Nitric Oxide Generation from Endogenous Substrates Using Metal

Oct 4, 2017 - Multivariate Metal–Organic Frameworks for Dialing-in the Binding and Programming the Release of Drug Molecules. Journal of the America...
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Cite This: ACS Appl. Mater. Interfaces 2017, 9, 35628-35641

Nitric Oxide Generation from Endogenous Substrates Using Metal− Organic Frameworks: Inclusion within Poly(vinyl alcohol) Membranes To Investigate Reactivity and Therapeutic Potential Megan J. Neufeld,† Alec Lutzke,† W. Matthew Jones,† and Melissa M. Reynolds*,†,‡,§ †

Department of Chemistry, ‡School of Biomedical Engineering, and §Chemical and Biological Engineering, Colorado State University, Fort Collins, Colorado 80523, United States S Supporting Information *

ABSTRACT: Cu-BTTri (H3BTTri = 1,3,5-tris[1H-1,2,3triazol-5-yl]benzene) is a water-stable, copper-based metal− organic framework (MOF) that exhibits the ability to generate therapeutic nitric oxide (NO) from S-nitrosothiols (RSNOs) available within the bloodstream. Immobilization of Cu-BTTri within a polymeric membrane may allow for localized NO generation at the blood−material interface. This work demonstrates that Cu-BTTri can be incorporated within hydrophilic membranes prepared from poly(vinyl alcohol) (PVA), a polymer that has been examined for numerous biomedical applications. Following immobilization, the ability of the MOF to produce NO from the endogenous RSNO S-nitrosoglutathione (GSNO) is not significantly inhibited. Poly(vinyl alcohol) membranes containing dispersions of Cu-BTTri were tested for their ability to promote NO release from a 10 μM initial GSNO concentration at pH 7.4 and 37 °C, and NO production was observed at levels associated with antithrombotic therapeutic effects without significant copper leaching (