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Neutralizing the Detrimental Effect of Glutathione on Precious Metal Catalysts
journal contribution
posted on 2014-06-25, 00:00 authored by Yvonne
M. Wilson, Marc Dürrenberger, Elisa S. Nogueira, Thomas R. WardWe
report our efforts to enable transition-metal catalysis in the
presence of cellular debris, notably Escherichia coli cell free extracts and cell lysates. This challenging goal is hampered
by the presence of thiols, mainly present in the form of glutathione
(GSH), which poison precious metal catalysts. To overcome this, we
evaluated a selection of oxidizing agents and electrophiles toward
their potential to neutralize the detrimental effect of GSH on a Ir-based
transfer hydrogenation catalyst. While the bare catalyst was severely
inhibited by cellular debris, embedding the organometallic moiety
within a host protein led to promising results in the presence of
some neutralizing agents. In view of its complementary to natural
enzymes, the asymmetric imine reductase based on the incorporation
of a biotinylated iridium pianostool complex within streptavidin (Sav)
isoforms was selected as a model reaction. Compared to purified protein
samples, we show that pretreatment of cell free extracts and cell
lysates containing Sav mutants with diamide affords up to >100
TON’s
and only a modest erosion of enantioselectivity.