Flavonolate Complexes Research Articles

Chelation behavior of various flavonols and transfer of flavonol-chelated zinc(II) to alanylaspartic dipeptide: A PCM/DFT investigation

Alanylaspartic dipeptide (AlaAsp) and zinc(II)-flavonol complex could represent a metal-binding site in proteins and a metal-ion releasing agent, respectively. Chelation of zinc(II) by either AlaAsp or flavonol ligands in aqueous solution has been examined using DFT methods with polarizable continuum model (PCM/DFT). Coordination geometry, complexation stoichiometry, coordination bond strength, preferable metal-binding site on ligands and effect of water coordination on the stability of complexes have been addressed. In several cases, the long-range corrected density functional CAM-B3LYP allows the most accurate prediction of both structural and spectroscopic data. The preferential transfer of flavonol-chelated zinc(II) to AlaAsp under solvation is attainable through the ligand-exchange reaction. The energy barrier of such reaction is significantly dependent on the degree of hydrogen bonding within the transition state. In summary, either hydroxylation or methoxylation at particular positions on the 3-hydroxyflavone backbone significantly affects the reactivity of flavonol chelates in the metal-ion transfer.

Design, synthesis and characterization of zinc–morin, a metal flavonol complex and evaluation of its antidiabetic potential in HFD–STZ induced type 2 diabetes in rats

The present study deals with the synthesis, characterization of zinc–morin complex and evaluation of its antidiabetic efficacy in High Fat Diet (HFD)-fedStreptozotocin (STZ) induced diabetic rats. Oral administration of zinc–morin complex to diabetic rats (5mg/kg body weight/day) for a period of 30days resulted in the decreased levels of blood glucose and HbA1c. Oral administrations of the zinc–morin complex for 30days significantly improved hyperglycemia, glucose intolerance, and insulin resistance. The elevated levels of lipid peroxides declined and the antioxidant competence was found to be improved in diabetic rats treated with the complex. The status of the lipid and lipoprotein profile in the serum was normalized upon treatment. Levels of TNFα decreased upon treatment with the complex. The altered levels of adipokines such as adiponectin and leptin were normalized upon treatment with the complex. In conclusion, the present study indicates that the zinc–morin complex possesses antidiabetic, antidyslipidemic and antioxidant potentials in HFD-fedSTZ induced diabetic rats.

Series of Structural and Functional Models for the ES (Enzyme–Substrate) Complex of the Co(II)-Containing Quercetin 2,3-Dioxygenase

A series of mononuclear Co(II)-flavonolate complexes [Co(II)L(R)(fla)] (L(R)H = 2-{[bis(pyridin-2-ylmethyl)amino]methyl}-p/m-R-benzoic acid; R = p-OMe (1), p-Me (2), m-Br (4), and m-NO2 (5); fla = flavonolate) were designed and synthesized as structural and functional models for the ES (enzyme-substrate) complexes to mimic the active site of the Co(II)-containing quercetin 2,3-dioxygenase (Co-2,3-QD). The metal center Co(II) ion in each complex shows a similar distorted octahedral geometry. The model complexes display high enzyme-type dioxygenation reactivity (oxidative O-heterocyclic ring opening of the coordinated substrate flavonolate) at low temperature, presumably due to the attached carboxylate group in the ligands. The reactivity exhibits a substituent group dependent order of -OMe (1) > -Me (2) > -H (3)14b > -Br (4) > -NO2 (5), and the Hammett plot is linear (ρ = -0.78). This can be explained as the electronic nature of the substituent group in the ligands may influence the conformation and redox potential of the bound flavonolate and finally bring different reactivity. The structures, properties, and reactivity of the model complexes show some dependence on the substituent group in the supporting model ligands, and there is some relationship among them. This study is the first example of a series of structural and functional ES models of Co-2,3-QD, with focus on the effects of the electronic nature of substituted groups and the carboxylate group of the ligands to the dioxygenation reactivity, that will provide important insights into the structure-property-reactivity relationship and the catalytic role of Co-2,3-QD.

