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Benign By Design: Synthetic Guidelines for Low Chronic Aquatic Toxicity

“Towards Rational Molecular Design for Reduced Chronic Aquatic Toxicity” Voutchkova-Kostal, A. M.; Kostal, J.; Connors, K. A.; Brooks, B. W.; Anastas, P. T.; Zimmerman, J. B. Green Chem. 2012, 14, 1001-1008. DOI: 10.1039/C2GC16385C

As a synthetic chemist with little (actually zero) training in toxicology, it’s difficult for me to imagine how to design safer chemicals at the start of a project. I can avoid nasty solvents, use safer reagents, but when designing a new molecule I haven’t a clue of its potential toxicological impact. This is frustrating and as the authors of the above paper in Green Chemistry point out, “with the growing number of new chemicals being introduced into the market, it is not economically or ethically reasonable to assume that each can undergo systematic toxicological testing […]”. Thus, possessing a set of easy-to-implement synthetic guidelines to reduce the toxicity of a synthetic target during the design stage, while maintaining (or better yet, augmenting) its function, is of high importance.

Recently, the Zimmerman group reported on guidelines for reducing acute aquatic toxicity and have now extended their work to chronic aquatic toxicity. This is an important next step because chronic toxicity studies are necessarily longer-term (and thus more resource intensive) than acute toxicity studies.

In the current work, they explore the relationships between 38 physicochemical properties of 865 chemicals with chronic aquatic toxicity toward three model organisms: the Japanese medaka, a cladoceran, and a green algae. The 38 properties include, for example, molecular weight, number of freely rotatable bonds, aqueous solubility, and number of hydrogen bond donors and acceptors. (more…)

Toxicity Prediction via Hard-Soft Acid-Base Theory

“Application of the Hard and Soft, Acids and Bases (HSAB) Theory to Toxicant–Target Interactions” LoPachin, R. M.; Gavin, T; DeCaprio, A.; Barber, D. S. Chem. Res. Toxicol. 201225, 239-251. DOI: 10.1021/tx2003257

I considered posting about the Carreira group‘s work on enantioselective amination of allylic alcohols, because I think it is an awesome example of direct functionalization of hydroxylated substrates–an issue that will be of increasing importance in terms of biomass utilization. However I chose instead to stray into the less familiar territory of the bioactivity of organic molecules. I am semi-familiar with quantitative structure activity relationship (QSAR) modeling, wherein a database of known molecules and their bioactivity is used to predict the bioactivity of a molecule about which there is no bioactivity data. However, relying solely on computers leaves me wanting a more intuitive grasp on which molecules are expected to be toxic/non-toxic and why. That’s why I got excited about the recent perspective article about using the familiar Hard-Soft Acid-Base theory to predict toxicant-target interactions.