Metal·lotensioactius i fosfolípids: estudi d’agregats supramoleculars com a sistemes alliberadors de monòxid de carboni
- Autores: Isabel Marín
- Directores de la Tesis: Ramón Barnadas Rodríguez (dir. tes.), Joan Suades Ortuño (codir. tes.)
- Lectura: En la Universitat Autònoma de Barcelona ( España ) en 2017
- Idioma: español
- Tribunal Calificador de la Tesis: Olga Iranzo (presid.), Ana Joaquina Perez Berna (secret.), Olga López Serrano (voc.)
- Programa de doctorado: Programa Oficial de Doctorado en Bioquímica, Biología Molecular y Biomedicina
- Materias:
- Enlaces
- Tesis en acceso abierto en: TESEO
- Resumen
Abstract Carbon monoxide (CO) has long been considered as a toxic gas to human health because of its lethal nature, causing death by asphyxia. The toxicity of CO is attributed in part to its high affinity for hemoglobin (Hb), which is about 220 times higher than that of Hb for O2. Against this dogma is the fact that small amounts of CO are produced endogenously in the human body and the production of CO is associated with a variety of physiological roles, such as anti-inflammatory and anti-proliferation effects. In order to use CO as a therapeutic agent, substantial research efforts have been devoted to the development of CO releasing molecules (CORMs) as an alternative for a safety and controlled delivery of the gas. With this aim in mind, two families of molybdenum carbonyl metallosurfactants (MTS) have been synthesized in the present work by means of the coordination of the surfactant phosphines Ph2P(CH2)nSO3Na; n = 2, 6 and 10, to the fragments {Mo(CO)4} and {Mo(CO)5}. This MTS are used to obtain mixed systems with phospholipids, in particular soy phosphatidylcholine (SPC), in order to use them as CORMs. It should be mentioned that there are no precedents of this type of systems used for this purpose.
In aqueous solution, and depending on the SPC/MTS ratio, different types of supramolecular aggregates are formed (basically metallosomes and nanoaggregates), showing the peculiarity that the metal atom is located in a characteristic hydrophobic environment. These systems are able to deliver CO, which can be modulated photochemically using UVA or visible radiation. So, they can be classified as a new type of PhotoCORMs.
Metallosomes prepared in this work show the characteristic properties of liposomes. They are kinetically stable upon dilution, presenting a toxicity at least tenfold lower than that of the metallosurfactant aggregates without phospholipids, and the presence of the MTS allows them to deliver CO upon irradiation. Moreover, studies with synchrotron radiation have shown the incorporation of MTS to cells after incubation with metallosomes. All these properties make these systems suitable for the preparation of new metal based pharmaceuticals.