Flavonolate Complexes of MII (M = Mn, Fe, Co, Ni, Cu, and Zn). Structural and Functional Models for the ES (Enzyme–Substrate) Complex of Quercetin 2,3-Dioxygenase

A series of flavonolate complexes [M(II)L(fla)] (M = Mn (1), Fe (2), Co (3), Ni (4), Cu (5), and Zn (6), LH: 2-{[bis(pyridin-2-ylmethyl)amino]methyl}benzoic acid, fla: flavonolate) have been synthesized as structural and functional models for the ES (enzyme-substrate) complexes of the active site of various M(II)-containing quercetin 2,3-dioxygenase (2,3-QD) and their structures, spectroscopic features, and redox properties, as well as the reactivity toward molecular oxygen, have been investigated. The metal centers of [Fe(II)L(fla)]·H2O (2), [Co(II)L(fla)]·CH3OH (3), and [Ni(II)L(fla)] (4) exhibit a distorted octahedral geometry with two oxygen atoms of fla, one oxygen atom of the benzoate group of ligand L, and three nitrogen atoms of ligand L, in which oxygen atom of the carbonyl group of fla and one of the pyridine nitrogen atoms occupy the axial positions. The complexes [M(II)L(fla)] exhibit relatively high reactivity in the oxidative ring-opening of the bound flavonolate at lower temperature, presumably due to the existing carboxylate group in the supporting ligand. Thus, our complexes act as good functional ES models of various metal(II)-containing 2,3-QD. In addition, complexes [Fe(II)L(fla)]·H2O (2), [Co(II)L(fla)]·CH3OH (3), and [Ni(II)L(fla)] (4) are the first structurally characterized Fe(II)-, Co(II)-, and Ni(II)-flavonolate complexes, as an active site ES model of Fe(II)-, Co(II)-, and Ni(II)-containing 2,3-QD, respectively. The model complexes exhibit notably different reactivity in the order of Fe (2) > Cu (5) > Co (3) > Ni (4) > Zn (6) > Mn (1). The differences in the reactivity among them may be attributed to the redox potential of the coordinated flavonolate of the complexes, which are remarkably influenced by the Lewis acidity of the metal ion and its coordination environment. Our study is the first example of the metal ion effects on the enzyme-like dioxygenation reactivity, providing important insights into the metal ion effects on the enzymatic reactivity of various metal(II)-containing 2,3-QD.

Synthesis, characterization, and photoinduced CO-release reactivity of a Pb(II) flavonolate complex: Comparisons to Group 12 analogs

The synthesis, characterization, and photoinduced CO-release reactivity of [(6-Ph2TPA)Pb(3-Hfl)]ClO4 (1; 6-Ph2TPA=N,N-bis((6-phenyl-2-pyridyl)methyl)-N-((2-pyridyl)methyl)amine; 3-Hfl=anion of 3-hydroxyflavone) is reported and compared with Group 12 analogues ([(6-Ph2TPA)M(3-Hfl)]ClO4 (M=Hg(II) (2), Cd(II) (3), Zn(II) (4)). The Pb(II) complex exhibits unique features within this group of complexes in terms of its structural and spectroscopic features involving the coordinated flavonolate ligand. Similar to the Group 12 compounds, irradiation of 1 at 300nm in an O2-containing environment results in the quantitative release of CO and the formation of a Pb(II) O-benzoylsalicylate (O-bs, depside) complex via a photoinduced dioxygenase-type reaction. Comparison of the quantum yield for the reaction of the Pb(II) flavonolate complex (Φ=0.21(6)) versus the reactions of the structurally-related Group 12 metal complexes (6-Ph2TPA)M(3-Hfl)]ClO4 (M=Hg(II) (2, Φ=0.31(2)), Cd(II) (3, Φ=0.28(2)), Zn(II) (4), Φ=0. 09(1)) revealed that flavonolate complexes of a heavy metal ion (Cd(II), Hg(II), Pb(II)) exhibit a higher reaction quantum yield than the Zn(II) derivative. Both Pb(II) and Zn(II) flavonolate complexes were found to be catalysts for the oxidative photoinduced degradation of 3-hydroxyflavone. The combined results of these investigations suggest that metal contaminants typically present in soil, including toxic heavy metal ions, might facilitate the oxidative decomposition of plant-derived flavonols via photoinduced reactions.

