Development of new transition metal complexes for their use in sustainable catalytic processes and as antitumoral agents

• Autores: Ester Manrique Salas
• Directores de la Tesis: María Isabel Romero García (dir. tes.), Montserrat Rodríguez Pizarro (codir. tes.)
• Lectura: En la Universitat de Girona ( España ) en 2018
• Idioma: español
• Tribunal Calificador de la Tesis: Maria Vilanova Brugués (presid.), Montserrat Corbella Cordomí (secret.), José Antonio Ayllon Esteve (voc.)
• Materias:
  • Química
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• Resumen

  • In this thesis we present the synthesis and characterization of different types of manganese and ruthenium complexes with the idea of studying their coordination chemistry, as well as the performance of the complexes synthesized in alkene epoxidation and nitrile hydration reactions. On the other hand, taking into account the importance and the advantages of the reutilization and heterogeneization of the catalysts for their use in a large-scale processes, ionic liquids have been used as a co-solvent allowing the design of a reusable catalytic system, and the immobilization of some of these complexes on silica-type and magnetic nanoparticles supports has also been carried out with the aim to apply them in the corresponding heterogeneous processes and evaluate their activity throughout successive reuses.

    In addition, taking into account the current importance of the metal complexes in chemotherapeutic treatments and the need to minimize its toxic side-effects derived from their use (in parallel to a decrease the production costs), some of the manganese and ruthenium complexes synthesized in this thesis have been evaluated as antitumor agents in the OVCAR-8 and NCI-H460 cell lines.

    In particular, in chapter 4 we describe the coordination of the pyrdine-pyrazole and phenol-pyrazole types of ligands to manganese (II) salts, obtaining different mononuclear complexes that have been fully characterized throughout structural and spectroscopic techniques. We also describe the performance of these complexes towards alkene epoxidation using peracetic acid as oxidant, leading in general to good conversion and selectivity values. Moreover, the use of the ionic liquid [bmim]:PF6 as a co-solvent has been studied for this purpose, allowing the design of a reusable catalytic system, and preliminary studies on the heterogenization of complex [MnII(CF3SO3)2(pypz-CH2COOEt)2] onto silica particles along with its performance towards alkene epoxidation have been carried out.

    In chapter 5 we describe the synthesis and characterization of new Ru(II)-dmso complexes which contain pyrdine-pyrazole and pyrazole-phenol types of ligands. We study the electron-transfer-induced linkage isomerization of the dmso ligands, from RuII(dmso-S) to RuIII(dmso-O), in compounds cis,cis-[RuIICl2(pypz-CH2COOEt)(dmso)2] and [RuIICl2(HOphpz-H)(dmso)2]. We also describe the catalytic performance of all complexes towards nitrile hydration in water, and better results are obtained for the activated substrates, but with a certain structural influence in the case of the complexes bearing ligands with bulky substituents.

    In chapter 6 we describe the synthesis, structure, spectroscopy and redox properties of new Ru-Cl i Ru-OH2 complexes which contain the neutral meridional trpy and the non-symmetric bidentate pypz-H ligands. The influence of electronic and geometrical effects of the ligands over the pKa and the electrochemical behaviour of these compounds is discussed, and a comparison with the analogous complexes previously synthesized in our group is also carried out. We describe the catalytic performance of the aqua-complex with regard to the alkene epoxidation reaction using iodobenzene diacetate as oxidant, obtaining better conversion values for the aliphatic substrates, which would indicate the involvement of an active electrophilic species.

    In chapter 7 we describe the heterogenization of the isomeric mixture cis,cis- and cis,trans-[RuIICl2(pypz-CH2COOEt)(dmso)2] onto silica and silica core-shell magnetic nanoparticles. A fully characterization of the new heterogeneous systems has been done using ICP-AES, IR, UV-Vis, SEM, TEM, TGA and XPS techniques, confirming the presence of the ligand pypz-CH2COOEt and the Ru(II) in all cases. The catalytic activity of these heterogeneous systems has been evaluated towards benzonitrile and acrylonitrile hydration in mild conditions and using water as solvent, obtaining better conversion and selectivity values than those observed for the analogous homogeneous system.

    Finally, in chapter 8 we have investigated the application of some of the manganese and ruthenium complexes synthesized in this thesis, together with some others previously synthesized in our research group, as antitumor agents in two cancerous cell lines, OVCAR-8 and NCI-H460. All the manganese complexes studied showed a higher cytotoxicity than their free ligands, confirming that the antitumor activity is favored when these ligands are coordinated to the metal. Complex [MnII(CF3SO3)2((-)-pinene[5,6]bipyridine)2] showed similar activities as cisplatin for both studied cell lines. On the other hand, the ruthenium complexes studied in this thesis presented relatively high IC50 value