Electrostatic Potential Field Effects on Amine Macrocyclizations within Yoctoliter Spaces: Supramolecular Electron...

Area of Science:

• Supramolecular Chemistry
• Physical Organic Chemistry
• Chemical Kinetics

Background:

• Electrostatic potential fields (EPFs) are crucial in enzyme catalysis and have inspired methods to control chemical reactivity.
• Supramolecular chemistry utilizes encapsulation for reaction control, but the impact of nanocontainer EPFs on reactivity remains underexplored.
• Previous work demonstrated charged supramolecular capsules modulating thiol guest properties.

Purpose of the Study:

• To investigate the effect of charged supramolecular capsules on the cyclization reaction of 14-bromotetradecan-1-amine.
• To analyze the reaction rate and activation thermodynamics (Eyring analysis) within these nanocontainers.
• To determine how external salt concentration, affecting the capsule's EPF, influences the cyclization kinetics.

Main Methods:

• Synthesis and utilization of positively and negatively charged supramolecular capsules.
• Encapsulation of 14-bromotetradecan-1-amine within the yoctoliter spaces of the capsules.
• Kinetic studies measuring cyclization rates under varying salt concentrations.
• Eyring analysis to determine activation thermodynamics.

Main Results:

• Cyclization rates and activation thermodynamics were similar in both positively and negatively charged capsules.
• Attenuation of the capsule's EPF by exogenous salts significantly slowed down the reaction rate.
• The capsules influenced the reaction by altering electron density and charge in the transition state, deviating from an idealized S_N2 mechanism.

Conclusions:

• Supramolecular capsules act similarly to covalently attached electron-donating/withdrawing groups, modifying reaction mechanisms.
• The electrostatic environment within the nanocontainer plays a critical role in modulating reaction kinetics.
• The lack of solvation in a theoretical neutral host makes the idealized S_N2 mechanism challenging.