Anion-Mediated Allosteric Catalysis of [2 + 2] Photocycloaddition Based on a Flexible Metallo-Amine Cage for High Diastereoselectivity

Abstract

Anions can exert a notable influence on the solubility and folding of protein structures, consequently altering their activity and stability due to the well-known Hofmeister effect. Herein, we report a protein-like allosteric metal–organic cage (MOC-68) with the solubility and conformation regulated through anion exchange, leading to conversion between the relaxed state (R-state) and the tensed state (T-state) to show distinct host–guest interactions. This conformational change enables allosteric catalysis of intermolecular [2 + 2] photocycloaddition of acyclic olefins with greatly enhanced yield and diastereoselectivity. Kinetic experiments reveal that the T-state of MOC-68 is superior in catalytic performance for the steric and thermodynamic unfavored syn-HH product, displaying a threefold rate enhancement over the R-state and totally a sevenfold increase owing to the reaction acceleration contributed by an enzymatic cage effect. Notably, this allosteric cage exhibits exceptional stability and recyclability, maintaining consistent catalytic efficiency and selectivity over five cycles. This work highlights the potential of structural allostery in flexible cages to enhance the substrate-binding ability and catalytic selectivity, providing a way to advance enzyme-mimicking cage catalysis to regulatable and efficient allosteric catalysis.

Multipocket Cage Enables the Binding of High-Order Bulky and Drug Guests Uncovered by MS Methodology

“…Distinct from the conventional guest-binding behaviors of the internal cavities of most synthetic cages, many proteins possess multiple recognition sites in open solvent-accessible peripheral pockets, which are able to bind multiple guests or different types of guests, leading to diverse protein functions. − Applying artificial receptors for high-order guest binding, ,− especially multivariant or multicomponent guest binding, remains underdeveloped, although anomalous physicochemical properties or catalytic performance may be brought forth. ,− On the one hand, synthesizing cages with multibinding sites requires elaborate structural design and preparation. On the other hand, reliable determination of high-guest-stoichiometry scenarios lacks effective analysis methods to acquire direct and valid binding information, which typically relies on Nuclear Magnetic Resonance (NMR) or X-ray crystallography.…”