Pub Date : 2026-01-11DOI: 10.1016/j.molstruc.2026.145316
Mallikarjuna B , Prabhakar Chavan , G Krishnamurthy , Mandara A M , Pradeepa K , Ganapati Pakirappa Yadav , Chethan Krishnamurthy , Surendranaik Y
In this study, we successfully synthesized a novel series of triazole-based azo dyes 3(a-d) via an azo coupling reaction at 0-5 °C. The structural integrity of these compounds was confirmed using FT-IR, 1H-NMR, 13C-NMR, and mass spectrometry. Computational analysis explored the molecular geometry and global reactivity descriptors, offering significant insights into their molecular properties. The evaluation of the HOMO-LUMO energy gaps, conducted through computational analysis and cyclic voltammetry, demonstrated a remarkable concordance between the theoretical predictions and experimental results. Compound 3c distinguished itself by its exceptional fluorescent properties, as evidenced by live-cell imaging studies. The biological potential of these dyes was evaluated for antibacterial and antioxidant activities. Compound 3c showed exceptional efficacy in both assays, likely due to its strong binding affinity.
{"title":"Hybrid triazole azo dyes as bioactive compounds: Synthesis, characterization, electrochemical analysis, DFT studies, docking, and live cell imaging investigations","authors":"Mallikarjuna B , Prabhakar Chavan , G Krishnamurthy , Mandara A M , Pradeepa K , Ganapati Pakirappa Yadav , Chethan Krishnamurthy , Surendranaik Y","doi":"10.1016/j.molstruc.2026.145316","DOIUrl":"10.1016/j.molstruc.2026.145316","url":null,"abstract":"<div><div>In this study, we successfully synthesized a novel series of triazole-based azo dyes <strong>3</strong>(<strong>a-d</strong>) via an azo coupling reaction at 0-5 °C. The structural integrity of these compounds was confirmed using FT-IR, <sup>1</sup>H-NMR, <sup>13</sup>C-NMR, and mass spectrometry. Computational analysis explored the molecular geometry and global reactivity descriptors, offering significant insights into their molecular properties. The evaluation of the HOMO-LUMO energy gaps, conducted through computational analysis and cyclic voltammetry, demonstrated a remarkable concordance between the theoretical predictions and experimental results. Compound <strong>3c</strong> distinguished itself by its exceptional fluorescent properties, as evidenced by live-cell imaging studies. The biological potential of these dyes was evaluated for antibacterial and antioxidant activities. Compound <strong>3c</strong> showed exceptional efficacy in both assays, likely due to its strong binding affinity.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1358 ","pages":"Article 145316"},"PeriodicalIF":4.7,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145981121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-10DOI: 10.1016/j.molstruc.2026.145319
Antonija Jelčić , Lajos Fodor , Erzsébet Szabó-Bárdos , Ottó Horváth , Irena Škorić
Various resveratrol-based carbamates display very promising butyrylcholinesterase inhibitory activity. These stilbene-like compounds with a C = C bond are prone to a photoinduced trans-cis isomerization. Their structure may affect both properties, which may be correlated. The efficiency of the trans-cis isomerization of these compounds with various carbamate substituents on their benzene ring is very high, with quantum yields in the range of 0.21–0.32, similar to that of the analogue with a much smaller hydroxy substituent. These results indicate that the structural deviations located far from the C = C bond of these compounds hardly influence this isomerization process. Accordingly, there is no correlation between the structure-dependent biological activity and the sensitivity to trans-cis photoisomerization. Since the bioactivity of the trans-isomers of these carbamate derivatives is much stronger than of their cis-isomers, the high light sensitivity of these potential active ingredients of medicines to trans-cis isomerization warrants their protection from exposure to UV radiation during both their production and storage, as well as their application. The second step of the photochemical transformation of these compounds is the cyclization of their cis-isomers. Deviating from the photoinduced trans-cis isomerization, the tendency of these derivatives toward cyclization indicates a relatively strong connection to the structural features, similarly to their bioactivity. The efficiency of cyclization is inversely proportional to the biological activity. The most active is the carbamate derivative with the bulkiest substituent, displaying a negligible tendency toward cyclization, while the bioactivity of its hydroxy analogue with the highest efficiency of cyclization is two orders of magnitude lower.
