Abstract
The development of transition metal catalysts capable of promoting non-natural transformations within living cells can open significant new avenues in chemical and cell biology. Unfortunately, the complexity of the cell makes it extremely difficult to translate standard organometallic chemistry to living environments. Therefore, progress in this field has been very slow, and many challenges, including the possibility of localizing active metal catalysts into specific subcellular sites or organelles, remain to be addressed. Herein, we report a designed ruthenium complex that accumulates preferentially inside the mitochondria of mammalian cells, while keeping its ability to react with exogenous substrates in a bioorthogonal way. Importantly, we show that the subcellular catalytic activity can be used for the confined release of fluorophores, and even allows selective functional alterations in the mitochondria by the localized transformation of inert precursors into uncouplers of the membrane potential.
Highlights
The development of transition metal catalysts capable of promoting non-natural transformations within living cells can open significant new avenues in chemical and cell biology
We provide some answers to these questions by describing a designed ruthenium conjugate that is capable of accumulating in the mitochondria of living cells and promoting a localized uncaging of alloc/allyl protected exogenous substrates, reaction that operates through typical pi-allyl-mediated mechanisms (Fig. 1a,b)
Mitochondria are complex organelles found in almost all eukaryotic cells that play vital roles in the regulation of cellular function and survival[4,26]
Summary
The development of transition metal catalysts capable of promoting non-natural transformations within living cells can open significant new avenues in chemical and cell biology. The complexity of the cell makes it extremely difficult to translate standard organometallic chemistry to living environments Progress in this field has been very slow, and many challenges, including the possibility of localizing active metal catalysts into specific subcellular sites or organelles, remain to be addressed. The living cell is a very complex, compartmentalized and dynamic entity, with a very high concentration of biomolecules, ions and other structures in complex equilibrium, and can be considered as a very stringent reaction medium Despite all these potential complications, recent data suggest that certain transition metal derivatives can promote intracellular reactions through typical organometallic mechanisms. While these results point to intracellular reactions, a recent publication by Waymouth and Wender suggests that, at least in 4T1 cells, these Ru complexes are readily washed out with PBS, and raises doubts on the intracellularity of the metal catalysis[16]
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