Journal of Molecular Modeling最新文献

{"title":"Rational design of triphenylamine-based sensitizers for DSSCs: a DFT comparison of pyridine and amine donor substituents","authors":"Damián Delgado-Montiel,&nbsp;Norma Flores-Holguín,&nbsp;Jesús Baldenebro-López,&nbsp;Rody Soto-Rojo,&nbsp;Manuel Luque-Roman,&nbsp;Tomás Delgado-Montiel,&nbsp;Daniel Glossman-Mitnik","doi":"10.1007/s00894-025-06498-2","DOIUrl":"10.1007/s00894-025-06498-2","url":null,"abstract":"<div><h3>Context</h3><p>The rational design of metal-free organic sensitizers is critical for developing cost-effective, high-efficiency dye-sensitized solar cells (DSSCs). This study uses density functional theory (DFT) to explore how modifying the triphenylamine (TPA) donor with pyridine rings or amino groups at ortho-, meta-, and para-positions affects the optoelectronic properties of D-π-A sensitizers. Our calculations show that para-position amino substitution (dye N3) yields the most red-shifted absorption (<span>({lambda }_{max})</span>=523, 50 nm beyond reference dyes), the highest theoretical open-circuit voltage (Voc = 1.77 eV, 0.3 eV higher than others), and enhanced charge transfer efficiency. These findings highlight para-position amines as a promising strategy for optimizing DSSC performance and identify N3 as a prime candidate for synthesis and experimental validation.</p><h3>Methods</h3><p>Ground-state geometries, vibrational frequencies, and frontier molecular orbitals were calculated using the M06 functional with the 6-31G(d) basis set, chosen for its accuracy in organic systems. UV–Vis absorption and excited-state properties were predicted via time-dependent DFT (TD-DFT) with the M06-2X functional, optimized for excited-state accuracy, and the 6-31G(d) basis set. Solvation effects in acetonitrile were modeled using the IEF-PCM polarizable continuum model. Calculations were performed with Gaussian 16.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"31 10","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136182","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 investigation on sensing of dopamine and tyramine neurotransmitters by the B9N9 nanoring","authors":"Ascharya Kumar Kar,&nbsp;Swetapadma Praharaj,&nbsp;Tarun Yadav,&nbsp;Somenath Garai,&nbsp;Dileep Kumar Gupta,&nbsp;Dibyaranjan Rout","doi":"10.1007/s00894-025-06478-6","DOIUrl":"10.1007/s00894-025-06478-6","url":null,"abstract":"<div><h3>Purpose</h3><p>The investigation concerns the first demonstration of employing the B₉N₉ nanoring as an active material for sensing dopamine and tyramine neurotransmitters.</p><h3>Method</h3><p>The calculations for optimization and vibrational frequencies of B₉N₉ ring, dopamine, and tyramine neurotransmitters have been executed by using density functional theory (DFT) available in the Gaussian09 suite. The standard functional (B3LYP) coupled with the basis set 6-311G(d, p) have been adopted for calculations. Natural bond orbital (NBO) analysis quantified charge transfer, while molecular electrostatic potential (MEP) mapping, electron localization function (ELF), reduced density gradient (RDG) analysis, and quantum theory of atoms in molecules (QTAIM) characterized intermolecular interactions.</p><h3>Results</h3><p>The responsiveness of B₉N₉ ring towards the considered neurotransmitters is characterized thoroughly by the optimized electronic structures, energies, electronic, and other properties using density functional theory (B3LYP/6-311G(d, p)). The interaction of dopamine and tyramine governs through formation of the N-B dative bond in the most favorable configurations. The interaction energies for the most stable configurations of dopamine@B₉N₉ and tyramine@B₉N₉ complexes are found to be −22.11 and −21.49 kcal/mol, respectively, which show a significant interaction of neurotransmitters to nanoring and elucidate the adoption of B₉N₉ ring in sensing applications for these neurotransmitters. The critical conventional electronic parameters, viz., HOMO, LUMO, Fermi energy, work function, and energy gap, are also computed, and the effect of an aqueous medium is investigated on these parameters. The ELF and RGD techniques are used to quantify the electron density distribution and explore the involved interactions. TD-DFT calculations are performed to simulate the UV-Vis spectra. Additionally, a quantum theory of atoms in molecules (QTAIM) analysis is conducted, which shows that dopamine@B₉N₉ and tyramine@B₉N₉ exhibit stronger hydrogen bond interactions, resulting in increased bond strengths.