Unusual liquid–liquid phase transition in aqueous mixtures of a well-known dendrimer

Abstract

Liquid-liquid phase separation (LLPS) has been extensively investigated for polymer and protein solutions due to its importance in mixture thermodynamics, separation science and self-assembly processes. However, to date, no experimental studies have been reported on LLPS of dendrimer solutions. Here, it is shown that LLPS of aqueous solutions containing a hydroxyl-functionalized poly(amido amine) dendrimer of fourth generation is induced in the presence of sodium sulfate. Both the LLPS temperature and salt-dendrimer partitioning between the two coexisting phases at constant temperature were measured. Interestingly, our experiments show that LLPS switches from being induced by cooling to being induced by heating as the salt concentration increases. The two coexisting phases also show opposite temperature response. Thus, this phase transition exhibits a simultaneous lower and upper critical solution temperature-type behavior. Dynamic light-scattering and dye-binding experiments indicate that no appreciable conformational change occurs as the salt concentration increases. To explain the observed phase behavior, a thermodynamic model based on two parameters was developed. The first parameter, which describes dendrimer-dendrimer interaction energy, was determined by isothermal titration calorimetry. The second parameter describes the salt salting-out strength. By varying the salting-out parameter, it is shown that the model achieves agreement not only with the location of the experimental binodal at 25 °C but also with the slope of this curve around the critical point. The proposed model also predicts that the unusual temperature behavior of this phase transition can be described as the net result of two thermodynamic factors with opposite temperature responses: salt thermodynamic non-ideality and salting-out strength.

Formation of Dendrimer Nanoassemblies by Oligomerization-Induced Liquid–Liquid Phase Separation

“…A given LLPS boundary is described by the LLPS temperature, T ph , as a function of C S and ϕ D . At constant temperature, the isothermal phase boundary ( C S , ϕ D ) is denoted as binodal . We have experimentally characterized T ph as a function of C S at several values of ϕ D .…”

“…To theoretically describe the observed LLPS boundary, we consider the thermodynamic model introduced in ref and applicable to ternary aqueous solutions of hydrophilic globular particles in the presence of salt at high concentration. This model, which was employed to explain the main features of salt-induced LLPS of aqueous mixtures of G4 PAMAM-OH, is based on the evaluation of an expression for the dendrimer osmotic pressure, Π­(ϕ D , C S , T ), in a ternary dendrimer–salt–water mixture with composition (ϕ D , C S ) in equilibrium dialysis with a binary salt-water reservoir with salt concentration C S * = C S /α, where α­(ϕ D ) is the volume fraction of the bulk domain in the ternary system. , The bulk domain is a binary salt-water solution with the same composition of the reservoir.…”

“…Salt-dendrimer partitioning measurements were performed as described in ref and references therein. The composition of the two coexisting phases, (ϕ D (I) , C S (I) ) and (ϕ D (II) , C S (II) ), was characterized using a spectrophotometric assay based on copper binding (for dendrimer) and a potentiometric assay (for salt).…”

“…It has been recently shown that LLPS of aqueous solutions of the hydroxyl-functionalized poly­(amido amine) dendrimer of fourth generation (G4 PAMAM-OH) can be induced in the presence of strong salting-out agents such as sodium sulfate . However, no LLPS study is reported on the corresponding amino-functionalized dendrimer (G4 PAMAM-NH 2 ), an ideal candidate for glutaraldehyde cross-linking .…”

Thermoregulated Coacervation, Metal-Encapsulation and Nanoparticle Synthesis in Novel Triazine Dendrimers

“…This phase transition has been extensively investigated for solutions of linear polymers due to their importance for mixture thermodynamics, separation technologies, self-assembly processes, catalysis and the preparation of thermoresponsive materials [1,2,3,4,5]. However, corresponding studies on dendrimer solutions are scarce [6], which is surprising given the significant overlap between the scopes of dendrimers and LLPS applications. In the case of catalysis, a thermoregulated formation of coacervates of dendrimers could be employed to separate these nanoreactors from the reaction products.…”