How To Design for a Tailored Subcellular Distribution of Systemic Agrochemicals in Plant Tissues

Abstract

Foliar-applied systemic agrochemicals require entrance into the plant vascular system or into specific subcellular compartments to reach their target in planta or to be imbibed by piercing/sucking pests. An inappropriate subcellular localization, like accumulation of aphicides in vacuoles, might lower the compound's efficiency due to reduced exposure to the target. Permeabilities and mass distributions of 16 compounds covering a broad range of properties were measured across a pH gradient in a PAMPA ("parallel artificial membrane permeability assay") system, providing experimental evidence for ion trapping of acids and bases in basic and acidic compartments, respectively. The results validated a predictive model which was then expanded to simulate a standardized plant cell (cytosol and vacuole) with a vascular system (phloem and xylem). This approach underlined that the absolute mass distribution across aqueous phases is defined by membrane retention, whereas the relative mass distribution is determined by the species (neutral, acidic, basic) of compounds. These processes depend largely on p K and log K of the test compounds, which subsequently determine the partitioning of the substances in plant cell compartments. The validated model can be used as a tool in agrochemistry research to tailor the subcellular distribution by chemistry design and to interpret biology results.

Comprehensive machine learning based study of the chemical space of herbicides

“…The nine physicochemical and simple molecular properties are, in general, associated with uptake and translocation of compounds through plants 41 , 42 . However, this observed dependence of the weed type selectivity may also be related to the specific sub- cellular/plastid location of target proteins (pathways) and/or to different characteristics of binding sites of herbicides on targets.…”

“…For synthetic herbicides distributions of physicochemical and simple molecular properties have already been reported 28 – 34 . These simple molecular properties and physicochemical features largely influence the mass distribution of herbicides across plants and plant cell compartments and hence may be applied for characterizing herbicide-likeness of compounds 41 , 42 . The phytotoxic effect of a herbicide largely depends upon its translocation through plants to its site of action analogously as pharmacological effects of drugs are considerably influenced by their absorption and distribution throughout the human body 44 .…”

UV-DIB: label-free permeability determination using droplet interface bilayers

“…Fundamental limitations have been apparent when studying simple diffusion through mimetic lipid membranes using techniques such as PAMPA or planar bilayers including; low sampling rate, reliance on fluorescence detection and inaccuracy in bio membrane representation. 17,18,24,35,36,60 A central advantage of the PAMPA method, has been its ability to employ UV-spectroscopy. With this technique now readily accessible in DIBs, the chemical space which can be sampled across lipid bilayer interfaces is significantly increased.…”

“…This particular pathway is understood to be a major indicator of oral bioavailability, as well as foliar uptake, [13][14][15] with many current assays placing focus on this particular transport route. [16][17][18] Therefore, biologically active chemistry, will interact with membranes whose varying properties will likely affect their efficacy, selectivity, and safety in patients and/or the environment. These affects are critical to the development of sustainable chemistry in agriculture as well as to personalised medicine in pharmaceuticals.…”

Measuring the passive cuticular membrane permeability of potassium with a parallel artificial membrane permeability assay and the implications for foliar nutrient formulations

“…PAMPA was first introduced in 1998 for evaluating the passive membrane permeability of pharmaceuticals in the gastrointestinal tract [12]. More recently PAMPA has also been used to evaluate the passive membrane permeability of crop protection compounds [13], but to our knowledge has not been used previously to simulate nutrient transport across a leaf cuticle. The PAMPA setup consists of an artificial lipid barrier resting on a filter support in a 96-well plate format.…”