Preparation and characterization of an improved Cu(2+)-cyclen polyurethane material that catalyzes generation of nitric oxide from S-nitrosothiols

Abstract

A new, stable and highly efficient Cu(2+)-cyclen-polyurethane material is described and shown to exhibit improved performance compared to prior materials for the catalytic decomposition of S-nitrosothiols to physiologically active nitric oxide.

Figure 1

Comparison of the newly synthesized (1) with the published (2–3) Cu²⁺-mediated NO generating polymers.

Figure 2

The measurements of catalytic NO generation by the small films of TPU-PEG-cyclen-Cu^II (1) (thickness: 30 μm, 0.47 wt % copper) in a solution of (a) 5 μM GSNO/GSH (area = 0.13 cm²) or (b) 0.5 μM CySNO/CySH (area = 0.31 cm²) in PBS buffer (10 mM, pH 7.4) containing 3 μM EDTA via chemiluminescence NOA at RT. Arrows indicate addition or removal of the given species into the mixture. All spikes in figures are artifacts due to opening the reaction vessel.

Figure 3

The evaluation of NO generation catalyzed by the same sized films (area = 0.23 cm²) of (a) TPU-PEG-cyclen-Cu^II (1) (thickness = 30 μm, Cu content = 0.47 wt %) and (b) polymer 2 (0.11 wt % Cu) in a solution of 0.5 μM CySNO/CySH in 10 mM PBS buffer (pH 7.4, 3 μM EDTA) before and after contacting with whole sheep blood or platelet-rich sheep plasma at 4 °C for 24 h via a chemiluminescence NOA.

Scheme 1

Synthesis of the new Cu²⁺-mediated NO generating polymer: TPU-PEG-cyclen-Cu^II (1).