Structural and functional comparison of manganese-, iron-, cobalt-, nickel-, and copper-containing biomimic quercetinase models

A series of divalent transition metal (Mn, Fe, Co, Ni, and Cu) flavonolate (Fla) complexes MII(Fla)(L1), and MII(Fla)(L2)X (X=Cl or ClO4) with the ligands N-propanoate-N,N-bis(2-pyridylmethyl)amine (L1=HPBMPA) and N-methylpropanoate-N,N-bis(2-pyridylmethyl)amine (L2=MPBMPA) have been prepared and characterized by spectroscopic methods and two cases by X-ray crystal analysis. The coordination sphere of the central ions is distorted octahedral with N3 or N3O donor sets, which are good structural models for the cupin-type metal-containing flavonol 2,4-dioxygenases (FDO). The dioxygenation of the metal flavonolate complexes results in the oxidative cleavage of the heterocyclic ring to give the corresponding O-benzoylsalicylate complexes and carbon monoxide as biomimic FDO models. The bathochromic shift of the absorption band I (π–π∗) of the coordinated flavonolate is influenced by the metals, and a linear correlation was observed between the logarithm of the reaction rate constant with O2 and the degree of the bathochromic shift (Δλ), providing a mechanistic insight into the stoichiometric dioxygenation reactions.

Antioxidant potential of zinc–flavonol complex studied in streptozotocin‐diabetic rats (锌黄酮醇复合物在链脲霉素‐糖尿病大鼠中的抗氧化作用)

Diabetic oxidative stress coexists with a reduction in the antioxidant status, which can further increase the deleterious effects of free radicals. Zinc is an essential trace element with significant antidiabetic activity. However, the acceptance of zinc compounds as promising therapeutic antidiabetic agents has been slowed due to concerns regarding chronic toxicity. Recently, we have designed, synthesized and characterized a novel zinc-flavonol complex and evaluated its antidiabetic efficacy in streptozotocin (STZ)-diabetic rats. The aim of the present study was to evaluate the role of the zinc-flavonol complex in the antioxidant status of diabetic rats. Diabetes was induced in rats by i.p. injection of STZ. Diabetic rats were then treated with the zinc-flavonol complex (5 mg/kg, p.o.) for 30 days. The extent of oxidative stress was assessed by determining lipid peroxide levels, pancreatic tissue antioxidant enzyme activities and plasma concentrations of non-enzymatic antioxidants. In addition, nuclear levels of nuclear factor (NF)-κB p65, pancreatic nitric oxide (NO), and plasma levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 were determined. Pancreatic tissues were examined histologically. Oral treatment with the zinc-flavonol complex significantly improved antioxidant levels and alleviated levels of oxidative stress markers. Furthermore, significant increases were seen in NF-κB p65, NO, TNF-α, IL-1β and IL-6 levels. Histological observations revealed that the zinc-flavonol complex effectively protects pancreatic β-cells against oxidative damage. The results of the present study indicate that the zinc-flavonol complex has an antioxidative and anti-inflammatory role in the diabetic milieu.

A novel insulin mimetic vanadium–flavonol complex: Synthesis, characterization and in vivo evaluation in STZ-induced rats

Since 1985, when Heyliger et al., first demonstrated a serendipitous discovery that oral administration of 0.8 mg/ml of sodium orthovanadate in drinking water to streptozotocin-induced diabetic rats resulted in normoglycemia, numerous extensive studies have been pursued on the anti-diabetic and insulinomimetic actions of vanadium. The acceptance of vanadium compounds as promising therapeutic antidiabetic agents has been slowed due to the concern for chronic toxicity associated with vanadium accumulation. In order to circumvent the toxic effects of vanadium, we have taken up a combinational approach wherein a novel vanadium–flavonol complex was synthesized, characterized and its toxic as well as insulin mimetic potential was evaluated in STZ-induced experimental diabetes in rats. The results indicate that the complex is non-toxic and possess anti-diabetic activity.

