Selective spontaneous reaction of flavonoids in CD-MOF-1

Abstract

Developing artificial reactors for the synthesis of peroxy (O–O) bonds offers a new route to the creation of flexible intermediate platforms. Herein, we report a selective spontaneous reaction of flavonoid with γ-cyclodextrin (γ-CD) in cyclodextrin metal–organic framework (CD-MOF-1). Remarkably, simple incubation of flavonoids within CD-MOF-1 at ambient conditions in the dark leads to the spontaneous formation of an O–O bond between flavonoid and γ-CD. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and nuclear magnetic resonance (NMR) results confirm that the isolated flavonoid–γ-CD compounds involve O–O bonds and preferentially form at the hydroxyl in the flavonol C ring (e.g., quercetin) or at the meta-phenol hydroxyl on the flavone B ring (e.g., epigallocatechin gallate, EGCG). Intriguingly, flavonoids bearing both meta- and para-hydroxyl groups in the B ring (e.g., EGCG) or those with an adjacent carbonyl on the C ring (e.g., quercetin) underwent this reaction, whereas flavonoids lacking these features (e.g., taxifolin, luteoline, apigenin, naringenin, hesperetin and daidzein) cannot trigger this reaction. Density functional theory (DFT) calculations indicate that potassium (K⁺) cations in the CD-MOF-1 reduce the bond dissociation energies (BDEs) of the relevant hydroxyl groups, catalyzing O–O bond formation. This work reveals that CD-MOF-1 can orchestrate the precise arrangement of reactants and activate their specific sites, enabling selective O–O bond formation under mild and dark conditions. We expect this discovery to encourage further development of CD-MOF-1-based platforms for mild, selective oxidative transformations and the generation of novel intermediates.