1. Click Chemistry

Click Chemistry (2291)

Structural Classification

Click chemistry is used to describe the selective, modular, wide range and high-yield chemical reactions that allow rapid synthesis of new compounds through heteroatom linking (C-X-C). Bertozzi developed click chemistry in a new dimension —Bioorthogonal chemistry. It is defined as a rapid and selective reaction that does not interfere with biological processes under physiological conditions. Common reaction structures of click chemistry, such as Azide, Alkyne, DBCO, BCN, TCO and Tetrazine. Click chemistry reactions can be categorized into three categories:

(1) Copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC);

(2) Strain-promoted alkyne-azide cycloaddition (SPAAC);

(3) Inverse-electron-demand Diels-Alder (iEDDA).

As a simple and efficient connection method, click chemistry is widely used in biomedical fields, such as fluorescence imaging, targeted therapy, ADC synthesis and PROTAC synthesis.

Classification of Application Fields

Many studies have demonstrated the great potential of click chemistry not only in chemical synthesis but also for biological and biomedical applications, especially copper-free click chemistry, including SPAAC and iEDDA reactions. Copper-free click chemistry has been shown to have favorable reaction rates and orthogonality in water, buffer solutions, and physiological conditions without toxic catalysts. A massive percentage of the research has been dedicated to the applications of bioconjugation, biomedical imaging, labeling, nanoparticle modification, and targeted delivery. For example, cellular membrane lipids and proteins could be selectively labeled with click chemistry in vitro. Metabolites, posttranslational modifications, and enzyme activities can be monitored in living systems with copper-free click chemistry.