In this work, a series of pyrrolidinone-containing 2-phenylpyridine derivatives were synthesized and evaluated as novel protoporphyrinogen IX oxidase (PPO, EC 1.3.3.4) inhibitors for herbicide development. At 150 g ai/ha, compounds 4d, 4f, and 4l can inhibit the grassy weeds of Echinochloa crus-galli (EC), Digitaria sanguinalis (DS), and Lolium perenne (LP) with a range of 60 to 90%. Remarkably, at 9.375 g ai/ha, these compounds showed 100% inhibition effects against broadleaf weeds of Amaranthus retroflexus (AR) and Abutilon theophrasti (AT), which were comparable to the performance of the commercial herbicides flumioxazin (FLU) and saflufenacil (SAF) and better than that of acifluorfen (ACI). Molecular docking analyses revealed significant hydrogen bonding and π–π stacking interactions between compounds 4d and 4l with Arg98, Asn67, and Phe392, respectively. Additionally, representative compounds were chosen for in vivo assessment of PPO inhibitory activity, with compounds 4d, 4f, and 4l demonstrating excellent inhibitory effects. Notably, compounds 4d and 4l induced the accumulation of reactive oxygen species (ROS) and a reduction in the chlorophyll (Chl) content. Consequently, compounds 4d, 4f, and 4l are promising lead candidates for the development of novel PPO herbicides.

中文翻译：

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作为新型原卟啉原氧化酶抑制剂的含吡咯烷酮 2-苯基吡啶衍生物的设计、合成和除草评价

在这项工作中，合成了一系列含吡咯烷酮的 2-苯基吡啶衍生物，并作为新型原卟啉原 IX 氧化酶（PPO，EC 1.3.3.4）抑制剂进行了除草剂开发的评估。在 150 g ai/ha 下，化合物4d、4f和4l可以抑制稗草( EC )、马唐( DS ) 和多年生黑麦草( LP ) 等禾本科杂草，抑制范围为 60 至 90%。值得注意的是，在 9.375 g ai/ha 下，这些化合物对反枝苋( AR )和苘麻( AT ) 等阔叶杂草显示出 100% 的抑制效果，与商业除草剂氟啶嗪 (FLU) 和苯嘧磺草胺 (SAF) 的性能相当。 ）并且优于三氟羧草醚（ACI）。分子对接分析揭示了化合物4d和4l分别与 Arg98、Asn67 和 Phe392之间存在显着的氢键和 π-π 堆积相互作用。此外，选择代表性化合物用于体内PPO抑制活性评估，其中化合物4d、4f和4l表现出优异的抑制效果。值得注意的是，化合物4d和4l诱导活性氧 (ROS) 的积累和叶绿素 (Chl) 含量的减少。因此，化合物4d、4f和4l是开发新型 PPO 除草剂的有希望的先导候选物。