Synthesis, structural analysis, and computational investigations of metronidazole and climbazole derivatives

IF 4.7 2区化学 Q2 CHEMISTRY, PHYSICAL

Journal of Molecular Structure Pub Date : 2025-09-30 DOI:10.1016/j.molstruc.2025.144223

Ebrar Nur Özkan , Melek Gökmen Karakaya , Özlem Gündoğdu Aytaç , Ertan Şahin , Abdullah Menzek

{"title":"Synthesis, structural analysis, and computational investigations of metronidazole and climbazole derivatives","authors":"Ebrar Nur Özkan , Melek Gökmen Karakaya , Özlem Gündoğdu Aytaç , Ertan Şahin , Abdullah Menzek","doi":"10.1016/j.molstruc.2025.144223","DOIUrl":null,"url":null,"abstract":"<div><div>This study details the synthesis, characterization, and in silico studies of two new molecules, 4-(3-(2-methyl-5-nitro-1H-imidazol-1-yl)propyl)phthalonitrile (5) and 1-(4-chloro-2-nitrophenoxy)-1-(1H-imidazol-1-yl)-3,3-dimethylbutan-2-one (7), which are derivatives of metronidazole and climbazole. The structural description of nitro-climbazole (7) was confirmed by single crystal X-ray analysis, which revealed the monoclinic crystal system with the space group P21/n. Complementary to the experimental findings, computational studies were carried out using Density Functional Theory (DFT) with Gaussian 09 software. These calculations, including geometry optimization and frequency analysis, were performed at the mPW1PW91/6-311G(d,p) level for molecule 5 and at the wb97xd/6-311G(d,p) level for molecule 7. These analyses yielded important data regarding the stability and electronic structures of the molecules. Hirshfeld surface analysis based on CIF data obtained from the crystal structure 7 revealed intermolecular H∙∙∙H, O∙∙∙H, and Cl∙∙∙H contacts, demonstrating the contribution of these interactions to the stability of the crystal structure. Energy framework analyses elucidated the internal interactions of the structure by visualizing the cohesive forces within the crystal lattice. Frontier Molecular Orbital (FMO) analysis of molecules 5 and 7 revealed the distribution of their HOMO and LUMO orbitals, providing insights into their electronic behavior and reactivity potential. Furthermore, surface Electrostatic Potential (ESP) mapping identified electron-rich and electron-poor regions within the molecules, providing complementary information regarding potential biological interaction sites. Furthermore, their antibacterial and antifungal activities were investigated using in silico methods. This study, which combines experimental and theoretical approaches, comprehensively reveals the structural and electronic properties of the synthesized molecules.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1351 ","pages":"Article 144223"},"PeriodicalIF":4.7000,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Molecular Structure","FirstCategoryId":"92","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0022286025028674","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, PHYSICAL","Score":null,"Total":0}

引用次数: 0

Abstract

This study details the synthesis, characterization, and in silico studies of two new molecules, 4-(3-(2-methyl-5-nitro-1H-imidazol-1-yl)propyl)phthalonitrile (5) and 1-(4-chloro-2-nitrophenoxy)-1-(1H-imidazol-1-yl)-3,3-dimethylbutan-2-one (7), which are derivatives of metronidazole and climbazole. The structural description of nitro-climbazole (7) was confirmed by single crystal X-ray analysis, which revealed the monoclinic crystal system with the space group P2₁/n. Complementary to the experimental findings, computational studies were carried out using Density Functional Theory (DFT) with Gaussian 09 software. These calculations, including geometry optimization and frequency analysis, were performed at the mPW1PW91/6-311G(d,p) level for molecule 5 and at the wb97xd/6-311G(d,p) level for molecule 7. These analyses yielded important data regarding the stability and electronic structures of the molecules. Hirshfeld surface analysis based on CIF data obtained from the crystal structure 7 revealed intermolecular H∙∙∙H, O∙∙∙H, and Cl∙∙∙H contacts, demonstrating the contribution of these interactions to the stability of the crystal structure. Energy framework analyses elucidated the internal interactions of the structure by visualizing the cohesive forces within the crystal lattice. Frontier Molecular Orbital (FMO) analysis of molecules 5 and 7 revealed the distribution of their HOMO and LUMO orbitals, providing insights into their electronic behavior and reactivity potential. Furthermore, surface Electrostatic Potential (ESP) mapping identified electron-rich and electron-poor regions within the molecules, providing complementary information regarding potential biological interaction sites. Furthermore, their antibacterial and antifungal activities were investigated using in silico methods. This study, which combines experimental and theoretical approaches, comprehensively reveals the structural and electronic properties of the synthesized molecules.

Abstract Image

查看原文本刊更多论文

甲硝唑和克里巴唑衍生物的合成、结构分析和计算研究

本研究详细介绍了甲硝唑和克里巴唑衍生物4-（3-（2-甲基-5-硝基- 1h -咪唑-1-基）丙基）邻苯二腈(5)和1-（4-氯-2-硝基苯氧基）-1-（1h -咪唑-1-基）-3,3-二甲基丁烷-2-酮(7)这两个新分子的合成、表征和硅研究。通过单晶x射线分析证实了硝基-克里巴唑(7)的结构描述，发现其为单斜晶系，空间群为P21/n。与实验结果相辅相成，利用密度泛函理论（DFT）和Gaussian 09软件进行了计算研究。这些计算包括几何优化和频率分析，在分子5的mPW1PW91/6-311G（d,p）水平和分子7的wb97xd/6-311G（d,p）水平上进行。这些分析产生了关于分子稳定性和电子结构的重要数据。基于从晶体结构中获得的CIF数据7的Hirshfeld表面分析揭示了分子间的H∙∙H、O∙∙H和Cl∙H接触，证明了这些相互作用对晶体结构稳定性的贡献。能量框架分析通过可视化晶格内的内聚力来阐明结构的内部相互作用。分子5和分子7的前沿分子轨道（FMO）分析揭示了它们的HOMO和LUMO轨道分布，为了解它们的电子行为和反应电位提供了新的思路。此外，表面静电电位（ESP）图谱确定了分子内的富电子和贫电子区域，为潜在的生物相互作用位点提供了补充信息。此外，用计算机方法研究了它们的抗菌和抗真菌活性。本研究采用实验和理论相结合的方法，全面揭示了合成分子的结构和电子性质。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of Molecular Structure 化学-物理化学

CiteScore

7.10

自引率

15.80%

发文量

2384

审稿时长

45 days

期刊介绍： The Journal of Molecular Structure is dedicated to the publication of full-length articles and review papers, providing important new structural information on all types of chemical species including: • Stable and unstable molecules in all types of environments (vapour, molecular beam, liquid, solution, liquid crystal, solid state, matrix-isolated, surface-absorbed etc.) • Chemical intermediates • Molecules in excited states • Biological molecules • Polymers. The methods used may include any combination of spectroscopic and non-spectroscopic techniques, for example: • Infrared spectroscopy (mid, far, near) • Raman spectroscopy and non-linear Raman methods (CARS, etc.) • Electronic absorption spectroscopy • Optical rotatory dispersion and circular dichroism • Fluorescence and phosphorescence techniques • Electron spectroscopies (PES, XPS), EXAFS, etc. • Microwave spectroscopy • Electron diffraction • NMR and ESR spectroscopies • Mössbauer spectroscopy • X-ray crystallography • Charge Density Analyses • Computational Studies (supplementing experimental methods) We encourage publications combining theoretical and experimental approaches. The structural insights gained by the studies should be correlated with the properties, activity and/ or reactivity of the molecule under investigation and the relevance of this molecule and its implications should be discussed.