Covalent anthocyanin–flavonol complexes from the violet-blue flowers of Allium ‘Blue Perfume’

Three covalent anthocyanin–flavonol complexes (pigments 1–3) were extracted from the violet-blue flower of Allium ‘Blue Perfume’ with 5% acetic acid-MeOH solution, in which pigment 1 was the dominant pigment. These three pigments are based on delphinidin 3-glucoside as their deacylanthocyanin and were acylated with malonyl kaempferol 3-sophoroside-7-glucosiduronic acid or malonyl-kaempferol 3-p-coumaroyl-tetraglycoside-7-glucosiduronic acid in addition to acylation with acetic acid.By spectroscopic and chemical methods, the structures of these three pigments 1–3 were determined to be: pigment 1, (6I-O-(delphinidin 3-O-(3I-O-(acetyl)-β-glucopyranosideI)))(2VI-O-(kaempferol 3-O-(2II-O-(3III-O-(β-glucopyranosylV)-β-glucopyranosylIII)-4II-O-(trans-p-coumaroyl)-6II-O-(β-glucopyranosylIV)-β-glucopyranosideII)-7-O-(β-glucosiduronic acidVI))) malonate; pigment 2, (6I-O-(delphinidin 3-O-(3I-O-(acetyl)-β-glucopyranosideI)))(2VI-O-(kaempferol 3-O-(2II-O-β-glucopyranosylIII)-β-glucopyranosideII)-7-O-(β-glucosiduronic acidVI))); and pigment 3, (6I-O-(delphinidin 3-O-(3I-O-(acetyl)-β-glucopyranosideI)))(2VI-O-(kaempferol 3-O-(2II-O-(3III-O-(β-glucopyranosylV)-β-glucopyranosylIII)-4II-O-(cis-p-coumaroyl)-6II-O-(β-glucopyranosylIV)-β-glucopyranosideII)-7-O-(β-glucosiduronic acidVI))) malonate.The structure of pigment 2 was analogous to that of a covalent anthocyanin–flavonol complex isolated from Allium schoenoprasum where delphinidin was observed in place of cyanidin. The three covalent anthocyanin–flavonol complexes (pigment 1–3) had a stable violet-blue color with three characteristic absorption maxima at 540, 547 and 618nm in pH 5–6 buffer solution. From circular dichroism measurement of pigment 1 in the pH 6.0 buffer solution, cotton effects were observed at 533 (+), 604 (−) and 638 (−) nm. Based on these results, these covalent anthocyanin–flavonol complexes were presumed to maintain a stable intramolecular association between delphinidin and kaempferol units closely related to that observed between anthocyanin and hydroxycinnamic acid residues in polyacylated anthocyanins. Additionally, an acylated kaempferol glycoside (pigment 4) was isolated from the same flower extract, and its structure was determined to be kaempferol 3-O-sophoroside-7-O-(3-O-(malonyl)-β-glucopyranosiduronic acid).

Selective fluorometric detection of pyrophosphate by 3-hydroxyflavone-diphenyltin(iv) complex in aqueous micellar medium

