Lignin-derivable alternatives to bisphenol A with potentially undetectable estrogenic activity and minimal developmental toxicity.

Lignin-derivable bisguaiacols/bissyringols are viable alternatives to commercial bisphenols; however, many bisguaiacols/bissyringols (e.g., bisguaiacol F [BGF]) have unsubstituted bridging carbons between the aromatic rings, making them more structurally similar to bisphenol F (BPF) than bisphenol A (BPA) - both of which are suspected endocrine disruptors. Herein, we investigated the estrogenic activity (EA) and developmental toxicity of dimethyl-substituted bridging carbon-based lignin-derivable bisphenols (bisguaiacol A [BGA] and bissyringol A [BSA]). Notably, BSA showed undetectable EA at seven test concentrations (from 10-12 M to 10-6 M) in the MCF-7 cell proliferation assay, whereas BPA had detectable EA at five concentrations (from 10-10 M to 10-6 M). In silico results indicated that BSA had the lowest binding affinity with estrogen receptors. Moreover, in vivo chicken embryonic assay results revealed that lignin-derivable monomers had minimal developmental toxicity vs. BPA at environmentally relevant test concentrations (8.7-116 µg/kg). Additionally, all lignin-derivable compounds showed significantly lower expression fold changes (from ∼1.81 to ∼4.41) in chicken fetal liver tests for an estrogen-response gene (apolipoprotein II) in comparison to BPA (fold change of ∼11.51), which was indicative of significantly reduced estrogenic response. Altogether, the methoxy substituents on lignin-derivable bisphenols appeared to be a positive factor in reducing the EA of BPA alternatives.

Lignin-derivable, thermoplastic, non-isocyanate polyurethanes with increased hydrogen-bonding content and toughness vs. petroleum-derived analogues.

The functionality inherent in lignin-derivable bisguaiacols/bissyringols can improve the processability and performance of the resulting polymers. Herein, non-isocyanate polyurethanes (NIPUs) were synthesized from bisguaiacols/bissyringols with varying degrees of methoxy substitution and differing bridging groups. Notably, the presence of increasing numbers of methoxy groups (0, 2, and 4) in bisphenol F (BPF)-, bisguaiacol F (BGF)-, and bissyringol F (BSF)-NIPUs led to higher percentages of hydrogen-bonded -OH/-NH groups (i.e., ∼65%, ∼85%, ∼95%, respectively). Increased hydrogen bonding between chains improved the elongation-at-break (εbreak) and toughness of lignin-derivable NIPUs over their petroleum counterparts without a reduction in Young's moduli and tensile strengths. For example, BSF-NIPU exhibited the highest εbreak ∼210% and toughness ∼62 MJ m-3, followed by BGF-NIPU (εbreak ∼185% and toughness ∼58 MJ m-3), and then BPF-NIPU (εbreak ∼140% and toughness ∼42 MJ m-3). Similar trends were found in the dimethyl-substituted analogues, particularly for the bisphenol A-NIPU and bisguaiacol A-NIPU. Importantly, the melt rheology of the lignin-derivable NIPUs was comparable to that of the petroleum-derived analogues, with a slightly lower viscosity (i.e., improved melt flow) for the bio-derivable NIPUs. These findings suggested that the added functionalities (methoxy groups) derived from lignin precursors improved thermomechanical stability while also offering increased processability. Altogether, the structure-property-processing relationships described in this work can help facilitate the development of sustainable, performance-advantaged polymers.

Hydrogenolysis of Poly(Ethylene-co-Vinyl Alcohol) and Related Polymer Blends over Ruthenium Heterogeneous Catalysts.

