Electrostatic Analysis Research Articles

Diastereomerically pure (S)‐verbenone‐isoxazoline hybrids: Synthesis, molecular structure, Hirshfeld surface analysis, density functional theory, cytotoxic effect, and apoptosis induction

AbstractIn this paper, a new diastereomerically pure isoxazolines were efficiently prepared from (S)‐verbenone, the procedure involves a regioselective and a diastereoselective 1,3‐dipolar cycloaddition of nitrile oxides on the monoterpene's enone. The structures of the newly obtained cycloadducts were confirmed by analytical and spectral studies (HRMS, 1H NMR, and 13C NMR). The relative stereochemistry of isoxazoline compounds 3a, 3c, and 3d were confirmed by x‐ray single crystal analysis. Hirshfeld surface analysis and two‐dimensional fingerprint plots were performed to analyze the different intermolecular contacts in crystal packing. Further, density functional theory calculations have been used to analyze the electronic and geometric frontier molecular orbital and molecular electrostatic map analyses of the compounds to predict the reactive site. All compounds were evaluated in vitro for their cytotoxic activity against four human cancer cell lines including fibrosarcoma HT‐1080, lung carcinoma A‐549 and breast adenocarcinoma (MCF‐7 and MDA‐MB‐231). Compound 3d was the most potent compound especially against HT‐1080 and A‐549 cancer cells with IC50 values of 21.35 ± 1.51 and 14.92 ± 1.74 μM, respectively. Mechanistically, the compound 3d induced apoptosis by significant caspase activation in HT‐1080 and A‐549 cancer cell lines utilizing flow cytometric analysis and caspase 3/7 activation assay. The examined compound 3d caused S cell cycle arrest in both HT‐1080 and A‐549 cells.

Structural, theoretical and optical investigations of two lateral twisting trinuclear Co(II) and Ni(II) salamo type complexes

Two trinuclear Co(II) and Ni(II) complexes, [{Co3(L)2(μ-OAc)2}2]·3CH2Cl2 (1) and [Ni3(L)2(μ-OAc)2(EtOH)2]·2EtOH (2) have been successfully obtained by a new nonsymmetrical salamo type ligand H2L with Co(OAc)2·4H2O and Ni(OAc)2·6H2O, respectively. Single crystal X-ray diffraction analysis revealed that complex 1 is an unsymmetric trinuclear structure, two tetradentate N2O2-donor ligand (L)2- units are coordinated to three Co(II) atoms where two terminal Co(II) atoms are penta-coordinated lateral twisting trigonal bipyramidal geometries but central Co(II) atom is hexa-coordinated lateral twisting octahedral configuration. Complex 2 is a centrosymmetrical trinuclear structure, all of the three Ni(II) atoms are hexa-coordinated lateral twisting octahedral configurations. In addition, complexes 1 and 2 have been characterized by physicochemical and spectroscopic methods. Molecular electrostatic potential analysis revealed that the phenolic oxygen atoms in the ligand H2L have nucleophilic reactions with Co(II) and Ni(II) atoms to form chemical bonds. Hirshfeld surfaces analyses showed that H···H/H···H interactions are the predominant, indicating the presence of great amount hydrogen bonds in complexes 1 and 2. IRI analyses indicated the presence of weak hydrogen bonding interactions that made complexes 1 and 2 more stable.

DFT Calculations of Some Important Radicals Used in the Nitroxide-Mediated Polymerization and Their HOMO‒LUMO, Natural Bond Orbital, and Molecular Electrostatic Potential Comparative Analysis

DFT Calculations of Some Important Radicals Used in the Nitroxide-Mediated Polymerization and Their HOMO‒LUMO, Natural Bond Orbital, and Molecular Electrostatic Potential Comparative Analysis

Manifesting Direction-Specific Complexation in [HFIP-H·H2O2]-: Exclusive Formation of a High-Lying Conformation.

