Progress in Strain Promoted Azide‐Alkyne Cycloaddition (SPAAC) Reaction and Their Applications

 Strain-promoted azide-alkyne cycloaddition (SPAAC) offers a rapid, catalyst free bioorthogonal strategy to form stable triazole adducts. This powerful chemistry enables precise live-cell imaging, selective tumor cell labeling and targeted drug delivery, advancing biomedical research and therapeutic applications.

Abstract

Bioorthogonal chemistry has emerged as one of the crucial techniques to study the biological processes at the molecular level without interfering with the native functional groups or biochemical pathways. This has led to the deciphering of functions of enzymes and their roles in health and diseases leading to the development of diagnostics and therapeutic agents. In this context, adoption of strain promoted azide-alkyne cycloaddition (SPAAC) reactions are pivotal because of their biocompatibility and nontoxicity. Furthermore, due to the compatibility of this reaction in aqueous media and moderate kinetics, it has also been utilized in the synthesis of drug molecules and inhibitors with minimal purifications. In this review, we have highlighted recent advances in the design and development of cyclooctyne analogs, as well as novel applications of SPAAC chemistry across interdisciplinary domains involving chemistry, biology, materials, and medical sciences.

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