Assembling Complex Macromolecules and Self-Organizations of Biological Relevance with Cu(I)-Catalyzed Azide-Alkyne, Thio-Bromo, and TERMINI Double Click Reactions

In 2022, the Nobel Prize in Chemistry was awarded to Bertozzi, Meldal, and Sharpless for the development of click chemistry and biorthogonal chemistry. Since 2001, when the concept of click chemistry was advanced by Sharpless laboratory, synthetic chemists started to envision click reactions as the preferred choice of synthetic methodology employed to create new functions. This brief perspective will summarize research performed in our laboratories with the classic Cu(I)-catalyzed azide-alkyne click (CuAAC) reaction elaborated by Meldal and Sharpless, with the thio-bromo click (TBC) and with the less-used, irreversible TERminator Multifunctional INItiator (TERMINI) dual click (TBC) reactions, the last two elaborated in our laboratory. These click reactions will be used to assemble, by accelerated modular-orthogonal methodologies, complex macromolecules and self-organizations of biological relevance. Self-assembling amphiphilic Janus dendrimers and Janus glycodendrimers together with their biological membrane mimics known as dendrimersomes and glycodendrimersomes as well as simple methodologies to assemble macromolecules with perfect and complex architecture such as dendrimers from commercial monomers and building blocks will be discussed. This perspective is dedicated to the 75th anniversary of Professor Bogdan C. Simionescu, the son of my (VP) Ph.D. mentor, Professor Cristofor I. Simionescu, who as his father, took both science and science administration in his hands, and dedicated his life to handling them in a tandem way, to their best.

Automated summary

The Nobel Prize in Chemistry for 2022 was awarded to Bertozzi, Meldal, and Sharpless for their contribution to the development of click chemistry and biorthogonal chemistry. Since 2001, when click chemistry was proposed by Sharpless's laboratory, synthetic chemists have favored click reactions as a preferred method to create new functions. This perspective summarizes the research conducted in our laboratories on CuAAC, TBC, and TERMINI click reactions, and their applications in assembling complex macromolecules and self-organizations with biological relevance.