{"title":"Comparison of photosensitivities of resveratrol-based carbamates with cholinesterase inhibitory activity","authors":"Antonija Jelčić , Lajos Fodor , Erzsébet Szabó-Bárdos , Ottó Horváth , Irena Škorić","doi":"10.1016/j.molstruc.2026.145319","DOIUrl":"10.1016/j.molstruc.2026.145319","url":null,"abstract":"<div><div>Various resveratrol-based carbamates display very promising butyrylcholinesterase inhibitory activity. These stilbene-like compounds with a C = C bond are prone to a photoinduced <em>trans-cis</em> isomerization. Their structure may affect both properties, which may be correlated. The efficiency of the <em>trans-cis</em> isomerization of these compounds with various carbamate substituents on their benzene ring is very high, with quantum yields in the range of 0.21–0.32, similar to that of the analogue with a much smaller hydroxy substituent. These results indicate that the structural deviations located far from the C = C bond of these compounds hardly influence this isomerization process. Accordingly, there is no correlation between the structure-dependent biological activity and the sensitivity to <em>trans-cis</em> photoisomerization. Since the bioactivity of the <em>trans</em>-isomers of these carbamate derivatives is much stronger than of their <em>cis</em>-isomers, the high light sensitivity of these potential active ingredients of medicines to <em>trans-cis</em> isomerization warrants their protection from exposure to UV radiation during both their production and storage, as well as their application. The second step of the photochemical transformation of these compounds is the cyclization of their <em>cis</em>-isomers. Deviating from the photoinduced <em>trans-cis</em> isomerization, the tendency of these derivatives toward cyclization indicates a relatively strong connection to the structural features, similarly to their bioactivity. The efficiency of cyclization is inversely proportional to the biological activity. The most active is the carbamate derivative with the bulkiest substituent, displaying a negligible tendency toward cyclization, while the bioactivity of its hydroxy analogue with the highest efficiency of cyclization is two orders of magnitude lower.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1358 ","pages":"Article 145319"},"PeriodicalIF":4.7,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145957723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-10DOI: 10.1016/j.molstruc.2026.145320
Yang Ji , Le Wang , Chenqi Liu , Wenwen Sun , Yongjie Lai , Yi Qu , Peng Yuan , Li-June Ming
A cyclotriphosphazene-based dual-module molecule (Cpz-AB) was synthesized via a facile two-step approach, and its in situ-generated Zn²⁺ complex (Cpz-AB-Zn) was employed as the active fluorescent probe for pyrophosphate (PPi) sensing. Following synthesis, comprehensive characterization and structural studies confirmed the molecular structure of Cpz-AB by 1D and 2D NMR, HRMS, and FT-IR spectroscopy. In the presence of PPi, the probe integrating a naphthalimide-triphenylamine fluorophore (Module A) and a terpyridine/Zn recognition site (Module B) exhibited a distinct fluorescence change from blue to red. The sensing system featured a large Stokes shift (180 nm) and a low detection limit of 0.93 μM. In addition, real samples including baking powder, toothpaste, seafood, and river water were tested, yielding excellent recoveries (97.8-102.5%) and low RSDs (0.33-1.29%). This work demonstrates the design potential of cyclotriphosphazene-based dual-module molecules and the performance of efficient and sensitive PPi detection.
