Enhanced Stability, Antioxidant, and Bioavailability Potency of 4‐Hydroxybenzoid Acid Encapsulated C‐Alkyl Calix[4]resorcinarenes Inclusion Complexes

This research addresses the challenge of enhancing the physiochemical properties and bioactivity of 4‐hydroxybenzoic acid encapsulated C‐alkyl calix[4]resorcinarene inclusion complexes. Systematic investigation via Job's plot and phase solubility analysis established the binding stoichiometric ratios and complexation efficiency revealing A L and A N ‐type solubility profile in aqueous media. Structural integration was rigorously confirmed through multi‐model characterization techniques UV–visible, Fluorescence, 1 H‐NMR, 13 C‐NMR spectroscopy, complemented by PXRD and SEM imaging to visualize morphological transformations. Complementing the experimental data, DFT/B3LYP 6‐31G basis set calculations were elucidated the most energetically favorable binding orientation providing molecular insight into the stabilization of 4‐hydroxybenzoic acid into the cavity of C‐alkyl calix[4]resorcinarenes through noncovalent interactions. Furthermore, the inclusion complexes demonstrated superior biological utility: phosphomolybdate assays revealed to enhance total antioxidant capacity (IC 50 values), while Kirby‐Bauer and disc‐diffusion assays confirmed potent synergistic effects against targeted bacterial and fungal pathogens compared to amikacin and nystatin standard antibiotics. These finding suggest that C‐alkyl calix[4]resorcinarenes serve as effective supramolecular carriers to improve the stability and therapeutic window of phenolic acids.