Acrylamide-Based Copolymers Bearing Photoreleasable Thiols for Subsequent Thiol–Ene Functionalization

A new set of monomers is presented in order to incorporate thiols into radical polymers using a protecting chemistry/photocleavage route. The (co)polymerization kinetics of an o -nitrobenzyl thioether-containing acrylamide derivative are reported. The presence of the o -nitrobenzyl moiety is found to strongly affect the polymerization. Nevertheless, water-soluble copolymers with N,N -dimethylacrylamide (DMAAm) as a comonomer are obtained either by free radical polymerization (10 000 ≤ M n ≤ 17 500 g mol –1; 1.5 ≤ PDI ≤ 1.8) or by reversible addition–fragmentation transfer (RAFT)-mediated controlled/living radical polymerization (2000 ≤ M n ≤ 5700 g mol –1; 1.1 ≤ PDI ≤ 1.2). Deprotection under UV light (λ = 366 nm) at ambient temperature is followed by UV/vis monitoring of the protecting group release, which proceeds to completion between 40 min and 2 h within the studied range of concentration as demonstrated by 1 H NMR spectroscopy. Thiol–maleimide addition is subsequently carried out and found to proceed with a nearly quantitative yield (ca. 90%) as measured by 1 H NMR. Different block copolymers (9400 ≤ M n ≤ 16 500 g mol –1; 1.3 ≤ PDI ≤ 1.4) with a PDMAAm water-soluble block, a polystyrene hydrophobic block, or a poly( N -isopropylacrylamide) thermosensitive block as the first segment and possessing the photoreleasable thiol moieties in the second block are subsequently synthesized by RAFT-mediated polymerization. We finally demonstrate the orthogonal sequential deprotection and reaction with benzyl maleimide of two different thiol species originating from the thiocarbonylthio functionality and the o -nitrobenzyl protected lateral groups, respectively.