Supramolecular Engineering of Melamine–Barbiturate Assemblies for Polyphenol Encapsulation and Antioxidant Delivery

Supramolecular assemblies of melamine–barbituric acid (Mel-BA) were engineered for the controlled encapsulation of polyphenols, as exemplified by epicatechin (EC). Quantum chemical (DFT) calculations verified the thermodynamic viability of incorporation, although steric and geometric constraints introduced structural defects. EC displayed a binding affinity for Mel-BA higher than that of gallic acid, facilitated by its additional aromatic rings. Encapsulation modulated particle morphology, yielding spherical Mel-BA-GT particles (∼10 μm) and larger, nonspherical Mel-BA-EC assemblies (∼15 μm). The hybrids demonstrated potent antioxidant activity (∼60% over 5 min) with sustained release profiles at pH 8.0, underscoring their delivery potential. The emergence of RHOD-channel fluorescence in the hybrids indicated lattice defect formation upon polyphenol inclusion. Remarkably, electron paramagnetic resonance revealed that carbon-centered radicals within Mel-BA-GT remained stable, implying spatial segregation between matrix-encapsulated polyphenols and surface-localized radicals. This work advances the design of multifunctional supramolecular platforms for targeted delivery and catalysis.