Thermodynamics of complex coacervation

Abstract Isothermal titration calorimetry has routinely been used to understand the thermodynamic characteristics of complexation and coacervation. Most commonly, built-in models that assume independent binding sites have been employed in these studies. However, the non-covalent nature of interactions and steric effects accompanying macromolecules require (i) usage of new models such as overlapping binding sites and Satake–Yang's two-state binding models and (ii) reformed interpretations of the data as two-stage structuring. Fitting data with these models, forces driving the interaction of polyelectrolytes with oppositely charged polyelectrolytes, surfactants, and proteins have been identified as electrostatics and/or counterion release with possible contributions from hydrogen bonding and hydrophobic interactions. Additionally, for surfactant–polyelectrolyte coacervation, ITC signals indicated separate regions for formation of polymer-induced micelles and free micelles. Regardless of the type of the coacervation system, thermodynamics of coacervation is affected by the following parameters: pH and ionic strength of the medium, charge density, molecular weight of the polyelectrolyte, concentration, and mixing order of macroions. Lastly, we present a brief comparison between ITC on one hand and surface plasmon resonance or capillary electrophoresis on the other regarding their application in coacervation.