Structure-Energetics-Property Relationships Support Computational Design of Photodegradable Pesticides

Development of high-performing pesticides with tunable degradation properties is vital to increasing the safety and effectiveness of tomorrow's analogs. Chromophoric dissolved organic matter in the excited triple state (³CDOM*) is known to play a key role in the removal of pesticides via indirect photodegradation. However, the potential of these transformations to guide the design of safer chemicals has not yet been fully realized. Here, we report a two-tier computational framework developed to probe and predict both kinetics and thermodynamics of ³CDOM*-pesticide interactions. In the first tier, robust in silico models were constructed by fitting free energies obtained from density functional theory (DFT) calculations to cell potentials and second-order rate constants for the ³CDOM*-pesticide electron transfer. In the second tier, Gibbs free energies and corresponding free energy barriers, determined in solution using the Marcus theory, were applied to develop a quick yet accurate screening approach based on the frontier molecular orbital (FMO) Theory. Being highly mechanistic and spanning ca. 1500 unique ³CDOM*-pesticide interactions, our approach is both robust and broadly applicable. To that end, the outcomes of our computational models were integrated into an easy-to-use decision framework that can guide structure-based design of less persistent pesticide analogs.