{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:42:54Z","timestamp":1787168574700,"version":"build-2736575974"},"reference-count":75,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100014824","name":"Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, India","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014824","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bioorganic Chemistry"],"published-print":{"date-parts":[[2025,4]]},"DOI":"10.1016\/j.bioorg.2025.108291","type":"journal-article","created":{"date-parts":[[2025,2,23]],"date-time":"2025-02-23T10:08:05Z","timestamp":1740305285000},"page":"108291","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":9,"special_numbering":"C","title":["Carbene reactive metabolite explains the hepatotoxicity of the hot flashes drug fezolinetant: A DFT investigation"],"prefix":"10.1016","volume":"157","author":[{"given":"Anila","family":"Nuthi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gauri","family":"Mishra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaibhav A.","family":"Dixit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bioorg.2025.108291_bb0005","series-title":"Center for drug evaluation and research application number: 216578orig1s000 cross discipline team leader review","year":"2025"},{"key":"10.1016\/j.bioorg.2025.108291_bb0010","author":"Astellas Pharma Europe B.V"},{"key":"10.1016\/j.bioorg.2025.108291_bb0015","author":"Fda, Cder"},{"key":"10.1016\/j.bioorg.2025.108291_bb0020","article-title":"In vitro Evaluation of CYP-mediated metabolism of Fezolinetant and pharmacokinetic interaction between Fezolinetant and fluvoxamine in healthy postmenopausal smokers and nonsmokers","author":"Iwai","year":"2024","journal-title":"J. Clin. Pharmacol."},{"key":"10.1016\/j.bioorg.2025.108291_bb0025","series-title":"OGEDA SA 6041 Charleroi (BE)","year":"2017"},{"key":"10.1016\/j.bioorg.2025.108291_bb0030","doi-asserted-by":"crossref","first-page":"2364","DOI":"10.1021\/acs.chemrestox.5b00364","article-title":"Toxicity originating from Thiophene containing drugs: exploring the mechanism using quantum chemical methods","volume":"28","author":"Jaladanki","year":"2015","journal-title":"Chem. Res. Toxicol."},{"key":"10.1016\/j.bioorg.2025.108291_bb0035","doi-asserted-by":"crossref","first-page":"10441","DOI":"10.1021\/jp308023g","article-title":"Density functional study on the cytochrome-mediated S-oxidation: identification of crucial reactive intermediate on the metabolic path of thiazolidinediones","volume":"116","author":"Taxak","year":"2012","journal-title":"J. Phys. Chem. A"},{"key":"10.1016\/j.bioorg.2025.108291_bb0040","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1021\/tx200110h","article-title":"Toxic metabolite formation from troglitazone (TGZ): new insights from a DFT study","volume":"24","author":"Dixit","year":"2011","journal-title":"Chem. Res. Toxicol."},{"key":"10.1016\/j.bioorg.2025.108291_bb0045","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1021\/tx060198m","article-title":"Inhibition of cytochrome P450 3A4 by a Pyrimidineimidazole: evidence for complex Heme interactions","volume":"19","author":"Hutzler","year":"2006","journal-title":"Chem. Res. Toxicol."},{"key":"10.1016\/j.bioorg.2025.108291_bb0050","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1124\/dmd.31.11.1391","article-title":"Human cytochrome P450 inhibition and metabolic-intermediate complex formation by goldenseal extract and its methylenedioxyphenyl components","volume":"31","author":"Chatterjee","year":"2003","journal-title":"Drug Metab. Dispos."},{"key":"10.1016\/j.bioorg.2025.108291_bb0055","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1124\/mol.116.103721","article-title":"N-heterocyclic Carbene capture by cytochrome P450 3A4","volume":"90","author":"Jennings","year":"2016","journal-title":"Mol. Pharmacol."},{"key":"10.1016\/j.bioorg.2025.108291_bb0060","doi-asserted-by":"crossref","first-page":"2833","DOI":"10.1021\/acs.molpharmaceut.6b00436","article-title":"Mechanism-based inhibition of CYP3A4 by Podophyllotoxin: aging of an intermediate is important for in vitro\/in vivo correlations","volume":"13","author":"Barnaba","year":"2016","journal-title":"Mol. Pharm."