Zn(II) complexation promotes isomerization and oxidative rearrangements of naringenin: evidence from IR ion spectroscopy and DFT calculations

Abstract

Flavonoids are widespread natural polyphenols whose biological activity is intimately connected to their ability to coordinate essential transition metals and modulate redox processes. In particular, complexation with metal ions such as Zn(II) can profoundly influence their structural, chemical, and antioxidant properties, with implications for metal trafficking and biological function. In this work, we combine tandem mass spectrometry, infrared multiple photon dissociation (IRMPD) spectroscopy, and density functional theory calculations to elucidate the gas-phase structures and dissociation pathways of Zn(II) complexes with the conjugate base of naringenin (Nar) and its structural chalcone (ChNar) isomer. IRMPD spectra of [Zn(Nar-H)] + reveal a well-defined coordination motif involving the O4 and O5 oxygen atoms of the flavanone scaffold. Notably, the Zn complex of naringenin chalcone displays an identical spectroscopic fingerprint, suggesting Znassisted isomerization of the chalcone into the naringenin form upon metal coordination. When activated, both complexes dissociate to form a fragment at m/z 271, corresponding to a formally oxidized naringenin species by hydride loss. Spectroscopic characterization of this product suggests a mixture of protonated apigenin and genistein isomers. Mechanistic insight from calculated potential energy surfaces supports this evidence, demonstrating how metal coordination can promote isomerization reactions. Overall, this study highlights the multifaceted role of Zn(II) in directing flavonoid reactivity, and redox chemistry, and underscores the potential of IRMPD spectroscopy to unravel metal-mediated transformations in bioinorganic systems.