On the back cover of the Macromolecular Rapid Communications for February 2016 (Issue 1), Alessio Zaccone from CEB together with colleagues from Germany and France presented a new method to quantify the binding energy between associating polymer molecules in water-alcohol mixtures using neutron scattering. The method is of general applicability and may lead to new developments in controlling molecular self-assembly (and dis-assembly) processes for drug delivery.
Macromolecules dissolved in liquids can self-assemble to form aggregates as soon as the liquid is no longer a good solvent. For example, a new important class of polymers with thermosensitive properties like Poly(N-isopropylacrylamide) (PNIPAM) has the ability to aggregate in water upon crossing a critical temperature of about 32C, at which the polymer starts to expose its more hydrophobic chain segments. The latter find it energetically favourable to associate with other hydrophobic segments of other macromolecules in solution and the reversible aggregation process begins. At lower temperatures, the more hydrophilic segments are instead exposed, which, in water, repel each other. PNIPAM is one of the most intensely studied polymers today because of its potential for making drug delivery capsules which can dissolve (dis-assemble) upon inducing a simple temperature trigger as soon as they reach the target in the body. It is of utmost importance, to this aim, to characterise and quantify the binding energy between these macromolecules which are fairly low, in the range between 1 and 10 kT’s (where k is Boltzmann’s constant and T is temperature), and depend sensitively on the solution parameters. Dr Alessio Zaccone, who recently joined CEB, has developed a new method to quantify the binding energy between two macromolecules in solution by simply measuring the size of growing aggregates as a function of time, starting from the instant at which the intermolecular attraction is switched on (in the case of PNIPAM, upon giving a temperature trigger). The method is based on the theoretical modelling of the dissociation rate of a macromolecular dimer. While the association rate is typically diffusion-limited and thus does not depend on the binding energy, the dissociation rate of a dimer, instead, depends on the binding energy in an exponential way, which makes this method very sensitive and applicable to quantify small energies on the order of kT. The theoretical foundations of this method were published in 2011 in Physical Review Letters. The method has now been successfully applied to the self-assembly of PNIPAM co-polymer micelles (where PNIPAM chains protrude from a polystyrene core) in water-alcohol mixtures using neutron scattering at the high-flux instrument D22 at the Institut Laue-Langevin in Grenoble (France), which is one of the world leading neutron sources. The presence of alcohol molecules in the water solution can significantly alter the binding energy between the macromolecules, such that the addition of alcohol can be exploited to more finely tune the self-assembly process in applications. By applying the method to these systems, it has been possible to quantify the change of binding energy as a function of the concentration of alcohol molecules, and of their molecular size (e.g. methanol versus acetone). The results led to a molecular model of solvation and its effect on the polymer-polymer interaction. In particular, it is suggested that the alcohol molecules disrupt the highly-structured hydration layers on the residual hydrophilic segments of PNIPAM, thus reducing the hydration repulsion and increasing the binding energy.
This method is much more practical and quantitative than the standard measurements of second virial coefficient, and requires a much lower number of measurements at small scattering angles, without having to span the whole range of scattering angles. This is an important advantage given the typical restrictions on beam-time availability at large-scale scattering facilities.
Furthermore, the method is applicable to different scattering techniques, depending on the size of the macromolecules or colloids, which include neutron, X-ray and light scattering, and in future studies it could be profitably applied to the quantitative study of biomolecule self-assembly.