Understanding Zinc(II) Chelation with Quercetin and Luteolin: A Combined NMR and Theoretical Study

Abstract

The Zn(II) chelation with natural flavonoids, quercetin and luteolin, was investigated by the use of NMR spectroscopy and various levels of ab initio calculations. Very sharp phenolic OH (1)H resonances in DMSO-d6 were observed for both free and complexed quercetin which allowed (i) the unequivocal assignment with the combined use of (1)H-(13)C HSQC and HMBC experiments and (ii) the determination of complexation sites which were found to be the CO-4 carbonyl oxygen and the deprotonated C-5 OH group of quercetin and CO-4 carbonyl oxygen and the deprotonated C-5 OH group of luteolin. DOSY experiments allowed the determination of the effective molecular weight of the Zn-quercetin complex which was shown to be mainly 1:1. DFT calculations of the 1:1 complex in the gas phase demonstrated that the C-3 O(-) and CO-4 sites are favored for quercetin at both GGA and LDA approximations and the C-5 O(-) and CO-4 groups of luteolin at the LDA approximation. Quantum chemical calculations were also performed by means of the conductor polarizable model in DMSO by employing various functionals. The energetically favored Zn chelation sites of the 1:1 complex were found to be either the C-3 O(-) and CO-4 or C-5 O(-) and CO-4 sites, depending on the functional used, for quercetin and the C-5 O(-) and CO-4 sites for luteolin.

A DFT study of molecular structure and 1H NMR, IR, and UV‐Vis spectrum of Zn(II)‐kaempferol complexes: A metal‐flavonoid complex showing enhanced anticancer activity

“…This is difficult to be achieved experimentally and also crucial for an understanding of biological activities at a molecular level. The importance of combined experimental NMR and ab initio calculations for accurate structural and electronic description of Zn(II)‐Quercetin flavonoid‐metal complex has been pointed out recently . From our results, it can be clearly seen that analysis of IR and UV‐Vis spectra does not allow a discrimination between planar and rotated ligand structure, as the DFT calculated corresponding absorption bands are very close, perhaps within the accuracy limitation of DFT methods for predicting infrared and electronic absorption bands.…”

“…The importance of combined experimental NMR and ab initio calculations for accurate structural and electronic description of Zn(II)-Quercetin flavonoid-metal complex has been pointed out recently. [51] From our results, it can be clearly seen that analysis of IR and UV-Vis spectra does not allow a discrimination between planar and rotated ligand structure, as the DFT calculated corresponding absorption bands are very close, perhaps within the accuracy limitation of DFT It is worth saying that structural date for Zn(II)-kaempferol complexes in solution, condition where the drug is usually administrated in patients, could not be found, and also the limited X-ray crystal data available on metal flavonoids complexes are mainly related to one binding site molecular structures. X-ray data have been reported for the parent free quercetin compound [52,53] revealing a planarity of the A, C, and B flavonoid rings in the solid state, what should also hold for kaempferol.…”

Review of polyphenol‐rich products as potential protective and therapeutic factors against cadmium hepatotoxicity

“…Data from the literature show that if consumption is reasonable, there are no negative side effects and possibility of overdose of polyphenolic compounds (Chang et al, ; Kelley et al, ; Pezeshki et al, ; Tresserra‐Rimbau et al, ). However, due to the ability of polyphenols to chelate metals (Borowska et al, ; Horniblow et al, ; Primikyri et al, ), it should be taken under consideration that some deficiencies of essential bioelements may occur during the very high and prolonged consumption of these compounds (Zijp, Korver, & Tijburg, ); however, this aspect needs more attention to evaluate fully the interaction between polyphenols and essential elements in the human body.…”

“…As the liver is one of the target organs for Cd and disturbances in the proper functioning of this organ have serious consequences for health (Brea et al, ; Chang et al, ; Targher et al, ), in the present review our attention has been focused on polyphenol‐rich food products as a possible effective strategy in the protection from Cd hepatotoxicity and treatment of this heavy metal‐induced liver damage. Owing to the ability of polyphenols to bind ions of divalent metals, including toxic metals (Borowska, Brzóska, & Tomczyk, ; Brzóska, Gałażyn‐Sidorczuk, et al, ; Dai, Dong, & Ma, ; Horniblow, Henesy, Iqbal, & Tselepis, ; Jayanta & Shukla, ; Primikyri et al, ; Ravichandran, Rajendran, & Devapiriam, ), and strong antioxidative potential of these compounds (Brzóska, Borowska, & Tomczyk, , Brzóska, Rogalska, et al, ), as well as their abundance in dietary products (Brzóska, Borowska, & Tomczyk, ; Brzóska, Rogalska, et al, ; Quideau, Deffieux, Douat‐Casassus, & Pouységu, ), it seems to be of high importance to consider the possibility of using polyphenols as potential preventive and therapeutic agents against Cd hepatotoxicity. As the knowledge on the mechanisms of this xenobiotic‐induced liver damage is imperative when looking for possible factors effective in the protection from Cd hepatotoxicity, the pathways of this organ injury by Cd are also presented in the current paper.…”

Complexation of common metal cations by cyanins: Binding affinity and molecular structure

“…Nevertheless, despite the interest of these complexes, computational studies dedicated to anthocyanin‐metal complexation are very scarce, especially, when compared to the number of studies carried out on metal‐quercetin, or on copigment‐anthocyanin …”