3-Hydroxyflavonate-diphenyltin(IV) chloride (Ph(2)Sn(Ofl)Cl) was prepared and characterized structurally by single crystal X-ray diffraction. The compound possesses high fluorescence (λ(max) 464 nm with excitation at 400 nm) in neutral aqueous solutions containing 5 mM cetyltrimethylammonium chloride and does not lose the flavonol ligand even at high dilution. The fluorescence is selectively quenched by pyrophosphate (PPi) (linear range 0-5 μM, detection limit 0.1 μM). Determination of 1 μM PPi tolerates the presence of 100-fold excess of AMP, ADP, inorganic phosphate and acetate, and 10-fold excess of ATP. From concentration profiles of the quenching effect it is concluded that quenching occurs due to formation of the complex (Ph(2)Sn(Ofl))(3)PPi, which is transformed at higher PPi concentrations to a simple 1 : 1 complex Ph(2)Sn(Ofl)(PPi). No flavonol ligand exchange with PPi is observed. A series of related organotin(IV) complexes were prepared in situ by reacting 3-hydroxyflavone with Me(2)SnCl(2), PhSnCl(3) and n-BuSnCl(3). The derivatives of Me(2)SnCl(2) and PhSnCl(3) behave similarly to Ph(2)Sn(Ofl)Cl but with lower sensitivity to PPi. However, the n-butyltin(IV) derivative tentatively of the composition n-BuSn(Ofl)(2) undergoes fluorescence enhancement rather than quenching in the presence of PPi in the μM concentration range. The results of this study demonstrate that the use of metal flavonol complexes as optical sensors for anions is a promising approach.

The blue anthocyanin pigments from the blue flowers of Heliophila coronopifolia L. (Brassicaceae)

Six acylated delphinidin glycosides (pigments 1– 6) and one acylated kaempferol glycoside (pigment 9) were isolated from the blue flowers of cape stock ( Heliophila coronopifolia) in Brassicaceae along with two known acylated cyanidin glycosides (pigments 7 and 8). Pigments 1– 8, based on 3-sambubioside-5-glucosides of delphinidin and cyanidin, were acylated with hydroxycinnamic acids at 3-glycosyl residues of anthocyanidins. Using spectroscopic and chemical methods, the structures of pigments 1, 2, 5, and 6 were determined to be: delphinidin 3- O-[2- O-(β-xylopyranosyl)-6- O-(acyl)-β-glucopyranoside]-5- O-[6- O-(malonyl)-β-glucopyranoside], in which acyl moieties were, respectively, cis- p-coumaric acid for pigment 1, trans-caffeic acid for pigment 2, trans- p-coumaric acid for pigment 5 (a main pigment) and trans-ferulic acid for pigment 6, respectively. Moreover, the structure of pigments 3 and 4 were elucidated, respectively, as a demalonyl pigment 5 and a demalonyl pigment 6. Two known anthocyanins (pigments 7 and 8) were identified to be cyanidin 3-(6- p-coumaroyl-sambubioside)-5-(6-malonyl-glucoside) for pigment 7 and cyanidin 3-(6-feruloyl-sambubioside)-5-(6-malonyl-glucoside) for pigment 8 as minor anthocyanin pigments. A flavonol pigment (pigment 9) was isolated from its flowers and determined to be kaempferol 3- O-[6- O-( trans-feruloyl)-β-glucopyranoside]-7- O-cellobioside-4′- O-glucopyranoside as the main flavonol pigment. On the visible absorption spectral curve of the fresh blue petals of this plant and its petal pressed juice in the pH 5.0 buffer solution, three characteristic absorption maxima were observed at 546, 583 and 635 nm. However, the absorption curve of pigment 5 (a main anthocyanin in its flower) exhibited only one maximum at 569 nm in the pH 5.0 buffer solution, and violet color. The color of pigment 5 was observed to be very unstable in the pH 5.0 solution and soon decayed. In the pH 5.0 solution, the violet color of pigment 5 was restored as pure blue color by addition of pigment 9 (a main flavonol in this flower) like its fresh flower, and its blue solution exhibited the same three maxima at 546, 583 and 635 nm. On the other hand, the violet color of pigment 5 in the pH 5.0 buffer solution was not restored as pure blue color by addition of deacyl pigment 9 or rutin (a typical flower copigment). It is particularly interesting that, a blue anthocyanin–flavonol complex was extracted from the blue flowers of this plant with H 2O or 5% HOAc solution as a dark blue powder. This complex exhibited the same absorption maxima at 546, 583 and 635 nm in the pH 5.0 buffer solution. Analysis of FAB mass measurement established that this blue anthocyanin–flavonol complex was composed of one molecule each of pigment 5 and pigment 9, exhibiting a molecular ion [M+1] + at 2102 m/z (C 93H 105O 55 calc. 2101.542). However, this blue complex is extremely unstable in acid solution. It really dissociates into pigment 5 and pigment 9.

