In this work, we showed for the first time that the conversion of aldehydes to alcohols can be achieved using “unprotected” iridium transfer hydrogenation catalysts inside living cells. A pentamethylcyclopentadienyl iridium(III) complex supported by a pyridine-carboxamidate ligand facilitates hydride transfer between reduced nicotinamide adenine dinucleotide (NADH) and aldehyde acceptors. A synthetically modified bodipy fluorophore containing an aldehyde group was used as a reaction probe. Upon treatment of live cells with the fluorophore and the Ir catalyst, the fluorophore’s aldehyde group was reduced to an alcohol, which exhibits significant increase in fluorescence intensity compared to the aldehyde precursor. The reactions were observed in real time by confocal fluorescence microscopy. The iridium complex and the aldehyde/alcohol fluorophores have moderate to low toxicity in mouse fibroblast cell viability studies. We propose that  NADH is a possible hydride source inside the cell based on studies using pyruvate as a cellular redox modulator. Control experiments and rigorous cell washing procedures were used to ensure that the transfer hydrogenation reactions occurred inside cells and not in the growth media. We expect that this biocompatible reductive chemistry will be broadly useful to practitioners working at the interface of chemistry and the life sciences.<br/> <br/>

Bioorthogonal transfer hydrogenation mediated by small molecule organoiridium catalysts

255th National Meeting (2018)

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