Journal of Molecular Structure最新文献

{"title":"A new method for synthesizing benzofuran-2-carboxamide derivatives with a symmetrical chemosensor for naked-eye detection of CN– ions based azo-thiazolidine-2,4‑dione (S-AT) and evaluation of antibacterial activity and molecular docking studies","authors":"Hadiseh Yazdani Nyaki ,&nbsp;Nosrat O. Mahmoodi ,&nbsp;Hossein Taherpour Nahzomi","doi":"10.1016/j.molstruc.2025.144289","DOIUrl":"10.1016/j.molstruc.2025.144289","url":null,"abstract":"<div><div>A new symmetric chemosensor including a thiazolidine-2,4-dions (TZD) and an azo chromophore was synthesized and employed as a colorimetric sensor. Visual investigations of detecting anions showed that the sensor acts as a highly sensitive and selective chromogenic detector of cyanide ions (CN⁻). The observable color change from Yellow to Orange for CN⁻ allows the detection of this ion without the use of advanced equipment, even with the naked eye. The sensor limit of detection (LOD) was determined to be 0.145 μM for CN⁻ ions. The Job plot indicates that the sensor (<strong>S-AT</strong>) binds to CN⁻ with a stoichiometric ratio of 1:2. This sensor can be used in the real world, including environmental monitoring and chemical analysis, because of its ability to quickly and accurately detect dangerous CN⁻<em>s</em>. Also, <strong>S-AT</strong> against Gram-positive bacteria (<em>S. aureus</em>) shows a significant result. An attempt has been made to clarify the results of the treatment of <strong>S-AT</strong> with CN⁻ to understand the mechanism in which the sequence of events leads to a change in the color of the reactant. It has been demonstrated computationally that in this case the basicity of CN⁻ is dominant over its nucleophilicity and causes proceeding a new route in which a five atoms 6π electrocyclic ring closure occurs that is followed by extrusion of carbonyl sulfide molecules and finally affords benzofuran-2-carboxamide moiety whose presence is compatible with the experimental FT-IR, UV–Vis spectra, and ¹H NMR. The effectiveness of some related proposed structures for treating Cancer and Alzheimer’s disease were explored through docking studies, and significant results were obtained.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1351 ","pages":"Article 144289"},"PeriodicalIF":4.7,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145270894","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}

{"title":"Engineered for impact: Multifunctional Co(II), Ni(II), Cu(II), and Cd(II) complexes of 2-aminobenzothiazole with potent antitumor, antibacterial, and antioxidant actions supported by theoretical approaches","authors":"Nasser Farhan ,&nbsp;Rehab S. Abo-Rehab ,&nbsp;Mohamed R. Shehata ,&nbsp;Ahmed M. Abu-Dief ,&nbsp;RA El-Kasaby ,&nbsp;Maher Fathalla ,&nbsp;Samar A. Aly ,&nbsp;Ensaf Aboul Kasim ,&nbsp;Ehab M. Abdalla","doi":"10.1016/j.molstruc.2025.144295","DOIUrl":"10.1016/j.molstruc.2025.144295","url":null,"abstract":"<div><div>We synthesized and analyzed four novel Co(II), Ni(II), Cu(II), and Cd(II) complexes utilizing a Schiff base ligand (L) derived from 4‑chloro-2-oxo-2H-chromene-3-carbaldehyde and 2-Aminobenzothiazole. Herein, the structural compositions of these compounds were elucidated through analytical and spectroscopic techniques, including IR, ^1HNMR , ^13CNMR , mass spectrometry, electronic spectra, PXRD, and thermal analysis. Based on physical and chemical, and theoretical studies, the general formula [ML(H₂O)Cl₂]<strong>·</strong>2H₂O was proposed, molecular modeling confirms that the complexes have an octahedral geometry. PXRD analysis demonstrated that the crystallite size of the synthesized compounds ranged between 20.97 and 49.56 nm. The complexes' biological activities were measured for their antibacterial, antitumor, and antioxidant properties utilizing cisplatin, ampicillin, gentamicin, and ascorbic acid as reference standards. The activity followed the sequence: [CuL(H₂O)Cl₂]<strong>·</strong>2H₂O&gt;[NiL(H₂O)Cl₂]<strong>·</strong>2H₂O&gt;[CoL(H₂O)Cl₂]<strong>·</strong>2H₂O&gt;[CdL(H₂O)Cl₂]<strong>·</strong>2H₂O&gt;L. Molecular