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.