Quantitative Determination of the Hydration Shell, Counterion Association and Intermolecular Distances in Nanoscale Macroionic Solutions and Their Correlations to the Self-Assembly Behaviors and Phase Transitions of Macroions

Conspectus Hydrophilic macroions with characteristic sizes of 1–6 nm represent a unique transition stage between simple ions and large colloidal particles. Typical macroions include well-defined molecular clusters, metal–organic cages (MOCs), small nanoparticles, and biomacromolecules such as globular proteins. In this regime, classic Debye–Hückel limiting theory is inapplicable due to the large sizes of macroions, while DLVO theory is also inadequate because macroionic solutions remain thermodynamically stable, with negligible van der Waals attractions compared to colloids. In the past two decades, our group has been devoted to understanding the behavior of macroionic solutions. We discovered the assembly behavior (formation of hollow, spherical, single-layered blackberry-type structures) and new phases (gelation and coacervation) in dilute macroionic solutions. However, it was not until recently that we were able to quantitatively determine the molecular-level interactions in macroionic solutions, clarifying the origin of these phenomena and leading us to discover more phase transitions and outline a whole picture of macroionic solutions. This fundamental progress will help scientists deal with more complex macroionic solutions, such as the poorly understood polyelectrolyte and biomolecular solutions. In this Account, we highlight how modern techniques enable the quantitative determination of intermolecular interactions in macroionic solutions and how these interactions dictate the self-assembly and macrophase transitions, summarized as follows: (1) Determination of the hydration shell thicknesses of metal-oxide molecular clusters in solution, achieved for the first time by using the analytical ultracentrifugation (AUC) technique and correlating this value with the macroionic charge density. (2) Determination of the number of associated counterions and their average distances to the central macroion for different metal counterions by using the anomalous synchrotron small-angle X-ray scattering (ASAXS) technique. (3) Determination of the intermolecular distances between macroions in their dimeric state with different counterions. The gradual decrease in the intermolecular distance reveals the increasing strength of counterion-mediated attraction. (4) Successful correlation of the change of intermolecular distance in the dimers with the self-assembly (into blackberry structures of different sizes) and macrophase transitions (gelation, coacervation, and crystallization) in macroionic solution. (5) Correlation of the delicate difference in intermolecular interactions/distance to the intriguing self-recognition and chiral recognition features of macroions, which we reported earlier.