Super-Resolution Single-Molecule Fluorescence Imaging for Studying Intracellular Transition-Metal Catalysis & Reductive Amination of Carbonyl Compounds Catalyzed by Half-Sandwich Iridium Complexes Under Mild Reaction Conditions



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In recent years, the field of intracellular catalysis has gained much popularity due to the ability of transition-metal complexes to promote selective reactions inside living organisms. Unfortunately, precise quantification of intracellular activity of a metal catalyst cannot be achieved using current ensemble-averaged methods. Instead, we proposed that single-molecule measurement techniques might provide valuable kinetic and mechanistic data that would enhance our understanding of intracellular catalytic behavior. Super-resolution fluorescence microscopy is an advanced optical technique that allows scientists to visualize individual biomolecules inside living cells. This method has been employed to observe and characterize various biological events at a molecular level. We herein describe our work using single-molecule imaging to evaluate the ruthenium-catalyzed uncaging of alloc-protected fluorescent probes inside living cells. This study will allow us to derive important kinetic and biological insights into the intracellular protecting group cleavage process. In the second project, we demonstrated that the conversion of aldehydes and ketones to primary amines could be promoted by half-sandwich iridium complexes using ammonium formate as both the nitrogen and hydride source. The reductive amination of a variety of carbonyl substrates in common polar solvents at 37 °C provided excellent selectivity for the amine over alcohol product. In aqueous media, selective reduction of carbonyls to primary amines was achieved in the absence of acids. Unfortunately, at catalyst concentrations of <1 mM in water, reductive amination efficiency dropped significantly, which suggests that this catalytic methodology might be not suitable for aqueous applications where very low catalyst concentration is required (e.g., inside living cells).



Super-resolution imaging, Single-molecule imaging, Intracellular catalysis, Allyl carbamate cleavage, Reductive amination


Portions of this document appear in: Nguyen, Dat P., Rudolph N. Sladek, and Loi H. Do. "Scope and limitations of reductive amination catalyzed by half-sandwich iridium complexes under mild reaction conditions." Tetrahedron letters 61, no. 32 (2020): 152196.