Photochemically-induced dioxygenase-type CO-release reactivity of group 12 metal flavonolate complexes

Exposure of 3-hydroxyflavonolate complexes of the group 12 metals to UV light under aerobic conditions results in oxidative carbon-carbon bond cleavage and CO release. This reactivity is novel in that it occurs under mild reaction conditions and suggests that light-induced CO-release reactivity involving metal flavonolate species may be possible in biological systems.

Synthesis, Characterization, and Ligand Exchange Reactivity of a Series of First Row Divalent Metal 3-Hydroxyflavonolate Complexes

A series of divalent metal flavonolate complexes of the general formula [(6-Ph(2)TPA)M(3-Hfl)]X (1-5-X; X = OTf(-) or ClO(4)(-); 6-Ph(2)TPA = N,N-bis((6-phenyl-2-pyridyl)methyl)-N-((2-pyridyl)methyl)amine; M = Mn(II), Co(II), Ni(II), Cu(II), Zn(II); 3-Hfl = 3-hydroxyflavonolate) were prepared and characterized by X-ray crystallography, elemental analysis, FTIR, UV-vis, (1)H NMR or EPR, and cyclic voltammetry. All of the complexes have a bidentate coordinated flavonolate ligand. The difference in M-O distances (Delta(M-O)) involving this ligand varies through the series, with the asymmetry of flavonolate coordination increasing in the order Mn(II) approximately Ni(II) < Cu(II) < Zn(II) < Co(II). The hypsochromic shift of the absorption band I (pi-->pi*) of the coordinated flavonolate ligand in 1-5-OTf (relative to that in free anion) increases in the order Ni(II) < Mn(II) < Cu(II) < Zn(II), Co(II). Previously reported 3-Hfl complexes of divalent metals fit well with this ordering. (1)H NMR studies indicate that the 3-Hfl complexes of Co(II), Ni(II), and Zn(II) exhibit a pseudo-octahedral geometry in solution. EPR studies suggest that the Mn(II) complex 1-OTf may form binuclear structures in solution. The mononuclear Cu(II) complex 4-OTf has a distorted square pyramidal geometry. The oxidation potential of the flavonolate ligand depends on the metal ion present and/or the solution structure of the complex, with the Mn(II) complex 1-OTf exhibiting the lowest potential, followed by the pseudo-octahedral Ni(II) and Zn(II) 3-Hfl complexes, and the distorted square pyramidal Cu(II) complex 4-OTf. The Mn(II) complex [(6-Ph(2)TPA)Mn(3-Hfl)]OTf (1-OTf) is unique in the series in undergoing ligand exchange reactions in the presence of M(ClO(4))(2).6H(2)O (M = Co, Ni, Zn) in CD(3)CN to produce [(6-Ph(2)TPA)M(CD(3)CN)(n)](X)(2), [Mn(3-Hfl)(2).0.5H(2)O], and MnX(2) (X = OTf(-) or ClO(4)(-)). Under similar conditions, the 3-Hfl complexes of Co(II), Ni(II), and Cu(II) undergo flavonolate ligand exchange to produce [(6-Ph(2)TPA)M(CD(3)CN)(n)](X)(2) (M = Co, Ni, Cu; n = 1 or 2) and [Zn(3-Hfl)(2).2H(2)O]. An Fe(II) complex of 3-Hfl, [(6-Ph(2)TPA)Fe(3-Hfl)]ClO(4) (8), was isolated and characterized by elemental analysis, FTIR, UV-vis, (1)H NMR, cyclic voltammetry, and a magnetic moment measurement. This complex reacts with O(2) to produce the diiron(III) mu-oxo compound [(6-Ph(2)TPAFe(3Hfl))(2)(mu-O)](ClO(4))(2) (6).

