Monohydroxyflavones: Distribution Coefficients and Affinities for Reverse-Phase (C18) and Immobilized Artificial Membrane (IAM) Adsorbents

Whaley, William L.; Tseng, Jen-Te; Rummel, Jeremy D.; Wommack, Cody L.

doi:10.1177/1934578x0700201005

Cited by 3 publications

(7 citation statements)

References 23 publications

(26 reference statements)

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“…The strong intramolecular hydrogen bond in 5HF was demonstrated in early work using infrared spectroscopy [41]. The effect of IHB to diminish the overall polarity of 5HF had also been demonstrated by reverse-phase liquid chromatography [18,42]. From the present study, the measured value of A for the position 5 hydroxyl group was 0.02.…”

Section: Hydrogen-bonding Acidity Of Flavonoidssupporting

confidence: 69%

“…It has been established that LogP Oct (and LogD Oct ) values are primarily affected by non-polar (hydrophobic) interactions and are essentially not affected by hydrogen bonding [49]. Values for the logarithm of the chromatographic capacity factor, Logk', were previously reported for the MHFs assayed on a reversephase (C-18) column using a mobile phase of 80/16/4 methanol/water/formic acid [18]. For the MHFs, the LogD Oct values were within a narrow range from 3.0 to 3.5 and the surface areas of the hydrophobic portions of these molecules were expected to be similar.…”

Section: Hydrogen-bonding Acidity Of Flavonoidsmentioning

confidence: 99%

“…The compound 3HF has been reported to self-associate in non-polar solvents and it was suspected that other MHFs and DHFs might also self-associate [17,18]. Therefore, an assay was needed to measure values of Δδ (D-C) and indicate if self-association was occurring.…”

mentioning

confidence: 99%

“…It is, therefore, important to compare distribution coefficients, or LogD Oct values, which are measured using 1-octanol equilibrated with an aqueous buffer, usually at a pH of 7.4. Values of LogP Oct and LogD Oct for monohydroxyflavones (MHFs) have been published; however, in both cases there was evidence that 3-hydroxyflavone (3HF) underwent self-association in the octanol phase [17,18]. Selfassociation of flavonoids in non-polar solvents has been commonly observed and represents a significant problem for measuring LogP Oct or LogD Oct values accurately [19].…”

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confidence: 99%

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Summation Solute Hydrogen Bonding Acidity Values for Hydroxyl Substituted Flavones Determined by NMR Spectroscopy

Whaley

Okoso-amaa

Womack

et al. 2013

Natural Product Communications

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The flavonoids are a structurally diverse class of natural products that exhibit a broad spectrum of biochemical activities. The flavones are one of the most studied flavonoid subclasses due to their presence in dietary plants and their potential to protect human cells from reactive oxygen species (ROS). Several flavone compounds also mediate beneficial actions by direct binding to protein receptors and regulatory enzymes. There is current interest in using Quantitative Structure Activity Relationships (QSARs) to guide drug development based on flavone lead structures. This approach is most informative when it involves the use of accurate physical descriptors. The Abraham summation solute hydrogen bonding acidity (A) is a descriptor in the general solvation equation. It defines the tendency of a molecule to act as a hydrogen bond donor, or acid, when surrounded by solvent molecules that are hydrogen bonding acceptors, or bases. As a linear free energy relationship, it is useful for predicting the absorption and uptake of drug molecules. A previously published method, involving nuclear magnetic resonance (NMR) spectroscopy, was used to evaluate A for the monohydroxyflavones (MHFs). Values of A ranged from 0.02, for 5-hydroxyflavone, to 0.69 for 4'-hydroxyflavone. The ability to examine separate NMR signals for individual hydroxyl groups allowed the investigation of intramolecular interactions between functional groups. The value of A for the position 7 hydroxyl group of 7-hydroxyflavone was 0.67. The addition of a position 5 hydroxyl group (in 5,7-dihydroxyflavone) increased the value of A for the position 7 hydroxyl group to 0.76. Values of A for MHFs were also calculated by the program ACD-Absolve and these agreed well with values measured by NMR. These results should facilitate more accurate estimation of the values of A for structurally complex flavones with pharmacological activities.