},{"key":"10.1016\/j.bioorg.2025.108291_bb0065","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1021\/acs.chemrestox.0c00483","article-title":"Mechanism-based inactivation of cytochrome P450 enzymes: computational insights","volume":"34","author":"Mirzaei","year":"2021","journal-title":"Chem. Res. Toxicol."},{"key":"10.1016\/j.bioorg.2025.108291_bb0070","doi-asserted-by":"crossref","first-page":"5097","DOI":"10.1021\/ic400010d","article-title":"Carbene generation by cytochromes and electronic structure of Heme-Iron-porphyrin-Carbene complex: a quantum chemical study","volume":"52","author":"Taxak","year":"2013","journal-title":"Inorg. Chem."},{"key":"10.1016\/j.bioorg.2025.108291_bb0075","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1021\/acsmedchemlett.5b00117","article-title":"Optimization of novel antagonists to the Neurokinin-3 receptor for the treatment of sex-hormone disorders (part II)","volume":"6","author":"Hoveyda","year":"2015","journal-title":"ACS Med. Chem. Lett."},{"key":"10.1016\/j.bioorg.2025.108291_bb0080","series-title":"FDA adds warning about rare occurrence of serious liver injury with use of Veozah (fezolinetant) for hot flashes due to menopause","author":"Fda, Cder","year":"2025"},{"key":"10.1016\/j.bioorg.2025.108291_bb0085","series-title":"Drug Interactions | Relevant Regulatory Guidance and Policy Documents","year":"2025"},{"key":"10.1016\/j.bioorg.2025.108291_bb0090","doi-asserted-by":"crossref","first-page":"2060","DOI":"10.1021\/acs.chemrestox.7b00129","article-title":"Biotransformation of isoniazid by cytochromes P450: analyzing the molecular mechanism using density functional theory","volume":"30","author":"Jaladanki","year":"2017","journal-title":"Chem. Res. Toxicol."},{"key":"10.1016\/j.bioorg.2025.108291_bb0095","doi-asserted-by":"crossref","first-page":"4158","DOI":"10.1021\/acs.jcim.3c00549","article-title":"Prediction of sites of metabolism of CYP3A4 substrates utilizing docking-derived geometric features","volume":"63","author":"Feng","year":"2023","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.bioorg.2025.108291_bb0100","doi-asserted-by":"crossref","first-page":"6571","DOI":"10.1002\/slct.201601051","article-title":"Advances in computational prediction of Regioselective and isoform-specific drug metabolism catalyzed by CYP450s","volume":"1","author":"Dixit","year":"2016","journal-title":"ChemistrySelect"},{"key":"10.1016\/j.bioorg.2025.108291_bb0105","doi-asserted-by":"crossref","DOI":"10.1002\/wcms.1323","article-title":"Recent advances in the prediction of non-CYP450-mediated drug metabolism","volume":"7","author":"Dixit","year":"2017","journal-title":"Wiley Interdiscip Rev. Comput. Mol. Sci."},{"key":"10.1016\/j.bioorg.2025.108291_bb0110","doi-asserted-by":"crossref","first-page":"15270","DOI":"10.1002\/chem.202003024","article-title":"How do metal ions modulate the rate-determining Electron-transfer step in cytochrome P450 reactions?","volume":"26","author":"Dixit","year":"2020","journal-title":"Chem. Eur. J."},{"key":"10.1016\/j.bioorg.2025.108291_bb0115","doi-asserted-by":"crossref","DOI":"10.1002\/minf.202400008","article-title":"Sulfotransferase-mediated phase II drug metabolism prediction of substrates and sites using accessibility and reactivity-based algorithms","author":"Vyas","year":"2024","journal-title":"Mol. Inform."},{"key":"10.1016\/j.bioorg.2025.108291_bb0120","doi-asserted-by":"crossref","first-page":"2328","DOI":"10.1038\/s41467-020-16201-z","article-title":"Prediction of organic homolytic bond dissociation enthalpies at near chemical accuracy with sub-second computational cost","volume":"11","author":"St","year":"2020","journal-title":"Nat. Commun."