A new synthetic method for nanoscale metal-organic frameworks and their application as contrast agents for magnetic resonance imaging

Abstract

The present Thesis has been dedicated to the synthesis of nanoscale Metal-Organic Frameworks (NMOFs) and the study of their potential application as Contrast Agents (CAs). Accordingly, two main lines of work can be distinguished through the lecture of this Thesis: i) the development of a novel synthetic methodology to synthesise NMOFs; and ii) the synthesis of new NMOFs that meet the specific requirements for their use as CAs. In the first Chapter, we review the evolution of the field of MOFs, from their antecedents that made their discovery possible to their current applications and prospects. We pay special attention to the current methodologies to synthesise MOFs at the nanoscale, and the advent of new applications resulting from their small size. Chapter 3 describes the validation of the Spray-Drying (SD) technique as a new methodology to synthesise NMOFs and their related hollow superstructures. The impact of the main experimental parameters on the synthesis of NMOFs is given as well as the different modes of operations that the SD technique offers for their synthesis. The versatility of the technique has allowed us to synthesise a wide panel of NMOFs belonging to the most representative subfamilies. In Chapter 4 the possibilities of combining NMOFs with other functional species using the SD technique to synthesise MOF-based composites is explained. We show how the MOF-based hollow superstructures can be used to encapsulate different materials, including NaCl crystals, dyes and FeOx inorganic nanoparticles (INPs). Furthermore, we also prove that NMOFs can also be easily encapsulated within functional matrices, such as polymers, by SD. Finally, we demonstrate that the unique capabilities of the SD to create MOF-based composites can be exploited to further expand the applications of NMOFs. In the second axis of this Thesis, Chapter 5 describes the synthesis of a new generation of NMOFs with CA properties. The strategy consists on using heterocyclic ligands currently employed in the synthesis of molecular CAs, which possess high chelating capabilities towards Gd(III) ions. The macrocyclic ligand DOTP is used to assemble a porous, heterometallic MOF. This MOF is miniaturizable down to the nanoscale to form stable colloids; is stable in physiological saline solution and cell culture media; and is not cytotoxic. It shows interesting relaxometric properties with a r1 at high field (500 MHz) of 5 mM-1·s-1 and a maximum in r1 of 15 mM-1·s-1 at 40 MHz, which remains constant over a wide pH range and increases with temperature.

Date of Award	10 Oct 2014
Original language	English
Supervisor	Daniel Maspoch Comamala (Director) & Inhar Imaz Gabilondo (Director)