{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T07:16:28Z","timestamp":1779002188751,"version":"3.51.4"},"reference-count":60,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T00:00:00Z","timestamp":1684713600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Higher Education and Scientific Research, Kurdistan Regional Government"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>[3+2] cycloaddition reactions play a crucial role in synthesizing complex organic molecules and have significant applications in drug discovery and materials science. In this study, the [3+2] cycloaddition (32CA) reactions of N-methyl-C-4-methyl phenyl-nitrone 1 and 2-propynamide 2, which have not been extensively studied before, were investigated using molecular electron density theory (MEDT) at the B3LYP\/6\u2013311++G(d,p) level of theory. According to an electron localization function (ELF) study, N-methyl-C-4-methyl phenyl-nitrone 1 is a zwitterionic species with no pseudoradical or carbenoid centers. Conceptual density functional theory (CDFT) indices were used to predict the global electronic flux from the strong nucleophilic N-methyl-C-4-methyl phenylnitrone 1 to the electrophilic 2-propynamide 2 functions. The 32CA reactions proceeded through two pairs of stereo- and regioisomeric reaction pathways to generate four different products: 3, 4, 5, and 6. The reaction pathways were irreversible owing to their exothermic characters: \u2212136.48, \u2212130.08, \u2212130.99, and \u2212140.81 kJ mol\u22121, respectively. The enthalpy of the 32CA reaction leading to the formation of cycloadduct 6 was lower compared with the other path owing to a slight increase in its polar character, observed through the global electron density transfer (GEDT) during the transition states and along the reaction path. A bonding evolution theory (BET) analysis showed that these 32CA reactions proceed through the coupling of pseudoradical centers, and the formation of new C-C and C-O covalent bonds did not begin in the transition states.<\/jats:p>","DOI":"10.3390\/ijms24109102","type":"journal-article","created":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T03:20:06Z","timestamp":1684812006000},"page":"9102","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Unveiling the Stereoselectivity and Regioselectivity of the [3+2] Cycloaddition Reaction between N-methyl-C-4-methylphenyl-nitrone and 2-Propynamide from a MEDT Perspective"],"prefix":"10.3390","volume":"24","author":[{"given":"Sabir A. Mohammed","family":"Salih","sequence":"first","affiliation":[{"name":"Faculty of Science, Department of Chemistry, University of Zakho, Duhok 42001, Iraq"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huda A.","family":"Basheer","sequence":"additional","affiliation":[{"name":"Faculty of Science, Department of Chemistry, University of Zakho, Duhok 42001, Iraq"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9403-8744","authenticated-orcid":false,"given":"Jesus Vicente","family":"de Juli\u00e1n-Ortiz","sequence":"additional","affiliation":[{"name":"Molecular Topology and Drug Design Research Unit, Department of Physical Chemistry, Pharmacy Faculty, University of Valencia, 46100 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9600-3446","authenticated-orcid":false,"given":"Haydar A.","family":"Mohammad-Salim","sequence":"additional","affiliation":[{"name":"Faculty of Science, Department of Chemistry, University of Zakho, Duhok 42001, Iraq"},{"name":"Molecular Topology and Drug Design Research Unit, Department of Physical Chemistry, Pharmacy Faculty, University of Valencia, 46100 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Feuer, H. 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