Yale scientists will lead a new four-year, $4.4 million project intended to promote the design of a new generation of chemicals and materials less toxic to humans and the environment.
The team, which also involves scientists from three other universities, will develop tools that help molecule designers predict toxic hazards when evaluating new and existing chemicals and modify their designs to reduce risks while maintaining efficacy.
“For the last two centuries, chemists have been increasingly able to design molecules, chemicals and materials so that they perform particular functions, from color to adhesion to conductivity," said Paul Anastas, a professor of chemistry at the Yale School of Forestry & Environmental Studies and the project’s principal investigator. "One thing that we haven’t been able to do is to design chemicals so that they have reduced toxicity, reduced adverse impact on humans and the environment.
"This project aims to get an understanding of the inherent basis of these adverse consequences."
Researchers from Baylor University, George Washington University, and the University of Washington will also participate in the project, which is supported by the National Science Foundation and the Environmental Protection Agency.
According to researchers, recent achievements in the science of toxicology and computational chemistry have made it possible to identify which mechanisms cause toxicity and design alternative strategies to reduce the potential risks.
The team will assess the chemical and physical properties that make particular molecules toxic, modeling the specific pathways that cause oxidative stress, a disruption in the normal redox state of cells. Oxidative stress is thought to be a critical node in the toxic pathway for numerous diseases.
"The proposed work is very timely in terms of need and of our capabilities to successfully address the challenges," said William L. Jorgensen, Sterling Professor of Chemistry at Yale and a co-principal investigator for the project. "Rational drug design has been an active, productive field for many years. It is time to turn attention to rational design of safe chemicals for wide-ranging use and impact on peoples' daily lives."
A primary goal will be the creation of computer software that helps designers assess whether a molecule is likely to cause toxicity, the specific factors that create that risk, and the modifications that would reduce potential toxic outcomes.
In addition to potential commercial applications, the software could emerge as a resource for consumers, policymakers, and students, said Julie Zimmerman, the Donna L. Dubinsky Associate Professor of Environmental Engineering at Yale and co-principal investigator.
"The idea is to train chemists and toxicologists early in their college careers about these approaches so that chemists actually learn what toxicology is and toxicologists learn how to use their knowledge to help chemists," she said.
Ultimately, the researchers hope innovations in the rational design of chemicals and products will yield safer alternatives to chemicals found to cause unintended toxicity.
"Designing chemicals that are important for society but that are also less toxic and more environmentally friendly is an important objective for sustainability," said Peter Crane, the Carl W. Knobloch, Jr. Dean of the Yale School of Forestry & Environmental Studies. "We are excited to play a leadership role in this groundbreaking work."
"Everybody talks about substituting for bad chemicals and assessing what the alternatives are," Anastas said. "There will not be substitutes and alternatives unless you invent them. And those alternatives and substitutes will not be nontoxic or non-harmful unless you design them to be that way."
The $4.4 million grant, which was awarded by the National Science Foundation’s EPA/NSF Networks for Sustainable Molecular Design and Synthesis, was announced on Sept. 30.