ao dmso, em posição trans entre si. Um outro grupo piridina protonado, que forma o cátion da estrutura, completa a estrutura. 5)[RuCl2(CO)2(AsPh3)2, Mr =840,43, cristaliza-se no sistema monoclínico, grupo espacial P21/n; com a=710,520(4)&#197, b=25,823(5)&#197, c=12,780(2)&#197; &#946=100,7401(1)&#176; V=3411,0(1)&#1973; Z=4; Dcalc =1,637gcm-3; &#955(CuK&#945)=1,54184 &#197; &#956=7,576 mm-1; F(000)=1672; R=0,0739 para 4284 reflexões independentes e 406 parâmetros refinados. O átomo de Ru está ligado a dois átomos de Cl e a duas moléculas CO, que formam aproximadamente um plano entre si. Os CO\'s estão em posição trans em relação aos Cl\'s. O átomo de Ru também apresenta coordenação com duas PPh3. 6)[Ru2ClBr4(CO)(AsPh3).CH2Cl2)<, Mr=154,88 cristaliza-se no sistema monoclínico, grupo espacial P21/c; com a=14,766(2)&#197, b=18,519(2)&#197, c=20,730(4)&#197; &#946=100,085(1)&#176; V=5581,2(1)&#1973; Dcalc =1,839gcm-3; &#955(CuK&#945)=1,54184 &#197; &#956=10,947mm-1; F (000)=3004; R=0,0955 para 5738 reflexões independentes e 493 parâmetros refinados. O complexo é formado por dois átomos de Ru em ponte através de três ânions Br. Um átomo de Ru é também coordenado a um átomo Br, a um Cl e a um ligante trifenilfosfina. O outro átomo de Ru está ligado a duas trifenilarsinas e a uma molécula de monóxido de carbono. No capítulo 3, apresentam-se as conclusões e planos futuros / In Chapter 1, the basic principles of X-ray crystallography that have been used in this work are briefly described. In Chapter 2, six small molecule structures with heavy atoms are presented. They are summarized as follows: 1)[Ru2Cl5(CO)(PPh3)3], Mr = 1194,21, crystallizes in the monoclinic system, space group P21/c com a =14,618(4)&#197, b=18,043(7)&#197, c=20,31(3)&#197; &#946=99,81(5)&#176; V=5277(8)&#1973; Z=4; Dcalc =1,503g/cm-3; &#955(MoK&#945) = 0,71073&#197; &#956 = 0,954 mm-1; F(000) = 2404; R=0,538 for 9281 independent reflections and 487 refined parameters. This triply chloro-bridged binuclear complex is formed by two Ru atoms bridged through three chloride anions. One Ru atom is further coordinated to two non-bridging Cl atoms and a triphenylphosphine ligand, whereas the other is bonded to two PPh3 ligands and to a carbon monoxide molecule. 2) 3(dppb)H2O], Mr = 651,88, crystallizes in the orthorhombic system, space group Pbca; a=14,932(1) &#197, b=18,133 (3)&#197, c=20,59(3)&#197; V=5576,0(1)&#1973; Z=8; Dcalc =1,553g/cm-3; &#955(MoK&#945) = 0,71073&#197; &#956 = 0,985 mm-1; F(000)=2648; R=0,0461 for 4892 independent reflections and 316 refined parameters. The complex is hexacoordinated. The P atoms are in cis position to each other, forming a octhaedrical structure. This structure shows an intermolecular interaction between one Cl atom from one complex and a water hydrogen of a neighboring complex in the lattice, with Cl...H distance of 2,48(2)A. 3)[FeC19H1919N19S19], Mr=377,28, crystallizes in the monoclinic system, space group P21/n; a=11,715(2)&#197, b=7,830(2)&#197, c=18,728(3)&#197; &#946=91,570(1)&#176; V=1717,1(6)&#1973; Z=4; Dcalc =1,459g/cm-3; &#955(MoK&#945) = 0,71073&#197; &#956 = 1,004 mm-1; F(000)=784; R=0,0453 for 3018 indepen dent reflections and 218 refined parameters. This complex shows a decacoordinated Fe atom in one end of the molecule and an aromatic ring in the other, showing that the gereric radicals in Section (2.5) are R\'= CH3, X=Sl and R\" =phenyl. 4)[pyH][RuCl4(dmso)(py)].(CH2Cl2)1/2, Mr=562,11, crystallizes in the triclinic system, space group P1; a= 7,7608(1)&#197, b=85451(1)&#197, c=15,095(5)&#197; &#945=88,27(2)&#186; &#946=79,33(2)&#186; &#947,=88,77(1)&#186; V=983,2(4)&#1973; Z=2; Dcalç=1,899gcm-3; &#955(CuK&#945)=1,54184 &#197; &#956=15,001 mm-1; F(000)=556; R=0,0886 for 2909 independent reflections and 204 refined parameters. The Ru ion is octahedrally coordinated to four co-planar chloride atoms and to the nitrogen of the pyridine ring, which are trans to each other. Another protonated pyridine group, which forms the counter-cation complete the crystal struet ure. 5)[RuCl2(CO)2(AsPh3)2, Mr =840,43, crystalizes in the monoclinic system, space group P21/n; a=710,520(4)&#197, b=25,823(5)&#197, c=12,780(2)&#197; &#946=100,7401(1)&#176; V=3411,0(1)&#1973; Z=4; Dcalc =1,637gcm-3; &#955(CuK&#945)=1,54184 &#197; &#956=7,576 mm-1; F(000)=1672; R=0,0739 for 4284 independent reflections and 406 refined parameters. This complex shows a Ru atom bonded to two Cl atoms and to two CO molecules, which aproximatelly form a plane between then. The CO\'s are trans to the chlorides and the Ru further presents a coordination to two PPh3. 