Nitric Oxide-Releasing Fumed Silica Particles: Synthesis, Characterization, and Biomedical Application
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- 作者：Huiping Zhang ; Gail M. Annich ; Judiann Miskulin ; Kelly Stankiewicz ; Kathryn Osterholzer ; Scott I. Merz ; Robert H. Bartlett ; and Mark E. Meyerhoff
- 刊名：Journal of the American Chemical Society
- 出版年：2003
- 出版时间：April 30, 2003
- 年：2003
- 卷：125
- 期：17
- 页码：5015 - 5024
- 全文大小：354K
- 年卷期：v.125,no.17(April 30, 2003)
- ISSN：1520-5126
文摘
The preparation, characterization, and preliminary biomedical application of various nitric oxide(NO)-releasing fumed silica particles (0.2-0.3 
m) are reported. The tiny NO-releasing particles aresynthesized by first tethering alkylamines onto the surface of the silica using amine-containing silylationreagents. These amine groups are then converted to corresponding N-diazeniumdiolate groups via reactionwith NO(g) at high pressure in the presence of methoxide bases (e.g., NaOMe). N-Diazeniumdiolate groupswere found to form more readily with secondary amino nitrogens than primary amino nitrogens tethered tothe silica. Different alkali metal cations of the methoxide bases, however, have little effect on the degreeof N-diazeniumdiolate formation. The N-diazeniumdiolate moieties attached on the silica surface undergoa primarily proton-driven dissociation to NO under physiological conditions, with an "apparent" reactionorder somewhat greater than 1 owing to local increases in pH at the surface of the particles as free aminegroups are generated. The rates of N-diazeniumdiolate dissociation are further related to the parent aminestructures and the pH of the soaking buffer. The N-diazeniumdiolate groups also undergo slow thermaldissociation to NO, with zero-order dissociation observed at both -15 and 23 
C. It is further shown thatthe resulting NO-releasing fumed silica particles can be embedded into polymer films to create coatingsthat are thromboresistant, via the release of NO at fluxes that mimic healthy endothelial cells (EC). Forexample a polyurethane coating containing 20 wt % of NO-releasing particles prepared with pendant hexanediamine structure (i.e., Sil-2N[6]-N2O2Na) is shown to exhibit improved surface thromboresistivity (comparedto controls) when used to coat the inner walls of extracorporeal circuits (ECC) employed in a rabbit modelfor extracorporeal blood circulation.
m) are reported. The tiny NO-releasing particles aresynthesized by first tethering alkylamines onto the surface of the silica using amine-containing silylationreagents. These amine groups are then converted to corresponding N-diazeniumdiolate groups via reactionwith NO(g) at high pressure in the presence of methoxide bases (e.g., NaOMe). N-Diazeniumdiolate groupswere found to form more readily with secondary amino nitrogens than primary amino nitrogens tethered tothe silica. Different alkali metal cations of the methoxide bases, however, have little effect on the degreeof N-diazeniumdiolate formation. The N-diazeniumdiolate moieties attached on the silica surface undergoa primarily proton-driven dissociation to NO under physiological conditions, with an "apparent" reactionorder somewhat greater than 1 owing to local increases in pH at the surface of the particles as free aminegroups are generated. The rates of N-diazeniumdiolate dissociation are further related to the parent aminestructures and the pH of the soaking buffer. The N-diazeniumdiolate groups also undergo slow thermaldissociation to NO, with zero-order dissociation observed at both -15 and 23 C. It is further shown thatthe resulting NO-releasing fumed silica particles can be embedded into polymer films to create coatingsthat are thromboresistant, via the release of NO at fluxes that mimic healthy endothelial cells (EC). Forexample a polyurethane coating containing 20 wt % of NO-releasing particles prepared with pendant hexanediamine structure (i.e., Sil-2N[6]-N2O2Na) is shown to exhibit improved surface thromboresistivity (comparedto controls) when used to coat the inner walls of extracorporeal circuits (ECC) employed in a rabbit modelfor extracorporeal blood circulation.