Journal of Molecular Modeling最新文献

{"title":"DFT and machine learning–assisted investigation of transition metal–doped γ-graphyne for DNA rare base sensing","authors":"Wenjin Miao,&nbsp;Yunhan Gao,&nbsp;YiHan Liu,&nbsp;Ruiying Zhang,&nbsp;Xia Zeng,&nbsp;Yiyao Ma,&nbsp;Jingyi Zhang,&nbsp;Xiaohui Ji,&nbsp;Jiufu Lu,&nbsp;Lingxia Jin","doi":"10.1007/s00894-026-06997-w","DOIUrl":"10.1007/s00894-026-06997-w","url":null,"abstract":"<div><h3>Background</h3><p>The development of high-performance biosensor materials for the selective detection of rare DNA bases is of great significance. Transition metal doping provides an effective strategy for regulating the electronic properties and adsorption behavior of two-dimensional carbon-based materials. However, the influence of different transition metals on the adsorption selectivity of rare DNA bases remains unclear.</p><h3>Methods</h3><p>In this study, the adsorption behavior of five rare DNA bases, including cytosine (Cyt), 5-methylcytosine (5meCyt), 5-carboxylcytosine (5caCyt), 5-formylcytosine (5fCyt), and 5-hydroxymethylcytosine (5hmCyt), on transition metal-doped γ-graphyne (TM-GY) surfaces was systematically investigated using first-principles calculations. Nine transition metals (Cr, Mn, Fe, Co, Ni, Cu, Zn, Ir, and Au) were considered, generating 45 nucleobase/TM-GY configurations. The calculated adsorption energies were further employed as a small dataset for machine learning analysis, where five regression algorithms were evaluated to identify the optimal predictive model.</p><h3>Results</h3><p>The machine learning models provided a complementary data-driven analysis rather than replacing density functional theory calculations or serving as a general-purpose prediction framework. The adsorption structures were optimized to elucidate the regulatory effect of transition metal doping on biosensing performance. Among the investigated systems, Cu-doped γ-graphyne exhibited relatively weak interactions with all five DNA bases, whereas Cr-doped γ-graphyne demonstrated the strongest adsorption capability toward Cyt and the weakest interaction with 5caCyt, indicating significant adsorption selectivity. Both Cu-GY and Cr-GY systems showed weak sensing responses toward 5fCyt.</p><h3>Conclusions</h3><p>This study reveals the regulatory mechanism of transition metal doping on the adsorption behavior of rare DNA bases and establishes a reliable adsorption energy prediction model based on machine learning. These findings provide theoretical insights into the rational design of high-performance γ-graphyne-based biosensor materials.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"32 11","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149132839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electronic, mechanical, vibrational, and thermodynamic properties of 5,5′-bis(1,4-dinitro-1H-pyrazol-3-yl)-2,2′-bi(1,3,4-oxadiazole) based on first‑principles calculations","authors":"Min Zhu,&nbsp;Xuan Zhang,&nbsp;Dai-He Fan,&nbsp;Zheng-Tang Liu","doi":"10.1007/s00894-026-06984-1","DOIUrl":"10.1007/s00894-026-06984-1","url":null,"abstract":"<div><h3>Context</h3><p>5,5′-Bis(1,4-dinitro-1H-pyrazol-3-yl)-2,2′-bi(1,3,4-oxadiazole) (C₁₀H₂N₁₂O₁₀) is a bis-heterocyclic compound that combines pyrazole, 1,3,4-oxadiazole, and nitro groups within a single framework. This combination offers a trade-off between high energy density and safety, a key objective in energetic materials research. Using first-principles density functional theory, we investigate the structural, electronic, mechanical, and vibrational properties of this compound. The results reveal that C₁₀H₂N₁₂O₁₀ is structurally stable, intrinsically ductile, and dynamically stable. We also clarify its electronic structure and chemical bonding characteristics, and assign the main vibrational modes. Together, these findings help establish structure-property relationships for this material and provide a theoretical basis for its potential use in high-performance energetic systems.</p><h3>Methods</h3><p>First-principles DFT calculations were carried out using the CASTEP code. The exchange-correlation potential was treated with the PBE functional within the GGA, and van der Waals interactions were incorporated using Grimme’s DFT-D3 scheme. Norm-conserving pseudopotentials generated according to the Hamann scheme were employed to describe core-valence electron interactions. A plane-wave basis set with a kinetic energy cutoff of 830 eV was used, and Brillouin zone sampling was performed with a 1 × 2 × 1 Monkhorst–Pack <i>k</i>-point grid.