Coupled molecular design diagrams to guide safer chemical design with reduced likelihood of perturbing the NRF2-ARE antioxidant pathway and inducing cytotoxicity

Lan-sun, Shen; Melnikov, Fjodor; Roethle, John; Gudibanda, Aditya; Judson, Richard S.; Zimmerman, Julie; Anastas, Paul T.

doi:10.1039/c6gc02073a

Cited by 7 publications

(2 citation statements)

References 72 publications

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“…This study’s logistic model is a sigmoid function that has been used to interpolate S-shaped data distributions for studies on topics such as tumor growth, toxicity and cytotoxicity, − biodegradability, catalysis, microbial growth, biotechnological processes, and food-texture evolution . In this work, the logistic regression model suggests that, for high substrate/enzyme ratios, the course of BC’s enzymatic hydrolysis stays in a silent phase for the first approximately 6–8 h, contrary to what was observed for the mixtures richest in enzymes (i.e., the 1:1 and 2:1 mixtures).…”

Section: Resultsmentioning

confidence: 92%

Enzymatic Hydrolysis in the Green Production of Bacterial Cellulose Nanocrystals

Rovera

Ghaani

Santo

et al. 2018

ACS Sustainable Chem. Eng.

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In this study, we extensively describe experimental models, with correlating experimental conditions, which were used to investigate the enzymatic hydrolysis of bacterial cellulose (BC) to obtain nanocrystals. Cellulase from Trichoderma reesei was used in five enzyme/BC ratios over a period of h. The turbidity data was modeled using both logistic regression and empirical regression to determine the fractal kinetics, resulting in unique kinetic patterns for the mixtures that were richest in BC and in enzymes. The evolution of the yield was inversely related to the turbidity, as confirmed through a semi-empirical approach that was adopted to model the experimental data. The yield values after 74 h of hydrolysis were higher for the substrate-rich mixtures (~20%) than for the enzyme-rich mixtures (~5%), as corroborated by cellobiose and glucose quantification. Transmission electron microscopy and atomic force microscopy analyses revealed a shift from a fibril network to a needlelike morphology (i.e., aggregated nanocrystals or individual nanocrystals ~6 nm width and 200-800 nm in length) as the enzyme/BC ratios went from lower to higher. These results were explained in terms of the heterogeneous substrate model and the erosion model. This work initiated a promising, environmental-friendly method that could serve as an alternative to the commonly used chemical hydrolysis routes.

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Section: Resultsmentioning

confidence: 92%

Enzymatic Hydrolysis in the Green Production of Bacterial Cellulose Nanocrystals

Rovera

Ghaani

Santo

et al. 2018

ACS Sustainable Chem. Eng.

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“…After 25 years of development of green chemistry, progress has been made toward achieving chemical sustainability. However, a strong need is still being recognized to develop new sustainable metrics to quantify sustainability for chemicals in both assessment − and design. − In this report, we have developed a new sustainability assessment tool that can estimate the likelihood of a chemical of incurring cytotoxicity and that can guide safer chemicals design to reduce their probabilities of causing cytotoxicity.…”

Section: Introductionmentioning

confidence: 99%

Introducing Membrane Transport Energy into the Design of Sustainable Chemicals against Cytotoxicity

Lan-sun

Nan

2018

ACS Sustainable Chem. Eng.

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Adverse outcomes associated with chemical use and spill have raised concerns over its sustainability. The traditional toxicity testing, using laboratory animals as the downstream safety check, is becoming less viable due to the economical and ethical liabilities. Green chemistry proposed an alternative strategy to attain chemical sustainability: designing chemicals to maximize their intrinsic sustainability and thus minimize their hazardous risk. Following decades of progress, there is still a need to develop new metrics to quantify the level of chemical sustainability. In this report, we developed a new double functional tool capable of estimating the sustainability probability of a chemical and designing new chemicals to meet a desired sustainability probability. This tool was built upon the Naive Bayesian algorithm with the design variables stemming from three sources. Molecular softness and polarizability were derived from density functional theory (DFT), and membrane transport free energy was computed using our in-house developed finite element algorithm. Model validation against the cytotoxicity measured in the U.S. EPA Toxicity ForeCaster (ToxCast) database (tested up to 100 μM) yielded a score of 0.82 for the area under the curve (AUC) of the receiver operating characteristic (ROC). On the basis of this model, we constructed the assessment tool with the dual capabilities of prediction and design.

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Combined effects of mixed per- and polyfluoroalkyl substances on the Nrf2-ARE pathway in ARE reporter-HepG2 cells

Ojo

Peng

2022

Journal of Hazardous Materials

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Coupled molecular design diagrams to guide safer chemical design with reduced likelihood of perturbing the NRF2-ARE antioxidant pathway and inducing cytotoxicity

Abstract: A probabilistic diagram presenting the complete solution in the variable space to guide safer chemical against NRF2-ARE pathway perturbation.

Cited by 7 publications

References 72 publications

Enzymatic Hydrolysis in the Green Production of Bacterial Cellulose Nanocrystals

Enzymatic Hydrolysis in the Green Production of Bacterial Cellulose Nanocrystals

Introducing Membrane Transport Energy into the Design of Sustainable Chemicals against Cytotoxicity

Combined effects of mixed per- and polyfluoroalkyl substances on the Nrf2-ARE pathway in ARE reporter-HepG2 cells

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