Entropic Control of the Helicity Inversion Rates of Twisted Metallomacrocycles by Reversible and Regioselective Deprotonation

The rate of molecular motion has been enthalpically controlled by external stimuli such as acids and bases, electrons, and light. However, controlling the rate of molecular motion through activation entropy remains a challenging task. Here, we report entropic control of the helicity inversion rate of a trinuclear Pd^II macrocycle with right- and left-handed twisted structures. Three of the six NH protons in this metallo-macrocycle were regioselectively deprotonated by a moderately strong base, inducing intramolecular proton transfer from the NH to N^- moieties in the helicity inversion. After the partial deprotonation, the helicity inversion rate of the twisted macrocycle decreased to 1/20 of that before deprotonation due to the dominant influence of the activation entropy term. The kinetic isotope effects on the inversion rate suggest that an orderly proton relay occurs between the NH and N^- moieties via multiple water molecules during the inversion process, resulting in a significant reduction in the activation entropy. The mechanism by which the activation entropy term controls the helicity inversion rate via a proton relay is expected to provide a guide for the design of more advanced molecular machines.