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"32 11","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149133058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First-principles study on the regulation of vacancy defects in two-dimensional MoSi2N4 as an anode material for potassium-ion batteries","authors":"Hua Wu,&nbsp;Hongyang Zhang,&nbsp;Yujie Zhao,&nbsp;Wenqi Shi,&nbsp;Shufan Yang,&nbsp;Chenyu Yang,&nbsp;Junqing Wen,&nbsp;Wanlin He","doi":"10.1007/s00894-026-06993-0","DOIUrl":"10.1007/s00894-026-06993-0","url":null,"abstract":"<div><h3>Context</h3><p>In this paper, the adsorption properties of K atoms on the surface of two-dimensional MoSi₂N₄ were investigated via density functional theory. It was found that the adsorption energies of K atom at the Mo-top, N-top and Si-top sites of pristine MoSi₂N₄ were − 0.03 eV, − 0.05 eV and − 0.08 eV, respectively. The diffusion barrier of K atom on the MoSi₂N₄ surface was calculated to be only 0.052 eV, indicating the excellent diffusion ability of K atom on MoSi₂N₄. With the increasing of adsorbed K atoms, stable adsorption of K atoms on the MoSi₂N₄ surface was no longer achievable. By introducing Si-vacancy defects, the adsorption energy of K atoms at the most favourable adsorption site on the MoSi₂N₄ surface reached − 3.92 eV. Compared with pristine MoSi₂N₄, the adsorption strength was enhanced by approximately 50 times. Meanwhile, the number of stably adsorbed K atoms increased from 1 to 6. Accordingly, a maximum theoretical K storage capacity of 773 mAh/g and an open-circuit voltage of 1.66 V were obtained. Moreover, the diffusion barrier of K atom on the V_Si-MoSi₂N₄ surface was calculated to be 0.053 eV. The modified two-dimensional MoSi₂N₄ combined excellent K atom transport capability with moderate adsorption strength, demonstrating its potential application as an anode material for potassium-ion batteries.</p><h3>Methods</h3><p>First-principles calculations based on density functional theory were performed to investigate the effects of vacancy defects on the potassium-storage properties of two-dimensional MoSi₂N₄. All calculations were performed using the Vienna ab initio Simulation Package. The generalized gradient approximation with the Perdew–Burke–Ernzerhof exchange–correlation functional was adopted for structural relaxation and energy calculation. The Heyd–Scuseria–Ernzerhof hybrid functional was utilized to calculate electronic band structures and acquire accurate band gap values. The projector augmented-wave method was employed to describe core–valence electronic interactions, and the DFT-D3(BJ) approach was used to account for van der Waals interactions. The CI-NEB method and AIMD simulations were separately adopted to evaluate the diffusion kinetics and thermal stability of the material system.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"32 11","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149132907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Young’s modulus from terahertz spectroscopy and first-principles calculations as an effective indicator of impact sensitivity for molecular perovskite energetic materials","authors":"Bingshuang Fan,&nbsp;Jiang Li,&nbsp;Qiangqiang Liu,&nbsp;Yonggang Liu,&nbsp;Qiao Liu,&nbsp;Tengxiao Guo,&nbsp;Jianbo Hu,&nbsp;Hang Zhang,&nbsp;Yunfan Yang,&nbsp;Wei Xiang,&nbsp;Qi Xiao,&nbsp;Huifen Zhang","doi":"10.1007/s00894-026-06980-5","DOIUrl":"10.1007/s00894-026-06980-5","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Context&lt;/h3&gt;&lt;p&gt;Impact sensitivity (IS) is a key indicator affecting the safety of energetic materials. Both lattice stability and elastic response are closely related to the IS of energetic materials. However, the microscopic mechanisms by which these two factors regulate sensitivity in molecular perovskite energetic materials remain unclear. In this study, molecular perovskite energetic materials (H&lt;sub&gt;2&lt;/sub&gt;dabco)[M(ClO&lt;sub&gt;4&lt;/sub&gt;)&lt;sub&gt;3&lt;/sub&gt;] (DAPs, dabco = 