6) [Ru2ClBr4(CO)(AsPh3).CH2Cl2)<, Mr=154,88, crystallizes in the monoclinic system, space group P21/c; com a=14,766(2)&#197, b=18,519(2)&#197, c=20,730(4)&#197; &#946=100,085(1)&#176; V=5581,2(1)&#1973; Dcalc =1,839gcm-3; &#955(CuK&#945)=1,54184 &#197; &#956=10,947mm-1; F (000)=3004; R=0,0955 for 5738 independent reflections and 493 refined parameters. This complex is formed by two Ru atoms bridged by three Br anions. One Ru atom is further coordenated to a Br atom, to a CI atom and to a triphenylphosphine ligand, whereas the other is bonded to two AsPh3 and to a carbon monoxide molecule. In chapter 3, conclusions and future plans are given.

An iterative protocol is a highly efficient strategy for the generation of large, complex molecules that has been applied in many different subfields of organic synthesis. The use of a tandem or cascade reaction is also an effective approach for the rapid introduction of molecular complexity into a system since the number of steps requiring independent optimization is greatly reduced. With the aim of creating new synthetic strategies to efficiently gain access to stereochemically complex small molecules, we envisioned the use of short iterative protocols to prepare reactive oligomers to which a diverse range of cascade cyclization processes could be applied. In an attempt to minimize reaction optimization and chromatographic purification steps during the development of our small molecule precursors, we first developed an iterative synthesis based on a conjugate addition/reduction sequence that has allowed us to access a diverse series of oligo-vinyl ether intermediates. Significantly, both the addition and reduction steps proceed in near-quantitative yield, and reaction co-products can be removed without column chromatography. At the same time, most of our vinyl ether intermediates are stable to silica gel, and so analytically pure samples can be prepared when desired. Except for when very sterically demanding substrates are employed as electrophiles, the intermediates are isolated as single geometrical isomers. We also developed an improved synthesis of a previously intractable class of alkynoate starting materials (4-aryl-2-butynoates) to ensure a diverse range of easily accessible monomeric building blocks were available for our use. With this effective iterative route in hand, we have several interesting small molecule targets at our disposal. We first applied our iterative route to synthesize oxygen-containing analogues of juvenile hormone III. These mono- and bis-vinyl ethers are currently undergoing biological testing (in collaboration with Dr. Steve Perlman and Dr. Michael Horst), and early results show promise as ecologically degradable insect control agents. We also developed an unprecedented 6-endo/5-exo radical cascade reaction across bis-vinyl ethers which proceeds in good yield, high diastereoselectivity, and excellent regiochemical control. This reaction represents the first cascading radical cyclization ever reported for a bis-vinyl ether system and validates our iterative approach to molecular complexity. / Graduate