docking studies, conducted using MOA2022 software, assessed the binding potential of these complexes by the active sites of <em>Bacillus subtilis</em> receptor (PDB ID: 5E6K) and methionine adenosyl-transferases in liver tumor (PDB ID: 5A19), breast cancer MCF-7 human (PDB ID: 4zvm). The binding strength correlated with increasingly negative binding energy, following the trend: L˂[CdL(H₂O)<em>Cl₂</em>]˂[CoL(H₂O)<em>Cl₂</em>]˂[NiL(H₂O)<em>Cl₂</em>]˂ [CuL(H₂O)<em>Cl₂</em>], suggesting that the Cu(II) complex exhibited the highest binding affinity and potential biological activity.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1351 ","pages":"Article 144295"},"PeriodicalIF":4.7,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145270615","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}

{"title":"Development and optimization of avanafil cocrystals: in silico molecular docking approach for enhanced aqueous solubility and dissolution rate","authors":"Suhas Shivaji Siddheshwar,&nbsp;Mr. Ankur Machhindra Jadhav,&nbsp;Someshwar Dattatraya Mankar,&nbsp;Arti Changdev Ghorpade,&nbsp;Pratibha Bhalerao","doi":"10.1016/j.molstruc.2025.144281","DOIUrl":"10.1016/j.molstruc.2025.144281","url":null,"abstract":"<div><h3>Background</h3><div>Avanafil, a second-generation phosphodiesterase type-5 inhibitor, demonstrates poor aqueous solubility (0.058 mg/mL) resulting in variable bioavailability and suboptimal therapeutic outcomes in erectile dysfunction treatment. The limited dissolution rate significantly impacts drug absorption and clinical efficacy.</div></div><div><h3>Objective</h3><div>To develop and optimize avanafil-nicotinamide cocrystals using systematic molecular docking approach for enhanced aqueous solubility and dissolution performance, addressing critical biopharmaceutical limitations.</div></div><div><h3>Methods</h3><div>Computational screening evaluated potential coformers through binding energy analysis using validated molecular docking protocols. Cocrystals were prepared via solvent evaporation method and optimized using three-factor factorial design. Comprehensive characterization employed differential scanning calorimetry, Fourier-transform infrared spectroscopy, powder X-ray diffraction, and dissolution studies. Optimized formulations were developed into immediate-release tablets and evaluated for pharmacokinetic performance in animal studies.</div></div><div><h3>Results</h3><div>Molecular docking successfully identified nicotinamide as optimal coformer with strongest binding energy and extensive interaction network. The optimized cocrystal demonstrated significant solubility enhancement with superior dissolution profiles compared to pure drug and marketed formulations. Tablet formulation exhibited accelerated drug absorption, enhanced bioavailability, and improved pharmacokinetic parameters including reduced time to maximum concentration and increased area under curve.</div></div><div><h3>Conclusion</h3><div>Systematic cocrystal engineering approach successfully enhanced avanafil's biopharmaceutical properties through rational molecular design, providing validated methodology for pharmaceutical development.</div></div><div><h3>Future Scope</h3><div>Human bioequivalence trials, GMP manufacturing validation, Zone IV stability studies, and patient acceptability assessments are essential for clinical translation.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1351 ","pages":"Article 144281"},"PeriodicalIF":4.7,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145270897","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}