{"title":"Design and synthesis of a novel cyclotriphosphazene-based dual-module molecule for pyrophosphate (PPi) sensing","authors":"Yang Ji , Le Wang , Chenqi Liu , Wenwen Sun , Yongjie Lai , Yi Qu , Peng Yuan , Li-June Ming","doi":"10.1016/j.molstruc.2026.145320","DOIUrl":"10.1016/j.molstruc.2026.145320","url":null,"abstract":"<div><div>A cyclotriphosphazene-based dual-module molecule (Cpz-AB) was synthesized via a facile two-step approach, and its <em>in situ</em>-generated Zn²⁺ complex (Cpz-AB-Zn) was employed as the active fluorescent probe for pyrophosphate (PPi) sensing. Following synthesis, comprehensive characterization and structural studies confirmed the molecular structure of Cpz-AB by 1D and 2D NMR, HRMS, and FT-IR spectroscopy. In the presence of PPi, the probe integrating a naphthalimide-triphenylamine fluorophore (Module A) and a terpyridine/Zn recognition site (Module B) exhibited a distinct fluorescence change from blue to red. The sensing system featured a large Stokes shift (180 nm) and a low detection limit of 0.93 μM. In addition, real samples including baking powder, toothpaste, seafood, and river water were tested, yielding excellent recoveries (97.8-102.5%) and low RSDs (0.33-1.29%). This work demonstrates the design potential of cyclotriphosphazene-based dual-module molecules and the performance of efficient and sensitive PPi detection.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1358 ","pages":"Article 145320"},"PeriodicalIF":4.7,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145981872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The goal of the investigation is to evaluate the chemical reactivity and molecular interactions of cocrystal hydrate to that of cocrystal. In this study, the molecular, electronic, and chemical properties of the drug hydrochlorothiazide (HCTZ) were determined after cocrystallization with isonicotinamide-monohydrate (INA.H2O). Analysis has been performed to understand how these variations lead to alteration of physical properties and chemical reactivity in the cocrystal hydrate HCTZ-INA·H₂O. IR and Raman characterizations were performed along with quantum chemical calculations. A theoretical investigation of hydrogen bonding interactions in HCTZ-INA·H₂O was conducted using the B3LYP functional. The results obtained for HCTZ-INA·H₂O (cocrystal hydrate) were compared with the results of our previous work consisting of hydrochlorothiazide-4 aminobenzoic acid (HCTZ-4ABA) (cocrystal). The chemical reactivity descriptors were used to understand various aspects of pharmaceutical properties. Natural bond orbital (NBO) analysis and quantum theory of atoms in molecules (QTAIM) were used to analyze the nature and strength of hydrogen bonding in HCTZ-INA·H₂O. QTAIM analysis indicated a moderate role of hydrogen bonding interactions in HCTZ-INA·H₂O. The calculated HOMO-LUMO energy gap shows that HCTZ-4ABA is more reactive than HCTZ-INA·H₂O. The results suggest that cocrystal hydrates display inferior physicochemical properties to that of cocrystals; accordingly, the latter multicomponent crystals could be viable solid forms of a drug.
{"title":"Exploring chemical reactivity and molecular interactions of hydrochlorothiazide-isonicotinamide cocrystal hydrate: A comparative spectroscopic and quantum chemical study using hydrochlorothiazide-4-aminobenzoic acid cocrystal","authors":"Areeba Khan , Neelam Agrawal , Rajni Chaudhary , Arti Yadav , Ayush Shukla , Preeti Prajapati , Jaya Pandey , Aditya Narayan , Yeganeh Donyanavard , Poonam Tandon , Venu R. Vangala","doi":"10.1016/j.molstruc.2026.145315","DOIUrl":"10.1016/j.molstruc.2026.145315","url":null,"abstract":"<div><div>The goal of the investigation is to evaluate the chemical reactivity and molecular interactions of cocrystal hydrate to that of cocrystal. In this study, the molecular, electronic, and chemical properties of the drug hydrochlorothiazide (HCTZ) were determined after cocrystallization with isonicotinamide-monohydrate (INA.H<sub>2</sub>O). Analysis has been performed to understand how these variations lead to alteration of physical properties and chemical reactivity in the cocrystal hydrate HCTZ-INA·H₂O. IR and Raman characterizations were performed along with quantum chemical calculations. A theoretical investigation of hydrogen bonding interactions in HCTZ-INA·H₂O was conducted using the B3LYP functional. The results obtained for HCTZ-INA·H₂O (cocrystal hydrate) were compared with the results of our previous work consisting of hydrochlorothiazide-4 aminobenzoic acid (HCTZ-4ABA) (cocrystal). The chemical reactivity descriptors were used to understand various aspects of pharmaceutical properties. Natural bond orbital (NBO) analysis and quantum theory of atoms in molecules (QTAIM) were used to analyze the nature and strength of hydrogen bonding in HCTZ-INA·H₂O. QTAIM analysis indicated a moderate role of hydrogen bonding interactions in HCTZ-INA·H₂O. The calculated HOMO-LUMO energy gap shows that HCTZ-4ABA is more reactive than HCTZ-INA·H₂O. The results suggest that cocrystal hydrates display inferior physicochemical properties to that of cocrystals; accordingly, the latter multicomponent crystals could be viable solid forms of a drug.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1358 ","pages":"Article 145315"},"PeriodicalIF":4.7,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145957706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Imidazole-acetamide conjugates are highly valued for their wide range of biological activities. They serve as promising scaffolds for the development of novel therapeutics and potent agents against plant pathogens, owing to their capacity to interact with diverse biological systems. The Kornblum oxidation and condensation method was used to generate a library of 24 novel imidazole-acetamide conjugates, and their antimicrobial and antioxidant efficacy were examined. The antifungal activity of compounds 6r, 6t, 6u, and 6x was remarkable, exceeding that of the standards against all the tested animal and plant pathogens. Also, compounds 6v and 6w showed excellent antibacterial activity against all the tested bacterial strains. Among all the synthesized compounds (6a-6x), compound 6l (IC50: 0.0129 μmol/mL) shows a good scavenging effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical. Overall, compounds having methyl and methoxy substituents demonstrated superior antioxidant potential compared to other derivatives. Furthermore, in silico Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) analysis indicated that most of the synthesized compounds (6a-6x) complied with the criteria for good oral bioavailability. The docking studies show the binding affinity of the docked complex 6v was −9.6 kcal/mol in the binding site of Escherichia coliDNA Gyrase, and that of compound 6j was −9.8 kcal/mol in the binding site of Candida albicans sterol 14-alpha demethylase. All compounds showed notable antibacterial and antifungal properties. Compounds 6v and 6w exhibited the highest antimicrobial potency, suggesting their potential as lead structures for developing new antimicrobial therapies, while compound 6l shows strong scavenging activity.
