Precision Self‐Assembly of Supramolecules with Heterogeneous Derivatives

Abstract Supramolecular self‐assembly with well‐defined building blocks like lipids, deoxyribonucleic acid, or ligands relies on accessible molecular structures and predictable interactions. However, assembling heterogeneous, undefined blocks, such as disordered proteins, amorphous solids, and catecholic derivatives, remains challenging due to their unpredictable assembly, leading to irreversible aggregation, severe precipitation, and unreliable performance. Here, the first programmable, sustainable, and durable self‐assembly strategy of supramolecules with heterogenous is presented, derived blocks via harmonizing multiple molecular interactions. This approach achieves reversible assembly/disassembly, ≈73.7% reduced precipitation, and salt‐ and alkaline‐durability under freeze‐thaw cycles in model catecholic derivatives, functioning effectively as robust adhesive primers and hydrogel interfacial strengtheners. Moreover, through molecular force measurements and computational simulations, the first general criterion and benchmark for high precision supramolecular self‐assembly is proposed, applicable to complex derivatives and interactions: with blocks bearing multiple binding sites existing, the co‐assembling blocks should bear at least two binding sites with minimum binding strength (≈17 to ≈37 kJ mol −1 ) to prevent disassembly. This study paves the way and provides benchmarks for precision self‐assembly of diverse supramolecules using heterogeneous derivatives for adhesion technology, nanomaterial synthesis and bio‐inspired applications.