Effect of Zinc (II) on the interactions of bovine serum albumin with flavonols bearing different number of hydroxyl substituent on B-ring

The impact of Zn(2+) ion on interactions of flavonols galangin (Gal), kaempferol (Kae), quercetin (Que) and myricetin (Myr) with bovine serum albumin (BSA) in aqueous solution were studied by fluorescence quenching technique. The results exhibited that Zn(2+) ion affected significantly the interactions and the effect was distinct for the flavonol bearing different number of B-ring hydroxyl. Each flavonol can quench the fluorescence of BSA, displaying a quenching extent of Myr>Que>Kae>Gal, which is in good agreement with the number variation of the B-ring hydroxyl. The presence of Zn(2+) ion promoted the quenching for the flavonols, exhibiting an extent of Que>Myr>Kae>Gal. The values of K(a) for Kae, Que and Myr decreased whereas K(SV) and k(q) for Gal, Kae and Que increased with the number of B-ring hydroxyl. The type of BSA fluorescence quenching for Gal, Kae and Que hardly changed but the preference of static quenching increased. The values of K(SV) and k(q) for Myr remarkably decreased and the fluorescence quenching of BSA alternatively occurred via both static and dynamic type instead of only one (static or dynamic). The results suggest the key role of the B-ring hydroxyl and the distinct effect of its number in the interactions. Each flavonol may capture the BSA-bound Zn(II) in the solution, forming Zn(II)-flavonol complex that is possibly responsible for BSA fluorescence quenching. The B-ring hydroxyl could establish hydrogen bonds with BSA in the absence of Zn(2+) and act as donors for chelating in the presence of Zn(2+). The formation of dinuclear Zn(II)-Myr complex together with the hydrogen bonds between the free B-ring hydroxyl and BSA may contribute to the exceptional behavior of Myr.

Structural evidence for the inhibition of grape dihydroflavonol 4-reductase by flavonols

Dihydroflavonol 4-reductase (DFR) is a key enzyme of the flavonoid biosynthesis pathway which catalyses the NADPH-dependent reduction of 2R,3R-trans-dihydroflavonols to leucoanthocyanidins. The latter are the precursors of anthocyans and condensed tannins, two major classes of phenolic compounds that strongly influence the organoleptic properties of wine. DFR has been investigated in many plant species, but little was known about its structural properties until the three-dimensional structure of the Vitis vinifera enzyme complexed with NADP(+) and its natural substrate dihydroquercetin (DHQ) was described. In the course of the study of substrate specificity, crystals of DFR-NADP(+)-flavonol (myricetin and quercetin) complexes were obtained. Their structures exhibit major changes with respect to that of the abortive DFR-NADP(+)-DHQ complex. Two flavonol molecules bind to the catalytic site in a stacking arrangement and alter its geometry, which becomes incompatible with enzymatic activity. The X-ray structures of both DFR-NADP(+)-myricetin and DFR-NADP(+)-quercetin are reported together with preliminary spectroscopic data. The results suggest that flavonols could be inhibitors of the activity of DFR towards dihydroflavonols.

Carboxylate-enhanced reactivity in the oxygenation of copper flavonolate complexes

The oxygenolytic cleavage of flavonolate coordinated to copper(II) with the auxiliary ligand 3,3′-iminobis(N,N-dimethylpropylamine), [CuII(fla)(idpa)]ClO4, is enhanced by the addition of acetate and benzoate. Monodentate coordination of the flavonolate forced by the carboxylate ligands is believed to be the reason for the higher reaction rates.

