Computational Insights into the Mechanism of Nitric Oxide Generation from S-Nitrosoglutathione Catalyzed by a Copper Metal–Organic Framework

Abstract

The controlled generation of nitric oxide (NO) from endogenous sources, such as S-nitrosoglutathione (GSNO), has significant implications for biomedical implants due to the vasodilatory and other beneficial properties of NO. The water-stable metal−organic framework (MOF) Cu-1,3,5-tris[1H-1,2,3-triazol-5-yl]benzene has been shown to catalyze the production of NO and glutathione disulfide (GSSG) from GSNO in aqueous solution as well as in blood. Previous experimental work provided kinetic data for the catalysis of the 2GSNO → 2NO + GSSG reaction, leading to various proposed mechanisms. Herein, this catalytic process is examined using density functional theory. Minimal functional models of the Cu-MOF cluster and glutathione moieties are established, and three distinct catalytic mechanisms are explored. The most thermodynamically favorable mechanism studied is consistent with prior experimental findings. This mechanism involves coordination of GSNO to copper via sulfur rather than nitrogen and requires a reductive elimination that produces a Cu(I) intermediate, implicating a redox-active copper site. The experimentally observed inhibition of reactivity at high pH values is explained in terms of deprotonation of a triazole linker, which decreases the structural stability of the Cu(I) intermediate. These fundamental mechanistic insights may be generally applicable to other MOF catalysts for NO generation.

Tunable metal–organic frameworks assist in catalyzing DNAzymes with amplification platforms for biomedical applications

“…60 One reason is that these methods can involve complex manipulation and synthesis processes, and they are generally less stable. 61 In addition, various Cu-MOFs may possess distinguished potential surfaces, affecting the binding of hybrid structures. Trimeric acid (H 3 BTC) and transition metal Cu 2+ were used to create a 3D MOF with a face-centered cubic structure, as described by Williams et al (HKUST stands for Hong Kong University of Science and Technology).…”

Low‐Valent Metals in Metal‐Organic Frameworks Via Post‐Synthetic Modification

“…[59b] An important implementation of in situ metal ion reduction is the stabilisation of low-valent intermediates during catalytic processes involving MOF supported catalysts. [61] Otake et al employed node-bound acidic functional groups to support Pd II sites in Hf IV -based MOFs, Hf-MOF-808-PO 4 and Hf-MOF-808-SO 4 . [65] The Pd functionalised materials displayed catalytic activity in the oxidative Heck reaction.…”

“…Instead, stable higher‐valent precursors can be installed within a host matrix and subsequently reduced in situ via thermal, [58] chemical [10,59] or photochemical means [16b,60] . In some cases, reduction occurs spontaneously under appropriate reaction conditions, forming transient low‐valent intermediates [59a,61] . For example, the exceptional photochemical CO 2 reduction activity of MOF‐525‐Co is attributed to the photochemical one—electron reduction of porphyrin bound Co II sites, which subsequently bind and reduce CO 2 [60a] .…”

“…An important implementation of in situ metal ion reduction is the stabilisation of low‐valent intermediates during catalytic processes involving MOF supported catalysts [61] . Otake et al.…”