},{"key":"10.1016\/j.bioorg.2025.108291_bb0125","doi-asserted-by":"crossref","first-page":"2834","DOI":"10.1016\/j.ejmech.2008.12.017","article-title":"Melatonin: quantum-chemical and biochemical investigation of antioxidant activity","volume":"44","author":"Velkov","year":"2009","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.bioorg.2025.108291_bb0130","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/j.ejmech.2006.03.003","article-title":"Computational approaches for predicting CYP-related metabolism properties in the screening of new drugs","volume":"41","author":"Crivori","year":"2006","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.bioorg.2025.108291_bb0135","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.ejmech.2012.08.017","article-title":"The impact of carbon\u2013hydrogen bond dissociation energies on the prediction of the cytochrome P450 mediated major metabolic site of drug-like compounds","volume":"56","author":"Drew","year":"2012","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.bioorg.2025.108291_bb0140","doi-asserted-by":"crossref","first-page":"4642","DOI":"10.1021\/jm0703690","article-title":"Use of density functional calculations to predict the Regioselectivity of drugs and molecules metabolized by aldehyde oxidase","volume":"50","author":"Torres","year":"2007","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2025.108291_bb0145","doi-asserted-by":"crossref","first-page":"2279","DOI":"10.1021\/cr030722j","article-title":"Theoretical perspective on the structure and mechanism of cytochrome P450 enzymes","volume":"105","author":"Shaik","year":"2005","journal-title":"Chem. Rev."},{"key":"10.1016\/j.bioorg.2025.108291_bb0150","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1517\/17425255.2014.864278","article-title":"Use of density functional theory in drug metabolism studies","volume":"10","author":"Rydberg","year":"2014","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"10.1016\/j.bioorg.2025.108291_bb0155","doi-asserted-by":"crossref","DOI":"10.1016\/j.comptc.2023.114296","article-title":"Quantum chemical exploration of the mechanism of Robinson\u2013Gabriel reaction","volume":"1228","author":"Hirlekar","year":"2023","journal-title":"Comput. Theor. Chem."},{"key":"10.1016\/j.bioorg.2025.108291_bb0160","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1021\/acs.jcim.9b00836","article-title":"The metabolic rainbow: deep learning phase I metabolism in five colors","volume":"60","author":"Le Dang","year":"2020","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.bioorg.2025.108291_bb0165","doi-asserted-by":"crossref","first-page":"W115","DOI":"10.1093\/nar\/gkac313","article-title":"BioTransformer 3.0\u2014a web server for accurately predicting metabolic transformation products","volume":"50","author":"Wishart","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.bioorg.2025.108291_bb0170","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.abb.2010.08.017","article-title":"Multi-step oxidations catalyzed by cytochrome P450 enzymes: Processive vs. distributive kinetics and the issue of carbonyl oxidation in chemical mechanisms","volume":"507","author":"Guengerich","year":"2011","journal-title":"Arch. Biochem. Biophys."},{"key":"10.1016\/j.bioorg.2025.108291_bb0175","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1139\/v77-185","article-title":"Kinetics and mechanism of decarboxylation of some pyridinecarboxylic acids in aqueous solution","volume":"55","author":"Dunn","year":"1977","journal-title":"II, Can J. Chem."},{"key":"10.1016\/j.bioorg.2025.108291_bb0180","doi-asserted-by":"crossref","first-page":"2453","DOI":"10.1021\/jo1000324","article-title":"Imidazole-2-carboxy Steroids from the Marine Sponge Phorbas amaranthus. C24- N - and C24- O -Analogues from a Divergent Oxidative Biosynthesis","volume":"75","author":"Morinaka","year":"2010","journal-title":"J. Organomet. Chem."},{"key":"10.1016\/j.bioorg.2025.108291_bb0185","doi-asserted-by":"crossref","first-page":"3493","DOI":"10.1021\/jo00392a001","article-title":"Synthesis of novel imidazole-containing DNA minor groove binding oligopeptides related to the antiviral antibiotic netropsin","volume":"52","author":"Krowicki","year":"1987","journal-title":"J. Organomet. Chem."},{"key":"10.1016\/j.bioorg.2025.108291_bb0190","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1021\/cr940472u","article-title":"Stable Carbenes","volume":"100","author":"Bourissou","year":"2000","journal-title":"Chem. Rev."