Mechanistic analysis of diverse click reactions along with their applications

Abstract

The emergence of click chemistry has changed the face of chemical synthesis in the direction of modular, high-yielding, and greener reactions. The past two decades have evidenced a tremendous pace in the development of click chemistry and its applications in synthetic, pharmaceutical and allied sciences. Click chemistry shakes hands with green chemistry and enables chemists to dive deeper into newer chemical transformations with minimal harm caused to the environment. The present review describes the principles of click chemistry, its origin and innovations. Most relevant reactions within the click chemistry framework, including copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), strain-promoted azide-alkyne cycloaddition (SPAAC), and other crucial methodologies like thiol-ene reactions are discussed along with their mechanisms. Furthermore, applications of click chemistry have been discussed in pharmacotherapeutic and chemical aspects. These reactions have demonstrated unparalleled versatility across all areas of science due to their biocompatibility, efficiency and reliability, making them into the spotlight for discovering new drugs and optimizing them. Applications of click chemistry in the bio labeling mechanism as it precisely produces molecular images or diagnostics while undertaking proteomics and proteolysis-targeting chimeras (PROTACs) are also discussed. This holistic review follows the transformative influence of click chemistry through interdisciplinary fields. It sets the impetus for biomedical innovation, chemical biology innovation, and materials science innovation in biomedical research. With its modularity and robustness, click chemistry will continue to stretch the paradigms of synthetic and applied chemistry and may become indispensable in solving complex scientific challenges.

Keywords: Biocompatibility; Bioorthogonal chemistry; Click chemistry; Copper-catalyzed cycloaddition; Drug delivery systems; Drug discovery; Modular reactions; Therapeutic agents.