Cofactor-Mediated Nucleophilic Substitution Catalyzed by a Self-Assembled Holoenzyme Mimic

A self-assembled Fe4L6 cage is capable of
co-encapsulating multiple carboxylic acid containing guests in its
cavity, and these acids can act as cofactors for cage-catalyzed nucleophilic
substitutions. The kinetics of the substitution reaction depend on
the size, shape, and binding affinity of each of the components, and
small structural changes in guest size can have large effects on the
reaction. The host is quite promiscuous and is capable of binding
multiple guests with micromolar binding affinities while retaining
the ability to effect turnover and catalysis. Substrate binding modes
vary widely, from simple 1:1 complexes to 1:2 complexes that can show
either negative or positive cooperativity, depending on the guest.
The molecularity of the dissociative substitution reaction varies,
depending on the electrophile leaving group, acid cofactor, and nucleophile
size: small changes in the nature of substrate can have large effects
on reaction kinetics, all controlled by selective molecular recognition
in the cage interior.