Anion‑π Enzymes
Yoann Cotelle
Vincent Lebrun
Naomi Sakai
Thomas R. Ward
Stefan Matile
10.1021/acscentsci.6b00097.s001
https://acs.figshare.com/articles/journal_contribution/Anion_Enzymes/3380764
In
this report, we introduce artificial enzymes that operate with
anion-π interactions, an interaction that is essentially new
to nature. The possibility to stabilize anionic intermediates and
transition states on an π-acidic surface has been recently demonstrated,
using the addition of malonate half thioesters to enolate acceptors
as a biologically relevant example. The best chiral anion-π
catalysts operate with an addition/decarboxylation ratio of 4:1, but
without any stereoselectivity. To catalyze this important but intrinsically
disfavored reaction stereoselectively, a series of anion-π catalysts
was equipped with biotin and screened against a collection of streptavidin
mutants. With the best hit, the S112Y mutant, the reaction occurred
with 95% <i>ee</i> and complete suppression of the intrinsically
favored side product from decarboxylation. This performance of anion-π
enzymes rivals, if not exceeds, that of the best conventional organocatalysts.
Inhibition of the S112Y mutant by nitrate but not by bulky anions
supports that contributions from anion-π interactions exist
and matter, also within proteins. In agreement with docking results,
K121 is shown to be essential, presumably to lower the p<i>K</i><sub>a</sub> of the tertiary amine catalyst to operate at the optimum
pH around 3, that is below the p<i>K</i><sub>a</sub> of
the substrate. Most importantly, increasing enantioselectivity with
different mutants always coincides with increasing rates and conversion,
i.e., selective transition-state stabilization.
2016-05-13 18:53:59
p K
anion
interaction
malonate half thioesters
catalyst
S 112Y