1,4-diazabicyclo[2.2.2]octane, M = Na&lt;sup&gt;+&lt;/sup&gt;, K&lt;sup&gt;+&lt;/sup&gt;, NH&lt;sub&gt;4&lt;/sub&gt;&lt;sup&gt;+&lt;/sup&gt;, and NH&lt;sub&gt;2&lt;/sub&gt;NH&lt;sub&gt;3&lt;/sub&gt;&lt;sup&gt;+&lt;/sup&gt; for DAP-1, DAP-2, DAP-4, and DAP-7, respectively) were investigated. By combining terahertz time-domain spectroscopy (THz-TDS), first-principles calculations, Hirshfeld surface (HS) analysis, and quantum theory of atoms in molecules (QTAIM), we systematically explored the correlations among Young’s modulus (reflecting elastic response), hydrogen bond (indicating lattice stability), and IS. The results indicate that the variation in hydrogen bond content does not follow the trends typically observed in conventional energetic materials. Assessing sensitivity based on hydrogen bond strength also has limitations. Moreover, Young’s modulus derived from low-frequency terahertz vibrations exhibits a negative correlation with experimental IS. First-principles calculations reveal that the relevant vibrational modes primarily arise from lattice vibrations, whose force constants directly determine the elastic response characteristics of the materials. Although local hydrogen bond also exert an influence on the IS, it remains difficult to evaluate the sensitivity based on any single characteristic of the hydrogen bond. Therefore, the regulation of IS in DAPs may be influenced by low-frequency lattice vibrations, which modulate mechanical energy transfer and dissipation processes. Lower force constants and Young’s modulus correspond to more deformable lattice potential energy surfaces and greater mechanical energy dissipation efficiency, thereby more effectively suppressing the reaction initiation processes induced by energy localization. This study proposes a new method and approach for evaluating the IS of energetic materials using terahertz spectroscopy. Furthermore, we propose new perspectives and criteria for molecular design based on lattice dynamical properties.&lt;/p&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;First-principles calculations of DAPs were performed using the CP2K software package. The PBE functional was selected, along with the pob-TZVP-rev2 basis set and DFT-D3 dispersion corrections, to perform structural optimization, vibrational analysis, and stress–strain curve calculations. The HS analysis and QTAIM were utilized to quantitatively analyze the hydrogen bond content and strength of each material. Vibrational mode analysis was performed under the harmonic approximation, and Multiwfn program was employed to broaden the calculated vibrational frequencies usin","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"32 11","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149098558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantum mechanical and molecular dynamics insights into the binding mechanism of tubulin-stabilizing agents at the taxol site of β-tubulin","authors":"Yonatan Dillu,&nbsp;Shatrughan Yadav,&nbsp;Ramachandran Vinayagam,&nbsp;Umesh Yadava","doi":"10.1007/s00894-026-06982-3","DOIUrl":"10.1007/s00894-026-06982-3","url":null,"abstract":"<div><h3>Context</h3><p>Microtubules, composed of α- and β-tubulin heterodimers, play a crucial role in cell division and are well-established targets for anticancer drugs known as tubulin-binding agents (TBAs). Targeting the Taxol-binding site of β-tubulin has been particularly effective in disrupting microtubule dynamics and inhibiting cancer cell proliferation. In this study, selected TBAs were evaluated to identify potential candidates capable of stabilizing microtubules through interactions at this binding site.</p><h3>Methods</h3><p>An integrated computational strategy combining molecular docking, density functional theory (DFT), and molecular dynamics (MD) simulations was employed to investigate the binding characteristics of TBAs. Initially, 97 compounds were screened using a stringent molecular docking approach. Based on binding affinity and interaction analysis, four compounds (TBA79, TBA80, TBA81, and TBA41) were identified as promising candidates. Interaction profiling assessed hydrogen bonding and hydrophobic interactions with key residues. MD simulations (500 ns each) were conducted to evaluate the stability of the protein–ligand complexes. Furthermore, MMGBSA binding free energy calculations and DFT analyses were performed to examine binding stability, reactivity, and charge transfer properties of the selected compounds.