Determination of the stability constants for the binding of sulfonated morin with Fe2+
Graphical abstract
Analysis of potentiometric titration data leads to the conclusion that three 1:1 species are formed between sulfonated morin and Fe2+. Only in the high pH region is a complex formed where 2 sulfonated morin anions are bound to the metal. Theoretical calculations support metal binding at the 3-hydroxy-4-keto site.
Introduction
Morin (1), a flavonoid found in the extract from osage orange (Maclura pomifera (Raf.) Schneid.) heartwood, helps protect wood from fungal decay even though it has extremely low fungicidal activity [1]. At least part of this protection may be attributed to the well documented antioxidant properties of hydroxyflavonoids [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13] knowing that it is postulated that the initial attack upon the wood structure by the fungus is a radical degradation resulting from a Fenton-type reaction [14], [15], [16], [17], [18], [19], [20], [21]. The Fenton reaction is the reduction of hydrogen peroxide by a metal ion (commonly Fe2+) to yield a very reactive oxidizing agent generally assumed to be the hydroxyl radical (Eq. (1)) [22], [23], [24], [25], [26]. This postulate is supported by the fact that iron concentration in wood increases as decay occurs [27].
In addition to their antioxidant activity, hydroxyflavonoids also have the ability to chelate metal ions [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45]. This metal chelation enhances the antioxidant behavior of the flavonoid in most studies [5], [46], [47] although one study reported no effect of metal chelation on antioxidant activity [48]. Most of the studies of metal complexation by hydroxyflavonoids were done in non-aqueous solvents or mixed solvent systems due to the limited solubility of most flavonoids in purely aqueous solution.
As with many physiological environments, the situation encountered during fungal decay of wood involves an aqueous solution in contact with an organic matrix. Therefore, it is important to determine the degree to which the metal ions complex with the hydroxyflavonoid in aqueous solution at the pH of the environment. This is facilitated in the case of morin because a water-soluble derivative, 2, has been synthesized [49], [50], [51]. Sulfonation of morin occurs at the 5′ position of the B ring which minimizes the substituent effect on the 3-hydroxy-4-keto or 5-hydroxy-4-keto metal binding sites.
In this paper, we report acid dissociation constants for sulfonated morin determined under our conditions and the results of theoretical calculations undertaken to assist in the prediction of the order of deprotonation for this compound. Also reported are the stability constants for the chelation of 2 with Fe2+ determined by potentiometric titration. These results will be discussed in relation to morin’s ability to help protect wood from fungal decay.
Section snippets
Materials
Morin was purchased from Sigma-Aldrich and used without purification. Complex 2 was synthesized as the Na+ salt with 2 waters of hydration as reported in the literature [49] and its purity was checked by 1H NMR spectroscopy in DMSO-d6. FeCl2 (99.5%) and KCl (99.997%) were purchased from Alfa Aesar and used as received. Water was distilled, deionized to a resistance of 18.0 MΩ-cm and boiled for 2 h to remove carbon dioxide. The water and all solutions subsequently prepared were stored under Ar.
Results and discussion
Prior to studying the chelation of Fe2+ with sulfonated morin (2), the acid dissociation constants for this compound were determined. There are five possible sites for deprotonation associated with the hydroxy groups. However, only four deprotonation reactions are observed in the pH range studied requiring 2 to be considered as an H4L species. Table 1 contains our results and those previously published.
It is of interest to know the order of deprotonation for 2. To gain insight into this
Conclusions
The complexation behavior of sulfonated morin with Fe2+ was determined in aqueous solution at 25 °C. Sulfonated morin coordinates with Fe2+ at pH values above 4.5 to form four different species. The only species having two ligands per metal occurs at high pH’s. Theoretical calculations predict that molecules deprotonated at the 7 position and molecules deprotonated at the 3 position will both be found in solution in the pH region where monodeprotonation occurs. This study verifies that part of
Acknowledgement
This project was supported by the National Research Initiative of the USDA Cooperative State Research, Education and Extension Service, Grant Number 2003-35103-13616.
References (69)
- et al.
Free Radical Biol. Med.
(1999) - et al.
Free Radical Biol. Med.
(2003) - et al.
Biochim. Biophys. Acta
(2005) - et al.
J. Biotechnol.
(2001) Free Radical Biol. Med.
(1993)Phytochemistry
(1992)- et al.
Inorg. Chim. Acta
(2001) - et al.
Anal. Biochem.
(1998) - et al.
Anal. Chim. Acta
(1976) - et al.
Phytochemistry
(1972)
Phytochemistry
J. Inorg. Biochem.
Spectrochim. Acta, Part A
Biochem. Pharmacol.
Chem. Phys. Lett.
J. Mol. Struct.
Inorg. Chim. Acta
Spectrochim. Acta, Part A
J. Inorg. Biochem.
J. Mol. Struct.
Spectrochim. Acta, Part A
Polyhedron
Holzforschung
Biochem. Biophys. Res. Commun.
J. Agric. Food Chem.
J. Am. Chem. Soc.
Food Sci. Tech. Int.
J. Agric. Food Chem.
J. Agric. Food Chem.
J. Health Sci.
Molecules
J. Nat. Prod.
Appl. Environ. Microbiol.
Microbiology
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