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Revisiting HCHs to explore their biological activity while improving key features is valuable and may lead to a new class of pesticides that utilizes the biological response of HCHs without their toxic characteristics. In this sense, the fluorine atom can be a possible alternative since a large number of therapeutics and agrochemicals have been developed with this halogen in their structure. We have evaluated herein the conformational behavior of HCHs and their bioisosteric fluorinated compounds, namely, hexafluorocyclohexanes (HFHs), through quantum\u2010chemical calculations. We also explored the potential of the HCH and HFH isomers as biological compounds by docking them inside three possible targets. It was demonstrated that HCH and HFH have similar ligand\u2010protein interactions with three pockets: the picrotoxin and barbiturate sites of the GABA<jats:sub>A<\/jats:sub> receptor and the ryanodine receptor. The results support HFHs as possible alternatives for HCHs since the replacement of Cl with F does not forfeit the main ligand\u2010protein interactions. Finally, we demonstrated that HFHs have a lower log <jats:italic>P<\/jats:italic> than HCHs by almost two logarithmic units. This result highlights the role of fluorine in distribution and bioaccumulation.<\/jats:p>","DOI":"10.1002\/cphc.202200450","type":"journal-article","created":{"date-parts":[[2022,10,5]],"date-time":"2022-10-05T07:44:58Z","timestamp":1664955898000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Theoretical Exploitation of 1,2,3,4,5,6\u2010Hexachloro\u2010 and 1,2,3,4,5,6\u2010Hexafluorocyclohexane Isomers as Biologically Active Compounds"],"prefix":"10.1002","volume":"24","author":[{"given":"Francisco A.","family":"Martins","sequence":"first","affiliation":[{"name":"Department of Chemistry Institute of Natural Sciences Federal University of Lavras  37200-900 Lavras MG Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7492-1801","authenticated-orcid":false,"given":"Matheus P.","family":"Freitas","sequence":"additional","affiliation":[{"name":"Department of Chemistry Institute of Natural Sciences Federal University of Lavras  37200-900 Lavras MG Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,11,22]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02987393"},{"key":"e_1_2_7_2_1","unstructured":"\u00a0"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-382032-7.10020-7"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/etc.5620140511"},{"key":"e_1_2_7_5_1","unstructured":"\u00a0"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0269-7491(99)00059-7"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0048-9697(01)01104-4"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0048-9697(95)04378-E"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1021\/es962399q"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2004.12.027"},{"key":"e_1_2_7_11_1","unstructured":"\u00a0"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1001-0742(11)61004-8"},{"key":"e_1_2_7_13_2","first-page":"664","volume":"6","author":"Das Y. 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