Scholarlink

<p>The pyridine ring system is a cornerstone of modern drug design, with its fundamental role in pharmacology directly leading to a multitude of widely used therapeutics. This propels the continued synthesis of novel, physiologically active compounds featuring the pyridine scaffold, promising a pipeline of new medicines for various diseases in the near future. Furthermore, scientific interest in N-heterocyclic compounds, including pyridine, has intensified due to their antiviral activity, with recent studies targeting SARS-CoV-2 and some derivatives even being developed into COVID-19 medications. All this requires detailed structural and electronic properties of the newly developed compounds to reveal their potential biological activity. In the present study, computational studies of the recently reported diazene derivative, namely (<i>E</i>)-1,1’-(diazene-1,2-diylbis(2-methyl-6-phenylpyridine-5,3-diyl))bis(ethan-1-one) (<b>1</b>), and its dihydrochloride salt, namely (<i>E</i>)-5,5’-(diazene-1,2-diyl)bis(3-acetyl-2-methyl-6-phenylpyridin-1-ium)dichloride (<b>2</b>), were conducted using density functional theory (DFT) at the WB97XD/6-311+G(d,p) level. The optimized geometry of <b>2</b> aligns closely with its experimental molecular structure and is stabilized by multiple non-covalent interactions: two C∙∙∙O tetrel bonds, two C–H∙∙∙Cl hydrogen bonds, one C∙∙∙Cl interaction, and one C–H∙∙∙C contact. Additionally, each chloride anion forms a strong N–H∙∙∙Cl hydrogen bond with the pyridinium NH groups. Compound <b>1</b> exhibits stabilization through two C∙∙∙O tetrel bonds and two C–H∙∙∙N interactions involving the diazene nitrogen atoms. Toxicity predictions address both compounds to the class 4. They also demonstrate potential as inhibitors of multiple SARS-CoV-2 proteins, with the strongest activity predicted against Nonstructural Protein 14 (N7–MTase), supported by ligand efficiency scores indicative of drug-like properties.</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

Sterically Hindered Diazene Derivative and its Dihydrochloride Salt: A DFT-based Investigation of Structural and Electronic Properties

  • 期刊论文

  • 发表日期：

    2026年2月9日

查看全文
  • Elizaveta V. Panova,
  • Tatyana M. Burkhanova,
  • Damir A. Safin

摘要

The pyridine ring system is a cornerstone of modern drug design, with its fundamental role in pharmacology directly leading to a multitude of widely used therapeutics. This propels the continued synthesis of novel, physiologically active compounds featuring the pyridine scaffold, promising a pipeline of new medicines for various diseases in the near future. Furthermore, scientific interest in N-heterocyclic compounds, including pyridine, has intensified due to their antiviral activity, with recent studies targeting SARS-CoV-2 and some derivatives even being developed into COVID-19 medications. All this requires detailed structural and electronic properties of the newly developed compounds to reveal their potential biological activity. In the present study, computational studies of the recently reported diazene derivative, namely (E)-1,1’-(diazene-1,2-diylbis(2-methyl-6-phenylpyridine-5,3-diyl))bis(ethan-1-one) (1), and its dihydrochloride salt, namely (E)-5,5’-(diazene-1,2-diyl)bis(3-acetyl-2-methyl-6-phenylpyridin-1-ium)dichloride (2), were conducted using density functional theory (DFT) at the WB97XD/6-311+G(d,p) level. The optimized geometry of 2 aligns closely with its experimental molecular structure and is stabilized by multiple non-covalent interactions: two C∙∙∙O tetrel bonds, two C–H∙∙∙Cl hydrogen bonds, one C∙∙∙Cl interaction, and one C–H∙∙∙C contact. Additionally, each chloride anion forms a strong N–H∙∙∙Cl hydrogen bond with the pyridinium NH groups. Compound 1 exhibits stabilization through two C∙∙∙O tetrel bonds and two C–H∙∙∙N interactions involving the diazene nitrogen atoms. Toxicity predictions address both compounds to the class 4. They also demonstrate potential as inhibitors of multiple SARS-CoV-2 proteins, with the strongest activity predicted against Nonstructural Protein 14 (N7–MTase), supported by ligand efficiency scores indicative of drug-like properties.