Size-selective, negative ion photoelectron spectroscopy in conjunction with quantum chemical calculations is employed to investigate the geometric and electronic structures of a protype system in catalytic olefin epoxidation research, that is, deprotonated hexafluoroisopropanol ([HFIP-H]-) complexed with hydrogen peroxide (H2O2). Spectral assignments and molecular electrostatic surface analyses unveil a surprising prevalent existence of a high-lying isomer with asymmetric dual hydrogen-bonding configuration that is preferably formed driven by influential direction-specific electrostatic interactions upon H2O2 approaching [HFIP-H]- anion. Subsequent inspections of molecular orbitals, charge, and spin density distributions indicate the occurrence of partial charge transfer from [HFIP-H]- to H2O2 upon hydrogen-bonding interactions. Accompanied with electron detachment, a proton transfer occurs to form the neutral complex of [HFIP·HOO•] structure. This work conspicuously illustrates the importance of directionality encoded in intermolecular interactions involving asymmetric and complex molecules, while the produced hydroperoxyl radical HOO• offers a possible new pathway in olefin epoxidation chemistry.

The Structure of Saccharomyces cerevisiae Arginyltransferase 1 (ATE1)

Eukaryotic post-translational arginylation, mediated by the family of enzymes known as the arginyltransferases (ATE1s), is an important post-translational modification that can alter protein function and even dictate cellular protein half-life. Multiple major biological pathways are linked to the fidelity of this process, including neural and cardiovascular developments, cell division, and even the stress response. Despite this significance, the structural, mechanistic, and regulatory mechanisms that govern ATE1 function remain enigmatic. To that end, we have used X-ray crystallography to solve the crystal structure of ATE1 from the model organism Saccharomyces cerevisiae ATE1 (ScATE1) in the apo form. The three-dimensional structure of ScATE1 reveals a bilobed protein containing a GCN5-related N-acetyltransferase (GNAT) fold, and this crystalline behavior is faithfully recapitulated in solution based on size-exclusion chromatography-coupled small angle X-ray scattering (SEC-SAXS) analyses and cryo-EM 2D class averaging. Structural superpositions and electrostatic analyses point to this domain and its domain-domain interface as the location of catalytic activity and tRNA binding, and these comparisons strongly suggest a mechanism for post-translational arginylation. Additionally, our structure reveals that the N-terminal domain, which we have previously shown to bind a regulatory [Fe-S] cluster, is dynamic and disordered in the absence of metal bound in this location, hinting at the regulatory influence of this region. When taken together, these insights bring us closer to answering pressing questions regarding the molecular-level mechanism of eukaryotic post-translational arginylation.

Experimental and Computational Evaluation of Syringic Acid – Structural, Spectroscopic, Biological Activity and Docking Simulation

The single crystal of syringic acid was crystallized by slow evaporation technique and characterized using XRD, FTIR, FT-Raman, and UV-Vis spectroscopy. XRD confirms the crystalline structure as centrosymmetric monoclinic with C2/c space group. The functional groups identified by FTIR and FT Raman studies and by UV-Vis give the cut off wavelength as 276 nm. Quantum chemical calculations were performed using density functional theory. The computed and experimental vibrational wavenumbers were assigned and compared. Frontier molecular orbital research reveals the reactivity and kinetic stability of the molecule. The molecule’s reactive site is further confirmed by the Mulliken atomic charge distribution and molecular electrostatic potential surface analysis. The molecule’s absorption spectra were computed in the liquid phase (ethanol), by TD-DFT with the same basic set, which established a π to π* electronic transition and was comparable to the observed UV-Vis spectrum. The Hirshfeld analysis was used to determine the effectiveness of interactions between distinct atoms as well as their contribution. The O…H and H…H contributions are highest due to the intermolecular hydrogen bonding. The natural bond orbital analysis demonstrates the molecule’s bioactivity. The biological activity such as anti-bacterial, antioxidant and anti-cancer has been evaluated through disk diffusion, DDPH assay and molecular docking method. The zone of inhibition was clearly observed on gram-positive and gram-negative bacterium that showed the anti-bacterial property of syringic acid. The syringic acid prevents breast cancer, according to molecular docking research. Seven different types of breast cancer proteins based on different mechanisms were utilized to test the syringic acid molecule’s docking efficiency, and it was revealed that PR and HER-2 have the highest docking scores with −7.7Kcal/mol. In addition, to better understand the safety profile of syringic acid, physicochemical and pharmacokinetic properties were investigated.