{"title":"Imidazole-acetamide conjugates: Design, synthesis, antimicrobial evaluation, antioxidant and in silico investigations","authors":"Ritika Chouhan , Vikas Verma , Sonia Rohilla , Ashwani Kumar , Meenakshi Bhatia , Vikramjeet Singh , Sweety Malik","doi":"10.1016/j.molstruc.2026.145310","DOIUrl":"10.1016/j.molstruc.2026.145310","url":null,"abstract":"<div><div>Imidazole-acetamide conjugates are highly valued for their wide range of biological activities. They serve as promising scaffolds for the development of novel therapeutics and potent agents against plant pathogens, owing to their capacity to interact with diverse biological systems. The Kornblum oxidation and condensation method was used to generate a library of 24 novel imidazole-acetamide conjugates, and their antimicrobial and antioxidant efficacy were examined. The antifungal activity of compounds <strong>6r, 6t, 6u</strong>, and <strong>6x</strong> was remarkable, exceeding that of the standards against all the tested animal and plant pathogens. Also, compounds <strong>6v</strong> and <strong>6w</strong> showed excellent antibacterial activity against all the tested bacterial strains. Among all the synthesized compounds (<strong>6a-6x</strong>), compound <strong>6l</strong> (IC<sub>50</sub>: 0.0129 μmol/mL) shows a good scavenging effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical. Overall, compounds having methyl and methoxy substituents demonstrated superior antioxidant potential compared to other derivatives. Furthermore, <em>in silico</em> Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) analysis indicated that most of the synthesized compounds (<strong>6a-6x</strong>) complied with the criteria for good oral bioavailability. The docking studies show the binding affinity of the docked complex <strong>6v</strong> was −9.6 kcal/mol in the binding site of <em>Escherichia coli</em>DNA Gyrase, and that of compound <strong>6j</strong> was −9.8 kcal/mol in the binding site of <em>Candida albicans</em> sterol 14-alpha demethylase. All compounds showed notable antibacterial and antifungal properties. Compounds <strong>6v</strong> and <strong>6w</strong> exhibited the highest antimicrobial potency, suggesting their potential as lead structures for developing new antimicrobial therapies, while compound <strong>6l</strong> shows strong scavenging activity.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1358 ","pages":"Article 145310"},"PeriodicalIF":4.7,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145981123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-09DOI: 10.1016/j.molstruc.2026.145309
Zhen-Yu Lian , Fu-Xiang Han , Yong-Hui Wen , Li-Jing Min , Tian-Ming Xu , Xing-Hai Liu
A novel series of pyrimidine-triazole hybrids containing a trifluoromethylbenzamide motif was designed and synthesized via an active substructure combination strategy. All target compounds were characterized by FT-IR, 1H NMR, 13C NMR, and HRMS. Their fungicidal activities were evaluated in vitro against ten plant pathogenic fungi at 50 μg/mL. Compounds 6o, 6p, and 6q exhibited potent, broad-spectrum antifungal activity, with inhibition rates surpassing 70% against multiple fungal strains. Notably, compound 6e demonstrated remarkable efficacy against Gibberella zeae(89%), while compound 6q showed highly effective against Colletotrichum gloeosporioides (82%). In silico investigations, comprising molecular property comparisons, ADMET predictions, and density functional theory (DFT) calculations, which provided valuable insights into the electronic characteristics and reactivity descriptors of the active compounds. These findings underscore the potential of pyrimidine–triazole hybrids as promising candidates for further development of antifungal agents.