</p><h3>Conclusion</h3><p>B₉N₉ nanoring shows significant interaction with both neurotransmitters and results in the change in the electronic properties helping in detection of both neurotransmitters.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"31 10","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136101","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":"Interactions of imidazole with water molecules","authors":"Alhadji Malloum,&nbsp;Jeanet Conradie","doi":"10.1007/s00894-025-06515-4","DOIUrl":"10.1007/s00894-025-06515-4","url":null,"abstract":"<div><h3>Context</h3><p>Understanding the interactions of imidazole and water molecules is essential for several chemical and biological activities. Literature mining shows that investigations of hydrated imidazole are rare. In this work, interactions between imidazole and explicit water molecules are investigated. The structures of the complexes formed by imidazole and water molecules are used to estimate imidazole’s hydration enthalpy and free energy. QTAIM investigation shows that imidazole accepts two strong hydrogen bondings while donating one. In addition, it also interacts with water molecules through weaker bonding interactions. The results reported in this work reproduce previous experimental observations and molecular dynamics simulations.</p><h3>Methods</h3><p>The investigation started by generating initial configurations through global optimizations using classical potential energy. Then, a suitable functional of density functional theory (DFT) is selected between 20 functionals, including dispersion corrections, by benchmarking to the DLPNO-CCSD(T1)/CBS. The M06L-D3 functional is found to be the most accurate. The structures of the imidazole-water clusters, <span>(text {IMZ}(text {H}_2text {O})_n)</span>, <span>(n=1-12,;64)</span>, are then optimized at the M06L-D3/def2-TZVPP level of theory. Hydration free energy and enthalpy are estimated using the cluster continuum solvation model. Calculations are performed using Gaussian 16 and ORCA suite of programs. Quantum theory of atoms in molecules (QTAIM) is performed using the AIMAll program.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"31 10","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00894-025-06515-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigate the potential inhibitors of sphingosine kinase 1 (SphK1) with molecular dynamics and artificial intelligence drug design methods","authors":"Yahui Zhang,&nbsp;Yiru Wang,&nbsp;Junfeng Wan,&nbsp;Mengxia Zhao,&nbsp;Qingjie Zhao,&nbsp;Huiyu Li,&nbsp;Yuanming Cao","doi":"10.1007/s00894-025-06503-8","DOIUrl":"10.1007/s00894-025-06503-8","url":null,"abstract":"<div><h3>Context</h3><p>Sphingosine kinase 1 (SphK1) is a sphingosine kinase that can catalyze the phosphorylation of sphingosine to generate sphingosine-1-phosphate. The J-type channel of SPHK1 plays an important role in processes such as cell signaling. Therefore, this study aims to investigate the interaction mechanism between Epidanshenspiroketallactone, PF-543, and SPHK1 in the J-type channel, and to design new small molecules using AI Drug Design (AIDD). Molecular dynamics (MD) simulations reveal that hydrophobic interactions and π-π stacking are of critical significance in stabilizing the J-channel conformation of Sphk1. With MD and AIDD methods, our research provides a novel potential approach for the exploration and design of SphK1 inhibitors.</p><h3>Methods</h3><p>The binding mechanism of Epidanshenspiroketallactone and PF-543 with SphK1 was predicted by the molecular dynamics (MD) method using Gromacs-2022–2. Molecular docking was carried out with MolAICal, and the structures were visualized with the Pymol software. The MD simulation force field was selected as the AMBER99SB force field, the temperature was set at 310 K, and the total MD simulation time was 7.2 μs. A recurrent neural network-long short-term memory (RNN-LSTM) machine model was employed for the design of novel inhibitors.