Dynamic covalent chemistry (DCC) offers adaptability, self-correction, and degradability, valuable for creating functional molecules, assemblies, and materials. Click chemistry enables modular covalent connections, while clip reactions focus on efficient bond cleavage. Combining DCC with light provides high spatiotemporal resolution, accessing high-energy species. Photoswitches, such as DTE, reversibly switch between states upon light irradiation, making them ideal for driving DCC. Previous work has explored photoswitchable Diels-Alder reactions and imine condensation/hydrolysis. This research aims to expand the scope of photoswitchable DCC by investigating photoswitchable dynamic conjugate addition-elimination reactions, a widely explored class of dynamic covalent reactions (DCRs). The goal is to develop a versatile platform for light-controlled covalent bond formation and scission.

Michael-type reactions are a cornerstone of DCRs and reversible click reactions. The structural diversity of Michael acceptors allows for manipulation of thermodynamic and kinetic features. The addition of a leaving group enables dynamic conjugate addition-elimination reactions, facilitating bond exchange. These reactions have applications in protein inhibitor identification, nanoparticle assembly, covalent organic framework construction, and adaptable polymer network creation. While light-induced thiol-ene click chemistry exists, photoswitchable dynamic conjugate addition-elimination reactions remain rare. This study addresses this gap by exploring the possibility of stabilizing/destabilizing Michael adduct intermediates using light.

A conjugate acceptor, 2-(ethoxymethylene)-4-cyclopentene-1,3-diketone, was fused with a DTE unit. The DTE's π-system rearrangement was hypothesized to alter the Michael acceptor's reactivity. The synthesis involved a Wittig-Horner reaction and condensation. Bidirectional photoswitching between open-ring (0-1) and closed-ring (c-1) forms was confirmed by ¹H NMR and UV-vis spectroscopy. Kinetics of conjugate addition-elimination reactions with various thiols and amines were tracked using ¹H NMR and UV-vis spectroscopy. The reactions were performed in CD₃CN or a CD₃CN:D₂O mixture. Density functional theory (DFT) calculations (M06-2X-D3/def2-SVPP level) were employed to study the reaction mechanism, including transition states and intermediates. Nucleus-independent chemical shift (NICS) values were calculated to assess aromaticity/antiaromaticity. Applications included light-mediated modification of solid surfaces (glass slides coated with porous silica and modified with 3-mercaptopropyltriethoxysilane), patterning on filter paper, the regulation of amphiphilic assemblies (using a thiol-containing hydrophilic oligo(ethylene glycol) chain), and the creation and degradation of covalent polymers (using a bifunctional Michael acceptor and a tetra-functional thiol cross-linker). Characterization techniques included ¹H NMR, ESI mass spectrometry, X-ray crystallography, UV-vis spectroscopy, TEM, SEM, FTIR, GPC, TGA, DSC, tensile tests, and rheology.

The study demonstrated that the closed-ring form (c-1) of the DTE-modified Michael acceptor reacted significantly faster with both thiols and amines than the open-ring form (o-1). A wide range of thiols and amines were successfully incorporated, showcasing the versatility of the system. Thiol/thiol and amine/amine exchange reactions were also achieved, with the closed-ring forms reacting much faster. DFT calculations revealed a concerted mechanism for nucleophilic attack and proton transfer, with the closed-ring forms exhibiting lower activation energies due to reduced antiaromaticity in the transition states and enol intermediates. Experimentally determined activation energies supported the computational findings. Light-mediated surface modification was achieved, with the surface wettability switched on and off by light. Light-controlled patterning was demonstrated on filter paper. Light-controlled amphiphilic assemblies were created and their morphology was manipulated by light and chemical triggers. Finally, light-mediated creation and degradation of covalent polymers were demonstrated, enabling on-demand polymer synthesis and controlled degradation using light and chemical triggers. The polymers were characterized using a range of techniques including oscillatory rheology, NMR, GPC, and mass spectrometry.

The findings demonstrate a successful strategy for creating photoswitchable dynamic conjugate addition-elimination reactions, expanding the toolkit of light-mediated click and clip chemistry. The significant rate enhancement observed for the closed-ring form over the open-ring form is attributed to the change in antiaromaticity. The applications showcased highlight the potential of this approach for creating responsive assemblies, intelligent materials, and sustainable chemical processes. The ability to control covalent bond formation and scission with light offers significant advantages in terms of spatiotemporal control and mild reaction conditions.

This work presents a versatile platform for light-controlled dynamic covalent conjugate addition-elimination reactions, using DTE photoswitches to regulate the reactivity of Michael acceptors. The mechanistic insights reveal the crucial role of antiaromaticity changes in driving the photoactivation. Demonstrated applications in surface modification, assembly control, and polymer synthesis/degradation highlight the broad potential of this approach for creating responsive materials and sustainable chemical processes. Future research could focus on exploring other photoswitches, expanding the scope of nucleophiles, and developing more complex applications in areas such as targeted drug delivery and biocompatible materials.

While the study demonstrates the efficacy of the system with a wide range of nucleophiles, it would be beneficial to further investigate the limitations of the system, such as potential side reactions or the effects of solvent and concentration. The long-term stability of the photoswitches under repeated cycles of light irradiation also warrants further investigation. Further exploring the scope of potential applications in more complex biological systems would strengthen the implications of the findings.