Covalent anthocyanin–flavonol complexes from flowers of chive, Allium schoenoprasum

The structures of eight anthocyanins have been determined in acidified methanolic extract of pale-purple flowers of chive, Allium schoenoprasum. Four of them have been identified as the anthocyanin–flavonol complexes (cyanidin 3- O-β-glucoside AII) (kaempferol 3- O-(2- O-β-glucosyl FIII-β-glucoside FII)-7- O-β-glucosiduronic acid FIV) malonate AIII (AII-6→AIII-1, FIV-2→AIII-3), 1, (cyanidin 3- O-(3- O-acetyl-β-glucoside AII) (kaempferol 3- O-(2- O-β-glucosyl FIII-β-glucoside FII)-7- O-β-glucosiduronic acid FIV) malonate AIII (AII-6→AIII-1, FIV-2→AIII-3), 2, and their 7- O-(methyl- O-β-glucosiduronate FIV) analogous, 3 and 4. Pigments 1 and 2 are the first final identification of covalent complexes between an anthocyanin and a flavonol, while 3 and 4 are formed during the isolation process. The other four anthocyanins ( 5– 8) were found to be the 3-acetylglucoside, 3-glucoside, 3-(6-malonylglucoside) and 3-(3,6-dimalonylglucoside) of cyanidin. The three latter pigments have earlier been identified as the major anthocyanins of the chive stem. The covalent anthocyanin–flavonol complexes show intramolecular association between the anthocyanidin (cyanidin) and flavonol (kaempferol) units, which influence the colour.

Quercetinase model studies. The oxygenation of flavonol catalyzed by a cationic 2,2′-bipyridine copper(II) flavonolate complex

The catalyst [Cu II(bpy)(fla)]ClO 4, 1, was prepared from Cu(CH 3CN) 4ClO 4, 2,2′-bipyridine (bpy), flavonol (flaH), and dioxygen in acetonitrile at ambient conditions. The flavonolato copper complex 1 reacts with molecular oxygen slowly at room temperature but reasonably fast at around 100°C in acetonitrile or DMF to the O-benzoylsalicylato copper complex [Cu II(bpy)( O-bs)]ClO 4 in good yield. Kinetics of the oxygenation of 1 shows that there are two kinetically not interpretable segments of the reaction, however 1 is a good catalyst for the oxygenation of flavonol to O-benzoylsalicylic acid ( O-bsH) at around 100°C. Kinetic studies of the catalytic reaction resulted in the rate expression −d[flaH]/d t= k obs[flaH][catalyst] 2[O 2] 2. The reaction constant at 100°C was found to be k obs=7.20±0.13×10 10 mol −4 dm 12 s −1, with activation parameters Δ H ‡=80.83±3.14 kJ mol −1, Δ S ‡=179.61±8.82 J mol −1 K −1.

Synthesis and characterization of copper(I) and copper(II) flavonolate complexes with phthalazine ligand, and their oxygenation and relevance to quercetinase

Copper(I) and copper(II) flavonolate (fla) complexes with 1,4-(di-2′-pyridyl)aminophthalazine ligand (PAPH 2) have been prepared by the reaction of copper salts with flavonol and the ligand in acetonitrile or dichloromethane. The copper(II) centers are bound to the tetradentate phthalazine ligand resulting in both mononuclear and binuclear complexes. Flavonol is oxygenated to the corresponding depside catalyzed by flavonolato copper(II) phthalazine complexes.

Crystal and molecular structure of a ketocarboxylatocopper(ii) intermediate in the oxygenation of a copper(i) flavonolate complex

Flavonol reacts with metallic copper in the presence of 2,2′-bipyridine to give dihydrogen and a mixture of compounds with the stoichiometric composition [Cu I (bpy)(fla)] from which on standing only [Cu I (bpy) 2 ] 2 [Cu I (fla) 3 ] can be isolated; oxygenation of the solution of the mixture results in the ketocarboxylatocopper(II) complex [Cu II (bpy)(fla)(2-HOC 6 H 4 COCO 2 )], which hints at a copper-mediated oxidative cleavage of the pyranone ring in the flavonolate ligand via a 1,2-dioxethane intermediate by 3 O 2 .