Kaempferol Binding to Zinc(II), Efficient Radical Scavenging through Increased Phenol Acidity

Abstract

Zinc(II) enhances radical scavenging of the flavonoid kaempferol (Kaem) most significantly for the 1:1 Zn(II)-Kaem complex in equilibrium with the 1:2 Zn(II)-Kaem complex both with high affinity at 3-hydroxyl and 4carboxyl coordination. In methanol/chloroform (7/3, v/v), 1:1 Zn(II)-Kaem complex reduces β-carotene radical cation, β-Car •+ , with a second-order rate constant, 1.88 × 10 8 L• mol −1 •s −1 , while both Kaem and 1:2 Zn(II)-Kaem complex are nonreactive, as determined by laser flash photolysis. In ethanol, 1:1 Zn(II)-Kaem complex reduces the 2,2-diphenyl-1-picrylhydrazyl radical, DPPH • , with a second-order rate constant, 2.48 × 10 4 L•mol −1 •s −1 , 16 times and 2 times as efficient as Kaem and 1:2 Zn(II)-Kaem complex, respectively, as determined by stopped-flow spectroscopy. Density functional theory calculation results indicate significantly increased acidity of Kaem as ligand in 1:1 Zn(II)-Kaem complex other than in 1:2 Zn(II)-Kaem complex. Kaem in 1:1 Zn(II)-Kaem complex loses two protons (one from 3-hydroxyl and one from phenolic hydroxyl) forming 1:1 Zn(II)-(Kaem−2H) during binding with Zn(II), while Kaem in 1:2 Zn(II)-Kaem complex loses one proton in each ligand forming Zn(II)-(Kaem−H) 2 , as confirmed by UV−vis absorption spectroscopy. Zn(II)-(Kaem−2H) is a far stronger reductant than Kaem and Zn(II)-(Kaem−H) 2 as determined by cyclic voltammetry. Significant rate increases for the 1:1 complex in both β-Car •+ scavenging by electron transfer and DPPH • scavenging by hydrogen atom transfer were ascribed to decreases of ionization potential and of bond dissociation energy of 4′-OH for deprotonated Zn(II)-(Kaem−2H), respectively. Increased phenol acidity of plant polyphenols by 1:1 coordination with Zn(II) may explain the unique function of Zn(II) as a biological antioxidant and may help to design nontoxic metal-based drugs derived from natural bioactive molecules.

Kinetic Studies on Radical Scavenging Activity of Kaempferol Decreased by Sn(II) Binding

“…The increase at 366 nm and the decrease at 433 nm in absorbance both giving the same first-order rate constant of 0.12 ± 0.01 min −1 . In contrast, apigenin (Scheme 1b) without 3-OH does not react with SnCl 2 (Figure 1c), which indirectly supports that Kaem chelate to SnCl 2 at 3-OH and 4-C=O excluding the possibility of Sn(II) chelating at 4-C=O and 5-OH [7,27,28]. This chelating mode is frequently found in metal-Kaem complexes like zinc(II) and ruthenium(II) [7,29,30].…”

“…Flavonoids are a group of natural products with a variety of biological activities such as antioxidant, anti-inflammatory and anti-cancer [1][2][3][4][5][6]. Antioxidant activities of most flavonoids have recently been found to be enhanced by coordination of metal ions as reported by us [7,8] and by other authors [9][10][11][12][13][14][15]. In some cases, the presence of metal ions have been found to reduce the antioxidant activities of flavonoids depending on solvent, pH and the nature of flavonoids and metal ions [16,17].…”

“…Moderate decreases in the radical scavenging of HKaem are observed by Sn(CH 3 COO) 2 coordination and by contact between Sn and HKaem, in agreement with the increase in the oxidation potential of the complex compared to HKaem, leading to a decrease in antioxidant efficiency for fruits and vegetables with Sn as package materials. be increased by the presence of copper (II), iron (III), and zinc (II) by other authors and our recent studies [7,8,[23][24][25][26]. In the present study, HKaem was selected as a typical flavonoid with two possible chelation sites (3,4 and 4,5) for metal ions, and complex formation by Sn(II) coordination to HKaem was investigated together with the complex as a radical scavenger.…”

“…This chelating mode is frequently found in metal-Kaem complexes like zinc(II) and ruthenium(II). [7,29,30]…”

“…The stability constant was calculated as 8.2 × 10 10 L 2 ·mol −2 , which is closed to the stability constants, 1.1 × 10 11 L 2 mol −2 for 1:2 Cu(II)-genistein complex [23] and 1.1 × 10 11 L 2 mol −2 for 1:2 Zn(II)-kaempferol complex [7].…”