Transient Allosteric Regulation of Catalysis by Effector Switching in a Pt2L4 Cage

Abstract

The complexity of allosteric enzymatic regulation continues to inspire synthetic chemists seeking to emulate interconnected biological systems. In this work, a Pt₂L₄ cage capable of catalyzing the cyclization reaction of an alkynoic tosyl amide is orthogonally coupled to a diacid-catalyzed carbodiimide-hydration cycle. This new Pt-catalyzed cyclization reaction is demonstrated to exhibit electronic regulation by inclusion of different guest effectors. The orthogonal diacid-catalyzed carbodiimide hydration cycle produces transiently diverse guests that influence the rate of the Pt-catalyzed cyclization reaction to different extents. Further complexity can be introduced to the system through displacing the transiently-formed, weakly bound anhydride guest with the stronger binding fumaronitrile, affecting the catalytic rate to a larger extent for the duration of the orthogonal reaction cycle. The modulation of a Pt-catalyzed cyclization reaction can thus be regulated transiently over the course of the reaction— either up- or down-regulating the turnover frequency (TOF)—via coupling with a temporally controllable orthogonal process. This study demonstrates that principles of allosteric enzymatic regulation can also be applied to simple artificial systems.