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"31 10","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136164","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":"Density functional theory study of Mg3TeO6 with excellent optical properties and p-type performance","authors":"Fei-Yu Chang,&nbsp;Mi Zhong,&nbsp;Zheng-Tang Liu,&nbsp;Qi-Jun Liu","doi":"10.1007/s00894-025-06506-5","DOIUrl":"10.1007/s00894-025-06506-5","url":null,"abstract":"<div><h3>Context</h3><p>Due to the limitations of existing p-type transparent conductive oxides (TCOs), this study aims to identify alternative p-type TCO materials with improved performance through first-principles calculations. The electronic, optical, and transport properties of Mg₃TeO₆ were systematically investigated. Calculations show that Mg₃TeO₆ is a TCOs with a wide bandgap and good visible light transmittance at different thicknesses, indicating its potential applications in the field of transparent materials. The transport properties of Mg₃TeO₆ at room temperature were calculated, and it was found that the p-type conductivity of Mg₃TeO₆ can reach 6.95 S cm⁻¹. It has certain comparability with some reported theoretical values of p-type TCO. These results suggest that Mg₃TeO₆ is a promising candidate for transparent electronics, although further experimental validation is required.</p><h3>Method</h3><p>First-principles calculations based on density functional theory and density functional perturbation theory were employed to execute all calculations in this work. The structural properties were optimized using GGA-PBE functionals, while HSE06 mixed functionals were used for accurate prediction of electronic band structures.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"31 10","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145110660","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":"DFT study on Pt-decorated (9,0) single-walled carbon nanotubes: hydrogen adsorption and sensing","authors":"Hongbing Shi,&nbsp;Shengping Yu,&nbsp;Fuming Chen,&nbsp;Minzhang Li","doi":"10.1007/s00894-025-06499-1","DOIUrl":"10.1007/s00894-025-06499-1","url":null,"abstract":"<div><h3>Context</h3><p>Carbon nanotubes are commonly used for hydrogen detection. However, pure carbon nanotubes exhibit limitations in this application. The Pt-decorated carbon nanotubes are considered to have the potential of hydrogen adsorption and sensing. The adsorption of H₂ on the outside wall of (9,0) single-walled carbon nanotubes (SWCNT(9,0)) were studied using density functional theory (DFT) calculations. The tiny adsorption energy (0.023 eV) implied a high barrier of the adsorption of H₂ on the outer wall of pure SWCNT, so metal atom (Pt, Fe, Ni) was used to decorate SWCNT. The result showed that Pt-SWCNT(9,0) exhibited the highest hydrogen adsorption capacity (0.791 eV) and meanwhile as the most stable catalyst structure. The hydrogen molecule underwent adsorption and dissociation on all three systems. Furthermore, the electronic structures of Pt-SWCNT(9,0) and H₂/Pt-SWCNT(9,0) were discussed. It is interesting that the interaction between Pt atom and SWCNT(9,0) changed the electronic state of carbon nanotubes and enhanced the adsorption energy of H₂. In the configurations involving multiple H₂ molecules, most molecules exhibited physical adsorption on Pt-SWCNT(9,0), whereas only one molecule was chemical adsorption. The electron transfer of Pt was promoted with the enhancement of orbital hybridization. In addition, the HOMO–LUMO gap (<i>E</i>_g) increased and the conductivity (<i>σ</i>) of Pt-SWCNT(9,0) changed after the adsorption of H₂, which was according with the experimental studies. Our calculations reveal that Pt-decorated SWCNT(9,0) has the capabilities of hydrogen adsorption and sensing. In the future, the design of the material structure will tune the conductivity for better H₂ sensor.</p><h3>Methods</h3><p>All DFT calculations were performed using the Gaussian 16 software. GaussView 6.0 software was utilized to visualize the molecular models, molecular orbitals, and electrostatic potential (ESP) of all relevant species. Multiwfn 3.8 software was utilized to plot localized orbital locator (LOL) graph and electron localization function (ELF) distribution maps. The DFT method was the B3LYP-D3BJ. The 6-31G(d,p) basis set was utilized for the C, H atoms, and Lanl2dz basis set for the Pt, Fe, and Ni atoms. No extraneous computational parameters were used in the structure optimization and frequency calculation that could affect calculation accuracy in the gas phase.