In this Perspective, we present a unique approach to the design and synthesis of giant molecules based on “nanoatoms” for engineering structures across multiple length scales and controlling their macroscopic properties. Herein, “nanoatoms” refer to shape-persistent molecular nanoparticles (MNPs) with precisely defined chemical structures and surface functionalities that can serve as elemental building blocks for the precision synthesis of giant molecules by methods such as sequential “click” approach. Typical “nanoatoms” include those MNPs based on fullerenes, polyhedral oligomeric silsesquioxanes, polyoxometalates, and folded globular proteins. The resulting giant molecules are precisely defined macromolecules. They include, but are not limited to, giant surfactants, giant shape amphiphiles, and giant polyhedra. Giant surfactants are polymer tail-tethered “nanoatoms” where the two components have drastic chemical differences to impart amphiphilicity. Giant shape amphiphiles not only are built up by covalently bonded MNPs of distinct shapes where the self-assembly is driven by chemical interactions but also are largely influenced by the packing constraints of each individual shape. Giant polyhedra are either made of a large MNP or by deliberately placing “nanoatoms” at the vertices of a polyhedron. In general, giant molecules capture the essential structural features of their small-molecule counterparts in many ways but possess much larger sizes. They are recognized in certain cases as size-amplified versions of those counterparts, and often, they bridge the gap between small molecules and traditional macromolecules. Highly diverse, thermodynamically stable and metastable hierarchal structures are commonly observed in the bulk, thin film, and solution states of these giant molecules. Controlled structural variations by precision synthesis further reveal a remarkable sensitivity of their self-assembled structures to the primary chemical structures. Unconventional nanostructures can be obtained in confined environments or through directed self-assembly. All the results demonstrate that MNPs are unique elements for macromolecular science, providing a versatile platform for engineering nanostructures that are not only scientifically intriguing but also technologically relevant.

Self-assembly of rigid building blocks with explicit shape and symmetry is substantially influenced by the geometric factors and remains largely unexplored. We report the selective assembly behaviors of a class of precisely defined, nanosized giant tetrahedra constructed by placing different polyhedral oligomeric silsesquioxane (POSS) molecular nanoparticles at the vertices of a rigid tetrahedral framework. Designed symmetry breaking of these giant tetrahedra introduces precise positional interactions and results in diverse selectively assembled, highly ordered supramolecular lattices including a Frank-Kasper A15 phase, which resembles the essential structural features of certain metal alloys but at a larger length scale. These results demonstrate the power of persistent molecular geometry with balanced enthalpy and entropy in creating thermodynamically stable supramolecular lattices with properties distinct from those of other self-assembling soft materials.

Complexation of proteins with polyelectrolytes or block copolymers can lead to phase separation to generate a coacervate phase or self-assembly of coacervate core micelles. However, many proteins do not coacervate at conditions near neutral pH and physiological ionic strength. Here, protein supercharging is used to systematically explore the effect of protein charge on the complex coacervation with polycations. Four model proteins were anionically supercharged to varying degrees as quantified by mass spectrometry. Proteins phase separated with strong polycations when the ratio of negatively charged residues to positively charged residues on the protein (α) was greater than 1.1-1.2. Efficient partitioning of the protein into the coacervate phase required larger α (1.5-2.0). The preferred charge ratio for coacervation was shifted away from charge symmetry for three of the four model proteins and indicated an excess of positive charge in the coacervate phase. The composition of protein and polymer in the coacervate phase was determined using fluorescently labeled components, revealing that several of the coacervates likely have both induced charging and a macromolecular charge imbalance. The model proteins were also encapsulated in complex coacervate core micelles and micelles formed when the protein charge ratio α was greater than 1.3-1.4. Small angle neutron scattering and transmission electron microscopy showed that the micelles were spherical. The stability of the coacervate phase in both the bulk and micelles improved to increased ionic strength as the net charge on the protein increased. The micelles were also stable to dehydration and elevated temperatures.