Ion‐Ion Cross‐Field Instability of Lower Hybrid Waves in the Inner Coma of Comet 67P

AbstractWe show that an ion‐ion cross‐field streaming instability between cold newborn cometary ions and heated heavy ions that were picked up upstream is likely a contributing source of observed lower hybrid (LH) waves in the inner coma of comet 67P/Churyumov‐Gerasimenko. Electric field oscillations in the LH frequency range are common here, and have previously been attributed mainly to the lower‐hybrid drift instability, driven by gradients associated with observed local density fluctuations. However, the observed wave activity is not confined to such gradients, nor is it always strongest there. Thus, other instabilities are likely needed as well to explain the observed wave activity. Several previous works have shown the existence of multiple populations of cometary ions in the inner coma of 67P, distinguished by differences in mass, energy and/or flow direction. We here examine two selected time intervals in October and November 2015, with substantial wave activity in the LH frequency range, where we identify two distinct cometary ion populations: a bulk population of locally produced, predominantly radially outflowing ions, and a more tenuous population picked up further upstream and accelerated back toward the comet by the solar wind electric field. These two populations exhibit strong relative drifts (∼20 km/s, or about five times the pickup ion thermal velocity), and we perform an electrostatic dispersion analysis showing that conditions should be favorable for LH wave generation through the ion‐ion cross‐field instability.

Structural and optical properties of salicyl-N-methyl-4-stilbazolium tosylate: Thermal, DFT, MEP and Hirshfeld surface analysis

The structural characteristics and optimized geometry of salicyl-N-methyl-4-stilbazolium tosylate (SMST), a derivative of the prominent electro-nonlinear optic crystal 4-(N,N-dimethylamino)-N-methyl-4-toluene sulfonate (DAST) is investigated. Its morphology, spectral, vibrational, thermal, and electronic features have been examined in studies like FT-IR, UV-Transmittance spectroscopy, single crystal XRD and TG-DTA analysis. Thermal parameters like activation energy, entropy, enthalpy, and Gibbs free energy suggest that the reaction is slower and non-spontaneous. The optical constants like energy band gap, absorption coefficient, extinction coefficient, refractive index, and skin depth of SMST have been calculated. The energy band gap value is found to be 2.69 eV, which makes SMST a potential and promising material for non-linear optical applications. The dielectric behavior of SMST is in agreement with the property needed for NLO materials. Theoretical calculations like density functional theory and frontier molecular orbitals- HOMO and LUMO are investigated to analyze the structural properties, atomic arrangement, oriented geometry, and dipole moment. Molecular electrostatic potential (MEP), Hirshfeld surface, and 2D fingerprint plot analysis are examined to provide information about the molecular interaction, crystal packing, electron density, and intermolecular properties of atomic contacts. Second Harmonic Generation of SMST shows greater efficiency than urea, which confirms that SMST crystal can leads to many applications in the optical field.

Isocyanide and Cyanide Entities Form Isostructural Halogen Bond-Based Supramolecular Networks Featuring Five-Center Tetrafurcated Halogen···C/N Bonding

A typical halogen bond (HaB) donor, 1,4-dibromo-2,3,5,6-tetrafluorobenzene (FBB), was cocrystallized with the isocyanide CNMes and the cyanide NCMes to give two isostructural cocrystals, (CNMes)·FBB and (NCMes)·FBB. Their solid-state architecture exhibits a close similarity between the isocyanide and cyanide groups in their HaB-accepting role. This similarity and particular bonding features of the HaBs were additionally verified by theoretical calculations (molecular electrostatic potential analysis, electron density/electrostatic potential profiles, atoms-in-molecules charge analysis, and calculations of pKa values and binding energies). Remarkably, both cocrystals form unusual heterohexamers where one Br atom of FBB simultaneously forms four contacts with two C (or N) and two Br atoms of neighboring molecules. On the basis of the geometric parameters and the theoretical data, these contacts can be defined as five-center tetrafurcated μ4-Br···(C, Br, C, Br) and μ4-Br···(N, Br, N, Br) HaBs; this is the first observation of the tetrafurcated HaB involving four disunited HaB acceptors.

Uncovering the Morphological Regulation Mechanism of Low Sensitivity and Highly Energetic Materials in Solvents: Changing Crystal Morphology Induced by Hydrogen Bonding