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"31 10","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145110658","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":"A nuclear chemical descriptor based on NMR databases for molecular information: characterization of π-conjugated oligomers","authors":"João P. C. Oliveira,&nbsp;Murillo H. Queiroz,&nbsp;Patricio F. Provasi,&nbsp;Roberto Rivelino","doi":"10.1007/s00894-025-06495-5","DOIUrl":"10.1007/s00894-025-06495-5","url":null,"abstract":"<div><h3>Context</h3><p>Structure–property relationships of increasing systems, such as conjugated oligomers, atomic chains, and H-bonding networks, constitute a problem involving multiple variables in quantum chemical studies. Defining a single parameter that allows investigating different properties of these systems (or even those belonging to a specific chemical group) is not always a simple task. Thus, it is difficult to rationalize the evolution of molecular properties of increasing molecular systems, assigning relevant physicochemical information correlated to their size and structure. For conjugated oligomers, we have proposed a nuclear magnetic resonance (NMR)–based descriptor from the fluctuations of indirect spin–spin coupling constants (SSCCs) between two adjacent ¹³C nuclei (¹<i>J</i>_CC) in the π-conjugated system. This parameter is called <i>J</i>-coupling alternation (JCA) and systematically gathers information from structural and electronic properties, allowing a rational evaluation of the molecular properties of growing oligomers. We employ JCA to obtain correlations with vibrational, electronic, and optical properties of conjugated oligomers, belonging to the groups of polypyrrole (PPy), polyfuran (PFu), polythiophene (PTh), and polyselenophene (PSe). This analysis yields excellent linear structure–property relationships, confirming the ability of JCA to characterize realistically different families of π-conjugated oligomers and providing a reliable parameter to design efficient molecular materials.</p><h3>Methods</h3><p>All the oligomers, PPy(<i>n</i>), PFu(<i>n</i>), PTh(<i>n</i>), and PSe(<i>n</i>), with <i>n</i> = 2, 3, 5, 7, 9, and 11, respectively, were fully optimized, without symmetry constraints, using density–functional theory (DFT) at the PBE0/6–311 + G(d,p) level. Next, the vibrational properties were computed within harmonic approximation and NMR spin–spin coupling constants using the GIAO method. Finally, optical properties were obtained via TD-DFT with the CAM-B3LYP/6–311 + G(d,p) method.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"31 10","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145110659","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":"Ab initio study of the simplest Criegee intermediate CH2OO: equilibrium structure, spectroscopic properties and anharmonic force fields","authors":"Lihan Chi,&nbsp;Yanli Liu,&nbsp;Meishan Wang,&nbsp;Qiushuang Xu","doi":"10.1007/s00894-025-06500-x","DOIUrl":"10.1007/s00894-025-06500-x","url":null,"abstract":"<div><h3>Context</h3><p>The simplest Criegee intermediate, play a critical role in the oxidizing capacity of the Earth’s troposphere. While substantial research has advanced our understanding of CH₂OO over the past decade, comprehensive investigations into the structure, spectroscopic properties and anharmonic force fields remain notably underexplored. Here, we report the equilibrium structures, ground-state rotational constants, fundamental frequencies, quartic and sextic centrifugal distortion constants of CH₂OO. The results indicate that the CAM-B3LYP is more suitable for this study than that of B3LYP and ωB97XD functionals. We hope that our work will serve as a reference for relevant studies on CH₂OO and other Criegee intermediates.</p><h3>Methods</h3><p>The calculations of structure optimization, spectroscopic properties, and anharmonic force fields of CH2OO are performed by B3LYP, CAM-B3LYP, and ωB97XD functionals in combination with 6–311 + + G** and aug-cc-pVQZ basis sets, respectively, by the Gaussian16 program suite.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"31 10","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145256837","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":"Modification of biochar by iron containing adsorption centers as a method to enhance the remediation of perfluorooctanoic (PFOA) and (PFOS) acids from water and soil: a density functional theory study","authors":"Leonid Gorb,&nbsp;Anita Sosnowska,&nbsp;Natalia Bulawska,&nbsp;Danuta Leszczynska,&nbsp;Tomasz Puzyn,&nbsp;Jerzy Leszczynski","doi":"10.1007/s00894-025-06491-9","DOIUrl":"10.1007/s00894-025-06491-9","url":null,"abstract":"<p>Perfluoroalkyl and polyfluoroalkyl substances (PFAS), with over 15,000 types listed in the US EPA’s CompTox database, are found in everyday items like textiles, packaging, firefighting foams, and medical devices. Their widespread use has led to concerning health effects—including cancers, elevated cholesterol, and fertility issues—with detectable levels present in 98% of Americans.