Selective nitrosation of modified dextran polymers

Abstract

The formation of stable nitric oxide (NO) moieties onto polymer substrates is a critical part of NO materials development. Depending upon the polymer functionality, nitrosation of the material can result in a variety of different NO moieties. Toward the ability to selectively load NO in the presence of other reactive sites on a polymer substrate, we investigate how the polymer functionality affects the ability to preferentially form S-nitrosothiol groups over unwanted byproducts, such as N-nitrosamines. Using modified dextran as our model polymer, we demonstrate that N-nitrosamines form on 2° amine sites under S-nitrosation conditions, but are not a significant source of released NO under physiological pH. By tuning the synthetic conditions associated with the polymer synthesis, we demonstrate that by replacing 2° amine sites on the polymer with amide sites, N-nitrosation is effectively eliminated, resulting instead in predominant S-nitrosation. The selectively S-nitrosated materials experience near-complete donor decomposition, giving rise to NO under physiological pH. The ability to tune the availability and reactivity of different functional groups is additionally helpful toward materials synthesis and application in general.