# Cooperative Ligand-Mediated Transitions in Simple Macromolecules

## TL;DR

The paper explores how synthetic macromolecules can undergo cooperative shape changes when ligands bind to them, similar to biological systems.

## Contribution

The study introduces synthetic systems that exhibit cooperative ligand-mediated transitions using external constraints.

## Key findings

- Hydrophobic polyelectrolytes show cooperative transitions due to ligand-macromolecule interactions.
- Oligomeric metal chelators exhibit higher cooperativity due to coordinated metal bonds.

## Abstract

In biology, ligand-mediated
transitions (LMT), where the binding
of a molecular ligand onto the binding site of a receptor molecule
leads to a well-defined change in the conformation of the receptor,
are often referred to as “the second secret of life.”
Sharp, cooperative transitions arise in many biological cases, while
examples of synthetic cooperative systems are rare. This is because
well-defined conformational states are hard to “program”
into a molecular design. Here, we impose an external constraint in
the form of two immiscible liquids that effectively define and limit
the available conformational states of two different synthetic and
relatively simple macromolecules. We show that the mechanism of the
observed cooperative transitions with ligand concentration is the
coupling of ligand binding and conformation, similar to more complex
biological systems. The systems studied are (1) hydrophobic polyelectrolytes
(HPE) which are (bio) polymers that consist of hydrophobic as well
as ionizable (proton and hydroxyl ligand binding) functional groups.
(2) Oligomeric metal chelators (OMC), which are oligomers composed
of metal ion chelating repeating groups that are able to bind metal
ions (considered as the “ligands”), resulting in gel-like
networks of oligomers cross-linked by coordinated metal ions. We find
that in HPE, interactions between ligands and individual macromolecules
explain the observed cooperative transitions. For OMC, coordinated
bonds significantly enhance the degree of cooperativity, compared
to HPE.