Determination of the overlapping pKa values of resorcinol using UV-visible spectroscopy and DFT methods

Blanco, Susana; Almandoz, M.C.; Ferretti, F.H.

doi:10.1016/j.saa.2004.03.020

Cited by 60 publications

(44 citation statements)

References 20 publications

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“…We used resveratrol, a plant-derived polyphenol, which was shown recently to increase the accumulation of the BCRP substrates mitoxantrone and BODIPY-FL-prazosin in two separate BCRP-overexpressing cell lines (Cooray et al, 2004). The pK a value of each phenol group of resveratrol is ϳ10, as has been determined by Blanco et al for the polyphenolic natural flavonoid resorcinol (pK a1 ϭ 9.20 and pK a2 ϭ 10.9) (Blanco et al, 2005;see Fig. 1 for structural formula of resveratrol).…”

Section: The Effect Of Low Ph On Transport Of Resveratrol By Bcrp (Abmentioning

confidence: 99%

The Effect of Low pH on Breast Cancer Resistance Protein (ABCG2)-Mediated Transport of Methotrexate, 7-Hydroxymethotrexate, Methotrexate Diglutamate, Folic Acid, Mitoxantrone, Topotecan, and Resveratrol in In Vitro Drug Transport Models

Breedveld

Pluim²,

Cipriani³

et al. 2006

Mol Pharmacol

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Some cellular uptake systems for (anti)folates function optimally at acidic pH. We have tested whether this also applies to efflux from cells by breast cancer resistance protein (BCRP; ABCG2), which has been reported to transport folic acid, methotrexate, and methotrexate di-and triglutamate at physiological pH. Using Spodoptera frugiperda-BCRP membrane vesicles, we showed that the ATP-dependent vesicular transport of 1 M methotrexate by BCRP is 5-fold higher at pH 5.5 than at physiological pH. The transport of methotrexate was saturable at pH 5.5, with apparent K m and V max values of 1.3 Ϯ 0.2 mM and 44 Ϯ 2.5 nmol/mg of protein/min, respectively, but was linear with drug concentration at pH 7.3 up to 6 mM methotrexate. In contrast to recent reports, we did not detect transport of methotrexate diglutamate at physiological pH, but we did find transport at pH 5.5. We also found that 7-hydroxy-methotrexate, the major metabolite of methotrexate, is transported by BCRP both at physiological pH and (more efficiently) at low pH. The pH effect was also observed in intact BCRP-overexpressing cells: we found a 3-fold higher level of resistance to both methotrexate and the prototypical BCRP substrate mitoxantrone at pH 6.5 as at physiological pH. Furthermore, with MDCKII-BCRP monolayers, we found that resveratrol, which is a neutral compound at pH Յ 7.4, is efficiently transported by BCRP at pH 6.0, whereas we did not detect active transport at pH 7.4. We conclude that BCRP transports substrate drugs more efficiently at low pH, independent of the dissociation status of the substrate.Uptake of weak acid and weak base chemotherapeutic drugs by tumors is greatly influenced by the dissociation properties of the drug itself and by the cellular pH gradient (i.e., the difference of extracellular pH in the tumor and the intracellular pH maintained by the cells) (Tannock and Rotin, 1989;Boyer and Tannock, 1992;Kozin et al., 2001;Mahoney et al., 2003). Whereas the median pH value in normal tissues is 7.5, in many tumor tissues, the extracellular pH is more acidic and may be as low as 5.8 (Tannock and Rotin, 1989). This is a consequence of a high rate of lactic acid production in tumors even under aerobic conditions (Tannock and Rotin, 1989;Boyer and Tannock, 1992;Gatenby and This work has been presented previously in abstract form: Breedveld P, Pluim D, Cipriani G, Dahlhaus F, van Eijndhoven MAJ, Borst P, and Schellens JHM (2005) The effect of low pH on BCRP(ABCG2)-mediated transport of methotrexate, 7-hydroxymetotrexate, methotrexate diglutamate, folic acid and resveratrol in in vitro drug transport models. N-(4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)ethyl]-phenyl)-9,10-dihydro-5-methoxy-9-oxo-4-acridine carboxamide; SN-38, 7-ethyl-10-hydroxycamptothecin; solution A, formic acid and acetonitrile 5%; solution B, formic acid and acetonitril 23%; Ko143,2,3,4,6,7,12,2Ј:1,6]pyrido [3,4-b]indol-3-yl)-propionic acid tert-butyl ester.

