Fully Degradable Thioester-Functional Homo- and Alternating Copolymers Prepared through Thiocarbonyl Addition–Ring-Opening RAFT Radical Polymerization

Abstract

The radical ring-opening polymerization (RROP) of thionolactones provides access to thioester backbone-functional copolymers but has, to date, only been demonstrated on acrylic copolymers. Herein, the thionolactone dibenzo[c,e]oxepane-5-thione (DOT) was subjected to AIBN-initiated free radical homopolymerization which produced a thioester-functional homopolymer with a glass transition temperature of 95 °C and the ability to degrade exclusively into predetermined small molecules. However, the homopolymerization was impractically slow and precluded the introduction of functionality. Conversely, the RAFT-mediated copolymerization of DOT with Nmethylmaleimide (MeMI), N-phenylmaleimide (PhMI), and N-2,3,4,5,6pentafluorophenylmaleimide (PFPMI) rapidly produced well-defined copolymers with the tendency to form alternating sequences increasing in the order MeMI ≪ PhMI < PFPMI, with estimated reactivity ratios of r DOT = 0.198 and r PFPMI = 0.0078 for the latter system. Interestingly, defects in the alternating structure were more likely caused by (degradable) DOT-DOT sequences rather than (non-degradable) MI-MI sequences, which was confirmed through paper spray mass spectrometric analysis of the products from aminolytic degradation. Upon the aminolysis of backbone thioesters, maleimide repeating units were ring-opened, forming bisamide structures. Conversely, copolymer degradation through a thiolate did not result in imide substitution but nucleophilic para-fluoro substitution on PFPMI comonomer units, indicating the ability of DOT-MI copolymers to degrade under different conditions and to form differently functional products. The RROP of thionolactones has distinct advantages over RROP of cyclic ketene acetals and is anticipated to find use in the development of well-defined degradable polymer materials.

Degradable Vinyl Random Copolymers via Photocontrolled Radical Ring‐Opening Cascade Copolymerization**

“…The gradient composition in turn resulted in highly dispersed degradation products and large non‐degradable fragments, as part of the copolymer lacked main‐chain degradable units. Although new cyclic monomer classes including macrocyclic allylic sulfides (MASs) [24–27] and dibenzo[ c,e ]oxepane‐5‐thiones (DOTs) [28–30] (Figure 1A) have demonstrated promising properties, ideal random copolymers of these cyclic monomers with acrylates or acrylamides, which require both comonomer reactivity ratios to equal one in copolymerization, remain challenging. In 2018, we reported an approach to thermally initiated radical ring‐opening cascade polymerization of allylic sulfone macrocyclic monomers [31] .…”

Degradable Vinyl Random Copolymers via Photocontrolled Radical Ring‐Opening Cascade Copolymerization**

“…[23] The gradient composition in turn resulted in highly dispersed degradation products and large nondegradable fragments, as part of the copolymer lacked main-chain degradable units. Although new cyclic monomer classes including macrocyclic allylic sulfides (MASs) [24][25][26][27] and dibenzo[c,e]oxepane-5-thiones (DOTs) [28][29][30] (Figure 1A) have demonstrated promising properties, ideal random copolymers of these cyclic monomers with acrylates or acrylamides, which require both comonomer reactivity ratios to equal one in copolymerization, remain challenging. In 2018, we reported an approach to thermally initiated radical ring-opening cascade polymerization of allylic sulfone macrocyclic monomers.…”

Biocompatibility and Physiological Thiolytic Degradability of Radically-made Thioester-functional Copolymers

“…Other approaches have involved the use of a difunctional disulfide initiator (providing one cleavable unit in the centre of a (co)polymer) 29 and the step-growth polycondensations of α,ω-functional prepolymers through S-S coupling 8 or thiol oxidation. 30 Recently, thiocarbonyl addition-ring-opening (TARO) 31 radical polymerization of thionolactones was shown to introduce thioester backbone units into acrylate-, 31,32 acrylamide-, 31,33 maleimide-, 34 and vinyl ester- 35,36 based polymers. The method is compatible with reversible addition-fragmentation chain transfer (RAFT) radical polymerization (a major RDRP method) and thus enables the preparation of degradable copolymers with controlled architectures, including block copolymers.…”