Design and Engineering of Metal Catalysts for Bio-orthogonal Catalysis in Living Systems

Abstract

In the past two decades, bio-orthogonal transformations mediated by biocompatible metal catalysts in living systems have shown enormous potential in both synthetic biology and medicinal chemistry. These metal-mediated bio-orthogonal reactions, many of which could not be accomplished by natural enzymes, have created more possibilities in organic chemistry and biological sciences. Despite all of the challenges for making those abiotic catalysts work in complicated biological environments, many catalytic systems working in living systems have been reported, mediating different transformations such as uncaging of fluorescent probes, pro-drug activation, glycan or protein activation, labeling of proteins or cell surfaces, and in situ drug synthesis. This review categorizes and summarizes the recent development of synthetic metal catalysts for bio-orthogonal reactions in living systems within two decades. Ranging from simple metal complexes and macromolecular-scaffold-based catalytic systems to heterogeneous nanomaterial-based systems, we show those catalysts of diverse nature and highlight the strategies for their design and engineering. We analyze and describe the structure−property relationship of those biocompatible metal catalysts and show the importance of structural diversification and optimization for their potential applications. A brief overview of metal-mediated bio-orthogonal reactions for biological applications is also given, and the challenges and opportunities of this field are discussed from a long-term perspective.

Molecularly pure miktoarm spherical nucleic acids: preparation and usage as a scaffold for abiotic intracellular catalysis

“…Intracellular catalysis has received increasing attention in recent years, as it provides a facile and efficient approach to directly governing biochemical processes or to generating molecules of interest in cells. [1][2][3] To obtain enhanced functions and to achieve usefulness for catalysis in cells, it would be desirable to expand the scope of "catalyzable" reactions using these intracellular catalysts, so that more abiotic transformations could be realized. However, most metal complexes with catalytic properties show decreased activity or even complete deactivation under biologically relevant conditions because of the poisoning of coordinating biomolecules in such environments.…”

Intracellular Activation of Anticancer Therapeutics Using Polymeric Bioorthogonal Nanocatalysts

“…ROMP tolerates a wide range of functional groups on monomer, [ 43 ] and can provide biomimetic semi‐rigid backbones through appropriate choice of monomer, [ 44 ] making ROMP polymers useful scaffolds for TMC encapsulation. [ 45–47 ]…”

Characterization of Chalkophomycin, a Copper(II) Metallophore with an Unprecedented Molecular Architecture

“…Biological life is metal-dependent, and multiple metal ions, e.g., zinc, iron, copper, and manganese, participate in numerous biological processes, including photosynthesis and oxygen transport. , By coordinating enzyme cofactors (e.g., vitamin B12 or heme) or proteins directly (e.g., metalloproteases and zinc finger proteins), they serve as key structural elements or catalytic centers to mediate electron transport and bond formation. − By understanding and discovering specific interactions and functions of metals in living systems, efficient abiotic reactions and artificial processes may be designed and produced . The coordination geometry and valence of metal ions to their ligands are pivotal for their functions.…”