Reversible deactivation radical polymerization (RDRP) has revolutionized modern polymer chemistry over the past two decades, thus laying the groundwork for the synthesis of complex macromolecules and enabling the preparation of previously inaccessible materials. Reversible addition-fragmentation chain transfer (RAFT) polymerization has emerged as one of the most promising techniques because of its functional group tolerance, applicability to a wide range of vinyl monomers, and its nondemanding experimental conditions. However, despite the promise and clearly demonstrated utility of RAFT, limitations of the method sometimes still exist, including the occasional need for extended polymerization times, limited access to high molecular weight polymers, low "livingness" due to unavoidable radical termination events, etc. This Perspective focuses on recent advances that have been specifically designed to address many of these perceived limitations to reinforce the promise of RAFT for the synthesis of complex and well-defined polymers under facile conditions.

Macromolecular architecture plays a pivotal role in determining the properties of polymers. When designing polymers for specific applications, it is not only the size of a macromolecule that must be considered, but also its shape. In most cases, the topology of a polymer is a static feature that is inalterable once synthesized. Using reversible-covalent chemistry to prompt the disconnection of chemical bonds and the formation of new linkages in situ, we report polymers that undergo dramatic topological transformations via a process we term macromolecular metamorphosis. Utilizing this technique, a linear amphiphilic block copolymer or hyperbranched polymer undergoes 'metamorphosis' into comb, star and hydrophobic block copolymer architectures. This approach was extended to include a macroscopic gel which transitioned from a densely and covalently crosslinked network to one with larger distances between the covalent crosslinks when heated. These architectural transformations present an entirely new approach to 'smart' materials.

Self-healing oxime-functional hydrogels have been developed that undergo a reversible gel-to-sol transition via oxime exchange under acidic conditions. Keto-functional copolymers were prepared by conventional radical polymerization of N,N-dimethylacrylamide (DMA) and diacetone acrylamide (DAA). The resulting water soluble copolymers (P(DMA-stat-DAA)) were chemically crosslinked with difunctional alkoxyamines to obtain hydrogels via oxime formation. Gel-to-sol transitions were induced by the addition of excess monofunctional alkoxyamines to promote competitive oxime exchange under acidic conditions at 25 °C. The hydrogel could autonomously heal after it was damaged due to the dynamic nature of the oxime crosslinks. In addition to their chemo-responsive behavior, the P(DMA-stat-DAA) copolymers exhibit cloud points which vary with the DAA content in the copolymers. This thermo-responsive behavior of the P(DMA-stat-DAA) was utilized to form physical hydrogels above their cloud point. Therefore, these materials can either form dynamic-covalent or physically-crosslinked gels, both of which demonstrate reversible gelation behavior.

In the two decades since the introduction of the “click chemistry” concept, the toolbox of “click reactions” has continually expanded, enabling chemists, materials scientists, and biologists to rapidly and selectively build complexity for their applications of interest. Similarly, selective and efficient covalent bond breaking reactions have provided and will continue to provide transformative advances. Here, we review key examples and applications of efficient, selective covalent bond cleavage reactions, which we refer to herein as “clip reactions.” The strategic application of clip reactions offers opportunities to tailor the compositions and structures of complex (bio)­(macro)­molecular systems with exquisite control. Working in concert, click chemistry and clip chemistry offer scientists and engineers powerful methods to address next-generation challenges across the chemical sciences.

Radical copolymerization of donor−acceptor (D-A) monomer pairs has served as a versatile platform for the development of alternating copolymers. However, due to the use of conventional radical polymerization, the resulting copolymers have generally been limited to nondegradable vinyl polymers. By combining radical D-A copolymerization with radical ring-opening polymerization (rROP), we have synthesized an alternating copolymer with a high incorporation of degradable backbone units. Copolymerization of N-ethyl maleimide (NEtMI) with the cyclic ketene acetal (CKA) 2-methylene-4-phenyl-1,3-dioxolane (MPDL) was demonstrated to proceed in an alternating fashion, and controlled polymerization was achieved using reversible addition−fragmentation chain transfer (RAFT) polymerization. Spontaneous copolymerization, in the absence of an exogenous initiating source, occurred when the mixture of monomers was heated, presumably due to the large electron disparity between the comonomers. Chain-extension with styrene afforded well-defined P(MPDL-alt-NEtMI)-bpolystyrene copolymers, and degradation of the homopolymers and block copolymers showed complete breakdown of the alternating copolymer.