L’objectif de ma thèse était d’améliorer les connaissances sur le rôle des liaisons métal-thiolates au sein des métalloenzymes en utilisant une approche bio-inspirée par l’étude des propriétés structurales, électroniques et/ou magnétiques de modèles chimiques ainsi que de leur réactivité.Dans ce contexte, nous avons synthétisé deux complexes de NiFe, modèle structuraux et fonctionnels de l’hydrogénase [NiFe], capables de produire H2 efficacement de manière électrocatalytique de H2. Des espèces intermédiaires ont été synthétisées et caractérisées par différentes techniques spectroscopiques. L’inhibition réversible de l’activité catalytique de ces catalyseurs en présence de CO a été étudiée et discutée.Nous décrivons également un nouvel exemple de complexe de Mn-thiolate, dont l’un des thiolates coordonné à un Mn est protoné. Ce complexe est capable d’activer l’oxygène moléculaire (O2) et de le réduire de manière catalytique par un processus à deux électrons en présence d’une source de protons et d’un agent de réduction. L’activation et la réduction de l’oxygène ont été étudiées en conditions stœchiométriques et catalytiques. Des complexes de Mn à hauts degrés d’oxydation résultant de l’activation d’O2 ont été isolés et caractérisés. Leur réactivité vis-à-vis de l’hydrogène (HAT) et de l’oxygène (OAT) a été évaluée.Une série de complexes métal-halogénure pentacoordinés, MIIIX (M = Mn ou Co ; X = Cl, Br, I) a été étudiée pour comprendre le rôle du métal dans la conversion disulfure/thiolate. Il a été montré que cette conversion est réversible pour les deux ions métalliques mais que le processus est plus rapide et quantitatif dans le cas du système à base de Co par rapport à celui du Mn. Ce travail nous a permis de comprendre comment les propriétés redox et électroniques du métal peuvent intervenir sur l’efficacité de cette interconversion.Enfin les propriétés magnétiques de la série des complexes de CoIII contenant un halogénure ont été étudiées. Ces complexes présentent un spin S = 1 intermédiaire et leur anisotropie magnétique est sensible à la nature de l’halogénure de manière inattendue : la plus grande valeur de D a été mesurée pour le complexe chloré et la plus petite pour le composé iodé. Ce comportement a été rationalisé au travers d’une étude théorique. / The aim of my thesis was to improve the knowledge on the role of metal-thiolate bonds in metalloenzymes using a bio-inspired approach by investigating the structural, electronic and/or magnetic properties of chemical models as well as their reactivity.In this context, we report the synthesis and analysis of two heterodinuclear NiFe complexes, structural and functional models of the active site of [NiFe] hydrogenase, which produce H2 electrocatalytically at high rates. Intermediate species have been generated and characterized by different spectroscopic techniques. The reversible inhibition of the catalytic activity by CO has been also investigated and discussed.We also describe the synthesis and characterization of a new manganese-thiolate complex, bearing a pendant thiol group bound (in its -SH form) to one MnII ion. This complex is capable of activating dioxygen, and is an active catalyst for selective 2-electron O2 reduction in the presence of a one-electron reducing agent and a proton source. The O2 activation and reduction pathways have been studied under both stoichiometric and catalytic conditions. Several high valent Mn complexes resulting from O2 activation have been isolated and characterized and their reactivity toward hydrogen or oxygen atom transfer (HAT or OAT, respectively) has been evaluated.A series of pentacoordinated metal-halide complexes MIIIX (M = Co and Mn ; X = Cl, Br, I) has been investigated with the aim of understanding the role of the metal ion in disulphide/thiolate interconversion. While such conversion is reversible in the presence of both Co and Mn, the process becomes much faster and quantitative for the Co–based system with respect to the Mn one. Besides, this work has allowed improving the understanding of how the electronic and redox properties of the metal centers should be fine-tuned to permit a disulphide/thiolate (inter)conversion, mediated by metal ions, to occur efficiently.Finally, the magnetic properties of the series of mononuclear CoIIIX complexes have been investigated. They display a rare intermediate S = 1 spin state and their magnetic anisotropy is sensitive to the nature of the halide in an unexpected way: the largest D-value has been measured for the chloride compound and the smallest for the iodide one. This behavior has been rationalized through a theoretical study.

