Scholarlink

<p>This study investigates the mechanistic pathways of the [3+2] cycloaddition (32CA) reaction between 2,4,6-trimethyl-3,5-dichlorobenzonitrile N-oxide <b>1</b> and arylacetylenes <b>2</b> (<b>2a</b>, <b>2b</b>, <b>2c</b>, and <b>2d</b>) using Molecular Electron Density Theory (MEDT). However, Density Functional Theory (DFT) calculations at the B3LYP/6-311++G(d,p) level were employed to analyze the electron density distribution and reaction energetics. Parr functions were employed to identify the most electrophilic and nucleophilic centers, providing insights into regioselectivity and reactivity trends. The Global Electron Density Transfer (GEDT) values confirm the polar nature of the reaction, indicating a forward electron density flux (FEDF) mechanism. Bonding Evolution Theory (BET) was applied along the Intrinsic Reaction Coordinate (IRC) to analyze electronic structure transformations, revealing a non-concerted, asynchronous bond formation pathway. However, Potential energy surface (PES) analysis, electron localization function (ELF) topology, and the quantum theory of atoms in molecules (QTAIM) methodologies were used to determine the electronic structure and bonding progression. The research investigates molecular docking interactions between the produced isoxazolidine derivatives and the KRAS G12C protein (PDB ID: 6OIM) to evaluate their potential for targeted cancer treatment. Furthermore, ADMET analysis was performed to assess drug-likeness and pharmacokinetic characteristics. The results elucidate the regioselectivity of [3+2] cycloaddition (32CA) reactions and their significance for rational drug design.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Computational investigation of the cycloaddition reaction mechanism of 2,4,6-trimethyl-3,5-dichlorobenzonitrile N-oxide with arylacetylenes: insights from density functional theory and molecular docking

  • 期刊论文

  • 发表日期：

    2025年5月16日

查看全文
  • Raad Nasrullah Salih,
  • Haydar Mohammad-Salim,
  • Muheb Algso

摘要

This study investigates the mechanistic pathways of the [3+2] cycloaddition (32CA) reaction between 2,4,6-trimethyl-3,5-dichlorobenzonitrile N-oxide 1 and arylacetylenes 2 (2a, 2b, 2c, and 2d) using Molecular Electron Density Theory (MEDT). However, Density Functional Theory (DFT) calculations at the B3LYP/6-311++G(d,p) level were employed to analyze the electron density distribution and reaction energetics. Parr functions were employed to identify the most electrophilic and nucleophilic centers, providing insights into regioselectivity and reactivity trends. The Global Electron Density Transfer (GEDT) values confirm the polar nature of the reaction, indicating a forward electron density flux (FEDF) mechanism. Bonding Evolution Theory (BET) was applied along the Intrinsic Reaction Coordinate (IRC) to analyze electronic structure transformations, revealing a non-concerted, asynchronous bond formation pathway. However, Potential energy surface (PES) analysis, electron localization function (ELF) topology, and the quantum theory of atoms in molecules (QTAIM) methodologies were used to determine the electronic structure and bonding progression. The research investigates molecular docking interactions between the produced isoxazolidine derivatives and the KRAS G12C protein (PDB ID: 6OIM) to evaluate their potential for targeted cancer treatment. Furthermore, ADMET analysis was performed to assess drug-likeness and pharmacokinetic characteristics. The results elucidate the regioselectivity of [3+2] cycloaddition (32CA) reactions and their significance for rational drug design.