2D, 3D and Hybrid QSAR Studies of Nostoclide Analogues as Inhibitors of the Photosystem II

Synthetic herbicides are widely used for weed control in crops. Continuous application of chemicals induces the adaptation of weeds, leading to the development of resistance. Therefore, research for novel synthetic herbicides plays an important role in crop protection and food production. Within this context, it is important to understand the relationship between the structures of a set of compounds endowed with herbicide activity and their biological response. In this work, a quantitative structure-activity relationship (QSAR) study of 34 nostoclide analogues was carried out in order to analyze their ability to inhibit the photosystem-II. Compounds were optimized using the DFT/B3LYP/Def2-TZVPP method. 2D and 3D (Lennard-Jones and electrostatic potential energies) molecular descriptors were calculated at the same theory level. QSAR models showed major importance of electrostatic ligand-acceptor interactions and indicated the presence of aromatic interaction in the benzyl group. A photoelectron transfer via hydrogen-bond was proposed to occur between His215 residue and the carbonyl group.

合成除草剂（Synthetic herbicides）被广泛应用于作物杂草防控。长期施用此类化学药剂会诱导杂草产生适应性，进而演化出抗药性。因此，研发新型合成除草剂对于作物保护与粮食生产具有重要意义。在此背景下，明确一类具备除草活性的化合物的结构与其生物响应之间的构效关系，具有重要研究价值。本研究针对34种念珠藻素类似物开展了定量构效关系（Quantitative Structure-Activity Relationship，QSAR）研究，以分析其抑制光系统II（Photosystem II）的能力。所有化合物均采用密度泛函理论（Density Functional Theory，DFT）/B3LYP/Def2-TZVPP方法进行结构优化。在相同理论水平下计算得到二维与三维分子描述符，涵盖伦纳德-琼斯势（Lennard-Jones）与静电势能（electrostatic potential energies）两类参数。构建的QSAR模型显示，配体-受体静电相互作用具有显著重要性，且表明苄基基团中存在芳香族相互作用。研究提出，组氨酸215残基与羰基之间可通过氢键介导光电子转移过程。