# Controlling cyclodextrin host-guest complexation in water with dynamic pericyclic chemistry

## TL;DR

Scientists used reversible chemical reactions to control how water-soluble molecules interact, which could help in drug delivery and material science.

## Contribution

A new method using dynamic pericyclic chemistry to control cyclodextrin host-guest interactions in water is introduced.

## Key findings

- Diels-Alder reactions between anthracene and alkenes can modulate β-cyclodextrin binding in water.
- The system allows for reversible molecular recognition under physiological conditions.
- Non-equilibrium steady states can be achieved by adjusting reaction conditions.

## Abstract

Water-soluble macrocycles are useful molecular hosts for drug delivery, stimuli-responsive materials, water purification and many other applications. However, controlling the host-guest chemistry of macrocycles such as cyclodextrins under physiologically relevant conditions is a major challenge. Here we demonstrate the use of dynamic pericyclic chemistry to derivatise guests for cyclodextrins under mild conditions, thereby turning off molecular recognition. We show that the Diels-Alder [4 + 2] cycloaddition reaction between anthracene derivatives and activated alkenes proceed rapidly, selectively and reversibly in water under ambient conditions. This reaction can be used to modulate binding of both native and modified β-cyclodextrins to the anthracene. By appropriate choice of conditions, the resulting chemical reaction network could also operate under non-equilibrium steady state conditions. Finally, alkene scavengers could induce the retro-Diels Alder reactions, allowing the use of the pericyclic reaction system as a molecular switch.

Water-soluble macrocycles are useful in drug delivery and other applications, yet controlling their host–guest interactions under physiological conditions remains challenging. Here, the authors employ reversible Diels-Alder cycloaddition reactions to control complexation between β-cyclodextrin hosts and anthracene-derived guests in water.