Modular Approach to Degradable Acetal Polymers Using Cascade Enyne Metathesis Polymerization

Abstract

A modular synthetic approach to degradable metathesis polymers is presented using acetal‐containing enyne monomers. The monomers are prepared in a short and divergent synthetic sequence that features two points of modification to tune polymerization behavior and introduce molecular cargo. Steric and stereochemical elements are critical in the monomer design in order to provide rapid and living polymerizations capable of generating block polymers. The developed polyacetal materials readily undergo pH‐dependent degradation in aqueous mixtures, and the rate of hydrolysis can be tuned through post‐polymerization modification with triazolinedione click chemistry. This presents a new scaffold for responsive metathesis polymers that may find use in applications that requires controllable breakdown and release of small molecules.

Cascade polymerizations: recent developments in the formation of polymer repeat units by cascade reactions

“…8C) which gave polymers with acetal linkages in the polymer backbone. 64 They also obtained their best results when using a bulky sulfonamide linker tethered to the opposite face of the ring relative to the other cycloalkene substituent. With their best performing monomer (34), they could achieve molecular weights up to 171 kDa with Đ values of 1.42 or less.…”

Sugar‐Based Polymers from d‐Xylose: Living Cascade Polymerization, Tunable Degradation, and Small Molecule Release

“…[45] Specifically,w ep repared SBMs from D-galactose and D-glucose with the alkyne attached at the anomeric carbon via a N-2,4,6-triisopropylbenzenesulfonyl (N-TPS) linker (that is, 5). While we could achieve high molecular weight polymers in acontrolled and living manner,compared to other cascade polymerizations,the polymerization of these monomers was relatively slow.F or example,atroom temperature (RT), our best monomer (5)reached full conversion in 7h with am onomer to initiator ratio (M/I) of 100, [45] compared to 30 min for 4 (M/I of 200 and similar concentration), [46] and 1min for 1 (M/I of 100 and slightly higher concentration). [47] We attributed the slower polymerization rates to the more substituted (sterically crowded) sugar ring.…”

Sugar‐Based Polymers from d‐Xylose: Living Cascade Polymerization, Tunable Degradation, and Small Molecule Release

“…While we could achieve high molecular weight polymers in a controlled and living manner, compared to other cascade polymerizations, the polymerization of these monomers was relatively slow. For example, at room temperature (RT), our best monomer ( 5 ) reached full conversion in 7 h with a monomer to initiator ratio (M/I) of 100, [45] compared to 30 min for 4 (M/I of 200 and similar concentration), [46] and 1 min for 1 (M/I of 100 and slightly higher concentration) [47] . We attributed the slower polymerization rates to the more substituted (sterically crowded) sugar ring.…”

“…Hawker and Gutekunst expanded upon this concept with macrocyclic monomers containing specific amino‐acid sequences that could be degraded under transesterification conditions [44] . Gutekunst and co‐workers also prepared modular monomers (such as 4 ), which gave polymers with acid‐sensitive acetals in each repeat unit [46] …”

“…Degradable polymers have also been prepared via the cascade metathesis polymerization of monomers bearing terminal alkynes and cyclic alkenes (also referred to as tandem ring-closing/ring-opening metathesis polymerization or enyne metathesis polymerization) using the third-generation Grubbs catalyst (G3). [42][43][44][45][46] This cascade metathesis polymerization (Figure 1A)was first developed in our group using monomers that do not yield degradable polymers. [47] Mechanistic studies supported that the catalyst first reacts with the alkyne then undergoes intramolecular ring-closing and ring-opening steps (Figure 1B).…”