</p><p>While perfluorooctanoic (PFOA) and perfluorooctanesulphonic (PFOS) are among the most studied, their environmental behavior and ecological interactions remain poorly understood. Advances in computer-based methods, including chemoinformatics and quantum modeling, now aid in predicting properties and simulating PFAS dynamics.</p><p>Biochar (BC), produced via biomass pyrolysis under limited oxygen, is known for its porosity and adsorption capabilities. Magnetic biochar (MBC), enhanced with iron-based compounds, adds the benefit of magnetic separation, making it ideal for water decontamination. This paper explores the use of MBC to remove PFOA and PFOS from the environment, leveraging computational tools to investigate molecular interactions and adsorption properties.</p><p>A doubled crystallographic unit of hematite (Fe₂₄O₃₆) was constructed and fully optimized using density functional theory (DFT) with the M06-2X functional. Geometry optimization used the 6-31G(d,p) basis set, while single-point energies were calculated with 6–311 + + G(d,p). Antiferromagnetic conditions were ensured by setting the total spin to zero (Sz = 0), and triplet instability analysis was performed to evaluate ferromagnetic potential.</p><p>To simulate bulk water effects on adsorption, the CPCM solvation model (<i>ε</i> = 78.3) was applied. Harmonic frequency analysis confirmed structural minima, and Gibbs free energies were calculated using Gaussian 16. PFOA and PFOS, with highly negative pKa values (~ –0.1 and &lt;).</p><p>Quadratic SCF convergence (scf = qc) addressed numerical challenges, and interaction energies were corrected for basis set superposition error using the counterpoise method. Calculated IR spectra and molecular visualizations were generated with Chemcraft, without applying scaling factors.</p>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"31 10","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00894-025-06491-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145037152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantum chemistry calculations and chemical kinetic studies on the tautomeric mechanism of creatinine","authors":"Yiqing Sun,&nbsp;Xiankai Jiang,&nbsp;Zhenhai Xiong,&nbsp;Junjian Miao","doi":"10.1007/s00894-025-06501-w","DOIUrl":"10.1007/s00894-025-06501-w","url":null,"abstract":"<div><h3>Context</h3><p>Thermal processing of meat typically leads to the formation of heterocyclic aromatic amines (HAAs), a class of highly toxic compounds. Although extensive research has been conducted on HAAs, the precise formation mechanisms of individual HAAs remain incompletely understood, with many critical details yet to be elucidated. Several unresolved aspects concern the number of tautomers of creatinine—the key precursor in HAA formation, the interconversion pathways among these tautomers and the time scales involved, and the equilibrium distribution ratios among the tautomeric forms. Addressing these questions is essential for achieving an accurate understanding of the mechanistic pathways underlying the formation of HAAs.</p><h3>Methods</h3><p>All possible tautomers were manually deduced and verified by RDkit, a chemoinformatics toolkit. Geometry optimizations and frequency analyses were performed using density functional theory (DFT). The distribution of various tautomers was evaluated under three different environments—gas phase, ethanol, and water—to simulate real conditions. Calculations were carried out at the B3LYP/def2QZVPP//6-31G(d,p) level of theory, with the polarizable continuum model (PCM) applied for ethanol and water. A similar computational approach to the calculations on distribution was employed to investigate tautomerization mechanisms. Tautomerization kinetics were analyzed within the framework of transition state theory (TST) to determine rate constants for each tautomeric interconversion. Tunneling correction factors (κ) were then calculated to account for quantum mechanical tunneling effects. Subsequently, the corresponding system of differential equations was solved to obtain the time-dependent concentration profiles of each tautomeric species.</p></div>","PeriodicalId":651,"journal":{"name":"Journal of Molecular Modeling","volume":"31 10","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145037155","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}