Oxygen-mediated enzymatic polymerization of thiol–ene hydrogels

Abstract

Materials that solidify in response to an initiation stimulus are currently utilized in several biomedical and surgical applications; however, their clinical adoption would be more widespread with improved physical properties and biocompatibility. One chemistry that is particularly promising is based on the thiol–ene addition reaction, a radical-mediated step-growth polymerization that is resistant to oxygen inhibition and thus is an excellent candidate for materials that polymerize upon exposure to aerobic conditions. Here, thiol–ene-based hydrogels are polymerized by exposing aqueous solutions of multi-functional thiol and allyl ether PEG monomers, in combination with enzymatic radical initiating systems, to air. An initiating system based on glucose oxidase, glucose, and Fe2+ is initially investigated where, in the presence of glucose, the glucose oxidase reduces oxygen to hydrogen peroxide which is then further reduced by Fe2+ to yield hydroxyl radicals capable of initiating thiol–ene polymerization. While this system is shown to effectively initiate polymerization after exposure to oxygen, the polymerization rate does not monotonically increase with raised Fe2+ concentration owing to inhibitory reactions that retard polymerization at higher Fe2+ concentrations. Conversely, replacing the Fe2+ with horseradish peroxidase affords an initiating system is that is not subject to the iron-mediated inhibitory reactions and enables increased polymerization rates to be attained.

Isocyanate‐Free, UV‐Crosslinked Poly(Hydroxyurethane) Networks: A Sustainable Approach toward Highly Functional Antibacterial Gels

“…Thiol–ene addition by nature is a radical reaction but has a superior oxygen resistance compared to the conventional radical reactions . Oxygen in the precursor system will not act as an inhibitor, which could have influence the conversion greatly . This is especially favorable in coating applications, where a complete inert gas atmosphere mostly cannot be guaranteed .…”

“…[22] Oxygen in the precursor system will not act as an inhibitor, which could have influence the conversion greatly. [23] This is especially favorable in coating applications, where a complete inert gas atmosphere mostly cannot be guaranteed. [24] However, the nature of the radical reaction makes the thiol-ene reaction a very fast process, which could induce a premature crosslinking.…”

Oxygen‐mediated polymerization initiated by oltipraz‐derived thiones

“…Of these, nitrogen and argon can be readily dismissed owing to their low reactivity; carbon dioxide can similarly be discarded for being relatively unreactive as well as its typically low atmospheric concentration. This leaves water and oxygen, both of which have been employed as polymerization initiation stimuli. The utilization of atmospheric moisture is especially well known for initiating the polymerization of alkyl cyanoacrylates.…”

“…Notably, the utilization of oxygen to initiate thiol–ene polymerization has already been established. One such system utilized oxidoreductase enzymes as the basis for initiating systems capable of converting aqueous thiol–ene monomer formulations into hydrogels upon exposure to the atmosphere . Another system employed alkylboranes, species capable of rapidly generating free radicals in the presence of oxygen .…”

In situ fabrication of paclitaxel‐loaded core‐crosslinked micelles via thiol‐ene “click” chemistry for reduction‐responsive drug release

“…The rise of thiol-ene "click" chemistry as a toolbox gathering only simple, high yielding, easily workable transformations, and mild reaction conditions has facilitated an extraordinary increase in the fabrication of biomaterials. [42][43][44][45][46][47][48][49] In this work, 2,2 0 -dithiodiethanol diacrylate was used to in situ crosslink paclitaxel (PTX)-loaded PEG-PBMS micelles in aqueous media via Michael addition type thiol-ene "click" reaction under physiological conditions (Scheme 1). These PTXloaded CCL micelles with disulfide bonds exhibited reduction-responsive behaviors in the presence of dithiothreitol (DTT).…”