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Section: Hydrogen-bonding Acidity Of Flavonoidssupporting

confidence: 69%

Section: Hydrogen-bonding Acidity Of Flavonoidsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Summation Solute Hydrogen Bonding Acidity Values for Hydroxyl Substituted Flavones Determined by NMR Spectroscopy

Whaley

Okoso-amaa

Womack

et al. 2013

Natural Product Communications

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“…This is due to the loss of the capacity of hydroxyl/phenol groups, once methoxylated, to form hydrogen bonds. This expected result is in accordance with previous reports [14].…”

Section: Physicochemical Characteristicssupporting

confidence: 94%

Correlation study on methoxylation pattern of flavonoids and their heme-targeted antiplasmodial activity

Ortíz

Vásquez-Ocmín

Cojean

et al. 2020

Bioorganic Chemistry

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A library of 33 polymethoxylated flavones (PMF) was evaluated for heme-binding affinity by biomimetic MS assay and in vitro antiplasmodial activity on two strains of P. falciparum. Stability of heme adducts was discussed using the dissociation voltage at 50% (DV 50). No correlation was observed between the methoxylation pattern and the antiparasitic activity, either for the 3D7 chloroquine-sensitive or for the W2 chloroquine-resistant P. falciparum strains. However, in each PMF family an increased DV 50 was observed for the derivatives methoxylated in position 5. Measurement of intra-erythrocytic hemozoin formation of selected derivatives was performed and hemozoin concentration was inversely correlated with heme-binding affinity. Kaempferol showed no influence on hemozoin formation, reinforcing the hypothesis that this compound may exert in vitro antiplasmodial activity mostly through other pathways. Pentamethoxyquercetin has simultaneously demonstrated a significant biological activity and a strong interaction with heme, suggesting that inhibition of hemozoin formation is totally or partially responsible for its antiparasitic effect.

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Construction of an Ultrahigh Pressure Liquid Chromatography-Tandem Mass Spectral Library of Plant Natural Products and Comparative Spectral Analyses

Lei

Qiu

et al. 2015

Anal. Chem.

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A plant natural product tandem mass spectral library has been constructed using authentic standards and purified compounds. Currently, the library contains 1734 tandem mass spectra for 289 compounds, with the majority (76%) of the compounds being plant phenolics such as flavonoids, isoflavonoids, and phenylpropanoids. Tandem mass spectra and chromatographic retention data were acquired on a triple quadrupole mass spectrometer coupled to an ultrahigh pressure liquid chromatograph using six different collision energies (CEs) (10-60 eV). Comparative analyses of the tandem mass spectral data revealed that the loss of ring substituents preceded the C-ring opening during the fragmentation of flavonoids and isoflavonoids. At lower CE (i.e., 10 and 20 eV), the flavonoids and isoflavonoid central ring structures typically remained intact, and fragmentation was characterized by the loss of the substituents (i.e., methyl and glycosyl groups). At higher CE, the flavonoid and isoflavonoid core ring systems underwent C-ring cleavage and/or rearrangement depending on the structure, particularly hydroxylation patterns. In-source electrochemical oxidation was observed for phenolics that had ortho-diphenol moieties (i.e., vicinal hydroxyl groups on the aromatic rings). The ortho-diphenols were oxidized to ortho-quinones, yielding an intensive and, in most cases, a base ion peak corresponding to a [(M - 2H) - H](-) ion in their mass spectra. The library also contains reverse-phase retention times, allowing for the construction, validation, and testing of an artificial neural network retention prediction of other flavonoids and isoflavonoids not contained within the library. The library is freely available for nonprofit, academic use and it can be downloaded at http://www.noble.org/apps/Scientific/WebDownloadManager/DownloadArea.aspx.

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Monohydroxyflavones: Distribution Coefficients and Affinities for Reverse-Phase (C18) and Immobilized Artificial Membrane (IAM) Adsorbents

Cited by 3 publications

References 23 publications

Summation Solute Hydrogen Bonding Acidity Values for Hydroxyl Substituted Flavones Determined by NMR Spectroscopy

Summation Solute Hydrogen Bonding Acidity Values for Hydroxyl Substituted Flavones Determined by NMR Spectroscopy

Correlation study on methoxylation pattern of flavonoids and their heme-targeted antiplasmodial activity

Construction of an Ultrahigh Pressure Liquid Chromatography-Tandem Mass Spectral Library of Plant Natural Products and Comparative Spectral Analyses

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