{"title":"Triterpene derivatives from Diospyros anisandra S. F. Blake against influenza A (H1N1) virus: In vitro and in silico assays","authors":"Mari Toña Juárez-Méndez ,&nbsp;Gloria Jiménez-Alcalá ,&nbsp;Rocío Borges-Argáez ,&nbsp;Ivan Chan-Zapata ,&nbsp;Guadalupe Ayora-Talavera ,&nbsp;Norma A. Caballero ,&nbsp;Francisco J. Melendez ,&nbsp;María Eugenia Castro","doi":"10.1016/j.molstruc.2025.144267","DOIUrl":"10.1016/j.molstruc.2025.144267","url":null,"abstract":"<div><div><em>Diospyros anisandra</em> S. F. Blake (Ebenaceae) is a quasi-endemic species of the Yucatan Peninsula, Mexico, that has shown activity against influenza A viruses. <em>D. anisandra</em> is rich in quinones and terpenes, with over 20 compounds of this type identified in extracts of the species. However, the cytotoxic and antiviral potential of uvaol, taraxerol, and taraxerone have not yet been investigated. This study aimed to determine the cytotoxic and the potential antiviral effects of five triterpenes (taraxerol, taraxerone, uvaol, betulin, and betulinic acid) identified in <em>D. anisandra</em>, as well as three triterpene-rich fractions (D567A7, 3F23, and 4R34). Cytotoxicity was evaluated using Madin-Darby canine kidney (MDCK) cells. To assess the antiviral activity, a cytopathic effect (CPE) reduction assay was performed using the influenza virus A/Yucatan/2370/09 (H1N1) pdm. Betulinic acid was the most cytotoxic compound, with a mean cytotoxic concentration (CC₅₀) of 28.64 μM. The other triterpenes and fractions demonstrated no cytotoxicity. All the triterpene compounds, fraction D567A7 (50 μg/mL), and fraction 4R34 (100 μg/mL) showed a CPE reduction below to 40 %. <em>In silico</em> study was conducted using crystallized viral proteins. All triterpenoids interacted with the key amino acid residues in the active site, albeit to a lesser extent than approved antivirals. This is the first report to evaluate uvaol, taraxerol, and taraxerone in viral assays and molecular docking calculations, contributing to the pharmacological and phytochemical knowledge of <em>D. anisandra</em> and its natural products.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1351 ","pages":"Article 144267"},"PeriodicalIF":4.7,"publicationDate":"2025-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145270896","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}

{"title":"Antidiabetic potential of Mentha piperita essential oil: GC–MS profiling, in vitro, in vivo and in silico analyses","authors":"Elhafnaoui Lanez ,&nbsp;Yahia Bekkar ,&nbsp;Lotfi Bourougaa ,&nbsp;Mohammed Larbi Benamor ,&nbsp;Rania Bouraoui ,&nbsp;Ouafa Boudebia ,&nbsp;Aicha Adaika ,&nbsp;Kaouther Nesba ,&nbsp;Housseyn Chaoua ,&nbsp;Lazhar Bechki ,&nbsp;Touhami Lanez ,&nbsp;Huda Alsaeedi ,&nbsp;Mikhael Bechelany ,&nbsp;Ahmed Barhoum","doi":"10.1016/j.molstruc.2025.144239","DOIUrl":"10.1016/j.molstruc.2025.144239","url":null,"abstract":"<div><div>In this study, <em>Mentha piperita</em> essential oil (EO) antidiabetic activity was thoroughly investigated using a multidisciplinary approach. Gas chromatography–mass spectrometry (GC–MS) identified some key bioactive compounds, including pulegone, α-terpineol, borneol, linalool acetate, menthone, eucalyptol, and trans-sabinene hydrate. Their relative percentages in the EO (&gt;1 % w/w) were indicative of biological importance. In vitro enzyme inhibitory assays displayed strong inhibitory effects of the EO on the carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase and stronger inhibitory action than the standard antidiabetic compound acarbose. In vivo research in diabetic rats induced by alloxan monohydrate reaffirmed the hypoglycemic effect of the EO with the lowering of fasting blood glucose level by 33 % after 14 days of treatment. Molecular docking experiments indicated greater binding affinities of pulegone for α-amylase (ΔG = –5.83 kcal·mol⁻¹) and linalool acetate for α-glucosidase (ΔG = –6.95 kcal·mol⁻¹) compared to acarbose (ΔG = –4.51 and –6.09 kcal·mol⁻¹, respectively). Molecular dynamics simulations also validated the structural stability and optimal interaction dynamics of principal EO components with α-amylase and α-glucosidase. Eucalyptol and linalool acetate possessed minimum root-mean-square deviation (RMSD) and solvent-accessible surface area (SASA) against α-amylase, showing high stability of complex, while α-terpineol and eucalyptol exhibited good binding affinity towards α-glucosidase. MM-PBSA binding free energy calculations revealed that linalool acetate and eucalyptol were the best inhibitory agents for α-amylase (–26.98 and –26.45 kcal·mol⁻¹) and α-glucosidase (–20.41 and –20.71 kcal·mol⁻¹), respectively. DFT analysis also yielded more insight into their electronic properties, reactivity, and stability, further establishing their enzyme inhibition activity. These findings introduce <em>M. piperita</em> EO as a natural agent with α-amylase and α-glucosidase inhibition potential for the management of diabetes and glycemia.