Entropy-Driven Supramolecular Ring-Opening Polymerization of a Cyclic Hemoglobin Monomer for Constructing a...

Area of Science:

• Polymer Chemistry
• Biomaterials Science
• Supramolecular Chemistry

Background:

• Cyclic hemoglobin (Hb) monomers, formed by binding two β subunits via a polyethylene glycol (PEG) chain, undergo reversible supramolecular ring-opening polymerization (S-ROP).
• Previous work demonstrated the formation of supramolecular Hb polymers with an alternating Hb-PEG structure.

Purpose of the Study:

• To investigate the thermodynamic driving forces of S-ROP.
• To evaluate the influence of polyethylene glycol (PEG) ring size on the S-ROP equilibrium.
• To understand the mechanism governing the formation of supramolecular Hb polymers.

Main Methods:

• Polymerization of cyclic Hb monomers with varying PEG ring sizes (2, 5, 10, and 20 kDa).
• Quantification of supramolecular Hb polymers and remaining cyclic Hb monomers at equilibrium.
• Thermodynamic analysis of the S-ROP equilibrium.

Main Results:

• Negligibly small enthalpy change (ΔHp ≤ 1 kJ·mol⁻¹) observed for S-ROP.
• Significantly positive entropy change (ΔSp = 26.8–33.2 J·mol⁻¹·K⁻¹) that increases with PEG ring size.
• Larger cyclic Hb monomers show a greater preference for forming supramolecular polymers.

Conclusions:

• Supramolecular ring-opening polymerization (S-ROP) of cyclic Hb is primarily driven by entropy.
• The size of the polyethylene glycol (PEG) chain plays a crucial role in the thermodynamic favorability of the polymerization.
• This S-ROP method offers potential for constructing structurally regular, submicrometer-sized Hb-PEG alternating polymers.