{"title":"Synthesis, biological activity and in silico study of pyrimidine-triazole hybrids","authors":"Zhen-Yu Lian , Fu-Xiang Han , Yong-Hui Wen , Li-Jing Min , Tian-Ming Xu , Xing-Hai Liu","doi":"10.1016/j.molstruc.2026.145309","DOIUrl":"10.1016/j.molstruc.2026.145309","url":null,"abstract":"<div><div>A novel series of pyrimidine-triazole hybrids containing a trifluoromethylbenzamide motif was designed and synthesized via an active substructure combination strategy. All target compounds were characterized by FT-IR, <sup>1</sup>H NMR, <sup>13</sup>C NMR, and HRMS. Their fungicidal activities were evaluated <em>in vitro</em> against ten plant pathogenic fungi at 50 μg/mL. Compounds <strong>6o, 6p</strong>, and <strong>6q</strong> exhibited potent, broad-spectrum antifungal activity, with inhibition rates surpassing 70% against multiple fungal strains. Notably, compound <strong>6e</strong> demonstrated remarkable efficacy against <em>Gibberella zeae</em>(89%), while compound <strong>6q</strong> showed highly effective against <em>Colletotrichum gloeosporioides</em> (82%). <em>In silico</em> investigations, comprising molecular property comparisons, ADMET predictions, and density functional theory (DFT) calculations, which provided valuable insights into the electronic characteristics and reactivity descriptors of the active compounds. These findings underscore the potential of pyrimidine–triazole hybrids as promising candidates for further development of antifungal agents.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1358 ","pages":"Article 145309"},"PeriodicalIF":4.7,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145957708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-09DOI: 10.1016/j.molstruc.2026.145308
Yasser A. El-Ossaily , Sherif M.H. Sanad , Ahmed A.M. Ahmed , Mohamed Y. El-Sayed , Ahmed E.M. Mekky
Methicillin-resistant Staphylococcus aureus (MRSA) still poses a serious public health risk, highlighting the need for new antimicrobial agents. A promising approach involves designing pyrazole-based hybrids, particularly those incorporating indole or benzimidazole units, as potential MRSA inhibitors. We explored the MRSA inhibitory potency of some new 1H-pyrazole-based hybrids that are linked to 1H-indole or 1H-benzimidazole units. The desired hybrids are obtained, in 81–93% yields, by reacting the appropriate 1H-indole- or 1H-benzimidazole-based acetohydrazides with acetylacetone or its arylhydrazineylidene derivatives. The protocol was conducted in DMSO at 100 °C for 5–8 h containing 25 mol% of p-toluenesulfonic acid. In general, the 1H-benzimidazole-based 1H-pyrazole hybrids outperformed those hybrids based on 1H-indole units in the obtained bacterial inhibitory potency. Moreover, integrating an aryldiazenyl unit into the pyrazole-C4 resulted in improved efficacy, especially those linked to p-Me or p-OMe groups. The 1H-benzimidazole-based 4-(p-tolyldiazenyl)-1H-pyrazole 4d and 4-((4-methoxyphenyl)diazenyl)-1H-pyrazole 4e displayed the best antibacterial efficacy with MIC/MBC of 1.31/2.62 and 1.26/2.51 µM, respectively, against S. aureus and Escherichia coli. Moreover, 4d and 4e had MIC/MBC of 2.62/5.24 and 2.51/5.03 µM, respectively, against E. faecalis and P. aeruginosa. 4d and 4e also displayed significant MRSA inhibitory potency, with MIC/MBC of 2.62/10.49 and 2.51/10.06 µM, respectively. 4e demonstrated promising inhibitory potency against S. aureus and E. coliDNA gyrase inhibitory potency with IC50 of 1.254 and 0.978 μM, respectively. The Ames test displayed that the new hybrids are not mutagenic to Salmonella strains. All hybrids are considered drug-like, according to Lipinski's rule of five.
