Toward Intracellular Bioconjugation Using Transition-Metal-Free Techniques

Bioconjugation is the chemical strategy of covalent modification of biomolecules, using either an external reagent or other biomolecules. Since its inception in the twentieth century, the technique has grown by leaps and bounds, and has a variety of applications in chemical biology. However, it is yet to reach its full potential in the study of biochemical processes in live cells, mainly because the bioconjugation strategies conflict with cellular processes. This has mostly been overcome by using transition metal catalysts, but the presence of metal centers limit them to in vitro use, or to the cell surface. These hurdles can potentially be circumvented by using metal-free strategies. However, the very modifications that are necessary to make such metal-free reactions proceed effectively may impact their biocompatibility. This is because biological processes are easily perturbed and greatly depend on the prevailing inter- and intracellular environment. With this taken into consideration, this review analyzes the applicability of the transition-metal-free strategies reported in this decade to the study of biochemical processes in vivo.