Organoiridium Complexes Enhance Cellular Defense Against Reactive Aldehydes Species.

Although reactive aldehyde species (RASP) are associated with the pathogenesis of many major diseases, there are currently no clinically approved treatments for RASP overload. Conventional aldehyde detox agents are stoichiometric reactants that get consumed upon reacting with their biological targets, which limits their therapeutic efficiency. To achieve longer-lasting detoxification effects, small-molecule intracellular metal catalysts (SIMCats) were used to protect cells by converting RASP into non-toxic alcohols.

Fluorescent half-sandwich iridium picolinamidate complexes for in-cell visualization.

In this work, we report on the development of fluorescent half-sandwich iridium complexes using a fluorophore attachment strategy. These constructs consist of pentamethylcyclopentadienyl (Cp*) iridium units ligated by picolinamidate donors conjugated to green-emitting boron-dipyrromethene (bodipy) dyes. Reaction studies in HO/THF mixtures showed that the fluorescent Ir complexes were active as catalysts for transfer hydrogenation, with activities similar to that of their non-fluorescent counterparts.

Intracellular Chemistry: Integrating Molecular Inorganic Catalysts with Living Systems.

This concept article focuses on the rapid growth of intracellular chemistry dedicated to the integration of small-molecule metal catalysts with living cells and organisms. Although biological systems contain a plethora of biomolecules that can deactivate inorganic species, researchers have shown that small-molecule metal catalysts could be engineered to operate in heterogeneous aqueous environments. Synthetic intracellular reactions have recently been reported for olefin hydrogenation, hydrolysis/oxidative cleavage, azide-alkyne cycloaddition, allylcarbamate cleavage, C-C bond cross coupling, and transfer hydrogenation.

Intracellular Transfer Hydrogenation Mediated by Unprotected Organoiridium Catalysts.

In the present work, we show for the first time that the conversion of aldehydes to alcohols can be achieved using "unprotected" iridium transfer hydrogenation catalysts inside living cells. The reactions were observed in real time by confocal fluorescence microscopy using a Bodipy fluorogenic substrate. We propose that the reduced cofactor nicotinamide adenine dinucleotide (NADH) is a possible hydride source inside the cell based on studies using pyruvate as a cellular redox modulator.

Innocent But Deadly: Nontoxic Organoiridium Catalysts Promote Selective Cancer Cell Death.

We demonstrate that nontoxic organoiridum complexes can selectively chemosensitize cancer cells toward platinum antiproliferative agents. Treatment of human cancer cells (breast, colon, eye/retina, head/neck, lung, ovary, and blood) with the iridium chemosensitizers led to lowering of the 50 % growth inhibition concentration (IC ) of the Pt drug carboplatin by up to ∼30-50 %. Interestingly, non-cancer cells were mostly resistant to the chemosensitizing effects of the iridium complexes.

Genetic factors that regulate the attenuation of the general stress response of yeast.

The general stress response of yeast involves the induction of approximately 200 genes in response to any one of several stresses. These genes are activated by Msn2 and repressed by the Srb10 kinase, a member of the mediator complex. Normally, Msn2 is exported from the nucleus, and Srb10 represses STRE gene expression.