ABSTRACT
Rational design of pesticides with tunable degradation properties and minimal ecotoxicity is among the grand challenges of green chemistry. While computational approaches have gained traction in predictive toxicology, current methods lack the necessary multifaceted approach and design-vectoring tools needed for system-based chemical development. Here, we report a tiered computational framework, which integrates kinetics and thermodynamics of indirect photodegradation with predictions of ecotoxicity and performance, based on cutoff values in mechanistically derived physicochemical properties and electronic parameters. Extensively validated against experimental data and applied to 700 pesticides on the U.S. Environmental Protection Agency's registry, our simple yet powerful approach can be used to screen existing molecules to identify application-ready candidates with desirable characteristics. By linking structural attributes to process-based outcomes and by quantifying trade-offs in safety, depletion, and performance, our method offers a user-friendly roadmap to rational design of novel pesticides.