Low sensitivity and highly energetic materials (LSHEMs) are currently the most promising high-energy materials due to their structural stability. However, many problems exist due to their abundant hydrogen bonding (HB) in the structure, such as low solubility and difficulty controlling the crystallization process. In this paper, aiming at regulating the crystal morphology of LSHEMs, 4,4′,5,5′-tetranitro-1H,1′H-[2,2′-biimidazole]-1,1′-diamine is used as a model substance to explore the mechanism of controlling the crystal morphology in solvents. The molecular structure, crystal structure, and HB sites on crystal faces were investigated by molecular electrostatic potential surface, Hirshfeld surface, and HB analyses, and it was found that the HB density [δ(HB)] of faces is of the order (011) > (11–1) > (110) > (100) in crystal or solution, determining the tendency of interaction with polar solvents. Then, using molecular dynamics simulation and the modified attachment energy model, we found that the attachment energy of crystal faces and the predicted crystal morphologies in different solvents were determined by HB sites on faces and strongly correlated with the solvent polarity. The experimental morphologies were consistent with the trend predicted including the aspect ratio trend, which confirmed our theoretical speculation. This work provides an effective method of choosing solvents for morphology customization of LSHEMs, which will help guide the morphology control and realize the industry application of LSHEMs.

Analysis of solid-liquid equilibrium behavior of highly water-soluble beet herbicide metamitron in thirteen pure solvents using experiments and molecular simulations

Metamitron (MET), a highly water-soluble herbicide for sugar beets, has posed a significant threat to aquatic species due to its high solubility in water; therefore, understanding its solid–liquid phase equilibrium data in different solvents is essential for the future development of more environmentally friendly forms. In this study, the solubility data of MET in 12 pure solvents were determined gravimetrically and analyzed using theoretical methods (primarily Molecular electrostatic potential surface analysis, Hirshfeld surface analysis, Reduced Density Gradient analysis, radial distribution function, and solute–solvent interaction energy) to further investigate the solid–liquid equilibrium behavior. Although MET's high solubility in water contributes to environmental contamination, its value is low in comparison to that of other organic solvents. Four models, including the Apelblat equation, the λh equation, the van't Hoff equation, and the NRTL, were used to examine all solid–liquid equilibrium data, and an ARD% below 5 confirmed its good correlation. The MET solubility data is anticipated to provide solid guidance for the future development of more effective and environmentally acceptable green formulations.

Multidimensional modeling assisted mining of GDB17 chemical database: A search for polymer donors for organic solar cells and machine learning assisted performance prediction

AbstractIndeed, the designing of efficient material for organic solar cells is challenging and time‐consuming task. In this work, we have proposed a design pipeline to screen efficient polymer donors. Machine learning based models are trained to predict the power conversion efficiency (PCE). Structural descriptors are used as input to train machine learning models. The data of organic molecules is extracted from Photovoltaics database. Best buildings blocks are selected on the basis of similarity analysis using PBT7‐Th and MP6 as reference (standard). New polymers are designed using building blocks having high similarity. The PCE is predicted with the help of high‐performance machine learning model. Top three candidates are studied by molecular dynamics (MD) simulations. Packing behavior of polymer donors and their blend with fullerene acceptor is studied using radial distribution function (RDF). Density functional theory analysis is also performed on selected polymers. Electrostatic potential analysis has indicated the highly polar behavior that can result higher charge generation. Our proposed pipeline has ability to design and screen the polymer donors, as well as can predict their PCE without any experimentation. More importantly computational cost is marginal.

A molecular dynamics study of graphyne-based electrode and biocompatible ionic liquid for supercapacitor applications

• Graphyne as a promising candidate for electrochemical energy storage systems. • Electrolytes based on aqueous mixtures of the biodegradable ionic liquid. • Efficiency of low toxicity cholinium-based ionic liquids electrolytes in supercapacitor. Atomistic molecular dynamics simulations were used to investigate the properties of electrolytes based on aqueous mixtures of the biodegradable ionic liquid [Ch][Gly] with the ionic liquid [Bmim][PF 6 ] as electrolytes in graphyne supercapacitors. Energetic, structural, and electrostatic analyses were performed to describe de Electrical Double Layer (EDL) formed near de graphyne electrodes revealing preferential adsorption of [Bmim][PF 6 ] additive in both, positive and negative electrodes. From the energetic analysis, we found that although the structure and formation of the EDL are governed by the complex interaction network of both van der Waals and electrostatics, its interaction with the electrode is drastically dominated by van der Waals interactions. From electrostatic results, we found a reduction in total capacitance as the concentration of [Bmim][PF 6 ] increases but overall, we observed that cholinium-based electrolytes can perform as well as most conventional ionic liquids, but with the advantage of having a low toxicity. The comparison between graphene and graphyne supercapacitors revealed a higher capacitance for graphyne, with 2.4 μF cm −2 at 2 V, even when we compare similar values for the drop potential (which occur for different values of charge density) the higher performance of the graphyne electrode is maintained; a result that corroborates the previous findings and that indicates graphyne as a promising candidate for electrochemical energy storage systems.

