Iridium-Triggered Allylcarbamate Uncaging in Living Cells

Abstract

Designing a metal catalyst that addresses the major issues of solubility, stability, toxicity, cell uptake, and reactivity within complex biological milieu for bioorthogonal controlled transformation reactions is a highly formidable challenge. Herein, we report an organoiridium complex that is nontoxic and capable of the uncaging of allyloxycarbonyl-protected amines under biologically relevant conditions and within living cells. The potential applications of this uncaging chemistry have been demonstrated by the generation of diagnostic and therapeutic agents upon the activation of profluorophore and prodrug in a controlled fashion within HeLa cells, providing a valuable tool for numerous potential biological and therapeutic applications.

Exporting Homogeneous Transition Metal Catalysts to Biological Habitats

“…[45] Recently, iridium catalysts have also been shown to catalyze the removal of alloc groups. [46] The group of Mascareñas developed in 2014 a Ru(II)catalyzed uncaging of the DNA binding agents DAPI and Ethidium Bromide. [47] These compounds when capped as allylcarbamates are distributed throughout the cell but, after the deprotection with a ruthenium (II) reagent, they recover their DNA binding ability and accumulate in the cell nuclei.…”

“…The system was further improved in 2017 by a third‐generation catalyst that boosted both the reaction rate and the TON of the previous iterations [45] . Recently, iridium catalysts have also been shown to catalyze the removal of alloc groups [46] …”

Photoactivatable o-Hydroxycinnamic Platforms for Bioimaging and Therapeutic Release

“…To achieve controlled release of a drug, a prodrug strategy has been adopted. To date, various strategies have been utilized for the site-selective activation of prodrugs, such as pH, redox, reactive oxygen species, enzymes, catalysts, temperature, light, etc. − Among these, the light-triggered prodrug activation strategy is superior to the others since the release of the drug can be modulated simply by adjusting the wavelength, intensity, or time of exposure of light, affording high spatiotemporal control over the release process. Along with spatiotemporally controlled activation of the prodrug, in recent years real-time monitoring of drug release systems has received considerable attention.…”

Transition Metal Scaffolds Used To Bring New‐to‐Nature Reactions into Biological Systems

“…As a result, iridium-activated uncaging of a fluorogenic substrate was shown possible for imaging in living cells. [70] Due to the widespread usage of cisplatin as an effective anticancer agent, there has been a natural propensity to develop dual drug strategies that can also utilize the catalytic activity of platinum. For example, one strategy designed a prodrug that contains separate moieties containing both a masked platinum(IV) and a propargyl protected N-methylethanolamine diazeniumdiolate.…”

“…Reactivity and stability were further optimized through incorporating chloro‐ and phosphine‐based ligands. As a result, iridium‐activated uncaging of a fluorogenic substrate was shown possible for imaging in living cells [70] …”