Comparison of different models predicting the phospholipid-membrane water partition coefficients of charged compounds

Bittermann, Kai; Spycher, Simon; Goss, Kai‐Uwe

doi:10.1016/j.chemosphere.2015.08.065

Cited by 60 publications

(78 citation statements)

References 48 publications

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“…COSMOmic was recently optimized for charged solutes, with regards to the membrane dipole potential [181]. COSMOmic has proved its usefulness for the determination of membrane/water partition coefficients for different solutes [77,126,[179][180][181][182][183][184][185][186][187] and for micelle/water partition coefficients [183,[188][189][190][191]. It was also shown that the results of COSMOmic and MD simulations are comparable [126,182].…”

Section: Cosmomicmentioning

confidence: 89%

“…However, these systems have been replaced by membrane model systems, which can provide an anisotropic environment that is similar to those observed in cell membranes [215]. Therefore, a better representation of the different interactions that occur in vivo are achieved, including the electrostatic interactions and hydrogen bonds that are not reproduced by octanol/water systems [187,214,215]. Liposomes have been used extensively as model systems, where the determination of the partition coefficient can be carried out by potentiometry, isothermal titration calorimetry, differential scanning calorimetry, equilibrium dialysis and different chromatographic techniques, namely, electrokinetic chromatography and immobilized liposome chromatography [193,[214][215][216].…”

Section: Partition Coefficientmentioning

confidence: 98%

See 1 more Smart Citation

Shedding light on the puzzle of drug-membrane interactions: Experimental techniques and molecular dynamics simulations

Lopes

Jakobtorweihen

Nunes

et al. 2017

Progress in Lipid Research

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Section: Cosmomicmentioning

confidence: 89%

Section: Partition Coefficientmentioning

confidence: 98%

Shedding light on the puzzle of drug-membrane interactions: Experimental techniques and molecular dynamics simulations

Lopes

Jakobtorweihen

Nunes

et al. 2017

Progress in Lipid Research

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“…No successful applications to environmental and biological processes have been reported so far (Endo and Goss, 2014a). However, since many complex/ multifunction chemicals may ionize in biota, there is a strong need for the investigation of ionic chemicals (Endo and Goss, 2014a;Bittermann et al, 2016). Meanwhile, the development of one-compartment models for ionic compounds indicated improved performance via consideration of partitioning processes to phospholipids (Armitage et al, 2013).…”

Section: Limitationsmentioning

confidence: 99%

Can poly-parameter linear-free energy relationships (pp-LFERs) improve modelling bioaccumulation in fish?

2018

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A wide range of studies have characterized different types of biosorbent, with regard to their interactions with chemicals. This has resulted in the development of poly-parameter linear free energy relationships (pp-LFERs) for the estimation of partitioning of neutral organic compounds to biological phases (e.g., storage lipids, phospholipids and serum albumins). The aims of this study were to explore and evaluate the influence of implementing pp-LFERs both into a one-compartment fish model and a multi-compartment physiologically based toxicokinetic (PBTK) fish model and the associated implications for chemical risk assessment. For this purpose, fish was used as reference biota, due to their important role in aquatic food chains and dietary exposure to humans. The bioconcentration factor (BCF) was utilized as the evaluation metric. Overall, our results indicated that models incorporating pp-LFERs (R = 0.75) slightly outperformed the single parameter (sp) LFERs approach in the one-compartmental fish model (R = 0.72). A pronounced enhancement was achieved for compounds with log K between 4 and 5 with increased R from 0.52 to 0.71. The minimal improvement was caused by the overestimation of lipid contribution and underestimation of protein contribution by the sp-approach, which cancelled each other out. Meanwhile, a greater improvement was observed for multi-compartmental PBTK models with consideration of metabolism, making all predictions fall within a factor of 10 compared with measured data. For screening purposes, the K-based (sp-LFERs) approach should be sufficient to quantify the main partitioning characteristics. Further developments are required for the consideration of ionization and more accurate quantification of biotransformation in biota.

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“…It must be noted that 28 of the compounds in our database were estimated to be in a predominantly ionized state at pH 7. For these compounds the comparison of the toxicity with the log K OW , constant toxic membrane concentration, and chemical activity may not be valid because it is biased by a potentially limited uptake and different partitioning of the predominant ionized chemical (Bittermann et al ). Therefore, the corresponding compounds have been labeled in Figure and are indicated in Supplemental Data, Tables S1 and S6.…”

Section: Discussionmentioning

confidence: 99%

“…Ionization could principally be considered by replacing the log K OW with the log membrane–water partition coefficient ( K lipw ) and calculating the K lipw for the charged species. However, for neutral compounds the K OW is very similar to the K lipw (Endo et al ), and the partitioning of charged species is often within a factor of approximately 10 compared with the corresponding neutral species for most classes of ionic organic chemicals (Bittermann et al ). Hence, the impact on baseline toxicity and/or toxic ratio calculation of ionizable compounds is limited and may only be observed with higher degrees of ionization.…”

Section: Methodsmentioning

confidence: 99%

Meta‐analysis of fish early life stage tests—Association of toxic ratios and acute‐to‐chronic ratios with modes of action

Scholz

Schreiber

Armitage

et al. 2018

Enviro Toxic and Chemistry

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Fish early life stage (ELS) tests (Organisation for Economic Co-operation and Development test guideline 210) are widely conducted to estimate chronic fish toxicity. In these tests, fish are exposed from the embryonic to the juvenile life stages. To analyze whether certain modes of action are related to high toxic ratios (i.e., ratios between baseline toxicity and experimental effect) and/or acute-to-chronic ratios (ACRs) in the fish ELS test, effect concentrations (ECs) for 183 compounds were extracted from the US Environmental Protection Agency's ecotoxicity database. Analysis of ECs of narcotic compounds indicated that baseline toxicity could be observed in the fish ELS test at similar concentrations as in the acute fish toxicity test. All nonnarcotic modes of action were associated with higher toxic ratios, with median values ranging from 4 to 9.3 Â 10 4 (uncoupling < reactivity < neuromuscular toxicity < methemoglobin formation < endocrine disruption < extracellular matrix formation inhibition). Four modes of action were also found to be associated with high ACRs: 1) lysyl oxidase inhibition leading to notochord distortion, 2) putative methemoglobin formation or hemolytic anemia, 3) endocrine disruption, and 4) compounds with neuromuscular toxicity. For the prediction of ECs in the fish ELS test with alternative test systems, endpoints targeted to the modes of action of compounds with enhanced toxic ratios or ACRs could be used to trigger fish ELS tests or even replace these tests. Environ Toxicol Chem 2018;37:955-969. C 2018 SETAC

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Comparison of different models predicting the phospholipid-membrane water partition coefficients of charged compounds

Cited by 60 publications

References 48 publications

Shedding light on the puzzle of drug-membrane interactions: Experimental techniques and molecular dynamics simulations

Shedding light on the puzzle of drug-membrane interactions: Experimental techniques and molecular dynamics simulations

Can poly-parameter linear-free energy relationships (pp-LFERs) improve modelling bioaccumulation in fish?

Meta‐analysis of fish early life stage tests—Association of toxic ratios and acute‐to‐chronic ratios with modes of action

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