{"doi":"10.1016/j.tox.2019.02.005","title":"Mechanisms of soft and hard electrophile toxicities","abstract":null,"journal":"Toxicology","year":2019,"id":656262,"datarank":0.6732954554598211,"base_score":4.48863636973214,"endowment":4.48863636973214,"self_citation_contribution":0.6732954554598211,"citation_network_contribution":0.0,"self_endowment_contribution":0.6732954554598211,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":88,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":542109,"name":"Brian C. Geohagen","orcid":null,"position":1,"is_corresponding":false},{"id":1713135,"name":"Lars U. Nordstroem","orcid":null,"position":2,"is_corresponding":false},{"id":541101,"name":"Richard M. LoPachin","orcid":"0000-0003-1903-4908","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Mechanisms of soft and hard electrophile toxicities","abstract":"Electron-deficient chemicals (electrophiles) react with compounds that have one or more unshared valence electron pairs (nucleophiles). The resulting covalent reactions between electrophiles and nucleophiles (e.g., Michael addition, S<sub>N</sub>2 reactions) are important, not only to Organic Chemistry, but also to the fields of Molecular Biology and Toxicology. Specifically, covalent bond formation is the operational basis of many critically important cellular processes; e.g., enzyme function, neurotransmitter release, and membrane-vesicle fusion. Given this context it is understandable that these reactions are also relevant to Toxicology, since a significant number of xenobiotic chemicals are toxic electrophiles that can react with endogenous nucleophilic residues. Therefore, the purpose of this Review is to discuss electrophile-nucleophile chemistry as it pertains to cell injury and resulting organ toxicity. Our discussion will involve an introduction to the Hard and Soft, Acids and Bases (HSAB) theory of Pearson. The HSAB concept provides a framework for calculation of quantum chemical parameters that classify the electrophile and nucleophile covalent components according to their respective electronic nature (softness/hardness) and reactivity (electrophilicity/nucleophilicity). The calculated quantum indices in conjunction with corroborative in vivo, in chemico (cell free) and in vitro research can offer an illuminating approach to mechanistic discovery. Accordingly, we will provide examples that demonstrate how this approach has been used to discern mechanisms and sites of electrophile action.","is_dataset_classified":null,"base_score":4.48863636973214,"endowment":4.48863636973214,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"30826385","pmcid":"PMC6494464","openalex_id":"https://openalex.org/W2919744532","authors":[],"funders":[{"funder_name":"National Institute of Environmental Health Sciences","grant_id":"RO1 ESO7912-11","title":null},{"funder_name":"National Institute of Environmental Health Sciences","grant_id":"RO1 ES03830-30","title":null},{"funder_name":"NIEHS NIH HHS","grant_id":"R01 ES007912","title":null},{"funder_name":"NIEHS NIH HHS","grant_id":"R01 ES003830","title":null},{"funder_name":"National Institutes of Health","grant_id":"","title":null}],"total_grants":5,"fwci":8.2111,"citation_percentile":0.98154235,"influential_citations":0,"citation_trend":[{"year":2017,"count":1},{"year":2019,"count":2},{"year":2020,"count":7},{"year":2021,"count":16},{"year":2022,"count":10},{"year":2023,"count":15},{"year":2024,"count":13},{"year":2025,"count":16},{"year":2026,"count":8}],"oa_status":"closed","license":"http://www.elsevier.com/open-access/userlicense/1.0/","oa_locations":[{"url":"https://api.elsevier.com/content/article/PII:S0300483X18305663?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0300483X18305663?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.tox.2019.02.005","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/30826385","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/6494464","host_type":"repository"}],"fields_of_study":["Chemical Reactions and Mechanisms","Cyclopropane Reaction Mechanisms","Asymmetric Synthesis and Catalysis","Animals","Cell Death","Environmental Exposure","Environmental Pollutants","Hardness","Humans","Models, Biological","Models, Molecular","Molecular Conformation","Risk Assessment","Structure-Activity Relationship","Xenobiotics"],"mesh_terms":["Animals","Environmental Exposure","Environmental Pollutants","Hardness","Humans","Models, Biological","Models, Molecular","Molecular Conformation","Structure-Activity Relationship","Xenobiotics","Cell Death","Risk Assessment"],"keywords":["Electrophile","Nucleophile","Chemistry","Covalent bond","Valence (chemistry)","Organic chemistry","Catalysis","Environmental pollution","Toxicity","Nucleophiles","Α,β-unsaturated Aldehydes","Electrophilic Toxicants","Type-2 Alkenes"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-11T20:19:08.895119Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}