{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T03:18:05Z","timestamp":1784085485430,"version":"3.55.0"},"reference-count":101,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T00:00:00Z","timestamp":1763596800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002713","name":"Deanship of Scientific Research at Imam Mohammad Ibn Saud Islamic University","doi-asserted-by":"publisher","award":["IMSIU-DDRSP2503"],"award-info":[{"award-number":["IMSIU-DDRSP2503"]}],"id":[{"id":"10.13039\/501100002713","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Understanding the molecular determinants of antioxidant activity in natural phenolic compounds is essential for explaining their biological performance and designing new radical scavengers. In this work, the radical-scavenging mechanisms of three major ginger phenolics\u20146-gingerol (GIN), 6-shogaol (SHO), and 6-paradol (PAR)\u2014were systematically investigated using density functional theory (DFT) thermochemistry at the M06-2X\/6-31+G(d,p) level in the gas phase, benzene, and water. Three canonical pathways\u2014hydrogen atom transfer (HAT), single-electron transfer followed by proton transfer (SET\u2013PT), and sequential proton loss\u2013electron transfer (SPLET)\u2014were evaluated through full optimization and frequency calculations at 298.15 K, combined with the SMD solvation model. Frontier molecular orbital (FMO), molecular electrostatic potential (MEP), and quantum theory of atoms in molecules (QTAIM) analyses were employed to correlate electronic structure with reactivity. The results reveal a distinct solvent-dependent mechanistic crossover. In the gas phase and benzene, the low dielectric constant suppresses charge separation, making HAT the thermodynamically dominant pathway. In water, strong stabilization of ionic species lowers both the ionization and deprotonation barriers, allowing SPLET and SET\u2013PT to become competitive or even preferred. Across all media, the phenolic O\u2013H group is the principal reactive site, while the aliphatic O\u2013H of GIN remains inactive. SHO exhibits the most versatile redox profile, combining a highly conjugated \u03b1,\u03b2-unsaturated chain with favorable charge delocalization; PAR is somewhat less redox-active, while GIN shows intermediate performance governed by intramolecular hydrogen bonding. The assembled thermodynamics for HOO\u2022 scavenging confirm that all three phenolics are thermodynamically competent antioxidants (\u0394G\u00b0 \u2248 \u22124 kcal mol\u22121 in water), with comparable driving forces; electronic descriptors indicate SHO is the most redox-flexible, GIN(phenolic) is moderately and PAR is somewhat less charge-transfer-prone, while GIN(aliphatic) remains inactive. These findings provide a comprehensive structure-to-mechanism correlation for ginger phenolics and establish a predictive framework for solvent-controlled antioxidant behavior in phenolic systems.<\/jats:p>","DOI":"10.3390\/ijms262211217","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T10:30:59Z","timestamp":1763634659000},"page":"11217","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Mechanistic Evaluation of Radical Scavenging Pathways in Ginger Phenolics: A DFT Study of 6-Gingerol, 6-Shogaol, and 6-Paradol"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8506-5759","authenticated-orcid":false,"given":"Hassane","family":"Lgaz","sequence":"first","affiliation":[{"name":"Innovative Durable Building and Infrastructure Research Center, Center for Creative Convergence Education, Hanyang University ERICA, 55 Hanyangdaehak-ro, Sangrok-gu, Ansan-si 15588, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mouslim","family":"Messali","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), P.O. Box 90950, Riyadh 11623, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9776-5859","authenticated-orcid":false,"given":"Han-seung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Architectural Engineering, Hanyang University ERICA, 55 Hanyangdaehak-ro, Sangrok-gu, Ansan-si 15588, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"R453","DOI":"10.1016\/j.cub.2014.03.034","article-title":"ROS Function in Redox Signaling and Oxidative Stress","volume":"24","author":"Schieber","year":"2014","journal-title":"Curr. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"8416763","DOI":"10.1155\/2017\/8416763","article-title":"Oxidative Stress: Harms and Benefits for Human Health","volume":"2017","author":"Pizzino","year":"2017","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/s42255-022-00591-z","article-title":"Guidelines for Measuring Reactive Oxygen Species and Oxidative Damage in Cells and in Vivo","volume":"4","author":"Murphy","year":"2022","journal-title":"Nat. Metab."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Hong, Y., Boiti, A., Vallone, D., Foulkes, N.S., Hong, Y., Boiti, A., Vallone, D., and Foulkes, N.S. (2024). Reactive Oxygen Species Signaling and Oxidative Stress: Transcriptional Regulation and Evolution. Antioxidants, 13.","DOI":"10.3390\/antiox13030312"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"S14","DOI":"10.1016\/0002-9343(91)90279-7","article-title":"Reactive Oxygen Species in Living Systems: Source, Biochemistry, and Role in Human Disease","volume":"91","author":"Halliwell","year":"1991","journal-title":"Am. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Sharifi-Rad, M., Anil Kumar, N.V., Zucca, P., Varoni, E.M., Dini, L., Panzarini, E., Rajkovic, J., Tsouh Fokou, P.V., Azzini, E., and Peluso, I. (2020). Lifestyle, Oxidative Stress, and Antioxidants: Back and Forth in the Pathophysiology of Chronic Diseases. Front. Physiol., 11.","DOI":"10.3389\/fphys.2020.00694"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.cnr.2006.09.006","article-title":"Neuroinflammation, Oxidative Stress, and the Pathogenesis of Parkinson\u2019s Disease","volume":"6","author":"Mosley","year":"2006","journal-title":"Clin. Neurosci. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2812","DOI":"10.3168\/jds.S0022-0302(93)77620-1","article-title":"Oxidative Stress, Antioxidants, and Animal Function","volume":"76","author":"Miller","year":"1993","journal-title":"J. Dairy Sci."},{"key":"ref_9","first-page":"2082145","article-title":"The Role of Oxidative Stress in Physiopathology and Pharmacological Treatment with Pro- and Antioxidant Properties in Chronic Diseases","volume":"2020","year":"2020","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Platzer, M., Kiese, S., Tybussek, T., Herfellner, T., Schneider, F., Schweiggert-Weisz, U., and Eisner, P. (2022). Radical Scavenging Mechanisms of Phenolic Compounds: A Quantitative Structure-Property Relationship (QSPR) Study. Front. Nutr., 9.","DOI":"10.3389\/fnut.2022.882458"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Kumar, N., and Goel, N. (2019). Phenolic Acids: Natural Versatile Molecules with Promising Therapeutic Applications. Biotechnol. Rep., 24.","DOI":"10.1016\/j.btre.2019.e00370"},{"key":"ref_12","first-page":"293","article-title":"Free Radical Scavenging Activity and Total Phenolic Content of Methanolic Extracts from Male Inflorescence of Salix Aegyptiaca Grown in Iran","volume":"9","author":"Sonboli","year":"2010","journal-title":"Iran. J. Pharm. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/S0891-5849(98)00190-7","article-title":"Quantitative Structure-Activity Relationship Analysis of Phenolic Antioxidants","volume":"26","author":"Lien","year":"1999","journal-title":"Free Radic. Biol. Med."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Yu, M., Gouvinhas, I., Rocha, J., and Barros, A.I.R.N.A. (2021). Phytochemical and Antioxidant Analysis of Medicinal and Food Plants towards Bioactive Food and Pharmaceutical Resources. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-89437-4"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1016\/0891-5849(95)02227-9","article-title":"Structure-Antioxidant Activity Relationships of Flavonoids and Phenolic Acids","volume":"20","author":"Miller","year":"1996","journal-title":"Free Radic. Biol. Med."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Star, B.S., van der Slikke, E.C., Ransy, C., Schmitt, A., Henning, R.H., Bouillaud, F., and Bouma, H.R. (2023). GYY4137-Derived Hydrogen Sulfide Donates Electrons to the Mitochondrial Electron Transport Chain via Sulfide: Quinone Oxidoreductase in Endothelial Cells. Antioxidants, 12.","DOI":"10.3390\/antiox12030587"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Mao, Q.-Q., Xu, X.-Y., Cao, S.-Y., Gan, R.-Y., Corke, H., Beta, T., Li, H.-B., Mao, Q.-Q., Xu, X.-Y., and Cao, S.