Hydrolysis of nonionic ester surfactants facilitated by potassium β‐glycyrrhizinate: Implication of catalytic functions played by the carboxyl groups

Abstract

Two different types of methyl esters of β-glycyrrhizinate (GK2) have been prepared to delineate the mechanism of the catalytic action of each carboxyl group of GK2 in the hydrolysis of nonionic fatty acid surfactants. In the acidic pH region of less than 4, the hydrolysis is catalyzed by the carboxyl groups of the sugar moiety, while in the close-to-neutral acidic region, the carboxyl group at the hydrophobic triterpenoid end becomes important in catalysis. JAOCS 74, 49-54 (1997).KEY WORDS: Acid catalysis, methyl glycyrrhizinates, nonionic surfactant ester hydrolysis.Dipotassium β-glycyrrhizinate (GK2) serves as an anionic surfactant as well as an antiallergic and antiinflammatory drug in eye lotions and injectable formulations (1). The structure of GK2 consists of two parts, a hydrophobic triterpenoidal part and a hydrophilic di-D-glucuronic (sugar) part. The three carboxyl groups in GK2 can be classified into two groups: the one present in the hydrophobic triterpenoid has a high pKa value of 8.5 (2), and the other two, one on each hydrophilic glucuronic part, are more acidic and not strictly distinguishable from each other in catalytic activity because of similarity of their acidities (pKa = 3.3 and 4.7). Scheme 1 depicts the structure of GK2 and its related derivatives, and their abbreviation symbols also are shown.Recently, we found that GK2 catalyzes the hydrolytic bond cleavage of nonionic fatty acid ester surfactants, such as polyoxyethylene(60) hydrogenated castor oil (HCO-60, Scheme 2), even in the pH range of 3 to 6 (3). Because HCO-60 is nontoxic, it has been occasionally employed in pharmaceutical formulations for solubilizing oil-soluble ingredients (4,5). The ester itself is virtually nonsusceptible to hydrolysis without GK2 in citrate buffer, indicating that a short-chain carboxylic acid has no influence on the rate (6). HCO-60 itself was reported to form a single micelle, spherical or nearly spherical, with a critical micelle concentration (CMC) of 0.0263 mM and an aggregation number of 92 (7). GK2 constitutes a rod-like micelle with a CMC of 0.68 mM and an aggregation number of 130 (pH 5.0) (8). Their mixture, used in these experiments, is expected to form a mixed anionic/nonionic micelle, which is responsible for the observed catalytic activity (2). Thus, we proposed that a GK2 molecule and a fatty acid ester molecule produce an energetically favorable complex for catalysis via hydrophobic interactions in the micellar aggregates that brings the ester carbonyl group in close contact with one of the three carboxyl groups in the GK2 molecule.In this paper, we report the results of a mechanistic study of the catalytic action of the individual carboxyl groups in the hydrolysis of fatty acid ester surfactants by GK2. To elaborate the functions of the GK2 molecule, we synthesized two different kinds of methylated GK2. EXPERIMENTAL PROCEDURESMaterials. GK2, glycyrrhetinic acid, and stearyl glycyrrhetinate from Maruzen Seiyaku (Hiroshima, Japan) were used as

Active curcumin nanoparticles formed from a volatile microemulsion template

“…This result was expected, since the surfactants are negatively charged at this pH (SbPC has isoelectric point of 4.15, 38 while the dissociation constants (pKa values) of at least two carboxylic groups of glycyrrhizic acid are below 5). 39,40 The resultant ζ-potential is sufficiently high to provide electrostatic stabilization to the particles and should be attributed to the adsorption of the surfactants onto particle surface.…”

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“…The increase in the size of the particles compared with the initial microemulsion droplet size can be attributed to the aggregation of the droplets during solvent removal . Measured ζ-potential was high enough in its absolute value to provide electrostatic stabilization to the resultant particles, stemming from the absorption of negatively charged surfactants − and from the possible presence of the anionic polymer on the surface. There was no significant change in the mean size or the mean ζ-potential of the particles in water after 5 h.…”

Supramolecular Organization of Neutral and Ionic Forms of Pharmaceutically Relevant Glycyrrhizic Acid—Amphiphile Self-Assembly and Inclusion of Small Drug Molecules

“…A closer inspection of the molecular structure reveals that a plane passing through the carbon atoms attached to the carboxylic groups divides the GA molecule in such a way that these groups are all located on one side of the plane whereas sugar hydroxyl groups are found on the opposite side. This seems to be an important feature of the GA molecular structure, as it has been shown that the carboxylic trio in potassium β-glycyrrhizinate catalyzes a pH dependent hydrolysis of nonionic ester surfactants. Moreover, three of the four ether oxygen atoms and the carbonyl O atom of GA are grouped on the same side of the plane as carboxylic groups and exposed as acceptors of hydrogen bonds (Figure ).…”