Les aptamères correspondent à de courtes séquences d'oligonucléotides possédant une forte affinité et spécificité envers un ligand (petites molécules organiques, peptides, acides nucléiques, protéines, cellules). Du fait de leurs remarquables propriétés, ils sont utilisés comme alternative aux anticorps dans les dispositifs de type biocapteur/biopuce, notamment pour la détection de petites molécules (PM < 2000 Da). L'imagerie de résonance des plasmons de surface (SPRi) est une technique de détection optique qui a gagné une attention croissante ces dernières années. Elle est basée sur un principe de variation de l'indice de réfraction d'une surface sélective lors de l'interaction sonde/cible. Sa sensibilité est néanmoins limitée aux molécules de poids moléculaire supérieur à 2000 Da. Dans le cadre de ces travaux, nous avons développé une biopuce à aptamères pour à la détection d'une petite molécule, l'adénosine, au moyen de la technique de résonance des plasmons de surface (SPR). Pour cela, deux différentes stratégies ont été développées. La première combine l'utilisation de nanoparticules d'or (AuNPs) pour l'amplification du signal SPRi avec l'ingénierie des séquences d'aptamères. La seconde stratégie est basée sur l'exploitation de la stabilité thermodynamique apportée par l'interaction de la cible (adénosine) avec les séquences d'aptamères. Le dispositif SPR est alors couplé à un système de régulation de température, permettant ainsi d'assurer la dissociation des complexes et d'établir des profils de dénaturation caractéristiques. Nos résultats initient ainsi une nouvelle approche dans la détection de petites molécules par SPRi et ouvrent de nouvelles perspectives de développement des biocapteurs à aptamères. / Aptamers are single-stranded DNA (ssDNA) or RNA molecules capable of binding to target molecules, including proteins, metal ions and drugs. Because of their specific binding abilities and many advantages over antibodies (higher stability, lower cost, easy chemical modification…), they provide a great opportunity to produce sensing surfaces for effective and selective detection of small molecules. Surface Plasmon Resonance imaging (SPRi) has become one of the most widely used label-free method for the study of biorecognition events on sensor surfaces. This technique provides a rapid approach, however, limited by low refractive index changes occurring when small molecules (<2000 Da) are captured on the sensor. Whereas significant reflectivity variation is observed upon the interaction of large molecules like proteins with the sensing interface, for small molecules targets such adenosine, the reflectivity variation is often too small to be detected by SPRi. Thereby, only few studies have been reported so far on SPRi-based biosensor for small molecules detection using aptamers. In this work, we developed two bioassay strategies for the detection of a model small molecule, adenosine, using Surface Plasmon Resonance imaging. The first one combines the SPRi signal enhancement effect induced by gold nanoparticles (AuNPs) with the advantage of using engineered DNA aptamers. The experimental results have demonstrated that the presence of gold nanoparticles and adenosine, which works as a molecular linker between engineered aptamer fragments, can significantly increase the SPRi response. The second strategy is based on the thermodynamics of binding between adenosine and its aptamer. To that end, SPRi technique was coupled with rigorous temperature control and aptamer duplex stability was monitored (affected by target binding) by quantification of melting transitions. Our results initiate a new approach for small molecule detection using SPRi with the aim to validate future prospects for integration in parallelized platform.

