S-nitrosothiol-modified hyperbranched polyesters

Abstract

Hyperbranched polyesters with a range of exterior thiol modifications were synthesized through a Michael addition thiol-ene reaction. S-Nitrosothiol nitric oxide (NO) donors were subsequently introduced onto the scaffolds to yield NO-releasing polyesters with total NO storage of ~2.0 μmol mg^-1. Multiple decomposition pathways (i.e., use of light, copper ions, and heat) triggered S-nitrosothiol NO donor breakdown and NO release under physiological conditions (37 °C, pH 7.4). The NO-releasing polyesters were characterized as a function of chemical modification and scaffold size or generation. The approaches described herein expand the scope of biodegradable NO-releasing materials with large NO payloads.

Keywords: 2,2-bis(hydroxymethyl)propionic acid (bis-MPA); Nitric oxide; S-nitrosothiol; hyperbranched polyesters; thiol-ene reaction.

Fig. 1

¹H NMR spectra for A) G2-HP; B) acrylate-; C) 1,2-ethanedithiol (ET)-; D) 2,3-butanedithiol (BT)-; E) dithiothreitol (DTT)-modified G2-HP.

Fig. 2

Total nitric oxide release from (1) G2-HP-ET/NO, (2) G2-HP-BT/NO, and (3) G2-HP-DTT/NO in: (A) 0.2 mg mL⁻¹ CuBr₂ solution (37 °C, pH 7.4) or (B) DTPA-supplemented PBS solution shielded from light (37 °C, pH 7.4).

Scheme 1.

Synthesis of A) acrylate-; B) 1,2-ethanedithiol (ET)-; C) 2,3-butanedithiol (BT)-; D) dithiothreitol (DTT)-modified G2-HP.