Vectorizing agrochemicals: enhancing bioavailability via carrier‐mediated transport

Abstract

Systemicity of agrochemicals is an advantageous property for controlling phloem sucking insects, as well as pathogens and pests not accessible to contact products. After the penetration of the cuticle, the plasma membrane constitutes the main barrier to the entry of an agrochemical into the sap flow. The current strategy for developing systemic agrochemicals is to optimize the physicochemical properties of the molecules so that they can cross the plasma membrane by simple diffusion or ion trapping mechanisms. The main problem with current systemic compounds is that they move everywhere within the plant, and this non‐controlled mobility results in the contamination of the plant parts consumed by vertebrates and pollinators. To achieve the site‐targeted distribution of agrochemicals, a carrier‐mediated propesticide strategy is proposed in this review. After conjugating a non‐systemic agrochemical with a nutrient (α‐amino acids or sugars), the resulting conjugate may be actively transported across the plasma membrane by nutrient‐specific carriers. By applying this strategy, non‐systemic active ingredients are expected to be delivered into the target organs of young plants, thus avoiding or minimizing subsequent undesirable redistribution. The development of this innovative strategy presents many challenges, but opens up a wide range of exciting possibilities. © 2018 Society of Chemical Industry

The influence of steric configuration of phenazine‐1‐carboxylic acid‐amino acid conjugates on fungicidal activity and systemicity

“…In the last few decades, with experimental assays on many of the known phloem mobile xenobiotics, the Kleier mathematical model was established based on the physicochemical properties of xenobiotics and the intermediate permeability hypothesis with the acid trap mechanism for weak acids, and then widely applied to predict the phloem mobility of xenobiotics . The application of the model is in broad agreement with many of the known phloem mobile herbicides, fungicides and insecticides, except for a few xenobiotics whose transport is carrier‐mediated …”

“…[34][35][36] The application of the model is in broad agreement with many of the known phloem mobile herbicides, fungicides and insecticides, except for a few xenobiotics whose transport is carrier-mediated. 6,13,14,37 We used the Kleier model to predict the phloem mobility of test compounds. The log K ow and pK a were calculated with the ALOGPS 2.1 program and ACD log Dv 6.00 software, respectively.…”

“…1,2 To date, the number of fungicides that have ambimobility activity (both phloem mobile and xylem mobile) in plants is very limited, exemplified by fungicides such as metalaxyl, 3 or phosethyl-Al. 4 Successful attempts have been made to achieve this goal by changing the physicochemical properties of molecular structures 1,5 or introducing a small molecule which is endogenous and can bi-directionally transport in plant, 6 such as an amino acid, [7][8][9][10][11] or a sugar [12][13][14] onto the non-phloem mobile agrochemicals. For example, to fit the Kleier prediction model widely employed to predict whether xenobiotics are capable of phloem transport ability based on their physical and chemical properties (log K ow and pKa, respectively), an acidic derivative of the fungicide fenpiclonil, N-carboxymethyl-3cyano-4-(2,3-dichlorophenyl)pyrrole, showing moderate phloem mobility was designed and synthesized, and it was found to exhibit high phloem mobility using the castor bean system.…”

Implication of human drug transporters to toxicokinetics and toxicity of pesticides

“…In most cases, pesticides are thought to be transported across biological membranes through passive diffusion or other processes like ion‐trapping mechanisms . Active transport can, however, be hypothesized to coexist with passive diffusion for a notable proportion of pesticides, as already demonstrated for drugs, but it remains yet understudied.…”

2019 – A year of continued growth

“…A mini‐review provided evidence to dispel the view that DEET is a mammalian neurotoxin . Prospects were provided for producing propesticides that move into crops more readily, but once in the crops, are altered to become active pesticides with limited systemic properties, thus reducing residues in plant parts consumed by vertebrates or pollinators …”