Clip Chemistry: Diverse (Bio)(macro)molecular and Material Function through Breaking Covalent Bonds

Abstract

In the two decades since the introduction of the “click chemistry” concept, the toolbox of “click reactions” has continually expanded, enabling chemists, materials scientists, and biologists to rapidly and selectively build complexity for their applications of interest. Similarly, selective and efficient covalent bond breaking reactions have provided and will continue to provide transformative advances. Here, we review key examples and applications of efficient, selective covalent bond cleavage reactions, which we refer to herein as “clip reactions.” The strategic application of clip reactions offers opportunities to tailor the compositions and structures of complex (bio)­(macro)­molecular systems with exquisite control. Working in concert, click chemistry and clip chemistry offer scientists and engineers powerful methods to address next-generation challenges across the chemical sciences.

Clip-off Chemistry: Synthesis by Programmed Disassembly of Reticular Materials

“…Similarly, other reactions involving the cleavage of bonds (e.g. photolysis) are potential candidates to be applied in reticular materials for their programmable disassembly (39)(40)(41). In summary, the results presented herein prove that the programmed disassembly of reticular materials is feasible, and that it can become an innovative new synthetic tool that researchers will use to synthesize myriad molecular architectures.…”

Photocatalysis in Chemical Biology: Extending the Scope of Optochemical Control and Towards New Frontiers in Semisynthetic Bioconjugates and Biocatalysis

“…An important contribution of chemistry to the biomedical research has been the development of bioorthogonal reactions that ligate two entities (click) and that uncage a molecule or disconnect two entities (clip). [10,11] Underpinning these developments is the identification of new reactivities and in particular, the ability to confine these reactions to the environment of a catalyst and control them in space and time through irradiation has proven to be incredibly empowering.…”

Protein Modification at Tyrosine with Iminoxyl Radicals

“…Much of the bond cleavage chemistry is not compatible with mild, nearphysiological, conditions (neutral pH at ambient temperature in aqueous media) and functional group-enriched circumstances. [51][52][53][54][55] Tyrosine (Tyr) exists in low abundance in protein primary sequences (~3.0%), 56 but is moderately exposed on protein surface due to amphiphilicity of the phenol functional group. Surface Tyr is often involved in protein functions in a variety of ways, as a target of PTM phosphorylation as well as a crucial functional motif for enzyme-substrate or protein-protein interactions (PPIs).…”