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1351 ","pages":"Article 144239"},"PeriodicalIF":4.7,"publicationDate":"2025-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145270498","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}

{"title":"Quinazoline-oxadiazole hybrids: Synthesis, SC-XRD, Hirshfeld surface analysis and computational investigations","authors":"Yogeesha N Nayak ,&nbsp;Deepika Dwarakanath ,&nbsp;Keshav Kumar Harish ,&nbsp;Sreedhara Ranganath Pai ,&nbsp;Mahendra Madegowda ,&nbsp;Santosh L. Gaonkar","doi":"10.1016/j.molstruc.2025.144212","DOIUrl":"10.1016/j.molstruc.2025.144212","url":null,"abstract":"<div><div>A novel series of twelve quinazoline-based oxadiazole hybrids was synthesized via a concise four-step synthetic route and comprehensively characterized by FTIR, ¹H NMR, ¹³C NMR, and high-resolution mass spectrometry. Single crystal-XRD results confirmed that the para-fluoro-substituted derivative adopts a monoclinic crystal system and is assigned to the <em>P2₁/c</em> space group. The molecular structure featured a nearly coplanar arrangement of the oxadiazole and quinazoline rings, with a dihedral angle of 1.5°, while the fluorophenyl–oxadiazole linkage displayed a dihedral angle of 12.8°, suggesting slight torsional deviation. Hirshfeld surface analysis indicated that intermolecular contacts such as H···F (26.3 %), H···N (8.7 %), H···O (7.3 %), and π···π stacking interactions play a key role in molecular packing and lattice stability.</div><div>Molecular docking studies were conducted to evaluate the interaction of the synthesized hybrids with histone deacetylase 7 (HDAC7), an epigenetic target implicated in oncogenesis. The docking analysis revealed favorable binding within the HDAC7 active site. Furthermore, a 100 ns molecular dynamics simulation revealed that the HDAC7–ligand complex maintained structural integrity, exhibited minimal RMSD deviations, and preserved key interactions throughout the simulation. ADME predictions using the QikProp module suggested favorable pharmacokinetic properties and drug-likeness. Collectively, the results offer comprehensive structural and computational insights into quinazoline–oxadiazole hybrids, providing a foundation for future biological evaluation.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1351 ","pages":"Article 144212"},"PeriodicalIF":4.7,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145270039","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}

{"title":"Theoretical and experimental investigation of a nimesulide-alginate hybrid composite: Physicochemical characterization, cytotoxicity and release profile","authors":"Ellen K.S. Pinho ,&nbsp;Jéssica A. Rodrigues ,&nbsp;Luiz F.L. Silva ,&nbsp;Adauto L. Cardoso ,&nbsp;Luís A. Santos do Nascimento ,&nbsp;João B.M. Godinho ,&nbsp;Ana C.S. Alcântara ,&nbsp;Adenilson O. Santos ,&nbsp;Waldomiro Paschoal Jr ,&nbsp;Renata C.R. Noronha ,&nbsp;Eliana B. Souto ,&nbsp;Francisco F. Sousa","doi":"10.1016/j.molstruc.2025.144261","DOIUrl":"10.1016/j.molstruc.2025.144261","url":null,"abstract":"<div><div>Nimesulide (NIM) is a selective COX-2 inhibitor non-steroidal anti-inflammatory drug (NSAID), generally administered orally, with a distinctive pharmacological profile, that may still lead to some gastrointestinal adverse effects. Its combination with natural polysaccharides to develop modified-release delivery systems has become a technological strategy to reduce the adverse effects. In this work, we propose the development and characterization of a