Kinetics ofS-Nitrosation Processes in Aqueous Polymer Solution for Controlled Nitric Oxide Loading: Toward Tunable Biomaterials

An understanding of the nitrosation processes that dictate S-nitrosothiol formation in the presence of a polymer is crucial toward the controlled synthesis of nitric oxide (NO)-releasing materials, an important class of biomaterials that mimic the natural function of cells. Herein, the kinetics of S-nitrosoglutathione (GSNO) formation in the presence of dextran under a variety of nitrosation conditions, including the nitrosating agent and the dextran concentration, are reported. When comparing nitrous acid and t-butyl nitrite as the nitrosating agent, the use of nitrous acid results in 100% nitrosation of the thiol sites within less than a minute and t-butyl nitrite requires more than 5 min to reach completion. This trend establishes nitrous acid as a highly efficient nitrosating agent. In the presence of increasing dextran concentration from 0 w/v% to 10 w/v%, the extent of nitrosation decreases by approximately 5% and 30% using nitrous acid and t-butyl nitrite, respectively. With sufficient reaction time, either reagent leads to 100% nitrosation. This indicates that t-butyl nitrite is the preferred reagent for fine-tuned NO loading of thiol sites as the extent of reaction is greatly impacted by the polymer concentration. Taken together, these studies provide valuable insights regarding the ability to tailor NO storage within biomaterials for use in a wide range of clinical applications.