Betanin (betanidin 5-O-β-D-glucoside) is a water-soluble plant pigment used as a color additive in food, drugs and cosmetic products. Despite its sensitivity to light and heat, betanin maintains appreciable tinctorial strength in low acidic and neutral conditions, where the color of other plant pigments, such as anthocyanins, quickly fades. However, betanin is an iminium natural product that experiences acid- and base-catalyzed hydrolysis to form the fairly stable betalamic acid and cyclo-DOPA-5-O-β-D-glucoside. Here, we show that the decomposition of betanin in aqueous phosphate solution pH 2-11 is subject to general base catalysis by hydrogen phosphate ion and intramolecular general acid and base catalysis, providing new insights on the mechanism of betanin hydrolysis. UV/Vis absorption spectrophotometry, H NMR spectroscopy and mass spectrometry were used to investigate product formation. Furthermore, theoretical calculations support the hypothesis that the nitrogen atom of the tetrahydropyridine ring of betanin is doubly protonated, as observed for structurally simpler amino dicarboxylic acids. Our results contribute to the study of betanin and other pigments belonging to the class of betalains and to deepen the knowledge on the chemical properties of imino acids as well as on iminium-catalyzed modifications of carbonyl compounds in water.

An improved procedure is described for the preparation of pyranoflavylium cations from the reaction of 5,7-dihydroxy-4-methylflavylium cation with aromatic aldehydes. Modifications of the procedure of Chassaing et al. ( Tetrahedron Lett . 2008 , 49 , 6999–7004; Tetrahedron 2015 , 71 , 3066–3078) circumvent the reported restriction to electron-rich benzaldehydes and provide access to a wide variety of substituted pyranoflavylium cations, including those with electron-withdrawing substituents or an attached heterocyclic or polycyclic aromatic ring. This opens the way for studies of substituent and structural effects on the ground and excited states of these pyranoanthocyanin analogues, the behavior of which should mirror fundamental aspects of the chemistry and photophysics of the pyranoanthocyanin chromophores present in mature red wines.

Betalains are phytochemicals of nutraceutical importance that emerged as potent antioxidants, preventing radical chain propagation and the deleterious health effects of oxidative stress. However, despite the wide application of betalains as color additives in products for human consumption, little is known about the relationship between their structure and antioxidant potential. Here we investigate the mechanism of antioxidant action of three regioisomeric phenolic betalains and show that the meta isomer has higher antiradical capacity than most natural betalains, anthocyanins and flavonoids. Structural and pH effects on redox and antiradical properties were investigated and the results are rationalized in light of quantum chemical calculations. Our results demonstrate that hydrogen atom transfer/proton-coupled electron transfer or sequential proton loss electron transfer mechanisms are plausible to explain the radical chain breaking properties of phenolic betalains in water. Furthermore, mesomeric effects are responsible for the stabilization of the resulting radical phenolic betalains. These findings are useful for the design of biocompatible antioxidants and for the development of novel additives for functional foods and cosmetics with high antioxidant potential.

The natural small molecule piperlongumine A is toxic selectively to cancer cells in vitro and in vivo. This toxicity has been correlated with cancer cell ROS, DNA damage and apoptotic cell death increases. We demonstrate here a new mechanistic property of piperlongumine: it inhibits selectively human immunoproteasome with no noticeable inhibition of human constitutive proteasome. This result suggests that immunoproteasome inhibition, a mechanism independent of ROS elevation, may also partly play a role in the anticancer effects observed with piperlongumine. Structure-activity relationships of piperlongumine analogs suggest that the lactam (piperidonic) ring of piperlongumine A may be replaced by the linear olefin -NHCO-CH=CH to improve both in vitro inhibitory efficiency against immunoproteasome and cellular toxicity.