A Tunable, Stable, and Bioactive MOF Catalyst for Generating a Localized Therapeutic from Endogenous Sources

Abstract

The versatile chemical and physical properties of metal organic frameworks (MOFs) have made them unique platforms for the design of biomimetic catalysts, but with only limited success to date due to instability of the MOFs employed in physiological environments. Herein, the use of Cu(II)1,3,5-Benzene-tris-triazole (CuBTTri) is demonstrated for the catalytic generation of the bioactive agent nitric oxide (NO) from endogenous sources, S -nitrosothiols (RSNOs). CuBTTri exhibits structural integrity in aqueous environments, including phosphate buffered saline (76 h, pH 7.4, 37 °C), cell media used for in vitro testing (76 h, pH 7.4, 37 °C), and fresh citrated whole blood (30 min, pH 7.4, 37 °C). The application of CuBTTri for use in polymeric medical devices is explored through the formation of a composite CuBTTripoly by blending CuBTTri into biomedical grade polyurethane matrices. Once prepared, the CuBTTri-poly material retains the catalytic function towards the generation of NO with tunable release kinetics proportional to the total content of CuBTTri embedded into the polymeric material with a surface fl ux corresponding to the therapeutic range of 1-100 n M cm −2 min −1 , which is maintained even following exposure to blood.

Nitric Oxide Generation from Endogenous Substrates Using Metal–Organic Frameworks: Inclusion within Poly(vinyl alcohol) Membranes To Investigate Reactivity and Therapeutic Potential

“…For example, Cu-BTTri has been blended with biomedically relevant polymers such as plasticized PVC, where it demonstrated the ability to promote NO release from RSNOs such as S -nitrosocysteine and S -nitroso-N-acetylpenicillamine (SNAP). 12,14 However, the ability of aqueous-phase, biological RSNOs to interact with blended Cu-BTTri (or other copper-based agents) is limited by the poor water uptake of hydrophobic polymers like PVC. In comparison, the promotion of NO release from an RSNO exposed to blended Cu-BTTri occurred more rapidly when the MOF was incorporated within chitosan, a hydrophilic polysaccharide.…”

“…Limited diffusion of the dissolved RSNO into hydrophobic polymer formulations resulted in an eightfold reduction in NO generation relative to an aqueous suspension of Cu-BTTri powder (i.e., not blended within a polymer). 14 In comparison, a 10 wt % Cu-BTTri/chitosan formulation induced a 65-fold increase in NO generation over the baseline thermal decomposition of S -nitrosoglutathione (GSNO) (Figure 1b), the most abundant small-molecule RSNO present in blood. 13 In this earlier example, no statistically significant difference in Cu-BTTri performance was observed following incorporation within the polymer.…”

A complex metal-organic framework catalyst for microwave-assisted radical polymerization

“…20-22 and Supplementary Tables 6 and 7). Given the performance of MOF-907, it is likely that the strong Lewis acidic sites, derived from the Fe 3 O SBUs [15][16][17] , contributed to fast activation and stabilization of free radicals and, thus, induced chain-growth propagation [35][36][37][38][39][40] . Indeed, these factors were critical in producing monodisperse, high molecular weight polyMMA.…”

Light-induced nitric oxide release from physiologically stable porous coordination polymers

“…[13][14][15] These distinctive characters provide the potentials for various applications including storage, separation, catalysis, and sensing as well as biomedicine. 21,22 The spontaneous release was observed as soon as RSNO was introduced into the suspension of copper-based frameworks. [16][17][18][19][20] Recently, several researches focused on NO storage and release using PCPs.…”