The engineering of structures across different length scales is central to the design of novel materials with controlled macroscopic properties. Herein, we introduce a unique class of self-assembling materials, which are built upon shape-and volume-persistent molecular nanoparticles and other structural motifs, such as polymers, and can be viewed as a size-amplified version of the corresponding small-molecule counterparts. Among them, "giant surfactants" with precise molecular structures have been synthesized by "clicking" compact and polar molecular nanoparticles to flexible polymer tails of various composition and architecture at specific sites. Capturing the structural features of small-molecule surfactants but possessing much larger sizes, giant surfactants bridge the gap between small-molecule surfactants and block copolymers and demonstrate a duality of both materials in terms of their self-assembly behaviors. The controlled structural variations of these giant surfactants through precision synthesis further reveal that their selfassemblies are remarkably sensitive to primary chemical structures, leading to highly diverse, thermodynamically stable nanostructures with feature sizes around 10 nm or smaller in the bulk, thin-film, and solution states, as dictated by the collective physical interactions and geometric constraints. The results suggest that this class of materials provides a versatile platform for engineering nanostructures with sub-10-nm feature sizes. These findings are not only scientifically intriguing in understanding the chemical and physical principles of the self-assembly, but also technologically relevant, such as in nanopatterning technology and microelectronics. giant molecules | shape amphiphiles | hybrid materials | microphase separation | colloidal particles P hysical properties of materials are dictated by the hierarchical arrangements of atoms, molecules, and supramolecular assemblies across different length scales. The construction and engineering of structures at each length scale, especially at the 2-to 100-nm scale (1), are critically important in achieving desired macroscopic properties. As the traditional top-down lithography techniques face serious challenges in fabricating 2D and 3D nanostructured materials with sub-20-nm feature sizes (2), the bottom-up approach based on self-organization or directed assembly of functional molecules provides a promising alternative. The past decades have witnessed the development of diverse self-assembly building blocks ranging from small-molecule surfactants (3), block copolymers (4), and dendrimers (5) to DNAs (6, 7), peptides (8), and proteins (9). Notably, these motifs have enabled the programmed self-assembly of nanomaterials as demonstrated in DNA-coated nanoparticles (10-13). These studies have greatly improved our understanding of the thermodynamics and kinetics of self-assembly processes and opened enormous possibilities in modern nanotechnology.Noncovalent interactions, such as hydrogen bonding, amphiphilic effect, π-π interacti...

for the help with size exclusion chromatography in their laboratory. W.-B.Z. acknowledges Lubrizol Corp. for a fellowship.

This work describes the first rigorous example of a single-component block copolymer system forming unconventional spherical phases. A library of discrete block polymers with uniform chain length and diverse architectures were modularly prepared through a combination of a step-growth approach and highly efficient coupling reactions. The precise chemical structure eliminates all the molecular defects associated with molar weight, dispersity, and compositional ratio. Complex spherical phases, including the Frank–Kasper phase (A15 and σ) and quasicrystalline phase, were experimentally captured by meticulously tuning the composition and architectures. A phase portrait with unprecedented accuracy was mapped out (up to one monomer resolution), unraveling intriguing details of phase behaviors that have long been compromised by inherent molecular weight distribution. This study serves as a delicate model system to bridge the existing gaps between experimental observations and theoretical assessments and to provide insights into the formation and evolution of the unconventional spherical phases in soft matter systems.

A series of shape amphiphiles based on functionalized polyhedral oligomeric silsesquioxane (POSS) head tethered with two polymeric tails of symmetric or asymmetric compositions was designed and synthesized using sequential “grafting-from” and “click” surface functionalization. The monofunctionalization of octavinylPOSS was performed using thiol–ene chemistry to afford a dihydroxyl-functionalized POSS that was further derived into precisely defined homo- and heterobifunctional macroinitiators. Polymer tails, such as polycaprolactone and polystyrene, could then be grown from these POSS-based macroinitiators with controlled molecular weight via ring-opening polymerization and atom transfer radical polymerization (ATRP). The vinyl groups on POSS were found to be compatible with ATRP conditions. These macromolecular precursors were further modified by thiol–ene chemistry to install surface functionalities onto the POSS cage. The polymer chain composition and POSS surface chemistry can thus be tuned separately in a modular and efficient way.

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