Characterization and anti-inflammatory studies of supramolecular assemblies of chlorogenic acids with metal ions.

Introduction: Self-assembled natural small molecules are believed to have numerous potential applications, particularly in the material and pharmaceutical industries, as self-assembly increases the anti-inflammatory, antitumor, antiviral, and other biological activities. In this study, we synthesized more potent potential anti-inflammatory agents by combining chlorogenic acids with metals (iron and copper). Methods: Supramolecular assemblies were synthesized by combining chlorogenic acids with iron and copper. The synthesis conditions were optimized using mass spectrometry. The resulting complexes were comprehensively characterized by ultraviolet-visible spectroscopy, Fourier-transform infrared spectroscopy, and mass spectrometry to confirm their formation and stoichiometry. The anti-inflammatory activity was evaluated in vitro using lipopolysaccharide-induced RAW264.7 macrophages. The production of inflammatory mediators (NO, IL-6, IL-1β, TNF-α) was measured. Mechanistic studies were conducted to assess the effects on the NF-κB signaling pathway and the expression of downstream proteins iNOS and COX-2. Results: Characterization data confirmed the successful formation of chlorogenic acid-metal supramolecules, primarily in a 1:1 stoichiometry. These metal-based complexes exhibited significantly enhanced anti-inflammatory effects compared to the parent chlorogenic acid molecules. Discussion: The findings confirm that complexation with metals (iron and copper) successfully enhances the anti-inflammatory efficacy of chlorogenic acids. The primary mechanism involves the inhibition of the NF-κB pathway. This study provides a novel and efficient strategy for augmenting the bioactivities of natural products and highlights the considerable potential of chlorogenic acid-metal supramolecular assemblies as a promising new class of anti-inflammatory agents.