Copper ion vs copper metal–organic framework catalyzed NO release from bioavailable S-Nitrosoglutathione en route to biomedical applications: Direct 1H NMR monitoring in water allowing identification of the distinct, true reaction stoichiometries and thiol dependencies

Copper containing compounds catalyze decomposition of S -Nitrosoglutathione (GSNO) in the presence of glutathione (GSH) yielding glutathione disulfide (GSSG) and nitric oxide (NO). Extended NO generation from an endogenous source is medically desirable to achieve vasodilation, reduction in biofilms on medical devices, and antibacterial activity. Homogeneous and heterogeneous copper species catalyze release of NO from endogenous GSNO. One heterogeneous catalyst used for GSNO decomposition in blood plasma is the metal-organic framework (MOF), H 3 [(Cu 4 Cl) 3 -(BTTri) 8 , H 3 BTTri = 1,3,5-tris(1H-1,2,3-triazol-5-yl) benzene] (CuBTTri). Fundamental questions about these systems remain unanswered, despite their use in biomedical applications, in part because no method previously existed for simultaneous tracking of [GSNO], [GSH], and [GSSG] in water. Tracking these reactions in water is a necessary step towards study in biological media (blood is approximately 80% water) where NO release systems must operate. Even the balanced stoichiometry remains unknown for copper-ion and CuBTTri catalyzed GSNO decomposition. Herein, we report a direct 1H NMR method which: simultaneously monitors [GSNO], [GSH], and [GSSG] in water; provides the experimentally determined stoichiometry for copper-ion vs CuBTTri catalyzed GSNO decomposition; reveals that the CuBTTri-catalyzed reaction reaches 10% GSNO decomposition (16 h) without added GSH, yet the copper-ion catalyzed reaction reaches 100% GSNO decomposition (16 h) without added GSH; and shows 100% GSNO decomposition upon addition of stoichiometric GSH to the CuBTTri catalyzed reaction. These observations provide evidence that copper-ion and CuBTTri catalyzed GSNO decomposition in water operate through different reaction mechanisms, the details of which can now be probed by 1H NMR kinetics and other needed studies. 1H NMR follows Cu2+ and copper-based metal-organic framework (MOF) catalyzed S -Nitrosoglutathione (GSNO) decomposition in water with glutathione (GSH) yielding nitric oxide and glutathione disulfide (GSSG). 1H NMR tracks [GSNO], [GSH], and [GSSG] simultaneously. Results establish distinct stoichiometries and inverse responses towards added GSH for Cu2+ and copper MOF-catalyzed systems. Unlabelled Image • 1H NMR tracks copper-catalyzed S -Nitrosoglutathione (GSNO) decomposition. • 1H NMR simultaneously and quantitatively tracks all germane aqueous species. • Stoichiometry of Cu2+/copper metal-organic framework (MOF) catalyzed reactions • Cu2+ and copper MOF catalyzed systems show inverse responses to added glutathione. • Reaction mechanisms differ for Cu2+ and copper MOF catalyzed GSNO decomposition. [ABSTRACT FROM AUTHOR]