No Capítulo 1, os fundamentos da cristalografia de raios X estão sucintamente descritos. No Capítulo 2, seis estruturas de pequenas moléculas contendo átomos pesados em sua constituição foram determinadas. As quais são resumidas a seguir: 1)[Ru2Cl5(CO)(PPh3)3], Mr = 1194,21, cristaliza-se no sistema monoclínico, grupo espacial P21/c com a =14,618(4)&#197, b=18,043(7)&#197, c=20,31(3)&#197; &#946=99,81(5)&#176; V=5277(8)&#1973; Z=4; Dcalç =1,503g/cm-3; &#955(MoK&#945) = 0,71073&#197; &#956 = 0,954 mm-1; F(000) = 2404; R=0,538 para 9281 reflexões independentes e 487 parâmetros refinados. Os átomos de Ru estão ligados em ponte através de três ânions Cl. Um átomo de Ru é coordenado a dois outros átomos de Cl e a um ligante PPh3, o outro átomo de Ru está coordenado a dois ligantes PPh3 e a uma molécula de CO. 2)[RuCl3(dppb)H2O], Mr = 651,88, cristaliza-se no sistema ortorrômbico, grupo espacial Pbca; com a=14,932(1) &#197, b=18,133 (3)&#197, c=20,59(3)&#197; V=5576,0(1)&#1973; Z=8; Dcalc =1,553g/cm-3; &#955(MoK&#945) = 0,71073&#197; &#956 = 0,985 mm-1; F(000)=2648; R=0,0461 para 4892 reflexões independentes e 316 parâmetros refinados. O complexo é hexacoordenado. Os átomos P encontram-se em posição cis, um em relação ao outro, formando um complexo próximo de uma estrutura octaédrica. Esta estrutura apresentou interação intermolecular Cl...H. A distância entre o H de uma molécula e o Cl é de 2,48(2)&#197. 3) FeC19H1919N19S19], Mr=377,28, cristaliza-se no sistema monoclínico, grupo espacial P21/n; com a=11,715(2)&#197, b=7,830(2)&#197, c=18,728(3)&#197; &#946=91,570(1)&#176; V=1717,1(6)&#1973; Z=4; Dcalc =1,459g/cm-3; &#955(MoK&#945) = 0,71073&#197; &#956 = 1,004 mm-1; F(000)=784; R=0,0453 para 3018 reflexões independentes e 218 parâmetros refinados. O complexo é formado por um átomo de ferro decacoordenado em uma extremidade e na outra existe um anel aromático, indicando que os radicais genéricos mostrados na Seção (2.5) são R\'=C\'H IND. 3\', X=S1 e R\"=fenil. 4)[pyH][RuCl4(dmso)(py)].(CH2Cl2)1/2, Mr=562,11 cristaliza-se no sistema triclínico, grupo espacial P1; com a= 7,7608(1)&#197, b=85451(1)&#197, c=15,095(5)&#197; &#945=88,27(2)&#186; &#946=79,33(2)&#186; &#947,=88,77(1)&#186; V=983,2(4)&#1973; Z=2; Dcalc=1,899gcm-3; &#955(CuK&#945)=1,54184 &#197; &#956=15,001 mm-1; F(000)=556; R=0,0886 para 2909 reflexões independentes e 204 parâmetros refinados. O Ru está octaedricamente coordenado a quatro átomos Cl coplanares, a um N do anel de uma piridina e ao dmso, em posição trans entre si. Um outro grupo piridina protonado, que forma o cátion da estrutura, completa a estrutura. 5)[RuCl2(CO)2(AsPh3)2, Mr =840,43, cristaliza-se no sistema monoclínico, grupo espacial P21/n; com a=710,520(4)&#197, b=25,823(5)&#197, c=12,780(2)&#197; &#946=100,7401(1)&#176; V=3411,0(1)&#1973; Z=4; Dcalc =1,637gcm-3; &#955(CuK&#945)=1,54184 &#197; &#956=7,576 mm-1; F(000)=1672; R=0,0739 para 4284 reflexões independentes e 406 parâmetros refinados. O átomo de Ru está ligado a dois átomos de Cl e a duas moléculas CO, que formam aproximadamente um plano entre si. Os CO\'s estão em posição trans em relação aos Cl\'s. O átomo de Ru também apresenta coordenação com duas PPh3. 6)[Ru2ClBr4(CO)(AsPh3).CH2Cl2)<, Mr=154,88 cristaliza-se no sistema monoclínico, grupo espacial P21/c; com a=14,766(2)&#197, b=18,519(2)&#197, c=20,730(4)&#197; &#946=100,085(1)&#176; V=5581,2(1)&#1973; Dcalc =1,839gcm-3; &#955(CuK&#945)=1,54184 &#197; &#956=10,947mm-1; F (000)=3004; R=0,0955 para 5738 reflexões independentes e 493 parâmetros refinados. O complexo é formado por dois átomos de Ru em ponte através de três ânions Br. Um átomo de Ru é também coordenado a um átomo Br, a um Cl e a um ligante trifenilfosfina. O outro átomo de Ru está ligado a duas trifenilarsinas e a uma molécula de monóxido de carbono. No capítulo 3, apresentam-se as conclusões e planos futuros / In Chapter 1, the basic principles of X-ray crystallography that have been used in this work are briefly described. In Chapter 2, six small molecule structures with heavy atoms are presented. They are summarized as follows: 1)[Ru2Cl5(CO)(PPh3)3], Mr = 1194,21, crystallizes in the monoclinic system, space group P21/c com a =14,618(4)&#197, b=18,043(7)&#197, c=20,31(3)&#197; &#946=99,81(5)&#176; V=5277(8)&#1973; Z=4; Dcalc =1,503g/cm-3; &#955(MoK&#945) = 0,71073&#197; &#956 = 0,954 mm-1; F(000) = 2404; R=0,538 for 9281 independent reflections and 487 refined parameters. This triply chloro-bridged binuclear complex is formed by two Ru atoms bridged through three chloride anions. One Ru atom is further coordinated to two non-bridging Cl atoms and a triphenylphosphine ligand, whereas the other is bonded to two PPh3 ligands and to a carbon monoxide molecule. 2) 3(dppb)H2O], Mr = 651,88, crystallizes in the orthorhombic system, space group Pbca; a=14,932(1) &#197, b=18,133 (3)&#197, c=20,59(3)&#197; V=5576,0(1)&#1973; Z=8; Dcalc =1,553g/cm-3; &#955(MoK&#945) = 0,71073&#197; &#956 = 0,985 mm-1; F(000)=2648; R=0,0461 for 4892 independent reflections and 316 refined parameters. The complex is hexacoordinated. The P atoms are in cis position to each other, forming a octhaedrical structure. This structure shows an intermolecular interaction between one Cl atom from one complex and a water hydrogen of a neighboring complex in the lattice, with Cl...H distance of 2,48(2)A. 3)[FeC19H1919N19S19], Mr=377,28, crystallizes in the monoclinic system, space group P21/n; a=11,715(2)&#197, b=7,830(2)&#197, c=18,728(3)&#197; &#946=91,570(1)&#176; V=1717,1(6)&#1973; Z=4; Dcalc =1,459g/cm-3; &#955(MoK&#945) = 0,71073&#197; &#956 = 1,004 mm-1; F(000)=784; R=0,0453 for 3018 indepen dent reflections and 218 refined parameters. This complex shows a decacoordinated Fe atom in one end of the molecule and an aromatic ring in the other, showing that the gereric radicals in Section (2.5) are R\'= CH3, X=Sl and R\" =phenyl. 4)[pyH][RuCl4(dmso)(py)].(CH2Cl2)1/2, Mr=562,11, crystallizes in the triclinic system, space group P1; a= 7,7608(1)&#197, b=85451(1)&#197, c=15,095(5)&#197; &#945=88,27(2)&#186; &#946=79,33(2)&#186; &#947,=88,77(1)&#186; V=983,2(4)&#1973; Z=2; Dcalç=1,899gcm-3; &#955(CuK&#945)=1,54184 &#197; &#956=15,001 mm-1; F(000)=556; R=0,0886 for 2909 independent reflections and 204 refined parameters. The Ru ion is octahedrally coordinated to four co-planar chloride atoms and to the nitrogen of the pyridine ring, which are trans to each other. Another protonated pyridine group, which forms the counter-cation complete the crystal struet ure. 5)[RuCl2(CO)2(AsPh3)2, Mr =840,43, crystalizes in the monoclinic system, space group P21/n; a=710,520(4)&#197, b=25,823(5)&#197, c=12,780(2)&#197; &#946=100,7401(1)&#176; V=3411,0(1)&#1973; Z=4; Dcalc =1,637gcm-3; &#955(CuK&#945)=1,54184 &#197; &#956=7,576 mm-1; F(000)=1672; R=0,0739 for 4284 independent reflections and 406 refined parameters. This complex shows a Ru atom bonded to two Cl atoms and to two CO molecules, which aproximatelly form a plane between then. The CO\'s are trans to the chlorides and the Ru further presents a coordination to two PPh3. 6) [Ru2ClBr4(CO)(AsPh3).CH2Cl2)<, Mr=154,88, crystallizes in the monoclinic system, space group P21/c; com a=14,766(2)&#197, b=18,519(2)&#197, c=20,730(4)&#197; &#946=100,085(1)&#176; V=5581,2(1)&#1973; Dcalc =1,839gcm-3; &#955(CuK&#945)=1,54184 &#197; &#956=10,947mm-1; F (000)=3004; R=0,0955 for 5738 independent reflections and 493 refined parameters. This complex is formed by two Ru atoms bridged by three Br anions. One Ru atom is further coordenated to a Br atom, to a CI atom and to a triphenylphosphine ligand, whereas the other is bonded to two AsPh3 and to a carbon monoxide molecule. In chapter 3, conclusions and future plans are given.