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Section: The Effect Of Low Ph On Transport Of Resveratrol By Bcrp (Abmentioning

confidence: 99%

The Effect of Low pH on Breast Cancer Resistance Protein (ABCG2)-Mediated Transport of Methotrexate, 7-Hydroxymethotrexate, Methotrexate Diglutamate, Folic Acid, Mitoxantrone, Topotecan, and Resveratrol in In Vitro Drug Transport Models

Breedveld

Pluim²,

Cipriani³

et al. 2006

Mol Pharmacol

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“…Blanco et al (2005) determined the maximum absorption for this phenolic compound, at 273.8 and 290.0 nm, respectively. The results of the UV-visible analysis in this study are presented in Fig. 1 Figure 1 shows that the liquid extract of merbau wood (λ=279 nm) consisted of conjugated or aromatic systems, similar to standard resorcinol (which was used as the reference), which had a wavelength (λ) of 274 nm.…”

Section: Uv-vis Identificationmentioning

confidence: 99%

Characterization of Merbau Extractives as a Potential Wood-Impregnating Material

et al. 2016

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aThis study aimed to investigate the major content of merbau extractives (ME) and their potential use as an impregnating material for low-quality timber. Extraction was done by maceration with ethanol, ethyl-acetate, and hot-water. Physico-chemical, phyto-chemical, UV-visible, and infrared spectroscopy, as well as py-GCMS analysis were then performed on dried extract. The results showed that organic solvent extractions resulted in much higher yields, by 12.50% than that of hot water (1.10%). The merbau extractives liquid obtained had a low acidity, with a pH ranging from 5 to 6, which is typical of phenolic compounds. Flavonoids and phenolics were found as the major compounds. UV-vis spectra showed that ME (λ=279 nm) consists of conjugated or aromatic systems, similar to standard resorcinol, which was used as the reference (λ=274 nm). The FTIR spectra showed the absorption bands at 3369 cm -1 that represent the functional group of hydroxyl (OH) bonds, and 1619 and 1510 cm -1 , representing the aromatic ring (C=C), which could be associated with resorcinol. The Py-GCMS showed that ME is predominated by resorcinol (C6H6O2) with a 79% concentration. The ME could be potentially used for producing phenolic/resorcinolic resin through polymerization, which could be applied for wood impregnation.

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“…These hydrogen bonds can be classified as strong, moderate, and weak, according to their lengths, angles, and energies (Cilli et al, 1996;Corradi et al, 2000). According to ref (Blanco, Almandoz, Ferretti, 2005), the properties of the moderate hydrogen bonds have the following classification: bond lengths of H·B is between (1.5 and 2.2) Å and the bond angle is 130° to 180°. For weak hydrogen bonds, the bond length and angle are (2.2 to 3.2) Å and 90° to 150°, respectively, and for strong hydrogen bonds are (1.2 to 1.5) Å and 175° to 180°, respectively.…”

Section: Second Ionization Constant Of Muscimolmentioning

confidence: 99%

Theoretically nanoscale study on ionization of muscimol nano drug in aqueous solution

Kiani

Abbaszadeh

Pousti

et al. 2015

Braz. J. Pharm. Sci.

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In the present work, acid dissociation constant (pK a ) values of muscimol derivatives were calculated using the Density Functional Theory (DFT) method. In this regard, free energy values of neutral, protonated and deprotonated species of muscimol were calculated in water at the B3LYP/6-31G(d) basis sets. The hydrogen bond formation of all species had been analyzed using the Tomasi's method. It was revealed that the theoretically calculated pK a values were in a good agreement with the existing experimental pK a values, which were determined from capillary electrophoresis, potentiometric titration and UV-visible spectrophotometric measurements.Uniterms: Nanodrug. Muscimol. Acid/dissociation constants. Computational chemistry. Density Functional Theory.No presente trabalho, calculou-se a constante de dissociação do ácido (pK a ) dos derivados de muscimol, utilizando-se o método da teoria do funcional de densidade (DFT). Com esse objetivo, calcularam-se os valores das espécies neutra, protonada e desprotonada do muscimol em água em base B3LYP/6-31G(d). A formação da ligação de hidrogênio de todas as espécies foi analisada utilizando o método de Tomasi. Demonstrou-se que os valores de pKa calculados teoricamente estavam em boa concordância com os valores experimentais disponíveis, determinados por eletroforese capilar, titulação potenciométrica e medidas por espectrofotometria UV-visível.Unitermos: Nanofármaco. Muscimol. Ácido/constantes de dissociação. Química computacional. Teoria do funcional de densidade.

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Determination of the overlapping pKa values of resorcinol using UV-visible spectroscopy and DFT methods

Cited by 60 publications

References 20 publications

The Effect of Low pH on Breast Cancer Resistance Protein (ABCG2)-Mediated Transport of Methotrexate, 7-Hydroxymethotrexate, Methotrexate Diglutamate, Folic Acid, Mitoxantrone, Topotecan, and Resveratrol in In Vitro Drug Transport Models

The Effect of Low pH on Breast Cancer Resistance Protein (ABCG2)-Mediated Transport of Methotrexate, 7-Hydroxymethotrexate, Methotrexate Diglutamate, Folic Acid, Mitoxantrone, Topotecan, and Resveratrol in In Vitro Drug Transport Models

Characterization of Merbau Extractives as a Potential Wood-Impregnating Material

Theoretically nanoscale study on ionization of muscimol nano drug in aqueous solution

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