Transition Metal‐Promoted Reactions in Aqueous Media and Biological Settings

Abstract

During the last decade, there has been a tremendous interest for developing non‐natural biocompatible transformations in biologically relevant media. Among the different encountered strategies, the use of transition metal complexes offers unique possibilities due to their high transformative power. However, translating the potential of metal catalysts to biological settings, including living cells or small‐animal models such as mice or zebrafish, poses numerous challenges associated to their biocompatibility, and their stability and reactivity in crowded aqueous environments. Herein, we describe the most relevant advances in this direction, with a particular emphasis on the systems’ structure, their mode of action and the mechanistic bases of each transformation. Thus, the key challenges from an organometallic perspective might be more easily identified.

Merging Whole‐cell Biosynthesis of Styrene and Transition‐metal Catalyzed Derivatization Reactions

“…These approaches to avoid incompatibilities, together with the development in the last decade of a range of metal catalysts for the in vivo activation of profluorophores or prodrugs in mammalian cells, indicate that the challenges and potential incompatibilities associated with using whole microbial cells with transition-metal catalysts can be overcome. [35][36][37][38][39][40][41][42][43][44][45][46][47] To date, only a few reports exist in which whole-cell biocatalysis is combined with transition-metal catalysis for synthetic purposes. Goss and co-workers reported a bromina-tion of tryptophan using a halogenase expressed by an E. coli RG-1500 strain, followed by incorporation of the obtained bromotryptophan into the antibiotic pacidamycin by engineered Streptomyces coelicolor.…”

In Vivo Assembly of Artificial Metalloenzymes and Application in Whole‐Cell Biocatalysis**

“…[6] Yet, application in whole cells present some major challenges, which include assembly of the artificial enzyme from a heterologously expressed protein and an exogenously added metal complex and the mutual incompatibility and inactivation of transition metal complexes and biological components, in particular glutathione. [7][8][9] Recently, the first reports of application of ArMs in cells appeared. In these studies, the above-mentioned challenges were circumvented by creating the ArM in the periplasm or on the cell surface, where the GSH concentration is minimal and there are less barriers to achieving incorporation of the metal cofactor.…”

Epoc group: transformable protecting group with gold(iii)-catalyzed fluorene formation

“…Recently, metal catalysts have been used for prodrug activation and uorescence labeling in biological systems. [16][17][18][19][20] If these catalysts perform the transformation in vivo, this could create potential new application of the Fmoc group in biological systems such as triggering drug release and hydrogelations.…”