ADMET & DMPK · 2026
Modelling an alternative lipophilicity scale of bisphenols using biomimetic chromatography: Relevance to membrane-driven baseline toxicity.
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Ciura Krzesimir, Nicman Julia, Zdybel Szymon, Russo Giacomo, Grumetto Lucia, Greber Katarzyna Ewa, Sosnowska Anita, Dołżonek Joanna, Jagiello Karolina
Аннотация
BACKGROUND AND PURPOSE: Bisphenol A and its structural analogues are ubiquitous environmental contaminants and potential endocrine disruptors, creating a need for mechanistically relevant descriptors that support early hazard assessment. This study asked whether lipophilicity indices derived from biomimetic chromatography better reflect baseline toxicity and membrane-relevant behaviour of bisphenols than commonly used in silico log P / log D descriptors.
EXPERIMENTAL APPROACH: A set of 18 bisphenol derivatives was analysed using phosphatidylcholine- and sphingomyelin-functionalised stationary phases and a conventional C18 column to obtain chromatographic hydrophobicity indices, which were then compared with predicted log P / log D values and related to mechanistically diverse toxicity endpoints (in vitro cytotoxicity in mammalian cells, ex vivo cardiotoxicity assessed as vasodilation, and aquatic toxicity towards Daphnids).
KEY RESULTS: Biomimetic chromatographic indices showed consistently stronger and more coherent relationships with biological activity than theoretical descriptors. They also uniquely captured structural effects, such as positional isomerism, which were largely indistinguishable using theoretical lipophilicity indices.
CONCLUSION: These findings support biomimetic chromatography as an early-tier IATA tool, providing membrane-relevant experimental indices linking bisphenol lipophilicity with baseline toxicity.
EXPERIMENTAL APPROACH: A set of 18 bisphenol derivatives was analysed using phosphatidylcholine- and sphingomyelin-functionalised stationary phases and a conventional C18 column to obtain chromatographic hydrophobicity indices, which were then compared with predicted log P / log D values and related to mechanistically diverse toxicity endpoints (in vitro cytotoxicity in mammalian cells, ex vivo cardiotoxicity assessed as vasodilation, and aquatic toxicity towards Daphnids).
KEY RESULTS: Biomimetic chromatographic indices showed consistently stronger and more coherent relationships with biological activity than theoretical descriptors. They also uniquely captured structural effects, such as positional isomerism, which were largely indistinguishable using theoretical lipophilicity indices.
CONCLUSION: These findings support biomimetic chromatography as an early-tier IATA tool, providing membrane-relevant experimental indices linking bisphenol lipophilicity with baseline toxicity.