Concurrent and orthogonal gold(I) and ruthenium(II) catalysis inside living cells

Abstract

The viability of building artificial metabolic pathways within a cell will depend on our ability to design biocompatible and orthogonal catalysts capable of achieving non-natural transformations. In this context, transition metal complexes offer unique possibilities to develop catalytic reactions that do not occur in nature. However, translating the potential of metal catalysts to living cells poses numerous challenges associated to their biocompatibility, and their stability and reactivity in crowded aqueous environments. Here we report a gold-mediated C–C bond formation that occurs in complex aqueous habitats, and demonstrate that the reaction can be translated to living mammalian cells. Key to the success of the process is the use of designed, water-activatable gold chloride complexes. Moreover, we demonstrate the viability of achieving the gold-promoted process in parallel with a ruthenium-mediated reaction, inside living cells, and in a bioorthogonal and mutually orthogonal manner.

Cancer-derived exosomes loaded with ultrathin palladium nanosheets for targeted bioorthogonal catalysis

“…Pd, Ru, Au) have been shuttled into living cells, tissues and animals in pursuit of tools capable of catalysing first-in-life reactions. From organometallic complexes, [1][2][3][4][5][6][7][8][9][10][11][12][13] artificial metalloenzymes [14][15][16] and metal-loaded nanocarriers [17][18][19][20][21][22][23][24] to larger-than-cells implantable devices, [25][26][27][28][29][30][31] a selected number of agents have demonstrated catalytic activity and maintained their functional compatibility with the biological milieu. Although the development of effective intracellular catalysts based on abiotic metals remains challenging, various examples reported in the literature have tested the feasibility of this concept.…”

Bright insights into palladium-triggered local chemotherapy

“…Our capacity to visualize and modulate physiological and pathological processes in the biological milieu has expanded enormously in the last 15 years through the development of a rich diversity of bioorthogonal tools and processes. 5 – 9 Among them, the use of abiotic transition metals (ruthenium, 10 – 14 palladium, 15 – 21 copper, 22 – 24 gold 25 – 27 ) has emerged to facilitate the catalytic modification or manufacture of biomolecules and xenobiotics in living systems, contributing to the advent of a new prodrug modality that is not activated by a metabolic event but through a bioorthogonal bond cleavage reaction. 9 Exploration of this novel prodrug paradigm in combination with heterogeneous Pd catalysis has stimulated the development of masking strategies that efficiently suppress the bioactivity of different classes of therapeutic agents while enabling selective drug activation – via Pd-mediated N - or O -dealkylation – both in vitro and in vivo .…”

Nanocatalosomes as Plasmonic Bilayer Shells with Interlayer Catalytic Nanospaces for Solar‐Light‐Induced Reactions

“…In addition, Pd‐Au‐based NCat also performed highly useful and industrially important Suzuki–Miyaura C−C cross‐coupling reaction affording efficient and clean production of biaryl products (>99 % yield, reaction time <15 min) with low Pd (0.01 mol %) and highest TOF (up to 17.5 s −1 ) reported so far, which is an impressive 20‐times increase in TOF over that obtained from Pd‐AuNR. Finally, Au‐based NCat were also found to be highly active for [Au]‐mediated alkyne‐activation‐annulation reactions (conversion up to 99 %, 30 min); such reactions were previously accomplished with only homogeneous Au I/III ‐based catalysts . We rationalized the consistent high catalytic performance of NCat ‐structures in variety of reactions is due to the presence of abundant and controllable few‐nm cavities in bilayer structure of NCat , where highly coupled plasmonic hot‐spots are well‐overlapped with confined catalytic sites, exhibiting synergistically enhanced reaction rates.…”

“…Au‐based catalysts have special place in organic synthesis due their selective affinity towards coordination with alkyne‐group in the presence of other functional groups, resulting a number of unique molecular transformations useful in pharmaceutical synthesis and biorthogonal chemistry; however, most of these alkyne‐activation‐based chemistries are only possible with non‐recyclable homogeneous Au I/III ‐complexes with only very few examples of AuNP‐based recyclable green catalysts showing low reactivity . With the use of metal‐bilayer structure of Au‐1–4‐NCat and by harnessing the interlayer plasmonic‐catalytic nanocavities for catalysis, we envisioned to compensate the low reactivity of [Au]‐catalyzed alkyne‐activation.…”