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

Pt-catalyzed cyclization of alkynoic tosylamides by cage C is moderated by its guest effector. Dissipative acid/anhydride switching is initiated by carbodiimide addition. ‘Medium binding’ guest fumaronitrile displaces weakly binding anhydride upon DIC addition, which is replaced by acid upon anhydride hydrolysis, thus modulating substrate cyclization under temporal control.

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.