School of Agriculture, Yangtze University, Jingmi Road 88, Jingzhou 434025, China.
Institute of Pesticides, Department of Plant Protection, School of Agriculture, Yangtze University, Jingmi Road 88, Jingzhou 434025, China.
Molecules. 2022 Aug 6;27(15):4999. doi: 10.3390/molecules27154999.
The Kleier model and Carrier-mediated theory are effective for molecularly designing pesticides with phloem mobility. However, the single Kleier model or Carrier-mediated theory cannot achieve a reliable explanation of the phloem mobility of all exogenous substances. A detailed investigation of the two models and the scope of their applications can provide a more accurate and highly efficient basis for the guidance of the design and development of phloem-mobile pesticides. In the present paper, a strategy using active ingredient-amino acid conjugates as mode compounds is developed based on Carrier-mediated theory. An N-alkylated amino acid is used to improve the pesticide’s physicochemical properties following the Kleier model, thus allowing the conjugates to fall on the predicted and more accessible transportation region of phloem. Moreover, the influence of this movement on phloem is inspected by the Kleier model and Carrier-mediated theory. To verify this strategy, a series of N-alkylated phenazine-1-carboxylic acid-glycine compounds (PCA-Gly) were designed and synthesized. The results related to the castor bean seeds (R. communis L.) indicated that all the target compounds (4a−4f) had phloem mobility. The capacity for phloem mobility shows that N-alkylated glycine containing small substituents can significantly improve PCA phloem mobility, such as 4c(i-C3H7-N) > 4a(CH3-N) ≈ 4b(C2H5-N) > 4d (t-C4H9-N) > PCA-Gly > 4e(C6H5-N) > 4f(CH2COOH-N), with an oil−water partition coefficient between 1.2~2.5. In particular, compounds 4a(CH3-N), 4b(C2H5-N), and 4c(i-C3H7-N) present better phloem mobility, with the average concentrations in phloem sap of 14.62 μΜ, 13.98 μΜ, and 17.63 μΜ in the first 5 h, which are 8 to 10 times higher than PCA-Gly (1.71 μΜ). The results reveal that the Kleier model and Carrier-mediated theory play a guiding role in the design of phloem-mobile pesticides. However, the single Kleier model or Carrier-mediated theory are not entirely accurate. Still, there is a synergism between Carrier-mediated theory and the Kleier model for promoting the phloem transport of exogenous compounds. Therefore, we suggest the introduction of endogenous plant compounds as a promoiety to improve the phloem mobility of pesticides through Carrier-mediated theory. It is necessary to consider the improvement of physicochemical properties according to the Kleier model, which can contribute to a scientific theory for developing phloem-mobile pesticides.
克莱尔模型和载体介导理论可有效用于设计具有韧皮部移动性的农药分子。然而，单一的克莱尔模型或载体介导理论并不能可靠地解释所有外源物质的韧皮部移动性。对这两种模型及其应用范围进行详细研究，可以为设计和开发具有韧皮部移动性的农药提供更准确、高效的指导。本文基于载体介导理论，采用活性成分-氨基酸缀合物作为模式化合物，开发了一种策略。根据克莱尔模型，用 N-烷基化氨基酸来改善农药的理化性质，从而使缀合物落入预测的、更易进入的韧皮部运输区。此外，还通过克莱尔模型和载体介导理论来检验这种运动对韧皮部的影响。为了验证这一策略，设计并合成了一系列 N-烷基化吩嗪-1-羧酸-甘氨酸化合物（PCA-Gly）。蓖麻种子（R. communis L.）的相关结果表明，所有目标化合物（4a-4f）均具有韧皮部移动性。具有韧皮部移动性的能力表明，含有小取代基的 N-烷基化甘氨酸可以显著提高 PCA 的韧皮部移动性，例如 4c(i-C3H7-N) > 4a(CH3-N) ≈ 4b(C2H5-N) > 4d (t-C4H9-N) > PCA-Gly > 4e(C6H5-N) > 4f(CH2COOH-N)，油水分配系数在 1.2~2.5 之间。特别是化合物 4a(CH3-N)、4b(C2H5-N)和 4c(i-C3H7-N)具有更好的韧皮部移动性，在前 5 小时内，韧皮部汁液中的平均浓度分别为 14.62 μΜ、13.98 μΜ和 17.63 μΜ，是 PCA-Gly（1.71 μΜ）的 8 到 10 倍。结果表明，克莱尔模型和载体介导理论在设计具有韧皮部移动性的农药方面具有指导作用。然而，单一的克莱尔模型或载体介导理论并不完全准确。载体介导理论与克莱尔模型之间仍然存在协同作用，可促进外源化合物的韧皮部运输。因此，我们建议引入内源性植物化合物作为促进剂，通过载体介导理论来提高农药的韧皮部移动性。根据克莱尔模型，需要考虑改善理化性质，这有助于为开发具有韧皮部移动性的农药提供科学理论。
