Insertion of fluorescent manganese compounds - models of catalase - into mesoporous nanoparticles of silica, resol-silica and carbon-silica

Abstract

ROS (Reactive Oxygen Species), such as H2O2, HO● and O2-●, are naturally produced by the metabolism of living beings. However, they can appear in large quantities in the case of certain diseases (Alzheimer's, Parkinson's, sclerosis, cancer). Overproduction of ROS leads to higher cell mortality.

Some microorganisms have an Mn-based enzyme capable of catalyzing the disproportionation reaction of H2O2 into O2 and H2O. Several molecules have been synthesized to reproduce this process, however very few of them are active in aqueous environment.

Recently, polynuclear synthetic Mn species have been introduced into mesoporous silica to protect them from the environment. Thus, these complexes of Mn are stable and even see their catalytic activity increase. In order to persevere in this way, this thesis presents new compounds of formula [Mn(bpy)(AntCO2)2]n and [{Mn(bpy)(AntCO2)}2(µ-AntCO2)2(µ-OH2)] for MnII (chain and dinuclear respectively) and [Mn4O2(AntCO2)6(bpy)2(ClO4)2] for MnIII (tetranuclear) based on this concept. These compounds have two types of ligands, 2,2'-bipyridine, commonly found for similar compounds and 9-anthracene carboxylate, a fluorescent ligand added for theragnostic purposes. The resolution of the crystal structure of the MnII dinuclear compound shows a compression along the axis on the direction of the monodentate anthracene carboxylate. Moreover, by hydrolysis the one- dimensional system can be converted to the dinuclear compound.

In the synthesis of the Mn(III) compound some oxidation of the anthracene is observed and two organic compounds are obtained, an anthraquinone and an ester formed by reaction between the quinone and the carboxylate.

The manganese compounds were inserted into silica nanoparticles (NPs), resol (a polyphenol resin) -silica and carbon-silica hybrids in order to allow their vectorization and to study the compatibility of hybrid NPs with this type of system.

This work explores the magnetic properties of the complexes and the luminescent properties of the coordination compounds and materials.

The Mn(II) compounds show weak antiferromagnetic interaction, and the best way to differentiate these compounds is by EPR spectroscopy: the chain shows a unique band at g~2 while for the dinculear compound the spectrum is more complex, with several features at low fields. Magnetic properties of the Mn(III) compound confirms that it is a tetranuclear with butterfly type geometry with stronger antiferromagnetic interaction between the central ions than between central-terminal ions.

The study of the porosity of the materials and the quantification of the presence of manganese inside the materials shows a good incorporation rate of the compounds. However it seems that the compounds are not present homogenously inside the support and that they are broken into smaller units. This is confirmed with the study of the magnetic properties of the hybrid [Mn]@NPs materials.

In addition, fluoresecence measurement show that both the support and the compounds are luminescent but that both emission are strongly quenched when the compounds are inside the nanoparticles. The study of the optic properties of the materials show that a large amount of the compounds is released when the loaded silica and carbon-silica nanoparticles are redispersed in ethanol. However, resol-silica nanoparticles seem a lot more efficient to retain the complexes inside

and apparently do not need further functionalization to achieve this goal.

Finally, some preliminary test of disproportionation of H2O2 catalyzed by the manganese systems show low to moderate activity of Mn compounds in acetonitrile and paves the way for optimizing hybrid systems in aqueous media.