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"32 11","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149098559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atomistic insight into the combustion mechanisms of Al-coated CL-20-based energetic cocrystals using reactive molecular dynamics simulations","authors":"Changxin Li,&nbsp;Yonghua Yu,&nbsp;Yu Qiu,&nbsp;Jincheng Ji,&nbsp;Yumin Da","doi":"10.1007/s00894-026-06976-1","DOIUrl":"10.1007/s00894-026-06976-1","url":null,"abstract":"<div><h3>Context</h3><p>This work focuses on hexanitrohexaazaisowurtzitane (CL-20)/2,4,6-trinitrotoluene (TNT) and CL-20/benzotrifuroxan (BTF) cocrystals, and aluminum (Al)-coated energetic composites with the core–shell structure were constructed. Reactive molecular dynamics (RMD) simulations were used to study combustion process of Al-coated CL-20-based cocrystal nanoparticles (CL-20/TNT@Al and CL-20/BTF@Al) in O₂ atmosphere, and the effects of Al on the combustion mechanism of CL-20-based cocrystal explosives are analyzed. The findings reveal that these systems undergo volume expansion during the reaction, and the reactions of Al-coated CL-20-based cocrystals initiate earlier than that of pure cocrystal systems. This is attributed to the Al shell could promote internal temperature rise and maintain the energetic state of the explosive molecules, facilitating easier reactions. The variation trends in product quantities during combustion indicate that the Al shell not only alters the initiation time of the combustion reaction but also participates in the combustion process, rapidly consuming reactive nitrogen–oxygen intermediates and promoting the formation of stable small molecular products. Moreover, the differences in CL-20-based cocrystal components lead to varying effects of Al on atomic diffusion, either promotes or inhibits it. Cluster analysis reveals that Al_mO_n clusters generated during the combustion of Al-coated CL-20-based cocrystal explosives exhibit spherical-like three-dimensional structures, while AlₘCₙ clusters adopt two-dimensional network configurations. This study provides a theoretical foundation for understanding the combustion mechanisms of energetic composites.</p><h3>Methods</h3><p>All RMD simulations were conducted using the ReaxFF implemented in LAMMPS, and the resulting configurations were visualized via the Ovito package. The time step was 0.1 fs, and the total simulation time was 300 ps. Temperature was controlled by the Nosé–Hoover thermostat, and Newton’s equations of motion were integrated using velocity-verlet algorithm.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"32 11","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149098562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular dynamics study on surface adsorption of hexyl trimethylammonium bromide, octyl trimethylammonium bromide, sodium hexyl sulfate, and sodium heptyl sulfate","authors":"Wenyan Zhang,&nbsp;Hao Yan,&nbsp;Shuyan Liu,&nbsp;Zongde Chen,&nbsp;Feiwu Chen,&nbsp;Chengwen Chai","doi":"10.1007/s00894-026-06977-0","DOIUrl":"10.1007/s00894-026-06977-0","url":null,"abstract":"<div><h3>Context</h3><p>Molecular dynamics simulations were performed on four surfactants (hexyl trimethylammonium bromide, octyl trimethylammonium bromide, sodium hexyl sulfate, and sodium heptyl sulfate) to investigate their surface adsorption behavior in aqueous solution. In this work of simulations, surfactant molecules were initially distributed in both the surface and bulk regions of the solution, enabling them to form micelles spontaneously within the aqueous solution. The results show that the solute surface concentration and bulk concentration for both cationic surfactants (hexyl trimethylammonium bromide and octyl trimethylammonium bromide) and anionic surfactants (sodium hexyl sulfate and sodium heptyl sulfate) can be accurately described by a Padé approximant, which is consistent with the results of our liquid surface adsorption theory. The type of hydrophilic head groups and the length of hydrophobic tail groups affect the speed of surface adsorption. Molecular dynamics simulation demonstrated that the thickness of the surface layer in surfactant solution increases as the temperature and concentration increase. This is due to the weak intermolecular interaction between solvent molecules.