| The bioactivity of nitric oxide (NO) is endogenously transduced by S-nitrosothiols (RSNOs), a class of NO donor that may decompose via thermal, photolytic, or reductive pathways. Recent research has focused on employing RSNOs as NO delivery agents for biomedical applications. As part of my doctoral work, I have designed NO-releasing sol-gel-derived materials using RSNOs. Thiol functionalities are readily incorporated throughout silica scaffolds via the hydrolysis and co-condensation of mercaptopropyltrimethoxysilane and alkoxysilanes. After nitrosation, NO storage levels up to 4.40 mumol mg-1 may be achieved. As anticipated, the NO release is dependent on heat, light, and/or copper concentration. For particle synthesis, a high degree of control over monodispersity and size may be obtained using controlled silane addition rates. Additionally, greater water concentrations during synthesis decrease particle size without altering NO storage.;To prolong NO release, tertiary RSNO functionalities were incorporated within xerogel films by hydrolysis and co-condensation of a novel tertiary thiol-bearing silane with alkoxy- and alkylalkoxysilanes. Nitrosation resulted in NO storage up to 1.78 mumol cm-2 dependent on the concentration of silane precursors and coating thicknesses. These materials exhibited enhanced stability due to steric hindrance surrounding the nitroso group, as evidenced by release of only ∼11% of the stored NO after 24 h at 37 °C. Photolysis may be used to trigger NO release from the films at physiological temperature irrespective of soak time. Indeed, NO fluxes were greater under irradiation than in the dark (e.g., ∼23 vs. 3 pmol cm-2 s-1, respectively). A benefit of such NO release was demonstrated whereby ∼90% less bacteria adhered to RSNO-modified xerogels when irradiated.;In the last phase of my dissertation research, RSNO decomposition to NO by visible photolysis was coupled with a NO-permselective electrode to develop a RSNO electrochemical sensor. Increasing the irradiation time enhanced sensitivity up to 1.56 nA muM-1 and lowered the theoretical detection limit to 30 nM for low molecular weight RSNOs. Detection of a nitrosated protein was also possible, but at decreased sensitivity (0.11 nA muM -1). This methodology was demonstrated by measuring RSNOs in plasma, illustrating the potential to elucidate the basal levels of RSNOs in circulation. |
