Abstract

In this work, we report synthesis, characterization and computational studies of the symmetric thiophene-based compound thiophene-2,5-diylbis((3-mesityl-3-methylcyclobutyl)methanone) (1) obtained from 2,2'-thiobis(1-(3-mesityl-3-methylcyclobutyl)ethan-1-one) and glyoxal using the Hinsberg thiophene ring synthesis approach. The Density Functional Theory (DFT) calculations were performed to probe the structure of 1, as well as its electronic and optical properties. The global reactivity descriptors, as well as molecular electrostatic potential (MEP), were revealed to probe the reactivity and to determine the reactive centers of 1. The DFT calculations were also applied to probe 1 as a potential corrosion inhibitor for some important metals used in implants. Electron charge transfer from the molecule of 1 to the surface of Ni, Au, Co, Cu, Mo, W, Fe and Cr was revealed. Bioavailability, druggability as well as absorption, distribution, metabolism, excretion and toxicity properties of 1 were predicted. Molecular docking was applied to examine the influence of this compound on a series of the SARS-CoV-2 proteins. Compound 1 exhibited the best binding affinity with the Nsp14 (N7-MTase), Papain-like protease (PLpro) and Nsp16 (MGP site) proteins as well as demonstrated a similar efficiency toward both the native and mutated Spike proteins, RDB.

摘要

在这项工作中，我们报告了从2,2'-thiobis( 1-(3-异三叉基-3-甲基环丁基)乙烷-1-酮)和乙二醛使用Hinsberg噻吩环合成方法。进行密度泛函理论 (DFT) 计算来探测1的结构及其电子和光学性质。揭示了全局反应性描述符以及分子静电势 (MEP)，以探测反应性并确定1的反应中心。DFT 计算也适用于探针1作为植入物中使用的一些重要金属的潜在腐蚀抑制剂。揭示了电子电荷从1分子到 Ni、Au、Co、Cu、Mo、W、Fe 和 Cr 表面的转移。预测了1的生物利用度、成药性以及吸收、分布、代谢、排泄和毒性特性。应用分子对接来检查该化合物对一系列 SARS-CoV-2 蛋白的影响。化合物1表现出与 Nsp14 (N7-MTase)、木瓜蛋白酶样蛋白酶 (PLpro) 和 Nsp16（MGP 位点）蛋白的最佳结合亲和力，并且对天然和突变 Spike 蛋白 RDB 具有相似的效率。