</p><h3>Method</h3><p>Molecular dynamics simulations were carried out in the NVT ensemble using the GROMACS software package. The interaction potential was chosen to be the Lennard–Jones 12–6 model, with long-range electrostatic interactions treated using the Particle Mesh Ewald (PME) method. A cutoff distance of 1.0 nm was taken for both non-bonded and electrostatic interactions. The V-rescale thermostat was used to realize a thermal equilibrium state at 298.15 K. The time steps were all taken as 2 fs. A typical total simulation time was 35 ns, of which the initial period was used to bring the system to equilibrium, and the remaining steps were used to dump the trajectories for subsequent analysis via VMD.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"32 11","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149098561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep learning-guided high-throughput screening and molecular dynamics simulations facilitate the discovery of potential FXIIa inhibitors","authors":"Fengze Cai,&nbsp;Wanjun Chen,&nbsp;Song Xie,&nbsp;Juhong Wu,&nbsp;Yongqi Zhang,&nbsp;Ping Gao,&nbsp;Han Zhang,&nbsp;Jinyu Li","doi":"10.1007/s00894-026-06981-4","DOIUrl":"10.1007/s00894-026-06981-4","url":null,"abstract":"<div><h3>Context</h3><p>Pathological thrombosis is a major cause of cardiovascular and cerebrovascular diseases. Current anticoagulants increase bleeding risk by impairing physiological hemostasis. Because coagulation factor XIIa (FXIIa) drives pathological thrombosis but is dispensable for normal hemostasis, inhibiting FXIIa may offer antithrombotic efficacy with reduced bleeding risk. However, the marked flexibility of its active site hampers the discovery of small-molecule inhibitors. Here, we developed an integrated computational workflow to address this challenge and screened a library of approximately 21 million compounds. Four structurally distinct hits (DR1-DR4) were identified. Microsecond-scale molecular dynamics simulations suggested stable binding of all four compounds to FXIIa, and binding free energy calculations suggested that DR1 and DR3 exhibited more favorable binding free energies than the reference inhibitor 1303. These compounds also showed favorable predicted pharmacokinetic properties, providing structurally distinct hits for FXIIa-targeted anticoagulant discovery.</p><h3>Methods</h3><p>The crystal structure of the FXIIa catalytic domain (PDB ID: 6B74) was prepared in PyMOL 3.1, and missing regions were modeled with MODELLER. To capture active-site flexibility, apo-FXIIa was subjected to three independent 1-µs molecular dynamics simulations, and a representative conformation selected by clustering was used for virtual screening. A hierarchical screening workflow was carried out in DrugFlow using KarmaDock for primary screening, CarsiDock for redocking, and RTMScore for rescoring. Drug-likeness and pharmacokinetic properties were predicted with SwissADME. Selected complexes were simulated in Amber18 using ff19SB for the protein, GAFF2 for ligands, OPC water, and AM1-BCC ligand charges, and trajectories were analyzed with CPPTRAJ in AmberTools. Binding free energies were estimated with MMPBSA.py using the MM/GBSA method, with entropy contributions evaluated by normal mode analysis. Structural visualization was performed with PyMOL and Discovery Studio Visualizer 2016.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"32 11","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149098462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic origin of halogen-dependent reactivity in metal-free C–3 halogenation of pyridine N-oxides: a DFT study","authors":"Zoramthara Khiangte,&nbsp;Zodinpuia Pachuau,&nbsp;B. Moiphen Phom,&nbsp;Lalhriatpuia Kawlni,&nbsp;Lalhruaitluangi Vanchhawng,&nbsp;Mary Lalmuankimi","doi":"10.1007/s00894-026-06970-7","DOIUrl":"10.1007/s00894-026-06970-7","url":null,"abstract":"<div><h3>Context</h3><p>Metal-free halogenation of pyridine N-oxides represents an important strategy for the functionalization of heteroaromatic compounds; however, the