hybrid composite based on sodium alginate (NaCHO), nimesulide (C₁₃H₁₂N₂O₅S), and calcium chloride (CaCl₂). The synthesized hybrid composite – NaCHO-NIM-CaCl₂ – was developed by adapting methods of calcium-induced ionotropic gelation, sonication, and solvent evaporation. The obtained hybrid was characterized in terms of its physicochemical properties using X-ray powder diffraction (XRPD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), Raman spectroscopy, and Fourier-transform infrared (FT-IR) spectroscopy. Theoretical studies of the vibrational properties of NIM, NIM-CaCl₂ and the hybrid NaCHO-NIM-CaCl₂ were performed using density functional theory (DFT) for the first time. Electronic properties of the NIM crystal were elucidated, revealing that it is a semiconductor compound. For proof of concept, cell viability assay and <em>in vitro</em> release tests were performed to evaluate the potential biological application of NaCHO-NIM-CaCl₂.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1351 ","pages":"Article 144261"},"PeriodicalIF":4.7,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145270257","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}

{"title":"Design and multifunctional characterization of bis[4-carbomethoxypyridinium] hexabromostannate(IV): A new organic–inorganic hybrid for nonlinear optical and dielectric applications","authors":"E.Sh. Samandarov ,&nbsp;Hela Ferjani ,&nbsp;Yasmeen G. Abou El-Reash ,&nbsp;Tarek A. Yousef ,&nbsp;L. Guganathan ,&nbsp;Sabokhat Sadikova ,&nbsp;Y.Y. Yakubov ,&nbsp;P.K. Kodamboev ,&nbsp;Lutfulla Bozorov ,&nbsp;A.B. Ibragimov ,&nbsp;C. Balakrishnan","doi":"10.1016/j.molstruc.2025.144260","DOIUrl":"10.1016/j.molstruc.2025.144260","url":null,"abstract":"<div><div>A new organic–inorganic hybrid, bis[4-carbomethoxypyridinium] hexabromostannate(IV) (4CPHBS), was synthesized and structurally characterized. Single-crystal X-ray diffraction revealed that the compound crystallizes in the monoclinic system (space group P2₁/<em>n</em>) with nearly ideal octahedral [SnBr₆]^2- anions stabilized by extensive hydrogen-bonding and π–π stacking interactions with organic cations. Hirshfeld surface analysis confirmed dominant Br···H contacts along with significant H···O and π–π interactions, highlighting the role of supramolecular forces in crystal stabilization. Vibrational spectra (FT-IR and Raman) identified characteristic modes of the pyridinium, carbomethoxy, and hexabromostannate groups. NMR studies supported protonation of the pyridinium ring, while optical measurements revealed a direct band gap of 3.17 eV and a sharp photoluminescence emission at 491 nm. Thermal analysis indicated stability up to ∼160 °C, and SEM–EDS/XRF/XPS confirmed phase purity and composition. Nonlinear optical (Z-scan) studies demonstrated reverse saturable absorption and self-defocusing with χ⁽³⁾=7.23×10^–11 esu, while dielectric and AC conductivity measurements exhibited strong frequency and temperature dependence. These multifunctional features highlight 4CPHBS as a promising candidate for optoelectronic and dielectric applications.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1351 ","pages":"Article 144260"},"PeriodicalIF":4.7,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145271219","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}

{"title":"Development of Pyrimidine-2,4-Dichlorophenyl Conjugates as Xanthine Oxidase Antagonists for Gout Therapy: Computational and Experimental Study","authors":"Islam Ragab ,&nbsp;Omar A. El-Khouly ,&nbsp;Rehab S. Abo-Rehab ,&nbsp;Heba H.S. Abdel-Naeem ,&nbsp;Samira M. Abozeid ,&nbsp;Ammar AL-Farga ,&nbsp;Esraa M.M. Mohammad ,&nbsp;Amany M. Hamed","doi":"10.1016/j.molstruc.2025.144263","DOIUrl":"10.1016/j.molstruc.2025.144263","url":null,"abstract":"<div><div>A novel group of pyrimidine-based hybrids containing a 2,4-dichlorophenyl core was designed, synthesized, and evaluated as potential xanthine oxidase (XO) inhibitors for treating gouty arthritis. Through established medicinal chemistry synthetic methods, these compounds were