Investigating Glutathione Tolerance of a Macrocyclic Dinuclear Organoiridium Catalyst in Transfer Hydrogenation



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Toxic aldehyde overload is a pathological condition that can lead to oxidative stress-related diseases in humans. A small-molecule intracellular metal catalyst (SIMCat) was synthesized to selectively convert these toxic aldehydes into less toxic alcohols. To assess the biocompatibility of the catalyst, transfer hydrogenation reactions were performed in the presence of biological nucleophiles, such as, glutathione (GSH). The aldehyde substrate scope was evaluated to confirm the specificity and selectivity of the catalyst. The SIMCat of interest, the caged organoiridium catalyst (Ir3) was prepared using a 7-step procedure. The products for each step were purified via silica gel column chromatography and characterized using 1H/13C-NMR spectroscopy and mass spectroscopy. Subsequently, the GSH tolerance of Ir3 was evaluated and compared to a control organoiridium catalyst, Ir1, using benzaldehyde as the substrate, sodium formate as the hydride source, and DMSO:H2O (1:9) as the solvent. The reaction was performed inside a vial at physiological temperature (37-38 degrees C) for 24 h on a 0.5 mol% scale for Ir3 and 1 mol% scale for Ir1. The substrates we studied included long-aliphatic and alpha,beta-unsaturated aldehydes, ketones, imines, oximes, and Beta-ketoesters. The yields of the products for each reaction, with and without GSH, were determined using gas chromatography. The significance of this project is the facilitation of scientific progress for the chemical reactivity and biocompatibility of intracellular catalysts. Future work includes the development of techniques for studying SIMCats and the synthesis of new transfer hydrogenation catalysts.