Unexpected role of two ortho-OH groups for the hydrogenation of CO2 to methanol catalyzed by Fe bipyridinol complexes

A density functional theory study of Fe-catalyzed hydrogenation of CO2 to methanol reveals an unexpected metal–ligand cooperation mechanism with two ortho-OH groups play key roles for the breaking of C–O and O–H bonds and formation of O–H…O hydrogen bonds. The formation of methanediol via hydride transfer from Fe to formic acid (4′ → TS6,7) is the rate-determining step with a total barrier of 30.8 kcal mol−1 in free energy. Furthermore, by replacing the two meta (R1) and two para (R2) hydrogen atoms in the bipyridinol ligand and the coordinated CN and CO with different functional groups, we built a series of stable iron complexes and computationally predicted their catalytic activities for hydrogenation of CO2 to methanol. Among all newly proposed iron complexes, 1t and 1u are promising catalyst candidates for hydrogenation of CO2 to methanol with rather low total free energy barriers of 26.6 and 28.8 kcal mol−1, respectively. The electrostatic potential map analysis indicates that stronger electron donating ligands on iron may lead to higher catalytic activities.

Hirshfeld surface and electrostatic potential surface analysis of clozapine and its solubility and molecular interactions in aqueous blends

Solubility and relevant thermodynamic properties as well as molecular interactions of clozapine in aqueous systems of protic cosolvent, e.g. isopropanol, and aprotic cosolvents such as acetonitrile, dimethyl sulfoxide (DMSO) and N-methyl-2-pyrrolidinone (NMP) are focus of this paper. The intermolecular interactions and overall charge distribution of clozapine were respectively investigated by using Hirshfeld surface analysis and molecular electrostatic potential surface. All experimentations were executed using a shake-flask approach under p = 101.2 kPa (local pressure) from 278.15 (293.15) to 323.15 (333.15) K. The minimum solubility data of clozapine appeared in neat water for each aqueous system at 278.15 K; and the maximum one, in neat cosolvent at 328.15 K. Correlation of the solubility data (mole fraction) through Jouyban–Acree and MRS models acquired acceptable results with relative average deviations (RAD) of no>9.15 %. The solvent descriptors of hydrogen-bonding basicity, solubility parameter and dipolarity-polarizability predominantly controlled the clozapine solubility variation through the quantitative analysis of linear solvation energy relationships in terms of the solubility data at 298.15 K. The extended Hildebrand solubility approach was also employed here to correlate the solubility and study the solvation behavior of solutions. Quantitatively analysis of preferential solvation of clozapine by solvent species in solutions was conducted by the method of inverse Kirkwood–Buff integrals. In the solutions with middle and cosolvent-rich compositions, the parameters of preferential solvation for DMSO, NMP, acetonitrile or isopropanol were positive, which specified that preferential solvation of clozapine was made by co-solvent. In addition, the thermodynamic properties of dissolution of clozapine along with enthalpy–entropy compensation were derived and deeply discussed.

Theoretical insight into the reaction mechanism of ammonia dehydrogenation on iron-based clusters

Ammonia (NH3) molecule decomposition is a promising approach for H2 production with COx-free. Density functional theory (DFT) calculations are employed to investigate the NH3 molecule stepwise dehydrogenation on Fe6M (M = Fe, Mo, Ni, and Co) clusters. The stability of these clusters has been investigated, and the result shows that the stability of Fe-based clusters is enhanced with doping of other metals. The catalytic activity of metal clusters for ammonia decomposition is systematically investigated by analyzing the adsorption property and reaction barriers. NH3 prefers to bind to the atop metal atom through the N end, which is agreement with the electrostatic potential analysis. Moreover, the adsorption energies of NH3 are related to the d-band center of Fe-based clusters. The reaction energy barriers show that the last dehydrogenation step (NH* + * ⇌ N* + H*) is the rate-determining step for most investigated clusters. The overall dehydrogenation process is exothermic reaction, and by comparing the rate-determining step, the Fe6Mo(l) and the Fe6Ni(l) clusters can efficiently promote the NH3 dissociation reaction.

