Enhancing Biofunctional Polymers via Click Chemistry

Sharpless and his colleagues first described click reactions as very effective, reliable, and stereoselective reactions that can make interesting structures in mild reaction conditions with easy-to-find starting materials (Kaur et al., 2021). As Semsarilar et al. (2010) and Cai et al. (2023) say, the most common click reaction is the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC). This reaction joins azides and terminal alkynes to make 1,2,3-triazoles. There are also inverse electron demand Diels-Alder reactions, thiol-ene reactions, SPAAC reactions, and SuFEx reactions (Cai et al., 2023) related to click reactions.

Some important ways to use click chemistry in polymerization are RAFT polymerization and RROP polymerization (Wang et al., 2012; Maji et al., 2012). Click reactions can be used with these controlled polymerization methods to make a lot of different functional materials, such as biofunctional polymers (Pereira et al., 2020). For instance, biomolecules like peptides or glycans that have been changed with alkynes can be clicked with azide-containing polymers to make glycopolymers and bioconjugates (Wang et al., 2012).

Click chemistry plays many roles in giving living things new functions, making materials better, and allowing specific drug delivery:

1. Biological functionality: Click reactions make it easy to attach biomolecules like proteins, peptides, and sugars to polymers, nanoparticles, and other materials. This lets certain biological functions be added (Wardiana et al., 2021; Battigelli et al., 2022).
2. Properties of the material: Click chemistry can be used to connect polymers, creating hydrogels and other materials that are stronger, more responsive to inputs, and easier to break down (Dai et al., 2018; Li & Xiong, 2022).
3. Targeted drug delivery: Tiny carriers with click functions, like ribosomes and liposomes, can be directed to specific cells or tissues. This makes drugs more effective and lessens their side effects (Alcaraz et al., 2017; Alam et al., 2015). Click chemistry can also be used to connect drugs to polymers, creating prodrugs that are more stable and easy to dissolve (Zolotarskaya et al., 2015; Zolotarskaya et al., 2012).

Click chemistry is a useful method for making biofunctional polymers and advanced materials that can be used in a wide range of biological tasks, such as drug delivery, imaging, and tissue engineering (Battigelli et al., 2022; Kaur et al., 2021).

References

Alam, S., Alves, D., Whitehead, S., Bayer, A., McNitt, C., Popik, V., … & Best, M. (2015). A clickable and photocleavable lipid analogue for cell membrane delivery and release. Bioconjugate Chemistry, 26(6), 1021-1031. https://doi.org/10.1021/acs.bioconjchem.5b00044

Alcaraz, N., Liu, Q., Hanssen, E., Johnston, A., & Boyd, B. (2017). Clickable cubosomes for antibody-free drug targeting and imaging applications. Bioconjugate Chemistry, 29(1), 149-157. https://doi.org/10.1021/acs.bioconjchem.7b00659

Battigelli, A., Almeida, B., & Shukla, A. (2022). Recent advances in bioorthogonal click chemistry for biomedical applications. Bioconjugate Chemistry, 33(2), 263-271. https://doi.org/10.1021/acs.bioconjchem.1c00564

Cai, J., Zhu, X., Guo, P., Rose, P., Liu, X., Liu, X., … & Zhu, Y. (2023). Recent updates in click and computational chemistry for drug discovery and development. Frontiers in Chemistry, 11. https://doi.org/10.3389/fchem.2023.1114970

Dai, Y., Chen, X., & Zhang, X. (2018). Recent developments in the area of click‐crosslinked nanocarriers for drug delivery. Macromolecular Rapid Communications, 40(3). https://doi.org/10.1002/marc.201800541

Kaur, J., Saxena, M., & Rishi, N. (2021). An overview of recent advances in biomedical applications of click chemistry. Bioconjugate Chemistry, 32(8), 1455-1471. https://doi.org/10.1021/acs.bioconjchem.1c00247

Li, X. and Xiong, Y. (2022). Application of “click” chemistry in biomedical hydrogels. Acs Omega, 7(42), 36918-36928. https://doi.org/10.1021/acsomega.2c03931

Maji, S., Mitschang, F., Chen, L., Jin, Q., Wang, Y., & Agarwal, S. (2012). Functional poly(dimethyl aminoethyl methacrylate) by combination of radical ring‐opening polymerization and click chemistry for biomedical applications. Macromolecular Chemistry and Physics, 213(16), 1643-1654. https://doi.org/10.1002/macp.201200220

Pereira, S., Trindade, T., & Barros‐Timmons, A. (2020). Biofunctional polymer coated au nanoparticles prepared via raft-assisted encapsulating emulsion polymerization and click chemistry. Polymers, 12(7), 1442. https://doi.org/10.3390/polym12071442

Semsarilar, M., Ladmiral, V., & Perrier, S. (2010). Highly branched and hyperbranched glycopolymers via reversible addition−fragmentation chain transfer polymerization and click chemistry. Macromolecules, 43(3), 1438-1443. https://doi.org/10.1021/ma902587r

Wang, X., Liu, L., Luo, Y., Shi, H., Li, J., & Zhao, H. (2012). Comb‐shaped glycopolymer/peptide bioconjugates by combination of raft polymerization and thiol‐ene “click” chemistry. Macromolecular Bioscience, 12(11), 1575-1582. https://doi.org/10.1002/mabi.201200274

Wardiana, A., Jones, M., Mahler, S., & Howard, C. (2021). Incorporation of unnatural amino acid into antibody fragment for creating a stable antibody drug conjugate. Indonesian Journal of Pharmacy, 96-105. https://doi.org/10.22146/ijp.1101

Zolotarskaya, O., Wagner, A., Beckta, J., Valerie, K., & Wynne, K. (2012). Synthesis of water-soluble camptothecin–polyoxetane conjugates via click chemistry. Molecular Pharmaceutics, 9(11), 3403-3408. https://doi.org/10.1021/mp3005066

Zolotarskaya, O., Xu, L., & Valerie, K. (2015). Click synthesis of a polyamidoamine dendrimer-based camptothecin prodrug. RSC Advances, 5(72), 58600-58608. https://doi.org/10.1039/c5ra07987j