-Y. (2019). Bioactive Compounds and Bioactivities of Ginger (Zingiber Officinale Roscoe). Foods, 8.","DOI":"10.3390\/foods8060185"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Ayustaningwarno, F., Anjani, G., Ayu, A.M., and Fogliano, V. (2024). A Critical Review of Ginger\u2019s (Zingiber officinale) Antioxidant, Anti-Inflammatory, and Immunomodulatory Activities. Front. Nutr., 11.","DOI":"10.3389\/fnut.2024.1364836"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Shaukat, M.N., Nazir, A., Fallico, B., Shaukat, M.N., Nazir, A., and Fallico, B. (2023). Ginger Bioactives: A Comprehensive Review of Health Benefits and Potential Food Applications. Antioxidants, 12.","DOI":"10.3390\/antiox12112015"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"109354","DOI":"10.1016\/j.lwt.2020.109354","article-title":"Total Phenolics, Total Carotenoids, Individual Phenolics and Antioxidant Activity of Ginger (Zingiber officinale) Rhizome as Affected by Drying Methods","volume":"126","author":"Ghafoor","year":"2020","journal-title":"LWT"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.jep.2009.10.004","article-title":"Comparative Antioxidant and Anti-Inflammatory Effects of [6]-Gingerol, [8]-Gingerol, [10]-Gingerol and [6]-Shogaol","volume":"127","author":"Dugasani","year":"2010","journal-title":"J. Ethnopharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Wei, C.-K., Tsai, Y.-H., Korinek, M., Hung, P.-H., El-Shazly, M., Cheng, Y.-B., Wu, Y.-C., Hsieh, T.-J., Chang, F.-R., and Wei, C.-K. (2017). 6-Paradol and 6-Shogaol, the Pungent Compounds of Ginger, Promote Glucose Utilization in Adipocytes and Myotubes, and 6-Paradol Reduces Blood Glucose in High-Fat Diet-Fed Mice. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18010168"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Sapkota, A., Park, S.J., and Choi, J.W. (2018). Neuroprotective Effects of 6-Shogaol and Its Metabolite, 6-Paradol, in a Mouse Model of Multiple Sclerosis. Biomol. Ther., 27.","DOI":"10.4062\/biomolther.2018.089"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Attallah, K.A., El-Dessouki, A.M., Abd-Elmawla, M.A., Ghaiad, H.R., Abo-Elghiet, F., Mustafa, A.M., El-Shiekh, R.A., and Elosaily, H. (2025). The Therapeutic Potential of Naturally Occurring 6-Shogaol: An Updated Comprehensive Review. Inflammopharmacology.","DOI":"10.1007\/s10787-025-01812-z"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Kim, J.E., Park, K.-H., Park, J., Kim, B.S., Kim, G.-S., Hwang, D.G., Kim, J.E., Park, K.-H., Park, J., and Kim, B.S. (2025). Immunomodulatory Potential of 6-Gingerol and 6-Shogaol in Lactobacillus Plantarum-Fermented Zingiber Officinale Extract on Murine Macrophages. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26052159"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.foodchem.2006.01.004","article-title":"The Antioxidant and Free Radical Scavenging Activities of Processed Cowpea (Vigna unguiculata (L.) Walp.) Seed Extracts","volume":"101","author":"Siddhuraju","year":"2007","journal-title":"Food Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4916","DOI":"10.1021\/jp037247d","article-title":"Antioxidant Properties of Phenolic Compounds:\u2009 H-Atom versus Electron Transfer Mechanism","volume":"108","author":"Leopoldini","year":"2004","journal-title":"J. Phys. Chem. A"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.comptc.2011.03.006","article-title":"Solvent Effects on the Antioxidant Activity of 3,4-Dihydroxyphenylpyruvic Acid: DFT and TD-DFT Studies","volume":"966","author":"Fifen","year":"2011","journal-title":"Comput. Theor. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Yoosefian, M., Esmaeili, A., and Abass, K.S. (2025). Pharmacokinetic, Toxicological, and Molecular Interaction Assessment of Ginger-Derived Phenolics for SARS-CoV-2 Main Protease Inhibition. Sci. Rep., 15.","DOI":"10.1038\/s41598-025-13094-0"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.jff.2017.05.017","article-title":"Protective Effects of Lactobacillus Plantarum C88 on Chronic Ethanol-Induced Liver Injury in Mice","volume":"35","author":"Zhao","year":"2017","journal-title":"J. Funct. Foods"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2639","DOI":"10.1021\/acs.jcim.2c00104","article-title":"Current Trends in Computational Quantum Chemistry Studies on Antioxidant Radical Scavenging Activity","volume":"62","author":"Spiegel","year":"2022","journal-title":"J. Chem. Inf. Model."