Control of the Inter‐ and Intra‐Domain Packing in Self‐Assembled Rigid Sphere–Rod Amphiphiles Via Subtle Changes in the Side Chain Sequence

Applying subtle variations in molecular structure to achieve significant response in the supramolecular assembly structures is an attractive goal in materials design. However, how such modifications govern molecular packing and assembly morphology remains poorly understood. Here, we demonstrate that side‐chain sequence regulates packing within and between hydrophobic domains in rigid sphere–rod amphiphiles. These molecules comprise a solvophilic Keggin cluster and a solvophobic oligodialkylfluorene (OF) rod containing four repeating units. Arranging long (C10) and short (C2) side chains along the rod produces two constitutional isomers: KTOF4‐IN (C2‐C10‐C10‐C2) and KTOF4‐OUT (C10‐C2‐C2‐C10). Despite their identical overall composition, KTOF4‐IN forms complete, concentric onion‐like structures, whereas KTOF4‐OUT forms incomplete onions lacking inner layers. These different morphologies are associated with differences in rod‐to‐rod packing induced by side‐chain placement. Longer chains near the rod center are proposed to favor radial expansion of the solvophobic domain, whereas those at the ends favor its axial extension. These distinct packing arrangements influence both intra‐ and inter‐domain organization and the accessible layer curvatures. This study demonstrates that small modifications in the side‐chain sequence of rigid sphere–rod amphiphiles can effectively regulate molecular packing and thereby direct the formation of distinct final assembly structures.