Coassembly-Induced Crystalline-to-Colloidal Transition of a Bioactive Phenazine Supramolecular Assembly.

Authors

Dongjun Baek, Sungchan Choi, Geunwoo Park, Bongjun Yeom, Sunihl Ma, Young-Hoon Kim, Yongju Kim

Published in

ACS applied bio materials. Oct 26, 2026. Epub Oct 26, 2026.

Abstract

The supramolecular organization of aromatic bioactive molecules in aqueous media critically governs their physicochemical accessibility and biological function, yet strategies to redirect their native crystalline assemblies into alternative colloidal states remain limited. Here, we show that CPUL1, a phenazine-derived anticancer molecule, undergoes strong self-association in water to form extended, ordered sheet-like microstructures. Screening of structurally related aromatic coassemblers identified an oligoether-functionalized partner (Carrier 1) that uniquely induces a crystalline-to-colloidal transition-defined primarily by the loss of sharp long-range diffraction features and the formation of finite dispersed nanoparticles, rather than implying a uniquely defined amorphous molecular structure-whereas closely related analogues fail to prevent macroscopic aggregation. Combined spectroscopic, microscopic, diffraction, and simulation analyses are consistent with a model in which aromatic association perturbs the native packing of CPUL1 while solvophilic oligoether chains stabilize the resulting colloidal state. This supramolecular reorganization produces stronger intracellular CPUL1-associated fluorescence and enhanced anticancer activity relative to CPUL1 alone. Together, these results provide a proof-of-concept that structurally matched coassembly can access an alternative assembly state of an aggregation-prone aromatic bioactive molecule and modify its cellular performance. Because only the CPUL1/Carrier 1 pair has been examined and the closely related Carriers 2 and 3 were ineffective, the generality of this strategy for other aromatic bioactive molecules and co-assembling partners remains to be established.

PMID:
42933981
Bibliographic data and abstract were imported from PubMed on 27 Oct 2026.

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