L’utilisation massive de ressources fossiles carbonées pour des applications énergétiques est aujourd’hui pointée du doigt comme responsable du changement climatique. Le CO₂ émis lors de la combustion de ces ressources augmente l’effet de serre, induisant ainsi un réchauffement de la planète. Afin d’atténuer ce changement climatique, l’utilisation des énergies renouvelables est de plus en plus favorisée et le stockage de cette énergie sous forme d’hydrogène semble prometteur pour pallier à l’intermittence saisonnière de ces ressources. Une voie de stockage de l’hydrogène consiste à le faire réagir avec du CO₂ afin d’obtenir des carburants liquides telles que l’acide formique et le méthanol. Ces liquides peuvent alors être transportés facilement et lorsque l’énergie vient à manquer l’hydrogène peut être régénéré par déshydrogénation de ces molécules grâce à des catalyseurs. Dans cette thèse nous avons développé des complexes organométalliques en vue d’activer CO₂ et H₂, ce qui nous a permis d’acquérir un savoir fondamental. Le ligand triphos étant très connu pour coordiner des complexes qui catalysent ces réactions d’hydrogénation et de déshydrogénation, nous nous sommes d’abord concentrés sur le développement de ligands similaires. Nous avons synthétisé de nouveaux complexes de Fe (II), Co (II) et Cu (I) avec ces ligands. Ceux-ci se sont révélés actifs en hydroboration du CO₂. Un complexe de ruthénium a été greffé sur silice par son ligand, afin de pouvoir être recyclé lors des catalyses. Dans une deuxième partie, nous avons synthétisé un nouveau ligand aux des propriétés participatives potentielles. Un complexe de cuivre(I) coordiné par ce ligand a permis d’activer H₂ grâce à une participation métal-ligand.Enfin, un complexe de cobalt(I) coordiné par ce ligand est le premier composé à base de cobalt capable de déshydrogéner l’acide formique. / The extensive use of fossile fuel is currently causing climate change. Anthropogenic emissions of CO₂ enhance the greenhouse effect, resulting in global warming. In order to mitigate this climate change, the share of renewable energy is increasing and hydrogen seems to be a good candidate to stock energy to compensate the seasonal variations of those energies. One way to store H₂ is the hydrogenation of CO₂ to synthesise liquid molecules as formic acid and methanol. Those liquids can be conveyed in an easier way. In case of a lack of energy, H₂ can be recovered through dehydrogenation of those molecules thinks to catalysts. In this thesis, we studied the synthesis of organometallic complexes able to activate those small molecules, thus, growing a fundamental knowledge. As a number of triphos-metal complexes are known to catalyse hydrogenation and dehydrogenation reactions, we focused on the elaboration of ligands alike. With those ligands in hand, several non-noble metal based complexes (Fe (II), Co (II) and Cu (I)) were synthesized, which are active in CO₂ hydroboration catalysis. A complex of ruthenium(II)was grafted on silica through one of this ligand, in order to recycle it when it used as a catalyst. On the second hand, we designed a new ligand which could favor metal-ligand cooperativity. H₂ was succesfully activated with a copper(I) complex coordinated by this ligand, demonstrating that cooperation of the ligand. Finally, the first known cobalt complex active in dehydrogenation of formic acid was synthesised.