Lignin-derivable bisphenols could serve as potentially safer replacements to BPA, a suspected endocrine disruptor. This work focuses on fundamentally understanding the structure-activity relationships of lignin-derivable bisphenols to predict estrogenic activity (EA) and design safer alternatives to existing bisphenols. Binding affinities to estrogen receptor alpha (ERα) were calculated via molecular docking simulations, and a correlation between the median effective concentration (EC50) values of commercially available (bis)phenols and their binding affinities was developed to predict the EC50 values of lignin-derivable bisphenols. On the basis of the correlation curve, lignin-based bisphenols with binding affinities weaker than -6.0 kcal/mol are expected to exhibit no EA. Two methoxy groups on the aromatic rings substantially weaken the binding affinities to ERα (~-6.0 kcal/mol) by blocking the binding pockets. Similarly, the bulkier bridging groups such as ethyl or methoxy on lignin-bisphenols reduce the binding affinities because of steric effects. Several of the lignin-derivable bisphenols with binding affinities weaker than -6.0 kcal/mol were synthesized and incorporated into additive manufacturing resins for stereolithography 3D printing. The thermal (e.g., glass transition temperature, thermal decomposition behavior) and mechanical (e.g., tensile strength, modulus) properties of the printed materials were characterized to elucidate key structure-property relationships. Together, the structure-activity and structure-property relationships developed in this work could be leveraged to design materials that can match or exceed the performance of existing bisphenol-based materials without endocrine disruption potential.

Molecular docking simulations to assess the estrogenic activity of lignin-derivable bisphenol A alternatives and their polymerization via additive manufacturing

ACS Spring Meeting 2021

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