Grupo de Química Teórica e Estrutural de Anápolis, Universidade Estadual de Goiás, Anápolis, GO, Brazil.
Escola de Ciências Médicas e da Vida, Pontifícia Universidade Católica de Goiás, Goiânia, GO, Brazil.
J Mol Model. 2023 Jul 12;29(8):241. doi: 10.1007/s00894-023-05629-x.
The design and synthesis of safe and highly active sulfonylurea herbicides is still a challenge. Therefore, following some principles of structure-activity relationship (SAR) of sulfonylurea herbicides, this work focuses on evaluating two sulfonylurea derivatives bearing electron-withdrawing substituents, namely, -(CO)OCH and -NO on the aryl group, on herbicidal activity. To understand the effects caused by the substituent groups, the molecular and electronic structures of the sulfonylureas were evaluated by density functional theory. Likewise, the crystalline supramolecular arrangements of both compounds were analyzed by Hirshfeld surface, QTAIM, and NBO, with the aim of verifying changes in intermolecular interactions caused by substituent groups. Finally, through a toxicophoric analysis, we were able to predict the interacting groups in their biological target, acetolactate synthase, and verify the interactions with the binding site.
All theoretical calculations were conducted using the highly parameterized empirical exchange-correlation functional M06-2X accompanied by the diffuse and polarized basis set 6-311++G(d,p). The atomic coordinates were obtained directly from the crystalline structures, and from the energies of the frontier molecular orbitals (HOMO and LUMO), chemical descriptors were obtained that indicated the influence of the functional groups in the sulfonylureas on the reactivity of the molecules. The intermolecular interactions in the crystals were analyzed using the Hirshfeld, QTAIM, and NBO surfaces. Toxicophoric modeling was performed by the PharmaGist webserver and molecular docking calculations were performed by the GOLD 2022.1.0 software package so that the ligand was fitted to the binding site in a 10 Å sphere. For this, genetic algorithm parameters were used using the ChemPLP scoring function for docking and ASP for redocking.
设计和合成安全且高效的磺酰脲类除草剂仍然是一个挑战。因此，本工作遵循磺酰脲类除草剂的一些构效关系（SAR）原则，重点评估了两个带有吸电子取代基的磺酰脲衍生物，即在芳基上带有-（CO）OCH 和-NO，评估其除草活性。为了了解取代基引起的影响，通过密度泛函理论评估了磺酰脲的分子和电子结构。同样，通过 Hirshfeld 表面、QTAIM 和 NBO 分析了这两种化合物的晶体超分子排列，目的是验证取代基引起的分子间相互作用的变化。最后，通过毒性分析，我们能够预测其生物靶标乙酰乳酸合酶中的相互作用基团，并验证与结合位点的相互作用。
所有理论计算均使用高度参数化经验交换相关函数 M06-2X 配合弥散和极化基组 6-311++G(d,p)进行。原子坐标直接从晶体结构中获得，从前沿分子轨道（HOMO 和 LUMO）的能量中获得化学描述符，这些化学描述符表明磺酰脲中的官能团对分子反应性的影响。使用 Hirshfeld、QTAIM 和 NBO 表面分析晶体中的分子间相互作用。通过 PharmaGist 网络服务器进行毒性模型构建，并使用 GOLD 2022.1.0 软件包进行分子对接计算，使配体拟合到 10 Å 球体内的结合位点。为此，使用遗传算法参数，使用 ChemPLP 评分函数进行对接，使用 ASP 进行重新对接。
