Architecture‐controlled synthesis of redox‐degradable hyperbranched polyglycerol block copolymers and the structural implications of their degradation

Abstract

We have successfully synthesized a series of redoxdegradable hyperbranched polyglycerols using a disulfide containing monomer, 2-((2-(oxiran-2-ylmethoxy)ethyl)disulfanyl) ethan-1-ol (SSG), to yield PSSG homopolymers and hyperbranched block copolymers, P(G-b-SSG) and P(SSG-b-G), containing nondegradable glycerol (G) monomers. Using these polymers, we have explored the structures of the hyperbranched block copolymers and their related degradation products. Furthermore, side reaction such as reduction of disulfide bond during the polymerization was investigated by employing the free thiol titration experiments. We elucidated the structures of the degradation products with respect to the architecture of the hyperbranched block copolymer under redox conditions using 1 H NMR and GPC measurements. For example, the degradation products of P(G-b-SSG) and P(SSG-b-G) are clearly different, demonstrating the clear distinction between linear and hyperbranched block copolymers. We anticipate that this study will extend the structural diversity of PG based polymers and aid the understanding of the structures of degradable hyperbranched PG systems.

Reduction‐Triggered Self‐Cross‐Linked Hyperbranched Polyglycerol Nanogels for Intracellular Delivery of Drugs and Proteins

“…To provide redox‐degradable hyperbranched polyglycerols, we first prepared the SSG monomer as reported previously . After synthesis of the SSG monomer, we performed the polymerization to PSSG homopolymers and P(G‐ co ‐SSG) copolymers via anionic ring‐opening multibranching polymerization methods.…”

“…To provide redox-degradable hyperbranched polyglycerols, we first prepared the SSG monomer as reported previously. [31,32] After synthesis of the SSG monomer, we performed the polymerization to PSSG homopolymers and P(G-co-SSG) copolymers via anionic ring-opening multibranching polymerization methods. Five different hyperbranched polymers (both homoand copolymers) of varying molecular weights ranging from 2240 to 10 890 g mol −1 were successfully prepared, as determined by 1 H NMR and GPC analyses ( Table 1).…”

“…Moreover, recent advances in the development of functional epoxide monomers have expanded the toolkit for the synthesis of functional hyperbranched PGs with responsive properties under specific biological cues. For example, a glycerol monomer containing a disulfide bond, that is, 2‐((2‐(oxiran‐2‐ylmethoxy) ethyl)disulfanyl) ethan‐1‐ol (SSG), was recently developed by our group to synthesize redox‐degradable hyperbranched PGs (PSSGs) . These PSSGs can offer new opportunities in smart drug delivery systems by taking advantage of considerable redox concentration gradients between intracellular and extracellular environments.…”

“…For example, a glycerol monomer containing a disulfide bond, that is, 2-((2-(oxiran-2-ylmethoxy) ethyl)disulfanyl) ethan-1-ol (SSG), was recently developed by our group to synthesize redox-degradable hyperbranched PGs (PSSGs). [31,32] These PSSGs can offer new opportunities in smart drug delivery systems by taking advantage of considerable redox concentration gradients between intracellular and extracellular environments. Even with these developments, the loading of active therapeutics for redox-responsive…”

One‐pot synthesis of hyperbranched polyamines based on novel amino glycidyl ether

“…After the successful synthesis of the BAG monomer, we performed the anionic ring‐opening multibranching polymerization using a potassium alkoxide initiator that was formed via the reaction of TMP and potassium methoxide solution. As demonstrated in previous studies, we employed a slow monomer addition of BAG monomer to the deprotonated TMP initiator and polymerized at 90 °C for 48 h to synthesize the polymers in a controlled manner. The successful polymerization of PBAG polymers was characterized by 1 H NMR and GPC measurements (Fig.…”