Free radical polymers with tunable and selective bio- and chemical degradability

Abstract

A versatile synthetic strategy has been developed which enables the facile incorporation of cleavable functional groups, i.e., esters, thioesters, and disulfides, into the carbon-carbon backbone of vinyl-based polymers. Through the synthesis of novel cyclic monomers, RAFT-mediated radical ring-opening copolymerizations with traditional vinyl monomers such as methyl methacrylate, N,N-dimethylaminoethyl methacrylate, and 2-hydroxyethyl methacrylate lead to the introduction of controlled degradability into these widely used vinyl copolymer systems. An additional benefit of this strategy is the inherent versatility available through the incorporation of cyclic monomers containing diverse functional groups such as esters, thioesters, disulfides, and silyl ether units that allow degradation under basic/acidic, reductive, or enzymatic conditions. By integrating multiple, orthogonal cyclic monomers into linear copolymer backbones, well-defined systems with programmable degradation profiles are obtained which allows for tunable, selective, and stepwise degradation of the vinyl polymer backbones.

Figure 1

Schematic representation of the building block nature of the cyclic monomers and their ability to introduce, multiple, disparate functional groups into the polymer chain.

Figure 2

Molecular structure and crystal packing of monomer 4. Thermal ellipsoids are drawn at the 50% probability level, and hydrogen atoms have been omitted for clarity.

Figure 3

Copolymers P1-4 based on MMA and cyclic monomers 2, 4, 5 and 6 respectively and degradation conditions for specific cyclic allylic monomers.

Figure 4

¹H NMR for the disulphide monomer, 4, and the corresponding copolymer with MMA, P2.

Figure 5

SEC traces of copolymers P1a-d (left) derived from MMA/2 and P2a-c (right) derived from MMA/4 and their corresponding degradation products (dashed lines). Percentage values indicate molar % of cyclic allylic sulfide monomer in polymer.

Figure 6

SEC traces of mixed copolymer P15 and its products after step-wise degradation.

Figure 7

SEC traces of copolymer P7 and P9, and their products after enzymatic degradation.

Scheme 1

Synthesis of cyclic monomer 2 via cyclization of the hydroxyl acid 1 under high dilution conditions.

Scheme 2

Synthesis of cyclic monomers 4–6 via the acid chloride route.

Scheme 3

Synthesis of silyl-ether monomer 8 from bis-alcohol 7.

Scheme 4

Cleavage of disulfides in copolymers P2a-c.