},{"key":"10.1016\/j.bioorg.2025.108291_bb0195","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1002\/prac.19973390170","article-title":"1,3,4-Triphenyl-4,5-dihydro-1H-1,2,4-triazol-5-ylidene - applications of a stable carbene in synthesis and catalysis","volume":"339","author":"Enders","year":"1997","journal-title":"J. F\u00fcr Praktische Chemie\/Chemiker-Zeitung"},{"key":"10.1016\/j.bioorg.2025.108291_bb0200","series-title":"Chemical Reactions of the Stable Carbene 1,3,4-Triphenyl-4,5-dihydro-1 H -1,2,4-triazol-5-ylidene, Liebigs Annalen 1996","first-page":"2019","author":"Enders","year":"1996"},{"key":"10.1016\/j.bioorg.2025.108291_bb0205","series-title":"Keith, AIMAll","author":"Todd","year":"2019"},{"key":"10.1016\/j.bioorg.2025.108291_bb0210","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.1021\/jp9805048","article-title":"Characterization of a dihydrogen bond on the basis of the Electron density","volume":"102","author":"Popelier","year":"1998","journal-title":"J. Phys. Chem. A"},{"key":"10.1016\/j.bioorg.2025.108291_bb0215","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.theochem.2010.09.020","article-title":"Intramolecular dihydrogen bond: a new perspective in Lewis acid catalyzed nucleophilic epoxide ring opening reaction","volume":"962","author":"Dixit","year":"2010","journal-title":"J. Mol. Struct. (THEOCHEM)"},{"key":"10.1016\/j.bioorg.2025.108291_bb0220","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1007\/s12039-016-1172-3","article-title":"Bader\u2019s theory of atoms in molecules (AIM) and its applications to chemical bonding","volume":"128","author":"Kumar","year":"2016","journal-title":"J. Chem. Sci."},{"key":"10.1016\/j.bioorg.2025.108291_bb0225","doi-asserted-by":"crossref","first-page":"4039","DOI":"10.1021\/acs.jpca.7b03405","article-title":"Carbenes as Electron-Pair Donors To CO 2 for C\u00b7\u00b7\u00b7C Tetrel Bonds and C\u2013C Covalent Bonds","volume":"121","author":"Del Bene","year":"2017","journal-title":"J. Phys. Chem. A"},{"key":"10.1016\/j.bioorg.2025.108291_bb0230","doi-asserted-by":"crossref","first-page":"9493","DOI":"10.1021\/acs.chemrev.8b00148","article-title":"Mesoionic and related less heteroatom-stabilized N-heterocyclic Carbene complexes: synthesis, catalysis, and other applications","volume":"118","author":"Vivancos","year":"2018","journal-title":"Chem. Rev."},{"key":"10.1016\/j.bioorg.2025.108291_bb0235","first-page":"12892","article-title":"Electronic structure trends in N-heterocyclic Carbenes (NHCs) with varying Number of nitrogen atoms and NHC transition-metal bond properties, chemistry \u2013 a","volume":"19","author":"Bernhammer","year":"2013","journal-title":"Eur. J. Dermatol."},{"key":"10.1016\/j.bioorg.2025.108291_bb0240","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1124\/mol.116.103721","article-title":"N -heterocyclic Carbene capture by cytochrome P450 3A4","volume":"90","author":"Jennings","year":"2016","journal-title":"Mol. Pharmacol."},{"key":"10.1016\/j.bioorg.2025.108291_bb0245","doi-asserted-by":"crossref","first-page":"5276","DOI":"10.1021\/acs.jmedchem.8b01808","article-title":"Applications of deuterium in medicinal chemistry","volume":"62","author":"Pirali","year":"2019","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2025.108291_bb0250","article-title":"An investigation on the mechanism of formation and reactivity of Olaparib metabolites","author":"Nuthi","year":"2025","journal-title":"Chem. Res. Toxicol."},{"key":"10.1016\/j.bioorg.2025.108291_bb0255","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1021\/cr900121s","article-title":"P450 enzymes: their structure, reactivity, and selectivity\u2014modeled by QM\/MM calculations","volume":"110","author":"Shaik","year":"2010","journal-title":"Chem. Rev."},{"key":"10.1016\/j.bioorg.2025.108291_bb0260","first-page":"1","article-title":"Predictive studies of oxygen atom transfer reactions by compound I of cytochrome P450. Aliphatic and aromatic hydroxylation, epoxidation, and sulfoxidation., Adv","volume":"64","author":"De Visser","year":"2012","journal-title":"Inorg. Chem."},{"key":"10.1016\/j.bioorg.2025.108291_bb0265","doi-asserted-by":"crossref","first-page":"16277","DOI":"10.1021\/acscatal.4c05330","article-title":"Diverse mechanisms for the aromatic hydroxylation: insights into the mechanisms of the Coumarin hydroxylation by CYP2A6","author":"Gan","year":"2024","journal-title":"ACS Catal."