{"title":"Synthesis and antibacterial activity of some new pyrazoles incorporating benzimidazole or indole moiety","authors":"Yasser A. El-Ossaily , Sherif M.H. Sanad , Ahmed A.M. Ahmed , Mohamed Y. El-Sayed , Ahmed E.M. Mekky","doi":"10.1016/j.molstruc.2026.145308","DOIUrl":"10.1016/j.molstruc.2026.145308","url":null,"abstract":"<div><div>Methicillin-resistant <em>Staphylococcus aureus</em> (MRSA) still poses a serious public health risk, highlighting the need for new antimicrobial agents. A promising approach involves designing pyrazole-based hybrids, particularly those incorporating indole or benzimidazole units, as potential MRSA inhibitors. We explored the MRSA inhibitory potency of some new 1<em>H</em>-pyrazole-based hybrids that are linked to 1<em>H</em>-indole or 1<em>H</em>-benzimidazole units. The desired hybrids are obtained, in 81–93% yields, by reacting the appropriate 1<em>H</em>-indole- or 1<em>H</em>-benzimidazole-based acetohydrazides with acetylacetone or its arylhydrazineylidene derivatives. The protocol was conducted in DMSO at 100 °C for 5–8 h containing 25 mol% of <em>p</em>-toluenesulfonic acid. In general, the 1<em>H</em>-benzimidazole-based 1<em>H</em>-pyrazole hybrids outperformed those hybrids based on 1<em>H</em>-indole units in the obtained bacterial inhibitory potency. Moreover, integrating an aryldiazenyl unit into the pyrazole-C4 resulted in improved efficacy, especially those linked to <em>p-</em>Me or <em>p-</em>OMe groups. The 1<em>H</em>-benzimidazole-based 4-(<em>p</em>-tolyldiazenyl)-1<em>H</em>-pyrazole <strong>4d</strong> and 4-((4-methoxyphenyl)diazenyl)-1<em>H</em>-pyrazole <strong>4e</strong> displayed the best antibacterial efficacy with MIC/MBC of 1.31/2.62 and 1.26/2.51 µM, respectively, against <em>S. aureus</em> and <em>Escherichia coli.</em> Moreover, <strong>4d</strong> and <strong>4e</strong> had MIC/MBC of 2.62/5.24 and 2.51/5.03 µM, respectively, against <em>E. faecalis</em> and <em>P. aeruginosa</em>. <strong>4d</strong> and <strong>4e</strong> also displayed significant MRSA inhibitory potency, with MIC/MBC of 2.62/10.49 and 2.51/10.06 µM, respectively. <strong>4e</strong> demonstrated promising inhibitory potency against <em>S. aureus</em> and <em>E. coli</em>DNA gyrase inhibitory potency with IC<sub>50</sub> of 1.254 and 0.978 μM, respectively. The Ames test displayed that the new hybrids are not mutagenic to <em>Salmonella</em> strains. All hybrids are considered drug-like, according to Lipinski's rule of five.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1357 ","pages":"Article 145308"},"PeriodicalIF":4.7,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145978718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-09DOI: 10.1016/j.molstruc.2026.145304
Ghulam Murtaza , Syed Shoaib Ahmad Shah , Rashid G Siddique , Waqas Ali Shah , Manzar Sohail
Metal-organic frameworks (MOFs) have recently served as compelling and captivating adsorbents for extracting industrial dyes from aqueous pollutants. MOFs have drawn substantial interest in environmental cleanup, effective simultaneous removal of oppositely charged dye ions, and optimization of MOFs for multi-dye absorption. However, the effective simultaneous removal of oppositely charged dye ions and the optimization of MOFs for multi-dye adsorption constitute a challenging and less studied aspect. In this work, the role of aluminum (Al), cobalt (Co), nickel (Ni), and zinc (Zn) metals in MOFs composed of benzene dicarboxylic acid (BDC), was evaluated for the adsorption and encapsulation of organic dyes such as methylene blue (cationic dye) and methyl orange (anionic dye) from a mixture of dyes solution. The results revealed that MOFs with aluminum ions as metal nodes demonstrated the highest efficiency in dye removal (88.00%), suggesting that metal ions significantly impact the adsorption efficiency of MOFs. The highest adsorption of Al-BDC MOF also possessed a high surface area (1296.26 m2/g). Interestingly, when methylene blue and methyl orange co-exist in solution, they mutually enhance each other's capability of adsorption. Notably, a push-pull mechanism is proposed to explain the mutual enhancement of adsorption in a mixture of oppositely charged dye solutions. Further, we used computational study, Monte Carlo simulations to look at the MOFs molecular structural, and adsorption features.
