Chemical Catalysis in Biological Environments
Introduction
Organometallics are increasingly gaining attention as tools in chemical biology due to their distinguished physicochemical properties, reactivities, and three-dimensional structures. Along these lines, the exceptional ability of organometallic compounds to catalyze a wide variety chemical transformations has not yet been sufficiently exploited for chemical biology, but could yield bioactive molecules with novel properties. For example, such catalysts could eventually be used to amplify signals by turning over a substrate multiple times, catalytically label or deactivate target biomolecules, or release prodrugs, and all this in a cellular environment. However, designing catalysts which work under physiological conditions is a significant challenge due to the combined presence of air, water, and a plethora of cellular components such as millimolar concentrations of thiols that are prone to poison organometallic catalysts, especially under protic and aerobic conditions.
Ruthenium-Induced Allylcarbamate Cleavage in Living Cells
We are currently screening organometallic and inorganic complexes for their ability to catalyze transformations under physiological conditions. So far we found that Cp*Ru(COD)Cl is able to catalyze the cleavage of allylcarbamates in presence of water, air, and thiols. This reaction can even be used to uncage amines in living mammalian cells (Figure 1).
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Figure 1. Influence of cell extract on the ruthenium-catalyzed allylcarbamate cleavage. a) Ruthenium-catalyzed deprotection of the caged fluorophore 4 to rhodamine 110 (5). b) Fluorescence development with 4. Reaction conditions: Entry 1: 0.5 mM 4 in DMSO/H2O 1:1. Entry 2: 0.5 mM 4, in 50% DMSO, 50% cell extract, and 3.5 mM GSH, yielding an overall pH of 7.0. Entry 3: Same as entry 2, but with additional Cp*Ru(COD)Cl at 100 micromolar. Entry 4: As entry 2, but with additional Cp*Ru(COD)Cl at 100 micromolar and 3.5 mM PhSH. Reactions were shaken at 120 rpm for 2.5 hours at 37 deg. Yields were then determined by comparing the fluorescence of diluted samples with a standard curve of different concentrations of rhodamine 110. For the shown vials, the solutions were diluted 20-fold with H2O:MeOH 1:1 and excited with a long wavelength UV lamp.