},{"key":"10.1016\/j.bioorg.2025.108291_bb0270","doi-asserted-by":"crossref","first-page":"407","DOI":"10.2174\/138920007780866807","article-title":"Mechanism-based inactivation of cytochrome P450 enzymes: chemical mechanisms, structure-activity relationships and relationship to clinical drug-drug interactions and idiosyncratic adverse drug reactions","volume":"8","author":"Kalgutkar","year":"2007","journal-title":"Curr. Drug Metab."},{"key":"10.1016\/j.bioorg.2025.108291_bb0275","doi-asserted-by":"crossref","first-page":"8016","DOI":"10.1021\/cr400611n","article-title":"Advances in the chemistry of Oxaziridines","volume":"114","author":"Williamson","year":"2014","journal-title":"Chem. Rev."},{"key":"10.1016\/j.bioorg.2025.108291_bb0280","doi-asserted-by":"crossref","first-page":"15004","DOI":"10.1021\/ja035590q","article-title":"Aromatic hydroxylation by cytochrome P450: model calculations of mechanism and substituent effects","volume":"125","author":"Bathelt","year":"2003","journal-title":"J. Am. Chem. Soc."},{"key":"10.1016\/j.bioorg.2025.108291_bb0285","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1021\/cr900121s","article-title":"P450 enzymes: their structure, reactivity, and selectivity\u2014modeled by QM\/MM calculations","volume":"110","author":"Shaik","year":"2010","journal-title":"Chem. Rev."},{"key":"10.1016\/j.bioorg.2025.108291_bb0290","doi-asserted-by":"crossref","first-page":"6098","DOI":"10.1021\/jm2006468","article-title":"Structure-based site of metabolism prediction for cytochrome P450 2D6","volume":"54","author":"Moors","year":"2011","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2025.108291_bb0295","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1021\/acs.jcim.8b00750","article-title":"Both reactivity and accessibility are important in cytochrome P450 metabolism: a combined DFT and MD study of Fenamic acids in BM3 mutants","volume":"59","author":"Leth","year":"2019","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.bioorg.2025.108291_bb0300","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/nrd4581","article-title":"Predicting drug metabolism: experiment and\/or computation?","volume":"14","author":"Kirchmair","year":"2015","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.bioorg.2025.108291_bb0305","doi-asserted-by":"crossref","first-page":"3405","DOI":"10.1016\/j.bmc.2005.03.011","article-title":"Electrophilicity as a possible descriptor for toxicity prediction","volume":"13","author":"Roy","year":"2005","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.bioorg.2025.108291_bb0310","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1007\/BF02708367","article-title":"A conceptual DFT approach towards analysing toxicity","volume":"117","author":"Sarkar","year":"2005","journal-title":"J. Chem. Sci."},{"key":"10.1016\/j.bioorg.2025.108291_bb0315","doi-asserted-by":"crossref","first-page":"4049","DOI":"10.1021\/ja00326a036","article-title":"Density functional approach to the frontier-electron theory of chemical reactivity","volume":"106","author":"Parr","year":"1984","journal-title":"J. Am. Chem. Soc."},{"issue":"1982","key":"10.1016\/j.bioorg.2025.108291_bb0320","first-page":"747","article-title":"Role of frontier orbitals in chemical reactions","volume":"218","author":"Fukui","year":"1979","journal-title":"Science"},{"key":"10.1016\/j.bioorg.2025.108291_bb0325","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1021\/ml100016x","article-title":"SMARTCyp: a 2D method for prediction of cytochrome P450-mediated drug metabolism","volume":"1","author":"Rydberg","year":"2010","journal-title":"ACS Med. Chem. Lett."},{"key":"10.1016\/j.bioorg.2025.108291_bb0330","doi-asserted-by":"crossref","first-page":"3373","DOI":"10.1021\/ci400518g","article-title":"XenoSite: accurately predicting CYP-mediated sites of metabolism with neural networks","volume":"53","author":"Zaretzki","year":"2013","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.bioorg.2025.108291_bb0335","first-page":"2","article-title":"BioTransformer: a comprehensive computational tool for small molecule metabolism prediction and metabolite identification","volume":"11","author":"Djoumbou-Feunang","year":"2019","journal-title":"J. Chemother."