{"title":"Synthesis and adsorptive comparison of terephthalate MOFs with varying metal ions for organic dyes removal","authors":"Ghulam Murtaza , Syed Shoaib Ahmad Shah , Rashid G Siddique , Waqas Ali Shah , Manzar Sohail","doi":"10.1016/j.molstruc.2026.145304","DOIUrl":"10.1016/j.molstruc.2026.145304","url":null,"abstract":"<div><div>Metal-organic frameworks (MOFs) have recently served as compelling and captivating adsorbents for extracting industrial dyes from aqueous pollutants. MOFs have drawn substantial interest in environmental cleanup, effective simultaneous removal of oppositely charged dye ions, and optimization of MOFs for multi-dye absorption. However, the effective simultaneous removal of oppositely charged dye ions and the optimization of MOFs for multi-dye adsorption constitute a challenging and less studied aspect. In this work, the role of aluminum (Al), cobalt (Co), nickel (Ni), and zinc (Zn) metals in MOFs composed of benzene dicarboxylic acid (BDC), was evaluated for the adsorption and encapsulation of organic dyes such as methylene blue (cationic dye) and methyl orange (anionic dye) from a mixture of dyes solution. The results revealed that MOFs with aluminum ions as metal nodes demonstrated the highest efficiency in dye removal (88.00%), suggesting that metal ions significantly impact the adsorption efficiency of MOFs. The highest adsorption of Al-BDC MOF also possessed a high surface area (1296.26 m<sup>2</sup>/g). Interestingly, when methylene blue and methyl orange co-exist in solution, they mutually enhance each other's capability of adsorption. Notably, a push-pull mechanism is proposed to explain the mutual enhancement of adsorption in a mixture of oppositely charged dye solutions. Further, we used computational study, Monte Carlo simulations to look at the MOFs molecular structural, and adsorption features.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1358 ","pages":"Article 145304"},"PeriodicalIF":4.7,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145982074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-09DOI: 10.1016/j.molstruc.2025.145165
Reham E Abdelwahab , Mostafa E. Salem , Mohammed Rashed Alsulami , Ahmed H.M. Elwahy , Karim Barakat , Amr Mohamed Abdelmoniem , Nadeem Raza , Ismail A. Abdelhamid
The cyclocondensation reaction of precursor 1-(1H-benzo[d]imidazol-2-yl)guanidine and the proper bis-aldehydes via base-catalyzed cyclization methodology successfully yielded bis(benzo[4,5]imidazo[1,2-a][1,3,5]triazines) linked to phenoxymethyl moieties tethered aliphatic and aromatic spacers. This technique had various benefits, including simple and mild reaction conditions, a short reaction time, and high yields. In most cases, we were able to isolate the non-oxidized form, whereas in few cases we isolated the oxidized constitutions. The structures of these compounds were confirmed using spectroscopic data. The minimum inhibitory concentration (MIC) against Enterococcus faecalis, Bacillus subtilis, Pseudomonas aeruginosa, and Proteus vulgaris was evaluated to investigate the effect of the spacer type of compounds 5a-c, and 6d,e bearing aliphatic spacer, 10a,b bearing phenyl spacer, 12 bearing naphthyl spacer, in addition to 14 linked by diphenyl ether group on the antibacterial activity of the compounds. Most of the compounds revealed a promising antibacterial effect against the tested strains. Comparative molecular docking studies were performed against three DNA gyrase inhibitors to evaluate the inhibitory potential of our compounds and the effect of modifying the spacers. Compounds 12 and 10a revealed the best binding, while all compounds exhibited favorable energy scores ranging from −6.57 to −8.35 kcal mol⁻¹. Furthermore, molecular docking against the MurE ligase enzyme revealed binding affinities ranging from −6.50 to −8.86 kcal mol⁻¹.
