Innovation and opportunities toward new molecules for the agrochemical industry: from theory to technology

Recently, the growing population has led to the increase of world food production and the intense use of pesticides in agriculture. This current outlook is still aggravated because organophousphorus (OP) compounds, which are potent EPSP synthase inhibitors, are the most widely used pesticides. Accordingly, their persistent overuse worldwide has caused an accumulation of their compounds in food, fertile land or wastewater runoff. Thus, it is also important to mention that the action of OP compounds, as toxic compounds and acetylcholinesterase (AChE) inhibitors, is well known. In fact, those compounds are able to stop the hydrolysis of the neurotransmitter acetylcholine and can lead to an irreversible inhibition of the AChE enzyme (aging), thus causing the cholinergic syndrome. In this line, the high frequency of contamination by pesticides suggests the need for more active and selective agrochemicals. As such, molecular modeling studies using molecular dynamics simulations and DFT techniques were performed to understand the interaction and the action mechanism of OP compounds with the wild type enzyme and Gly96Ala mutant EPSP synthase. In addition, we investigated the reaction mechanism of the natural substrate. It is important to keep in mind that studies about the reaction mechanism can indicate a pathway to understand how these compounds work in biological systems. In this line, molecular modeling studies, quantum calculations and experiments were performed in order to understand the molecular behavior of those compounds in solution and in the enzyme active site. Our findings indicate some key points for the design of new and more selective agrochemicals. The insightful microscopic explanations for the biological and physical-chemical properties can demonstrate the power of joint experimental-computational approaches to environmental problems.