A prodrug hydrogelator serves as an effective immune booster for checkpoint blocker–based cancer immunotherapy.

This paper reports our recent investigations in the synthesis, characterization, and solution self-assembly of giant gemini surfactants consisting of two hydrophilic carboxylic acid-functionalized polyhedral oligomeric silsesquioxane (APOSS) heads and two hydrophobic polystyrene (PS) tails covalently linked via a rigid spacer (p-phenylene or biphenylene) (PS–(APOSS)₂–PS). The sequential “click” approach was employed in the synthesis, which involved thiol–ene mono-functionalization of vinyl-functionalized POSS, Cu(I)-catalyzed Huisgen [3 + 2] azide–alkyne cycloadditions for “grafting” polymer tails onto the POSS cages, and subsequent thiol–ene “click” surface functionalization. The study of their self-assembly in solution revealed a morphological transition from vesicles to wormlike cylinders and further to spheres as the degree of ionization of the carboxylic acid groups on POSS heads increases. It was found that the PS tails are generally less stretched in the micellar cores of these giant gemini surfactants than those of the corresponding single-tailed (APOSS–PS) giant surfactant. It was further observed that the PS tail conformations in the micelles were also affected by the length of the rigid spacers where the one with longer spacer exhibits even more stretched PS tail conformation. Both findings could be explained by the topological constraint imposed by the short rigid spacer in PS–(APOSS)₂–PS gemini surfactants. This constraint effectively increases the local charge density and leads to an anisotropic head shape that requires a proper re-distribution of the APOSS heads on the micellar surface to minimize the total electrostatic repulsive free energy. The study expands the scope of giant molecular shape amphiphiles and has general implications in the basic physical principles underlying their solution self-assembly behaviors.

Low molecular weight gels are formed by the self-assembly of a suitable small molecule gelator into a three-dimensional network of fibrous structures. The gel properties are determined by the fiber structures, the number and type of cross-links and the distribution of the fibers and cross-links in space. Probing these structures and cross-links is difficult. Many reports rely on microscopy of dried gels (xerogels), where the solvent is removed prior to imaging. The assumption is made that this has little effect on the structures, but it is not clear that this assumption is always (or ever) valid. Here, we use small angle neutron scattering (SANS) to probe low molecular weight hydrogels formed by the self-assembly of dipeptides. We compare scattering data for wet and dried gels, as well as following the drying process. We show that the assumption that drying does not affect the network is not always correct.

Herein we introduce a unique synthetic methodology to prepare a library of giant molecules with multiple, precisely arranged nano building blocks, and illustrate the influence of minute structural differences on their self-assembly behaviors. The T₈ polyhedral oligomeric silsesquioxane (POSS) nanoparticles are orthogonally functionalized and sequentially attached onto the end of a hydrophobic polymer chain in either linear or branched configuration. The heterogeneity of primary chemical structure in terms of composition, surface functionality, sequence, and topology can be precisely controlled and is reflected in the self-assembled supramolecular structures of these giant molecules in the condensed state. This strategy offers promising opportunities to manipulate the hierarchical heterogeneities of giant molecules via precise and modular assemblies of various nano building blocks.