{"title":"Synthesis, antibacterial activities, and molecular docking of bis(1,3,4a,9-tetraza-4H-fluoren-2-amines) derivatives bearing aliphatic or aromatic spacers via (phenoxy) linkages","authors":"Reham E Abdelwahab , Mostafa E. Salem , Mohammed Rashed Alsulami , Ahmed H.M. Elwahy , Karim Barakat , Amr Mohamed Abdelmoniem , Nadeem Raza , Ismail A. Abdelhamid","doi":"10.1016/j.molstruc.2025.145165","DOIUrl":"10.1016/j.molstruc.2025.145165","url":null,"abstract":"<div><div>The cyclocondensation reaction of precursor 1-(1<em>H</em>-benzo[<em>d</em>]imidazol-2-yl)guanidine and the proper bis-aldehydes via base-catalyzed cyclization methodology successfully yielded bis(benzo[4,5]imidazo[1,2-<em>a</em>][1,3,5]triazines) linked to phenoxymethyl moieties tethered aliphatic and aromatic spacers. This technique had various benefits, including simple and mild reaction conditions, a short reaction time, and high yields. In most cases, we were able to isolate the non-oxidized form, whereas in few cases we isolated the oxidized constitutions. The structures of these compounds were confirmed using spectroscopic data. The minimum inhibitory concentration (MIC) against <em>Enterococcus faecalis, Bacillus subtilis, Pseudomonas aeruginosa,</em> and <em>Proteus vulgaris</em> was evaluated to investigate the effect of the spacer type of compounds <strong>5a-c</strong>, and <strong>6d,e</strong> bearing aliphatic spacer, <strong>10a,b</strong> bearing phenyl spacer, <strong>12</strong> bearing naphthyl spacer, in addition to <strong>14</strong> linked by diphenyl ether group on the antibacterial activity of the compounds. Most of the compounds revealed a promising antibacterial effect against the tested strains. Comparative molecular docking studies were performed against three DNA gyrase inhibitors to evaluate the inhibitory potential of our compounds and the effect of modifying the spacers. Compounds <strong>12</strong> and <strong>10a</strong> revealed the best binding, while all compounds exhibited favorable energy scores ranging from −6.57 to −8.35 kcal mol⁻¹. Furthermore, molecular docking against the MurE ligase enzyme revealed binding affinities ranging from −6.50 to −8.86 kcal mol⁻¹.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1357 ","pages":"Article 145165"},"PeriodicalIF":4.7,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145978960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-09DOI: 10.1016/j.molstruc.2026.145311
Huajie Zhu , Xinliang Guo , Zhi-Yong Xu , Shao-Jiang Song , Maria Y. Rios
The natural products ciquitin A and ciquitin B exhibit two distinct sets of NMR signals in solution, a phenomenon previously attributed to an equilibrium between its ring-open and ring-closed hemiacetal isomers. Through a comprehensive re-evaluation of NMR data, complemented by variable-temperature NMR experiments, potential energy surface (PES) scanning, and magnetic shielding constant calculations, we have redefined ciquitin A as a natural pseudo-resonance structure. Prior to successful crystallization for X-ray analysis, structural identification remained challenging when facing two sets of NMR spectra. However, conversion of any pseudo-resonance structure (like ciquitin A, a hemiacetal type) to its corresponding acetal derivatives (in this case (9S)-naproxyl-ciquitin A) resulted in a single set, thereby enabling clear identification of the structure. This work represents one of the most unequivocal examples of such a structure discovered in nature.
{"title":"Unmasking the true nature of ciquitin A: VT-NMR and computational evidence for a pseudo-resonance structure","authors":"Huajie Zhu , Xinliang Guo , Zhi-Yong Xu , Shao-Jiang Song , Maria Y. Rios","doi":"10.1016/j.molstruc.2026.145311","DOIUrl":"10.1016/j.molstruc.2026.145311","url":null,"abstract":"<div><div>The natural products ciquitin A and ciquitin B exhibit two distinct sets of NMR signals in solution, a phenomenon previously attributed to an equilibrium between its ring-open and ring-closed hemiacetal isomers. Through a comprehensive re-evaluation of NMR data, complemented by variable-temperature NMR experiments, potential energy surface (PES) scanning, and magnetic shielding constant calculations, we have redefined ciquitin A as a natural pseudo-resonance structure. Prior to successful crystallization for X-ray analysis, structural identification remained challenging when facing two sets of NMR spectra. However, conversion of any pseudo-resonance structure (like ciquitin A, a hemiacetal type) to its corresponding acetal derivatives (in this case (9<em>S</em>)-naproxyl-ciquitin A) resulted in a single set, thereby enabling clear identification of the structure. This work represents one of the most unequivocal examples of such a structure discovered in nature.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1357 ","pages":"Article 145311"},"PeriodicalIF":4.7,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145979656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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