successfully prepared and their structures confirmed using detailed spectroscopic analyses, including high-resolution mass spectrometry (HRMS), Fourier-transform infrared (FT-IR), and multinuclear NMR (¹H and ¹³C). In vitro screening, nine candidates (<strong>2, 3, 9, 10, 11a, 11d, 11e, 12a</strong>, and <strong>12b</strong>) assessed their XO inhibitory activity, ability to prevent protein denaturation, and capability to stabilize erythrocyte membranes. Notably, compound <strong>12b</strong> emerged as the most promising agent, displaying superior XO inhibition (IC₅₀ = 2.8 μM), effective protein denaturation suppression (89.4% at 100 μg/mL), and significant reduction in hemolysis (92.1% efficacy), surpassing standard drugs like allopurinol and diclofenac. Molecular docking simulations indicated strong binding between the compounds and the XO active site, with <strong>12b</strong> showing optimal interactions through hydrogen bonding and hydrophobic contacts. These computational results were consistent with experimental outcomes, suggesting a mechanism of competitive inhibition. The overall findings highlight the therapeutic potential of <strong>12b</strong> as a leading candidate for gout management, providing a foundation for further optimization in developing advanced XO inhibitors with improved efficacy and selectivity.</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1351 ","pages":"Article 144263"},"PeriodicalIF":4.7,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145270511","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}

{"title":"Infrared and Raman spectra, conformational stability, normal coordinate analysis, barriers to internal rotations and novel DFT calculations of alicyclic 1,1-Dimethyl-1-silacyclobutane","authors":"Tarek A. Mohamed ,&nbsp;Gamil A. Guirgis ,&nbsp;James R. Durig","doi":"10.1016/j.molstruc.2025.144254","DOIUrl":"10.1016/j.molstruc.2025.144254","url":null,"abstract":"<div><div>The mid-infrared spectra (3500-400 cm^-1) of gaseous and solid 1,1-Dimethyl-1-silacyclobutane (DMSCB) have been reported. Additionally, the Raman spectra (3500-10 cm^-1) of the gas, liquid and solid phases have been recorded. Moreover, we have carried out quantum chemical (QC) calculations for (CH₂)₃Si(CH₃)₂ molecule (DMSCB) obeying C_2v/C_s point group, respectively. Initially the structures are optimized followed by frequency calculations with RHF, B3LYP and MP2 methods using 6-31G(d) and 6-31++G(d,p) basis sets. Preliminary computations favor the puckered ring conformation (C_s) by 823-1336 cm⁻¹ (2.352-3.820 kcal/mol) but an imaginary torsional frequency was obtained for configuration that obeys C_2v point group, therefore most likely excluded. The optimized structural parameters (SPs) of the puckered conformer are well correlated to those obtained from electron diffraction techniques. Aided by MP2 potential surface scans (PSS) based on the optimized structural parameters (SPs), single-point energies at 6-31++G(d,p) basis set, the (CH₃)ₐₓ/(CH₃)ₑ_q three-fold barriers of 544/506 cm⁻¹ (1.56/1.45 kcal.mol⁻¹) were estimated compared to 460/431 cm⁻¹ (1.32/1.23 kcal.mol⁻¹), employing B3LYP method. The observed infrared (IR) and Raman (R) spectra are compared with the simulated IR and Raman spectra using the estimated infrared intensities and the Raman activities, respectively from the above-mentioned methodsy. Nevertheless, frequencies were also estimated for, (CD₂)₃Si(CH₃)₂-d₆ and (CH₂)₃Si(CD₃)₂-d₆ to confirm our interpretations based on blue shifts of methylene and methyl fundamentals upon deuteration, respectively. Consequently, we have proposed a new spectral analysis for DMSCB based on C_S symmetry, which is supported by NCA, unscaled force constants (FCs) in internal coordinates and potential energy distributions (PEDs).</div></div>","PeriodicalId":16414,"journal":{"name":"Journal of Molecular Structure","volume":"1351 ","pages":"Article 144254"},"PeriodicalIF":4.7,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145270043","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}