The hydrogenolysis of polymers is emerging as a promising approach to deconstruct plastic waste into valuable chemicals. Yet, the complexity of plastic waste, including multilayer packaging, is a significant barrier to handling realistic waste streams. Herein, we reveal fundamental insights into a new chemical route for transforming a previously unaddressed fraction of plastic waste - poly(ethylene-co-vinyl alcohol) (EVOH) and related polymer blends - into alkane products. We report that Ru/ZrO2 is active for the concurrent hydrogenolysis, hydrogenation, and hydrodeoxygenation of EVOH and its thermal degradation products into alkanes (C1-C35) and water. Detailed reaction data, product analysis, and catalyst characterization reveal that the in-situ thermal degradation of EVOH forms aromatic intermediates that are detrimental to catalytic activity. Increased hydrogen pressure promotes hydrogenation of these aromatics, preventing catalyst deactivation and improving alkane product yields. Calculated apparent rates of C-C scission reveal that the hydrogenolysis of EVOH is slower than low-density polyethylene. We apply these findings to achieve hydrogenolysis of EVOH/polyethylene blends and elucidate the sensitivity of hydrogenolysis catalysts to such blends. Overall, we demonstrate progress towards efficient catalytic processes for the hydroconversion of waste multilayer film plastic packaging into valuable products.

Reduced genotoxicity of lignin-derivable replacements to bisphenol A studied using in silico, in vitro, and in vivo methods.

Bisguaiacols, lignin-derivable bisphenols, are considered promising and possibly safer alternatives to bisphenol A (BPA), but comprehensive toxicity investigations are needed to ensure safety. Most toxicity studies of BPA and its analogues have focused on potential estrogenic activity, and only limited toxicological data are available on other toxicity aspects, such as genotoxicity at low exposure levels. In this study, the genotoxicity of six lignin-derivable bisguaiacols with varying regioisomer contents and degrees of methoxy substitution was investigated using a multi-tiered method, consisting of in silico simulations, in vitro Ames tests, and in vivo comet tests. The toxicity estimation software tool, an application that predicts toxicity of chemicals using quantitative structure-activity relationships, calculated that the majority of the lignin-derivable bisguaiacols were non-mutagenic. These results were supported by Ames tests using five tester strains (TA98, TA100, TA102, TA1535, and TA1537) at concentrations ranging from 0.5 pmol/plate to 5 nmol/plate. The potential genotoxicity of bisguaiacols was further evaluated using in vivo comet testing in fetal chicken livers, and in addition to the standard alkaline comet assay, the formamidopyrimidine DNA glycosylase enzyme-modified comet assay was employed to investigate oxidative DNA damage in the liver samples. The oxidative stress analyses indicated that the majority of lignin-derivable analogues showed no signs of mutagenicity (mutagenic index < 1.5) or genotoxicity, in comparison to BPA and bisphenol F, likely due to the methoxy groups on the lignin-derivable aromatics. These findings reinforce the potential of lignin-derivable bisphenols as safer alternatives to BPA.

Estrogenic activity of lignin-derivable alternatives to bisphenol A assessed via molecular docking simulations.

Lignin-derivable bisphenols are potential alternatives to bisphenol A (BPA), a suspected endocrine disruptor; however, a greater understanding of structure-activity relationships (SARs) associated with such lignin-derivable building blocks is necessary to move replacement efforts forward. This study focuses on the prediction of bisphenol estrogenic activity (EA) to inform the design of potentially safer BPA alternatives. To achieve this goal, the binding affinities to estrogen receptor alpha (ERα) of lignin-derivable bisphenols were calculated via molecular docking simulations and correlated to median effective concentration (EC50) values using an empirical correlation curve created from known EC50 values and binding affinities of commercial (bis)phenols. Based on the correlation curve, lignin-derivable bisphenols with binding affinities weaker than ∼-6.0 kcal mol-1 were expected to exhibit no EA, and further analysis suggested that having two methoxy groups on an aromatic ring of the bio-derivable bisphenol was largely responsible for the reduction in binding to ERα. Such dimethoxy aromatics are readily sourced from the depolymerization of hardwood biomass. Additionally, bulkier substituents on the bridging carbon of lignin-bisphenols, like diethyl or dimethoxy, were shown to weaken binding to ERα. And, as the bio-derivable aromatics maintain major structural similarities to BPA, the resultant polymeric materials should possess comparable/equivalent thermal (e.g., glass transition temperatures, thermal decomposition temperatures) and mechanical (e.g., tensile strength, modulus) properties to those of polymers derived from BPA. Hence, the SARs established in this work can facilitate the development of sustainable polymers that maintain the performance of existing BPA-based materials while simultaneously reducing estrogenic potential.