Click Chemistry and Bioorthogonal Chemistry: General Consideration from Discovery to Applications

Click chemistry and bioorthogonal chemistry have significantly advanced the field of chemical biology by enabling the precise and selective modification of biomolecules in complex biological environments. Click chemistry, characterized by reactions such as copper-catalyzed azide-alkyne cycloaddition (CuAAC), Ru-catalyzed azide-alkyne cycloaddition (RuAAC), organocatalyzed AAC, and strain-promoted azide-alkyne cycloaddition (SPAAC), provides efficient and high-yielding methods for covalent bond formation under mild conditions. Bioorthogonal chemistry extends these principles to reactions that can occur inside living organisms without interfering with native biochemical processes. The method facilitates the labeling, tracking, and functionalization of biomolecules, including proteins, nucleic acids, and lipids, with unparalleled specificity and efficiency. Applications span from imaging and diagnostics to the development of targeted therapeutics and drug delivery systems. This chapter explores the introductory core concepts of click chemistry and bioorthogonal chemistry, highlighting their growing scope in chemistry and transformative impact on molecular biology and therapeutic innovation.