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1016\/j.crfs.2022.08.003","article-title":"Effects and Mechanism of Natural Phenolic Acids\/Fatty Acids on Copigmentation of Purple Sweet Potato Anthocyanins","volume":"5","author":"Lv","year":"2022","journal-title":"Curr. Res. Food Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.comptc.2012.10.004","article-title":"An Extensive Methodological Theoretical Study of the Kinetics of the Benzylperoxy Radical Isomerization","volume":"1002","author":"Canneaux","year":"2012","journal-title":"Comput. Theor. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.1016\/j.ejmech.2008.10.022","article-title":"Synthesis, Antimicrobial Evaluation and QSAR Study of Some 3-Hydroxypyridine-4-One and 3-Hydroxypyran-4-One Derivatives","volume":"44","author":"Fassihi","year":"2009","journal-title":"Eur. J. Med. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"114097","DOI":"10.1016\/j.comptc.2023.114097","article-title":"Revisiting the Hydrogen Atom Transfer Reactions through a Simple and Accurate Theoretical Model: Role of Hydrogen Bond Energy in Polyphenolic Antioxidants","volume":"1223","author":"Rohman","year":"2023","journal-title":"Comput. Theor. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Vo, Q.V., Nam, P.C., Bay, M.V., Thong, N.M., Cuong, N.D., and Mechler, A. (2018). Density Functional Theory Study of the Role of Benzylic Hydrogen Atoms in the Antioxidant Properties of Lignans. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-30860-5"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1021\/ja002455u","article-title":"Predicting the Activity of Phenolic Antioxidants:\u2009 Theoretical Method, Analysis of Substituent Effects, and Application to Major Families of Antioxidants","volume":"123","author":"Wright","year":"2001","journal-title":"J. Am. Chem. Soc."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.comptc.2016.04.004","article-title":"Deprotonation of Flavonoids Severely Alters the Thermodynamics of the Hydrogen Atom Transfer","volume":"1085","author":"Klein","year":"2016","journal-title":"Comput. Theor. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"20382","DOI":"10.1021\/acsomega.0c02354","article-title":"Density Functional Theory Studies on the Antioxidant Mechanism and Electronic Properties of Some Bioactive Marine Meroterpenoids: Sargahydroquionic Acid and Sargachromanol","volume":"5","author":"Farrokhnia","year":"2020","journal-title":"ACS Omega"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"115470","DOI":"10.1016\/j.comptc.2025.115470","article-title":"Mechanism Engineering of Polyphenol Antioxidants: DFT\/TD-DFT Evidence for HAT \u2194 SPLET Switching via Targeted Functional Blocking in Curcumin, Quercetin, and Resveratrol Derivatives","volume":"1254","year":"2025","journal-title":"Comput. Theor. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Soltani, S., Sowlati-Hashjin, S., Feugmo, C.G.T., Karttunen, M., Soltani, S., Sowlati-Hashjin, S., Feugmo, C.G.T., and Karttunen, M. (2022). Structural Investigation of DHICA Eumelanin Using Density Functional Theory and Classical Molecular Dynamics Simulations. Molecules, 2.","DOI":"10.3390\/molecules27238417"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Bakheit, A.H., Wani, T.A., Al-Majed, A.A., Alkahtani, H.M., Alanazi, M.M., Alqahtani, F.R., and Zargar, S. (2024). Theoretical Study of the Antioxidant Mechanism and Structure-Activity Relationships of 1,3,4-Oxadiazol-2-Ylthieno [2,3-d]Pyrimidin-4-Amine Derivatives: A Computational Approach. Front. Chem., 12.","DOI":"10.3389\/fchem.2024.1443718"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.compbiolchem.2019.03.009","article-title":"DFT and QTAIM Based Investigation on the Structure and Antioxidant Behavior of Lichen Substances Atranorin, Evernic Acid and Diffractaic Acid","volume":"80","author":"Ahamed","year":"2019","journal-title":"Comput. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.comptc.2013.03.015","article-title":"A Density Functional Theory Study of the Reactivity Descriptors and Antioxidant Behavior of Crocin","volume":"1013","author":"Akhtari","year":"2013","journal-title":"Comput. Theor. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"113658","DOI":"10.1016\/j.comptc.2022.113658","article-title":"A DFT Study of the Chemical Reactivity Properties, Spectroscopy and Bioactivity Scores of Bioactive Flavonols","volume":"1210","author":"Akintemi","year":"2022","journal-title":"Comput. Theor. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/s00214-007-0310-x","article-title":"The M06 Suite of Density Functionals for Main Group Thermochemistry, Thermochemical Kinetics, Noncovalent Interactions, Excited States, and Transition Elements: Two New Functionals and Systematic Testing of Four M06-Class Functionals and 12 Other Functionals","volume":"120","author":"Zhao","year":"2008","journal-title":"Theor. Chem. Acc."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"6378","DOI":"10.1021\/jp810292n","article-title":"Universal Solvation Model Based on Solute Electron Density and on a Continuum Model of the Solvent Defined by the Bulk Dielectric Constant and Atomic Surface Tensions","volume":"113","author":"Marenich","year":"2009","journal-title":"J. Phys. Chem. B"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1007\/s11224-022-01895-2","article-title":"Structure\u2013Antioxidant Activity Relationships of Dendrocandin Analogues Determined Using Density Functional Theory","volume":"33","author":"Zhang","year":"2022","journal-title":"Struct. Chem."},{"key":"ref_49","unstructured":"Morin, J., and Pelletier, J.M. (2013). Density Functional Theory: Principles, Applications and Analysis, Nova Science Pub Inc."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1088\/1674-0068\/24\/02\/173-180","article-title":"DFT Study on Molecular Structures and ROS Scavenging Mechanisms of Novel Antioxidants from Lespedeza Virgata","volume":"24","author":"Li","year":"2011","journal-title":"Chin. J. Chem. Phys."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1002\/bkcs.10132","article-title":"Quantum-Chemical Studies to Approach the Antioxidant Mechanism of Nonphenolic Hydrazone Schiff Base Analogs: Synthesis, Molecular Structure, Hirshfeld and Density Functional Theory Analyses","volume":"36","author":"Alam","year":"2015","journal-title":"Bull. Korean Chem. Soc."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.molstruc.2018.09.046","article-title":"Synthesis, X-Ray, Spectroscopic Characterization, DFT and Antioxidant Activity of 1,2,4-Triazolo[1,5-a]Pyrimidine Derivatives","volume":"1177","author":"Lahmidi","year":"2019","journal-title":"J. Mol. Struct."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2354","DOI":"10.1002\/jcc.26012","article-title":"DFT Calculations on Molecular Structures, HOMO\u2013LUMO Study, Reactivity Descriptors and Spectral Analyses of Newly Synthesized Diorganotin(IV) 2-Chloridophenylacetohydroxamate Complexes","volume":"40","author":"Choudhary","year":"2019","journal-title":"J. Comput. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1002\/qua.560340840","article-title":"Molecular Hardness and Softness Parameters and Their Use in Chemistry","volume":"34","author":"Nalewajski","year":"1988","journal-title":"Int. J. Quantum Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"108331","DOI":"10.1016\/j.rinp.2025.108331","article-title":"Computational Exploration of a Chlorinated Tetrahydroisoquinoline: Geometry, Reactivity, Noncovalent Interactions, and Molecular Docking Evaluation","volume":"75","author":"Messali","year":"2025","journal-title":"Results Phys."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"5781","DOI":"10.1039\/C4OB00555D","article-title":"Electrophilicity and Nucleophilicity of Commonly Used Aldehydes","volume":"12","author":"Pratihar","year":"2014","journal-title":"Org. Biomol. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1002\/poc.719","article-title":"Relationship between Nucleophilicity\/Electrophilicity Indices and Reaction Mechanisms for the Nucleophilic Substitution Reactions of Carbonyl Compounds","volume":"17","author":"Campodonico","year":"2004","journal-title":"J. Phys. Org. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"31548","DOI":"10.1021\/acsomega.3c04922","article-title":"Spectroscopic, Biological, and Topological Insights on Lemonol as a Potential Anticancer Agent","volume":"8","author":"Selvaraj","year":"2023","journal-title":"ACS Omega"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"143102","DOI":"10.1016\/j.molstruc.2025.143102","article-title":"Hydrazide Compounds Incorporating with Aldehyde Moiety: Synthesis, Spectroscopy, Crystal Structure Analysis, Theoretical Studies and Molecular Docking Studies of (E)-4-Amino-N\u2019-(Substituted Benzylidene) Benzohydrazide","volume":"1346","author":"Umamaheswari","year":"2025","journal-title":"J. Mol. Struct."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1007\/s00214-023-02970-5","article-title":"Antioxidant Activity of Hibiscetin and Hibiscitrin: Insight from DFT, NCI, and QTAIM","volume":"142","author":"Ragi","year":"2023","journal-title":"Theor. Chem. Acc."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1007\/s11224-020-01630-9","article-title":"A Theoretical Study of the Structural and Electronic Properties of Some Titanocenes Using DFT, TD-DFT, and QTAIM","volume":"32","author":"Nono","year":"2021","journal-title":"Struct. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.molstruc.2012.05.065","article-title":"DFT and QTAIM Study of the Tetra-Tert-Butyltetraoxa[8]Circulene Regioisomers Structure","volume":"1026","author":"Baryshnikov","year":"2012","journal-title":"J. Mol. Struct."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4070","DOI":"10.1021\/acs.jpcb.9b01799","article-title":"Structure and Dynamics in Amino Acid Choline-Based Ionic Liquids: A Combined QTAIM, NCI, DFT, and Molecular Dynamics Study","volume":"123","author":"Moosavi","year":"2019","journal-title":"J. Phys. Chem. B"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2621","DOI":"10.1007\/s00894-011-1274-2","article-title":"A QSAR Study of Radical Scavenging Antioxidant Activity of a Series of Flavonoids Using DFT Based Quantum Chemical Descriptors\u2014The Importance of Group Frontier Electron Density","volume":"18","author":"Sarkar","year":"2012","journal-title":"J. Mol. Model."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1142\/S0219633612500599","article-title":"A DFT Study on the Role of Different Oh Groups in the Radical Scavenging Process","volume":"11","author":"Sadasivam","year":"2012","journal-title":"J. Theor. Comput. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1007\/s11483-012-9276-x","article-title":"A DFT Study on the Structural and Antioxidant Properties of Three Flavonols","volume":"8","author":"Rong","year":"2013","journal-title":"Food Biophys."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"54136","DOI":"10.1039\/C7RA11496F","article-title":"Synthesis, Antioxidant Activity, and Density Functional Theory Study of Catechin Derivatives","volume":"7","author":"Wang","year":"2017","journal-title":"RSC Adv."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s00894-022-05120-z","article-title":"Antioxidant Activity of Eugenol and Its Acetyl and Nitroderivatives: The Role of Quinone Intermediates\u2014A DFT Approach of DPPH Test","volume":"28","author":"Marinho","year":"2022","journal-title":"J. Mol. Model."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Ami\u0107, A., and Masti\u013e\u00e1k Cagardov\u00e1, D. (2023). A DFT Study on the Kinetics of HOO\u2022, CH3OO\u2022, and O2\u2022\u2212 Scavenging by Quercetin and Flavonoid Catecholic Metabolites. Antioxidants, 12.","DOI":"10.3390\/antiox12061154"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1007\/s00706-014-1341-3","article-title":"Mechanisms of the Hydroxyl and Superoxide Anion Radical Scavenging Activity and Protective Effect on Lipid Peroxidation of Thymoquinone: A DFT Study","volume":"146","author":"Akhtari","year":"2015","journal-title":"Monatshefte Chem."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Rossi, M., Caruso, F., Thieke, N., Belli, S., Kim, A., Damiani, E., Morresi, C., and Bacchetti, T. (2024). Examining the Antioxidant and Superoxide Radical Scavenging Activity of Anise, (Pimpinella anisum L. Seeds), Esculetin, and 4-Methyl-Esculetin Using X-Ray Diffraction, Hydrodynamic Voltammetry and DFT Methods. Pharmaceuticals, 17.","DOI":"10.3390\/ph17010067"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"11417","DOI":"10.1039\/D5RA01364J","article-title":"Theoretical Study on the Influence of OH Group Position on the Free Radical Scavenging Ability of Tryptamine Derivatives","volume":"15","author":"Huong","year":"2025","journal-title":"RSC Adv."