mechanistic origin of halogen-dependent reactivity remains incompletely understood. In this study, density functional theory calculations were employed to investigate the C–3 halogenation of pyridine N-oxide using N-fluorosuccinimide (NFSu), N-chlorosuccinimide (NCS), and N-bromosuccinimide (NBS). The computed free-energy profiles support a common stepwise ionic mechanism involving <span>(sigma )</span>-complex intermediates and two transition states. Solvent effects significantly influence the reaction energetics and alter the rate-determining step across the halogen series. In the gas phase, the calculated activation barriers follow the order <span>(textrm{F}&gt; textrm{Cl} &gt; textrm{Br})</span>, whereas the solution-phase rate-determining barriers follow the order <span>(textrm{Cl}&gt; textrm{F} &gt; textrm{Br})</span> with activation free energies of 59.94, 51.27, and 42.13 kcal mol<span>(^{-1})</span>, respectively. This difference highlights the significant influence of differential solvation on the relative stabilization of the transition states. Frontier molecular orbital, conceptual DFT, and natural bond orbital analyses further indicate that variations in N–X bond cleavage, halogen-dependent electronic interactions, and stabilization within the pyridine N-oxide framework contribute to the observed energetic differences.</p><h3>Methods</h3><p>All calculations were performed using density functional theory as implemented in Gaussian 16. Geometry optimizations, frequency calculations, and intrinsic reaction coordinate analyses were carried out at the B3LYP/6-31+G(d,p) level of theory. Solvent effects were included using the SMD implicit solvation model with acetonitrile as the solvent. Frontier molecular orbital analysis, global reactivity descriptor calculations, and natural bond orbital analysis were performed to investigate electronic structure, donor–acceptor interactions, and the mechanistic origin of halogen-dependent reactivity.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"32 11","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149098268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Theoretical insights into two types of Se···N Chalcogen Bonds between phenylselenium halides (PhSeX, X = F, Cl, Br, I) and pyridine: perpendicular versus linear binding modes via tunable σ-holes","authors":"Mengna Huang,&nbsp;Junyong Wu,&nbsp;Hua Yan","doi":"10.1007/s00894-026-06994-z","DOIUrl":"10.1007/s00894-026-06994-z","url":null,"abstract":"<div><h3>Context</h3><p>In this work, the Se···N chalcogen-bonding interactions in pyridine-phenylselenium halides (C₅H₅N-PhSeX, X = F, Cl, Br, and I) complexes were systematically investigated at the ωB97XD/def2-TZVPD theoretical level. Two typical structural configurations, namely perpendicular and linear orientations, were identified for all studied complexes. The calculated binding energies suggest that the linear-oriented systems exhibit remarkably stronger intermolecular interactions (− 6 to − 12 kcal/mol) than their perpendicular counterparts (− 2 to − 4 kcal/mol). For the perpendicular-oriented structures dominated by chalcogen-bonding with secondary hydrogen-bonding interactions, the intermolecular interaction strength increases in the order F &gt; I &gt; Br &gt; Cl. In contrast, the interaction strength of linear-oriented chalcogen-bonding complexes follows the sequence of F &gt; Cl &gt; Br &gt; I. Energy component analysis indicates that both electrostatic and dispersion contributions dominate the attractive forces in perpendicular chalcogen-bonded systems. By comparison, the stabilization of linear complexes is predominantly governed by electrostatic interactions.</p><h3>Methods</h3><p>Geometry optimizations of all complexes and the corresponding monomers were carried out at the ωB97XD/def2-TZVPD level. The nature of the intermolecular interactions was then characterized by NBO population analysis, QTAIM (AIM), and IRI analyses.In addition,the interaction energies of the two types of chalcogen-bonded complexes were further decomposed by means of symmetry-adapted perturbation theory (SAPT).</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"32 11","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149098105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}