Elucidation of the Kinetic Behavior of Quercetin, Isoquercitrin, and Rutin Solubility by Physicochemical and Thermodynamic Investigations

Abstract

International audienceThe solubility of flavonoids in organic media is a complex and important process. It is a key factor in extraction, formulation, and biocatalysis processes of flavonoids. In this work, dissolution experiments showed that the solubility of quercetin, isoquercitrin, and rutin in tert-amyl alcohol is higher (20, 30, and 36 g/L) than in acetonitrile (1.7 g/L). Moreover, dissolution kinetic of quercetin in tert-amyl alcohol showed an unusual behavior of the amount dissolved over time. High concentrations of dissolved quercetin were measured at the beginning of the experiment. The maximum concentration was followed by a decrease later on in time until the saturation concentration was obtained. To explain these results, thermodynamic (enthalpy of dissolution and mixing) and physicochemical (microscopy, particle size measurement) experiments were carried out. The enthalpies of dissolution (Delta H-diss) and mixing (Delta H-mix), measured in this work, are consistent with the experimental solubility scale for quercetin and rutin, i.e. rutin/tert-amyl alcohol < isoquercitrin/tert-amyl alcohol < quercetin/tert-amyl alcohol < quercetin/acetonitrile, with values ranging from ca. 12 to 180 J/g and -123 to 43 J/g, respectively. Microscopic observations and particle size measurement showed an increase of quercetin particles size, in tert-amyl alcohol, throughout the dissolution process (0.4 and 8 mu m at 5 min, 14-60 mu m after 68 min of dissolution). This surprising behavior, in contrast to the experience in common dissolution experiments (quercetin, isoquercitrin, and rutin in acetonitrile, isoquercitin and rutin in tert-amyl alcohol), has never been observed for flavonoids and is called kinetic size effect

Mesoscale Modeling Approach To Study the Dispersion and the Solubility of Flavonoids in Organic Solvents

“…The high solubility of quercetin, isoquercitrin, and rutin in tert-amyl alcohol was explained, experimentally, by low values of enthalpies of dissolution and mixing. 7 Moreover, calculated free energies of solvation are consistent with the experimental solubility scale for quercetin. 8 To complete the experimental observation, molecular modeling simulation was used.…”

Isoquercitrin Esters with Mono- or Dicarboxylic Acids: Enzymatic Preparation and Properties

“…Its health benefits seem to be very attractive for food, cosmetic and pharmaceutical industries [ 11 ]. However, such applications might be limited by its low solubility in organic (1.8, 30 and 14 g/L at 50 °C in acetonitrile, tert -amyl alcohol and acetone, respectively [ 13 , 14 ]) or aqueous (95 mg/L in water [ 15 ]) solvents. To overcome this problem, isoquercitrin modified by additional glucose units (enzymatically modified isoquercitrin, α-glucosyl isoquercitrin, enzymatically decomposed rutin) is being extensively studied [ 11 , 15 ].…”

“Sweet Flavonoids”: Glycosidase-Catalyzed Modifications

“…Similarly, in the case of hesperetin, the most soluble in both water and 10% ethanol was hesperetin-7- O -glucoside, followed by the rutinoside hesperidin and the aglycone was the least soluble [ 44 ]. On the other hand, glycosylated flavonoids such as isoquercitrin and rutin are less soluble than their aglycone in polar organic solvents [ 45 , 46 ].…”

“…The impact of glycosylation on the biological activity of flavonoids have been reviewed recently [ 45 , 63 ] and therefore, this aspect will be only briefly summed up and illustrated by several examples here. Glycosylated flavonoids generally display lower antioxidant capacity compared to the corresponding aglycones, the activity usually decreases with increasing number of glycosidic moieties and the position and structure of the sugar(s) play important roles [ 1 , 7 , 64 , 65 ].…”