Conformational enantiomerism of bilirubin and pamoic acid induced by protonated aminocyclodextrins

Kawasaki, Koji; Arimoto, Shinji; Ishimura, Taizo

doi:10.1039/p29950001661

Cited by 20 publications

(16 citation statements)

References 46 publications

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“… UCB binding to β-cyclodextrin at various pH values . Experimental data (black squares) from Kano et al ., 1995 [ 14 ]. Curve A, calculated ellipticity assuming pKa values for UCB of 8.12 and 8.44, with B = dimers [ 4 ].…”

Section: Resultsmentioning

confidence: 99%

“…These 12 papers and one abstract are summarized in Additional files 1 , 2 and 3 (Tables S1, S2 & S3), which specify experimental deficiencies for each study. Finally, we confined our detailed analyses to the four best studies; binding of UCB to phosphatidylcholine (PC) [ 12 ], dodecylmaltoside micelles [ 13 ], β-cyclodextrins [ 14 ], and sodium taurocholate [ 15 ].…”

Section: Methodsmentioning

confidence: 99%

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Interactions of unconjugated bilirubin with vesicles, cyclodextrins and micelles: New modeling and the role of high pKa values

Mukerjee

Ostrow

2010

BMC Biochemistry

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BackgroundUnconjugated bilirubin (UCB) is an unstable substance with very low aqueous solubility. Its aqueous pKa values affect many of its interactions, particularly their pH-dependence. A companion paper shows that only our prior solvent partition studies, leading to pKa values of 8.12 and 8.44, met all essential requirements for valid pKa determinations. Other published values, generally lower, some below 5.0, were shown to be invalid. The present work was designed to derive suitable models for interpreting published data on the pH-dependent binding of UCB with four agents, mentioned below, chosen because they are not, themselves, sensitive to changes in the pH range 4-10, and the data, mainly spectrometric, were of reasonable quality.ResultsThese analyses indicated that the high pKa values, dianion dimerization constant and solubilities of UCB at various pH values, derived from our partition studies, along with literature-derived pH- and time-dependent supersaturation effects, were essential for constructing useful models that showed good qualitative, and sometimes quantitative, fits with the data. In contrast, published pKa values below 5.0 were highly incompatible with the data for all systems considered. The primary species of bound UCB in our models were: undissociated diacid for phosphatidylcholine, dianion for dodecyl maltoside micelles and cyclodextrins, and both monoanions and dianion for sodium taurocholate. The resulting binding versus pH profiles differed strikingly from each other.ConclusionsThe insights derived from these analyses should be helpful to explore and interpret UCB binding to more complex, pH-sensitive, physiological moieties, such as proteins or membranes, in order to understand its functions.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Interactions of unconjugated bilirubin with vesicles, cyclodextrins and micelles: New modeling and the role of high pKa values

Mukerjee

Ostrow

2010

BMC Biochemistry

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“…The critique will focus especially on the purity of the UCB used, the presence of supersaturation with UCB in the systems studied, and extrapolation from results in non-aqueous solvents [53,54]. The review will also include a critical discussion of the extremely important role of pKa values of UCB in determining its pH-dependent interactions with phospholipid vesicles [1,55], bile salts [56,57] and cyclodextrins[58]. …”

Section: Resultsmentioning

confidence: 99%

Revalidation and rationale for high pKa values of unconjugated bilirubin

Ostrow

Mukerjee

2007

BMC Biochem

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“…Methylation at the sugar carboxyl groups interferes with their capacity to either hydrogen-bond or protonate the ester carbonyl oxygen. The observation that GMe is always more effective than GK2 throughout the pH range below 5.5 suggests that the hydrophobicity of the catalyst itself is a primarily significant factor for ester activation because the major hydrolysis process would occur in a hydrophobic environment, which would strengthen hydrogen bonding interactions that make significant contributions to transition state stabilization (11); the mixed micellization of POES with GMe is capable of providing a more hydrophobic micellar environment than that with GK2, judging from their surface tension and CMC values. Figure 4A shows the most plausible structure of the association complex formed in acidic solution, where the sugar carboxyl participates in hydrogen-bonding to the ester carbonyl oxygen (3).…”

Section: Resultsmentioning

confidence: 94%

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

Koide

Ukawa

Tagaki

et al. 1997

J Americ Oil Chem Soc

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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

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Conformational enantiomerism of bilirubin and pamoic acid induced by protonated aminocyclodextrins

Cited by 20 publications

References 46 publications

Interactions of unconjugated bilirubin with vesicles, cyclodextrins and micelles: New modeling and the role of high pKa values

Interactions of unconjugated bilirubin with vesicles, cyclodextrins and micelles: New modeling and the role of high pKa values

Revalidation and rationale for high pKa values of unconjugated bilirubin

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

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