- 10:30 AM

Kinetics of Nitric Oxide Interactions with a Cysteine-Modified Polymer

Jun Gu, Chemical Engineering, Oklahoma State University, 423 Engineering North, Stillwater, OK 74078 and Randy S. Lewis, Department of Chemical Engineering, Brigham Young University, 350 Clyde Building, Provo, UT 84604.

Our previous work with a cysteine-modified polymer showed that endogenous nitric oxide (NO) can be scavenged and then released to inhibit platelet adhesion to the polymer. The mechanism appears to be the preferential transfer of NO from circulating S-nitrosothiols (i.e. S-nitrosated albumin) to the cysteine, followed by the release of NO from the polymer. The released NO interferes with the platelet adhesion process. Numerous studies have shown that NO is a strong inhibitor of platelet adhesion.

This work addresses the kinetic modeling of the above described process. Oxidation of cysteine on the polymer occurs although the oxidation is independent of the interactions with NO. The oxidation is catalyzed by trace metal ion(s) in the solution and shows a third order decay. A kinetic model was developed that included NO transfer from S-nitrosated bovine serum albumin (BSANO- a model S-nitrosated albumin), NO release from the polymer, and oxidation of cysteine NO. The experimental results agreed well with the model and the model showed that the cysteine surface concentration has a major effect on the NO release rate.

As for storage of the polymer, further studies showed that the cysteine on the polymer will go through a comparatively slower oxidation in the existence of both light and air- again with a third order decay. However, light or air alone cannot oxidize the cysteine.

In order to prevent or slow down the oxidation reaction and extend the functioning time for the polymer, various reducing candidates were tested. Experiment shows that ascorbic acid does not have significant effect on mitigating the oxidation although glutathione and DTT (both have free thiol group) can help the cysteine from being oxidized. Exposure of the polymer to human blood, the natural application environment of the polymer, was also evaluated.