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1007\/s00214-003-0544-1","article-title":"Density Functional Computations of the Energetic and Spectroscopic Parameters of Quercetin and Its Radicals in the Gas Phase and in Solvent","volume":"111","author":"Leopoldini","year":"2004","journal-title":"Theor. Chem. Acc."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1021\/jp035901j","article-title":"Structure, Conformation, and Electronic Properties of Apigenin, Luteolin, and Taxifolin Antioxidants. A First Principle Theoretical Study","volume":"108","author":"Leopoldini","year":"2004","journal-title":"J. Phys. Chem. A"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"100904","DOI":"10.1016\/j.chphi.2025.100904","article-title":"Investigation of Free Radical Scavenging Activities of Some Isatin Schiff Bases (OH versus NH). A DFT Study","volume":"11","author":"Boudiaf","year":"2025","journal-title":"Chem. Phys. Impact"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e70019","DOI":"10.1002\/wcms.70019","article-title":"Software Update: The ORCA Program System\u2014Version 6.0","volume":"15","author":"Neese","year":"2025","journal-title":"WIREs Comput. Mol. Sci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1740","DOI":"10.1002\/jcc.10318","article-title":"An Improvement of the Resolution of the Identity Approximation for the Formation of the Coulomb Matrix","volume":"24","author":"Neese","year":"2003","journal-title":"J. Comput. Chem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/wcms.81","article-title":"The ORCA Program System","volume":"2","author":"Neese","year":"2012","journal-title":"WIREs Comput. Mol. Sci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1002\/jcc.26942","article-title":"The SHARK Integral Generation and Digestion System","volume":"44","author":"Neese","year":"2023","journal-title":"J. Comput. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.chemphys.2008.10.036","article-title":"Efficient, Approximate and Parallel Hartree\u2013Fock and Hybrid DFT Calculations. A \u2018Chain-of-Spheres\u2019 Algorithm for the Hartree\u2013Fock Exchange","volume":"356","author":"Neese","year":"2009","journal-title":"Chem. Phys."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1080\/00268976.2015.1025114","article-title":"Efficient Implementation of the Analytic Second Derivatives of Hartree\u2013Fock and Hybrid DFT Energies: A Detailed Analysis of Different Approximations","volume":"113","author":"Bykov","year":"2015","journal-title":"Mol. Phys."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.1002\/jcc.25833","article-title":"Efficient Implementation of the Analytical Second Derivatives of Hartree\u2013Fock and Hybrid DFT Energies within the Framework of the Conductor-like Polarizable Continuum Model","volume":"40","author":"Neese","year":"2019","journal-title":"J. Comput. Chem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1002\/jcc.26139","article-title":"Effect of the Solute Cavity on the Solvation Energy and Its Derivatives within the Framework of the Gaussian Charge Scheme","volume":"41","author":"Neese","year":"2020","journal-title":"J. Comput. Chem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"104109","DOI":"10.1063\/5.0058766","article-title":"An Improved Chain of Spheres for Exchange Algorithm","volume":"155","author":"Neese","year":"2021","journal-title":"J. Chem. Phys."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1002\/jcc.27284","article-title":"Predicting the Activity of Methoxyphenol Derivatives Antioxidants: II\u2014Importance of the Nature of the Solvent on the Mechanism, a DFT Study","volume":"45","author":"Khelifi","year":"2024","journal-title":"J. Comput. Chem."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"114287","DOI":"10.1016\/j.comptc.2023.114287","article-title":"Predicting the Activity of Methoxyphenol Derivatives Antioxidants: I. Structure and Reactivity of Methoxyphenol Derivatives, a DFT Approach","volume":"1229","author":"Khelifi","year":"2023","journal-title":"Comput. Theor. Chem."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"101","DOI":"10.3184\/146867818X15161889114484","article-title":"Investigation of Reaction Mechanisms and Kinetics of the Radical Scavenging Ability of 5-Tert-Butylbenzene-1,2,3-Triol and 3,5-Di-Tert-Butylbenzene-1,2-Diol Compounds Towards OOH Radical","volume":"43","author":"Mekelleche","year":"2018","journal-title":"Prog. React. Kinet. Mech."