Traditionally, organic chemical reactions require organic solvents, toxic catalysts, heat, or high pressure. However, copper-free click chemistry has been shown to have favorable reaction rates and orthogonality in water, buffer solutions, and physiological conditions without toxic catalysts. Strain-promoted azide-alkyne cycloaddition and inverse electron-demand Diels–Alder reactions are representative of copper-free click chemistry. Artificial chemical reactions via click chemistry can also be used outside of the laboratory in a controllable manner on live cell surfaces, in the cytosol, and in living bodies. Consequently, copper-free click chemistry has many features that are of interest in biomedical research, and various new materials and strategies for its use have been proposed. Herein, recent remarkable trials that have used copper-free click chemistry are described, focusing on their applications in molecular imaging and therapy. The research is categorized as nanoparticles for drug delivery, imaging agents for cell tracking, and hydrogels for tissue engineering, which are rapidly advancing fields based on click chemistry. The content is based primarily on the experience with click chemistry-based biomaterials over the last 10 years.
Bibliographical noteFunding Information:
H.Y.Y. and D.L. contributed equally to this work. This work was supported by the Basic Research Program (2021R1F1A1061286 and 2021R1A4A3031875) and the Mid‐Career Researcher Program (NRF‐2019R1A2C3006283) through the National Research Foundation of Korea (NRF) funded by the Korean government (Ministry of Science, ICT, and Future Planning). This work was also supported by the KU‐KIST Graduate School of Converging Science and Technology (Korea University).
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- click chemistry
- drug delivery
- imaging probe
- metabolic glycoengineering