Temperature-Responsive Cocrystal Engineering for Efficacious Delivery of Poorly Water-Soluble Herbicide

Addressing the challenges posed by the low water solubility of numerous herbicides is crucial as it directly affects their bioavailability and efficacy. This limited solubility often results in overapplication, increasing both environmental persistence and risks to human health and aquatic ecosystems. Atrazine (ATR), a widely recognized photosynthesis inhibitor, is emblematic of this dilemma, often requiring doses that far exceed the optimal levels for effective weed control. Cocrystal engineering has emerged as a promising solution. In our study, we synthesized cocrystals of ATR with propanedioic acid (PA) and succinic acid (SA). These cocrystals displayed a marked enhancement in intrinsic dissolution rates, with increases up to most 22.518-fold across a temperature range of 10–30 °C, which in turn greatly improved ATR's release dynamics. In addition, the solubility varied, increasing to different degrees at different temperatures. This augmentation not only elevated its herbicidal potency, evident from the preferential order of ATR-PA over ATR-SA and then ATR, but also safeguarded against any negative impacts on crop corn. Intriguingly, an increment of just 10 °C in temperature had a more pronounced effect than doubling the herbicide dosage, highlighting the pivotal role of ambient conditions. Overall, our findings highlight the potential of cocrystal engineering to optimize the performance and mitigate the environmental impact of herbicides with restricted water solubility.