{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T19:29:05Z","timestamp":1791487745193,"version":"4.3.4"},"reference-count":79,"publisher":"Wiley","issue":"67","license":[{"start":{"date-parts":[[2020,10,22]],"date-time":"2020-10-22T00:00:00Z","timestamp":1603324800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry A European J"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The concepts of nucleophilicity and protophilicity are fundamental and ubiquitous in chemistry. A case in point is bimolecular nucleophilic substitution (S<jats:sub>N<\/jats:sub>2) and base\u2010induced elimination (E2). A Lewis base acting as a strong nucleophile is needed for S<jats:sub>N<\/jats:sub>2 reactions, whereas a Lewis base acting as a strong protophile (i.e., base) is required for E2 reactions. A complicating factor is, however, the fact that a good nucleophile is often a strong protophile. Nevertheless, a sound, physical model that explains, in a transparent manner, when an electron\u2010rich Lewis base acts as a protophile or a nucleophile, which is not just phenomenological, is currently lacking in the literature. To address this fundamental question, the potential energy surfaces of the S<jats:sub>N<\/jats:sub>2 and E2 reactions of X<jats:sup>\u2212<\/jats:sup>+C<jats:sub>2<\/jats:sub>H<jats:sub>5<\/jats:sub>Y model systems with X, Y = F, Cl, Br, I, and At, are explored by using relativistic density functional theory at ZORA\u2010OLYP\/TZ2P. These explorations have yielded a consistent overview of reactivity trends over a wide range in reactivity and pathways. Activation strain analyses of these reactions reveal the factors that determine the shape of the potential energy surfaces and hence govern the propensity of the Lewis base to act as a nucleophile or protophile. The concepts of \u201ccharacteristic distortivity\u201d and \u201ctransition state acidity\u201d of a reaction are introduced, which have the potential to enable chemists to better understand and design reactions for synthesis.<\/jats:p>","DOI":"10.1002\/chem.202003831","type":"journal-article","created":{"date-parts":[[2020,8,31]],"date-time":"2020-08-31T14:50:30Z","timestamp":1598885430000},"page":"15538-15548","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["A Unified Framework for Understanding Nucleophilicity and Protophilicity in the S<sub>N<\/sub>2\/E2 Competition"],"prefix":"10.1002","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2100-6837","authenticated-orcid":false,"given":"Pascal","family":"Vermeeren","sequence":"first","affiliation":[{"name":"Department of Theoretical Chemistry Amsterdam Institute of, Molecular and Life Sciences (AIMMS) Amsterdam Center for Multiscale, Modeling (ACMM) Vrije Universiteit Amsterdam  De Boelelaan 1083 1081 HV Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6291-1569","authenticated-orcid":false,"given":"Thomas","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department of Theoretical Chemistry Amsterdam Institute of, Molecular and Life Sciences (AIMMS) Amsterdam Center for Multiscale, Modeling (ACMM) Vrije Universiteit Amsterdam  De Boelelaan 1083 1081 HV Amsterdam The Netherlands"},{"name":"Leiden Institute of Chemistry Leiden University  Einsteinweg 55, 2333 CC Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2520-0258","authenticated-orcid":false,"given":"Paul","family":"Jansen","sequence":"additional","affiliation":[{"name":"Department of Theoretical Chemistry Amsterdam Institute of, Molecular and Life Sciences (AIMMS) Amsterdam Center for Multiscale, Modeling (ACMM) Vrije Universiteit Amsterdam  De Boelelaan 1083 1081 HV Amsterdam The Netherlands"},{"name":"Laboratory of Physical Chemistry ETH Zurich  Vladimir-Prelog-Weg 2 8093 Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8174-8488","authenticated-orcid":false,"given":"Marcel","family":"Swart","sequence":"additional","affiliation":[{"name":"ICREA  Pg. Llu\u00eds Companys 23 08010 Barcelona Spain"},{"name":"IQCC &amp; Dept. Qu\u00edmica Universitat de Girona  Campus Montilivi (Ci\u00e8ncies) 17003 Girona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5128-1004","authenticated-orcid":false,"given":"Trevor A.","family":"Hamlin","sequence":"additional","affiliation":[{"name":"Department of Theoretical Chemistry Amsterdam Institute of, Molecular and Life Sciences (AIMMS) Amsterdam Center for Multiscale, Modeling (ACMM) Vrije Universiteit Amsterdam  De Boelelaan 1083 1081 HV Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4655-7747","authenticated-orcid":false,"given":"F. Matthias","family":"Bickelhaupt","sequence":"additional","affiliation":[{"name":"Department of Theoretical Chemistry Amsterdam Institute of, Molecular and Life Sciences (AIMMS) Amsterdam Center for Multiscale, Modeling (ACMM) Vrije Universiteit Amsterdam  De Boelelaan 1083 1081 HV Amsterdam The Netherlands"},{"name":"Institute for Molecules and Materials Radboud University  Heyendaalseweg 135 6525 AJ Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,10,22]]},"reference":[{"key":"e_1_2_6_1_1","volume-title":"March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure","author":"Smith M. B.","year":"2013"},{"key":"e_1_2_6_2_1","unstructured":"\u00a0"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/cphc.201701363"},{"key":"e_1_2_6_4_2","first-page":"1","volume":"51","author":"Uggerud E.","year":"2017","journal-title":"Adv. Phys. Org. 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