Cu^II Lewis Acid, Proton-Coupled Electron Transfer Mechanism for Cu-Metal–Organic Framework-Catalyzed NO Release from S-Nitrosoglutathione

Abstract

Evidence is provided for a previously unknown proton-coupled electron transfer (PCET) mechanism for nitric oxide (NO) release from endogenous S-Nitrosoglutathione (GSNO) catalyzed by the metal−organic framework (MOF) H 3 [(Cu 4 Cl) 3 (BTTri) 8 ] (CuBTTri) in the presence of glutathione (GSH). The balanced reaction stoichiometry, active site characterization, and the experimental rate law are used to systematically disprove competing mechanistic hypotheses, leading unexpectedly to PCET as the proposed basic mechanism. The PCET mechanism contrasts traditionally proposed, either formally Cu II to Cu I redox or other formally Cu II Lewis acid mechanisms for NO generation by other Cu-based catalysts. The proposed PCET mechanism sets the stage for mechanistically guided syntheses of improved Cu-MOF catalysts for GSNO to NO conversion and for computational investigations on the CuBTTri/GSNO/GSH/NO system as further tests of the well-defined structure of CuBTTri, structures of hypothesized reaction intermediates, and specific questions and hypotheses generated by the proposed PCET mechanism.

MOF Polymer Composites Exhibit Faster Nitric Oxide Catalysis than MOF Crystallites

“…More NO is generated for both the powder and the composite in a shorter amount of time with added GSH versus without (Table ). The observation of complete NO release within 2 h for the powder with added GSH is identical with the results we have reported previously and is in line with other findings that the reaction is first order in [GSH]. , The composite, however, still releases more NO in less time than the powder, requiring approximately 1/5th to 1/6th the time as the powder to achieve 100% NO recovery with added GSH.…”

“…We explored this question by repeating the reactions with a stoichiometric amount of GSH added (Figure ) under otherwise identical conditions. It is known that the rate law for GSNO to NO conversion catalyzed by CuBTTri powder is first order in [GSH] with saturation kinetics observed at increased [GSH] . We reasoned that if a different GSNO to NO conversion reaction mechanism was at play in the MOF composite system than for the powder, it would be unlikely that the first order dependence on [GSH] would be preserved for the composite material.…”

“…Our current mechanistic hypothesis for the CuBTTri powder is that GSH is retained over the course of the catalytic cycle, and the disulfide product (GSSG) is formed exclusively from GSNO. 33 However, it is possible that there is a minor, alternative pathway which involves conversion of GSNO into GSH within the polymer and hence incorporation of GSH into to the GSSG product. In this second alternative hypothesis, the induction period is explained by the gradual buildup of a small amount of GSH as GSNO begins to oxidize within the polymer.…”

“…Our second hypothesis is that the formation of byproducts from the MOF-catalyzed oxidation of GSNO within the polymer involves more steps than our currently favored, minimalistic mechanism for the CuBTTri powder. Our current mechanistic hypothesis for the CuBTTri powder is that GSH is retained over the course of the catalytic cycle, and the disulfide product (GSSG) is formed exclusively from GSNO . However, it is possible that there is a minor, alternative pathway which involves conversion of GSNO into GSH within the polymer and hence incorporation of GSH into to the GSSG product.…”

Cooperative Catalysis between Dual Copper Centers in a Metal–Organic Framework for Efficient Detoxification of Chemical Warfare Agent Simulants

“…The higher activity of ZZU-282 than UiO-66 suggested that ZZU-282 is a promising candidate for detoxifying nerve agents. To determine whether the catalytic activity might be due to the open metal sites of the Cu cluster, we examined the catalytic efficiency by potassium thiocyanate (KSCN) poisoning experiments. − As depicted in Figures c, S17, and S18, the degradation of DECP dramatically declined to 42% upon the addition of KSCN, demonstrating that the copper sites in ZZU-282 played a dominant role in activating DECP. Then, a control experiment involving MOF-199 with an open channel structure and exposed Cu­(II) metal sites was conducted (Figure S19).…”