Influence of Rosmarinic Acid on Zinc(II)–Amyloid Beta Coordination

Natural polyphenols such as rosmarinic acid (RA) are gaining attention for their antioxidant, anti-inflammatory, and neuroprotective properties, attributed in part to their ability to chelate redox-active metals. While RA's interactions with Cu(II) have been linked to modulation of amyloid beta (Aβ) aggregation and redox cycling, its coordination with Zn(II)—a key player in Aβ aggregation but redox-inert—remains poorly understood. Given that Zn(II) stabilizes toxic Aβ oligomers and is abundant in amyloid plaques, clarifying whether RA can modulate Zn(II)-Aβ interactions is of high interest. Here, we systematically investigated RA's coordination behavior toward Zn(II) under physiologically relevant conditions, both alone and in the presence of Aβ. Using NMR and UV–vis spectroscopy, we characterized RA-Zn(II) complex formation and explored how RA influences Zn(II)-mediated Aβ associations. These findings provide new insights into the molecular basis of RA's potential neuroprotective effects and underscore the importance of targeting metal–amyloid interactions in Alzheimer's disease.