Exploring the binding mechanism and adverse toxic effects of chiral phenothrin to human serum albumin: Based on multi-spectroscopy, biochemical and computational approach

To understand the binding mechanism of a mixture of chiral phenothrin with human serum albumin (HSA), we used multi-spectroscopy, including steady-state fluorescence spectroscopic titration, three-dimensional fluorescence spectroscopy, circular dichroism, and FTIR spectra to explore the precise interactions between the complex. Based on the modified Stern–Volmer equation, the binding constant (Ka) was calculated under three temperatures, which revealed that phenothrin interacts with HSA through a static quenching mechanism. The thermodynamic parameters including enthalpy change (ΔH) and entropy change (ΔS) were determined by fitting the experimental data with van’t Hoff equation, which indicates that electrostatic force and hydrogen bonds dominate the interplay in the phenothrin-HSA complex. Circular dichroism and FTIR showed the addition of phenothrin changed the secondary structure of proteins, in which the α-helicity decreased from 52.37% in free HSA to 50.02%. The esterase-like activity was reduced with the increase of phenothrin concentration, which may be attributed to the perturbated senior structure of HSA. Competitive displacement experiments confirmed that phenothrin inserted into the subdomain IIA (site I) of HSA. Several computational approaches such as molecular docking, frontier molecular orbital analysis, and electrostatic potential analysis were utilized to probe into the binding mode of the phenothrin-HSA complex. The binding behaviors of the chiral phenothrin mixture differed during the complexation. In conclusion, both the experimental and theoretical investigations provide useful information for better understanding and reducing the potential deleterious effects of the chiral phenothrin mixture on human long-term physio-pathological status.

Application of Molecular-Modeling, Scaffold-Hopping, and Bioisosteric Approaches to the Discovery of New Heterocyclic Picolinamides.

Macrocyclic natural products and their derivatives are a valuable source for biologically active crop protection products and have had significant impact on the development of conventional agrochemicals. However, they can be challenging starting points for lead-generation efforts because of their size, structural complexity, and developability. Using molecular modeling and electrostatic analysis, alternative bicyclic isosteres were identified as replacements for the antifungal nine-membered macrocycle UK-2A. By application of a structure-based conformational approach, a series of heterocyclic replacements were derivatized to deliver promising fungicidal activity and scaffold bioisosteres were further diversified to investigate structure-activity relationships.

Sumanene as a delivery carrier for methimazole drug: DFT, AIM, SERS and solvent effects

In this work, Density Functional Theory (DFT) and Quantum theory of atoms-in-molecules (QTAIM) were employed to help determine nature of binding the model graphene hydrocarbon sumanene (SME) and 3-methyl-1H-imidazole-2-thione (methimazole) (MZE) which is an anti-thyroid drug. Metrics on binding energies for different molecular configurations help both identify the thermodynamics and structure; illustrations visualize the non-covalent interactions between MZE and SME that might be relevant to both drug delivery and molecular recognition. MZE binds to the concave side of SME and stronger than other configurations tested herein. The importance of the electrostatic component was emphasized by means of molecular orbital, molecular electrostatic potential (MEP) and charge analysis. Simulation of the Ultra-Violet (UV) spectra was performed in vacuum and aqueous phase to check whether the binding of MZE to SME could be tracked and monitored.

Reaction site evolution during low-temperature oxidation of low-rank coal

In-depth and comprehensive analysis of reaction sites evolution has important enlightening significance for understanding the chemical reaction sequence during low-temperature oxidation. For this purpose, FT-IR, XPS and 13C NMR were combined to analyze the changes in reaction sites. As the oxidation temperature increased, the CH3/CH2 ratio continuously increases, indicating that methylene has a higher reactivity. Before the oxidation temperature reached 150 °C, the relative content of C-H decreased slightly while that of C-O increased. Then, the C-O gradually transformed into C=O. When the oxidation temperature exceeds 150 °C, the ratio of aliphatic carbon has been significantly reduced and that of aromatic carbon is greatly increased. The ratio of carbonyl carbon also has a small increase. Based on these results, representative macromolecular models are established and electrostatic potential analysis is performed. The results show that the main active site is the hydroxyl, methyl and methylene groups, especially the hydroxyl in the carboxyl group. In summary, it can be considered that the main active sites for coal oxidation at low temperature are hydroxyl and methylene groups. At higher temperatures, the hydroxyl group will be further oxidized and the main active site will gradually evolve into carboxyl groups.