},{"key":"10.1016\/j.bioorg.2025.108291_bb0340","unstructured":"M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman, G. Scalmani, V. Barone, G.A. Petersson, H. Nakatsuji, X. Li, M. Caricato, A. V. Marenich, J. Bloino, B.G. Janesko, R. Gomperts, B. Mennucci, H.P. Hratchian, J. V. Ortiz, A.F. Izmaylov, J.L. Sonnenberg Williams, F. Ding, F. Lipparini, F. Egidi, J. Goings, B. Peng, A. Petrone, T. Henderson, D. Ranasinghe, V.G. Zakrzewski, J. Gao, N. Rega, G. Zheng, W. Liang, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven, K. Throssell, J.A. Jr Montgomery, J.E. Peralta, F. Ogliaro, M.J. Bearpark, J.J. Heyd, E.N. Brothers, K.N. Kudin, V.N. Staroverov, T.A. Keith R, Kobayashi J, Normand K, Raghavachari A.P, Rendell J C, Burant S S, Iyengar J, Tomasi M, Cossi J M, Millam M, Klene C, Adamo R, Cammi J W, Ochterski R L, Martin K, Morokuma O, Farkas J B, Foresman D J, Fox Gaussian, Inc., (2016)."},{"key":"10.1016\/j.bioorg.2025.108291_bb0345","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1021\/ci034033k","article-title":"Assessment of experimental bond dissociation energies using composite ab initio methods and evaluation of the performances of density functional methods in the calculation of bond dissociation energies","volume":"43","author":"Feng","year":"2003","journal-title":"J. Chem. Inf. Comput. Sci."},{"key":"10.1016\/j.bioorg.2025.108291_bb0350","doi-asserted-by":"crossref","first-page":"8044","DOI":"10.1021\/jp060566v","article-title":"S-trans \u22121,3-butadiene and Isotopomers: vibrational spectra, scaled quantum-chemical force fields, Fermi resonances, and C\u2212H bond properties","volume":"110","author":"McKean","year":"2006","journal-title":"J. Phys. Chem. A"},{"key":"10.1016\/j.bioorg.2025.108291_bb0355","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1021\/ct600185a","article-title":"Critical assessment of the performance of density functional methods for several atomic and molecular properties","volume":"3","author":"Riley","year":"2007","journal-title":"J. Chem. Theory Comput."},{"key":"10.1016\/j.bioorg.2025.108291_bb0360","doi-asserted-by":"crossref","first-page":"D1265","DOI":"10.1093\/nar\/gkad976","article-title":"DrugBank 6.0: the DrugBank knowledgebase for 2024","volume":"52","author":"Knox","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.bioorg.2025.108291_bb0365","doi-asserted-by":"crossref","first-page":"5535","DOI":"10.1021\/acs.jcim.1c01078","article-title":"Flexible CDOCKER: hybrid searching algorithm and scoring function with side chain conformational entropy","volume":"61","author":"Wu","year":"2021","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.bioorg.2025.108291_bb0370","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1002\/jcc.10306","article-title":"Detailed analysis of grid-based molecular docking: a case study of cdocker\u2014a charmm-based MD docking algorithm","volume":"24","author":"Wu","year":"2003","journal-title":"J. Comput. Chem."},{"key":"10.1016\/j.bioorg.2025.108291_bb0375","series-title":"Discovery Studio","author":"BIOVIA, Dassault Syst\u00e8mes","year":"2025"}],"container-title":["Bioorganic Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0045206825001713?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0045206825001713?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T21:34:24Z","timestamp":1763847264000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0045206825001713"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4]]},"references-count":75,"alternative-id":["S0045206825001713"],"URL":"https:\/\/doi.org\/10.1016\/j.bioorg.2025.108291","relation":{},"ISSN":["0045-2068"],"issn-type":[{"value":"0045-2068","type":"print"}],"subject":[],"published":{"date-parts":[[2025,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Carbene reactive metabolite explains the hepatotoxicity of the hot flashes drug fezolinetant: A DFT investigation","name":"articletitle","label":"Article Title"},{"value":"Bioorganic Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bioorg.2025.108291","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"108291"}}