Metal-Organic Framework/Chitosan Hybrid Materials Promote Nitric Oxide Release from S-Nitrosoglutathione in Aqueous...

It has been previously demonstrated that copper-based metal-organic frameworks (MOFs) accelerate formation of the therapeutically active molecule nitric oxide (NO) from S-nitrosothiols (RSNOs). Because RSNOs are naturally present in blood, this function is hypothesized to permit the controlled production of NO through use of MOF-based blood-contacting materials. The practical implementation of MOFs in this application typically requires incorporation within a polymer support, yet this immobilization has been shown to impair the ability of the MOF to interact with the NO-forming RSNO substrate. Here, the water-stable, copper-based MOF H₃[(Cu₄Cl)₃-(BTTri)₈] (H₃BTTri = 1,3,5-tris(1H-1,2,3-triazol-5-yl)benzene), or Cu-BTTri, was incorporated within the naturally derived polysaccharide chitosan to form membranes that were evaluated for their ability to enhance NO generation from the RSNO S-nitrosoglutathione (GSNO). This is the first report to evaluate MOF-induced NO release from GSNO, the most abundant small-molecule RSNO. At a 20 μM initial GSNO concentration (pH 7.4 phosphate buffered saline, 37 °C), chitosan/Cu-BTTri membranes induced the release of 97 ± 3% of theoretical NO within approximately 4 h, corresponding to a 65-fold increase over the baseline thermal decomposition of GSNO. Furthermore, incorporation of Cu-BTTri within hydrophilic chitosan did not impair the activity of the MOF, unlike earlier efforts using hydrophobic polyurethane or poly(vinyl chloride). The reuse of the membranes continued to enhance NO production from GSNO in subsequent experiments, suggesting the potential for continued use. Additionally, the major organic product of Cu-BTTri-promoted GSNO decomposition was identified as oxidized glutathione via mass spectrometry, confirming prior hypotheses. Structural analysis by pXRD and assessment of copper leaching by ICP-AES indicated that Cu-BTTri retains crystallinity and exhibits no significant degradation following exposure to GSNO. Taken together, these findings provide insight into the function and utility of polymer/Cu-BTTri systems and may support the development of future MOF-based biomaterials.