Preparation of CBs immobilized on different types of magnetic nanoparticles for application in selective complexation and catalysis

Abstract

Cucurbiturils are known to present potential applications in molecular recognition, self- assembly, and nanotechnology. The discovery of ultra-high affinity CB–guest complexes with binding constant values similar than those found in natural complexes beckoned the attention of many groups, that focused their research in the functionalization of cucurbiturils in order to modify their structure and properties, to enhance their solubility, and to provide different functional groups for further transformations. In fact, cucurbiturils have been supported onto different solid surfaces such as gold surface, polymer beads, or nanoparticles. Iron is a bioactive metal with magnetic properties and low toxicity to mammalian cells. The formation of 10 nm magnetic nanoparticles (MNPs) of iron oxide (Fe3O4) can be achieved in an affordable and easily reproducible manner by thermal decomposition. This small size of nanoparticles provides a double advantage: first, biodegradability, because particles up to 100 nm can be phagocytosed through liver cells; second, superparamagnetic behavior, so that they become magnetized upon exposure to a magnetic field but have no permanent magnetization once the field is turned off. Prompted by the breadth of possible applications provided by cucurbiturils and our previous experience immobilizing organic molecules on MNPs of Fe3O4 and polystyrene resin (PR) (generally, to covalently immobilize catalysts for the preparation of easily recoverable and recyclable catalysts), we speculated that covalently attached cucurbiturils onto MNPs could open up new routes concerning drug delivery and biocatalysis, enable applications in many areas including sensor, transport, separation, and nanomaterials. Hence, the first research project included in this dissertation (chapter II), unveils the development of polystyrene and magnetic nanoparticles coated with a cucurbituril layer. The intrinsic properties of these compounds have been tested on the extraction of selected molecules (guests that bind to cucurbiturils). Also, in this chapter, the preparation and characterization of a library of these novel compounds—that exhibit a potential use in molecular recognition, transport, and separation—is described. The second project, described in chapter III, illustrates the synthesis of catalysts tagged with an adamantyl moiety to enhance their affinity towards cucurbiturils—for their selective extraction from the reaction media. This is achieved by covalent linking of the cucurbituril receptor to the superparamagnetic Fe3O4 nanoparticles to allow magnetic decantation. These compounds were prepared, and their catalytic activity and reusability were tested: first, on the model aldol reaction between ketones and benzaldehydes; secondly, on the enantioselective Robinson annulation with the well-established Wieland-Miescher ketone. Chapter IV showcases the preparation of a quaternary amino

derivatizing reagent decorated with an adamantyl moiety. This reagent reacts with ketone-containing steroids such as testosterone. Upon reaction, the resulting derivative can be selectively extracted from the solution mixture and driven away by the magnetically powered nanoparticles. Finally, chapter V provides some computational insights on the nature and the strength of the cucurbit[7]uril interactions with some adamantyl-based guests. The studies are built on novel and unprecedented computational models able to reproduce experimental procedures on the determination of enthalpic and entropic changes. Therefore, the main goal of the present thesis is the development of novel magnetically powered nanodevices for the efficient and selective extraction of chemical cargos. Supramolecular chemistry—especial emphasis on cucurbiturils—will play a central lead in this manuscript due to the endogenous chemical properties of the supramolecules, and the robust and modulable nature of their guests. Moreover, we will cover the entire manufacture of the nanodevices or chemical shuttles, their potential use in asymmetric catalysis, and their applicability in molecular recognition and enrichment.

El primer projecte de recerca, inclòs al capítol II, revela el desenvolupament de poliestirè i nanopartícules magnètiques recobertes amb una capa de cucurbituril. Durant aquesta secció, s’han provat les propietats intrínseques d’aquests compostos per a l’extracció de molècules seleccionades (hostes) que s’uneixen als cucurbiturils. A més, en aquest capítol, s’ha fet un esforç per caracteritzar amb precisió una varietat d’aquests nous compostos que presenten un potencial ús en el reconeixement molecular, el transport i la separació. El segon projecte, descrit al capítol III, il·lustra la síntesi de catalitzadors etiquetats amb un fragment adamantil per millorar la seva afinitat cap als cucurbiturils, i promoure la seva extracció selectiva. Això s’aconsegueix per mitjà de l’enllaç covalent entre el receptor de cucurbituril i les nanopartícules superparamagnètiques (Fe3O4), que permetent la decantació magnètica del sistema format. Una varietat d’aquests compostos s’ha preparat, i la seva activitat catalítica així com la reutilitzabilitat s’han posat també a prova: primer, en la reacció aldòlica entre cetones i benzaldehids; després, en la reacció enantioselectiva de Robinson, amb la ben consolidada cetona de Wieland i Miescher. Al capítol IV es mostra la preparació d’un reactiu derivatitzant que inclou una amina quaternària i un grup adamantil. Aquesta molècula presenta reactivitat amb esteroides que contenen cetones com la testosterona. Després de reaccionar, el derivat resultant es pot extreure selectivament de la barreja de solució i desplaçar-lo a parer, fent ús de les propietats magnètiques de les nanopartícules. Finalment, el capítol V aporta unes idees sobre la naturalesa i força de les interaccions entre els cucurbiturils i uns determinats hostes, basant-nos en uns models computacionals innovadors i sense precedents que són capaços de reproduir resultats experimentals per a la determinació de canvis entàlpics i entròpics.