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1007\/s00894-016-3118-6","article-title":"Benchmarking the DFT Methodology for Assessing Antioxidant-Related Properties: Quercetin and Edaravone as Case Studies","volume":"22","author":"Rutkowski","year":"2016","journal-title":"J. Mol. Model."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1758-2946-4-17","article-title":"Avogadro: An Advanced Semantic Chemical Editor, Visualization, and Analysis Platform","volume":"4","author":"Hanwell","year":"2012","journal-title":"J. Cheminform."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"e202500393","DOI":"10.1002\/anie.202500393","article-title":"GOAT: A Global Optimization Algorithm for Molecules and Atomic Clusters","volume":"64","year":"2025","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1021\/acs.jctc.8b01176","article-title":"GFN2-xTB\u2014An Accurate and Broadly Parametrized Self-Consistent Tight-Binding Quantum Chemical Method with Multipole Electrostatics and Density-Dependent Dispersion Contributions","volume":"15","author":"Bannwarth","year":"2019","journal-title":"J. Chem. Theory Comput."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"e1493","DOI":"10.1002\/wcms.1493","article-title":"Extended TIGHT-BINDING Quantum Chemistry Methods","volume":"11","author":"Bannwarth","year":"2021","journal-title":"WIREs Comput. Mol. Sci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1350024","DOI":"10.1142\/S0219633613500247","article-title":"DFT Insight into the UV-Vis Spectra and Radical Scavenging Activity of Aurantio-Obtusin","volume":"12","author":"Xu","year":"2013","journal-title":"J. Theor. Comput. Chem."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.comptc.2012.01.028","article-title":"A DFT Study on the Structural, Electronic Properties and Radical Scavenging Mechanisms of Calycosin, Glycitein, Pratensein and Prunetin","volume":"985","author":"Kumaresan","year":"2012","journal-title":"Comput. Theor. Chem."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"12196","DOI":"10.1021\/jp8058905","article-title":"A DFT Study on the Radical Scavenging Activity of Maritimetin and Related Aurones","volume":"112","author":"Nenadis","year":"2008","journal-title":"J. Phys. Chem. A"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1002\/jcc.22885","article-title":"Multiwfn: A Multifunctional Wavefunction Analyzer","volume":"33","author":"Lu","year":"2012","journal-title":"J. Comput. Chem."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"082503","DOI":"10.1063\/5.0216272","article-title":"A Comprehensive Electron Wavefunction Analysis Toolbox for Chemists, Multiwfn","volume":"161","author":"Lu","year":"2024","journal-title":"J. Chem. Phys."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.jmgm.2017.09.020","article-title":"DFT, QTAIM, and NBO Studies on the Trimeric Interactions in the Protrusion Domain of a Piscine Betanodavirus","volume":"78","author":"Astani","year":"2017","journal-title":"J. Mol. Graph. Model."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Obot, I.B., Onyeachu, I.B., and Kaya, S. (2023). Density Functional Theory: Practical Application and Their Limitations in Corrosion Inhibition Research. Corrosion Science, Apple Academic Press.","DOI":"10.1201\/9781003328513-6"},{"key":"ref_100","unstructured":"Kaya, S., von Szentpaly, L., Serdaroglu, G., and Guo, L. (2023). Chemical Reactivity: Volume 1: Theories and Principles, Elsevier."},{"key":"ref_101","unstructured":"Locatelli, M., and Kaya, S. (2025). Chapter 3\u2014Conceptual Density Functional Theory\u2013Based Applications in Extraction Studies. Green Analytical Chemistry, Elsevier."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/22\/11217\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T10:35:11Z","timestamp":1763634911000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/22\/11217"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,20]]},"references-count":101,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["ijms262211217"],"URL":"https:\/\/doi.org\/10.3390\/ijms262211217","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,20]]}}}