Hybrid silica materials for detection of toxic species and clinical diagnosis

Abstract

The present PhD thesis entitled Silica Hybrid Materials for detection of toxic species and clinical diagnosis is focused on the design and synthesis of new hybrid materials, using different silica supports as inorganic scaffolds, with applications in recognition, sensing and diagnostic protocols. The first chapter of the PhD thesis is devoted to the definition and classification of hybrid materials, relying on concepts of Nanotechnology, Supramolecular and Materials Chemistry. State of art of this field of knowledge is described using numerous examples of applications for molecular recognition, especially about gated materials. In the second chapter, the general and specific objectives of the PhD thesis are presented. The third chapter shows the synthesis, characterization and sensing performances of hybrid silica nanoparticles for the chromogenic detection of formaldehyde. Commercially available silica nanoparticles are functionalized with thiol and polyamine moieties. These hybrid nanoparticles were used for the chromogenic recognition of formaldehyde using a blue squaraine indicator. In the absence of formaldehyde, suspensions of the functionalized nanoparticles are able to bleach the blue squaraine solutions due to a reaction between the grafted thiol moieties and the added dye. In the presence of formaldehyde, -SH moieties onto the surface reacts with this molecule with the subsequent inhibition of thiol-squaraine reaction. As a consequence suspension remains blue and formaldehyde is detected. These nanoparticles allows detection of formaldehyde in a selective and sensitive fashion in aqueous and in gas phase. The fourth chapter deals with the preparation of acetylcholinesterase capped mesoporous silica nanoparticle that are used for the selective and sensitive sensing of diisopropylfluorophosphate (DFP), a nerve agent mimic. Mesoporous silica nanoparticles are prepared and the pores loaded with rhodamine B dye. Then, the external surface of the loaded nanoparticles is functionalized with a pyridostigmine derivative (a reversible inhibitor of acetylcholinesterase enzyme). Finally the pores are capped upon acetylcholinesterase addition (by coordination with the grafted inhibitor). In the absence of DFP nanoparticles are tightly closed whereas in the presence of nerve agent simulant pore opening and dye release is observed (due to preferential coordination of DFP with the enzyme active sites and detachment from the nanoparticles surface). In an extension of the previous results, nanoparticles functionalized with a neostigmine derivative are prepared and characterized and its controlled release features studied in the presence of several acetylcholinesterase inhibitors. The selective recognition of Mycoplasma fermentans genomic DNA using capped mesoporous silica nanoparticles is presented in chapter fifth. Sensing nanodevices are based on mesoporous silica nanoparticles loaded with rhodamine B and with the external surface functionalized with isocyanatopropyl moieties. Then, a short DNA sequence was covalently attached to the surface of the nanoparticles through the formation of urea linkages. Finally, the pores were capped by adding a single stranded oligonucleotide which is a highly conserved sequence of the 16S ribosomal subunit of the mycoplasma species genome. Aqueous suspensions of the DNA-capped nanoparticles showed negligible dye release. However, only in the presence of Mycoplasma fermentans genomic DNA the pores are opened and a marked rhodamine B release is observed. Using these nanoparticles a limit of detection as low as 70 DNA copies uL-1 is achieved.