{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/67247"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/67247","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Estrogens Containing Alkylating Substituents: The Synthesis and Estrogen Receptor Interactions of Estradiol and Hexestrol Affinity Labels","abstract":"A series of chemically-reactive derivatives of estradiol and the non-steroidal estrogen hexestrol have been synthesized as potential affinity labels for the uterine estrogen receptor, or as cytotoxic agents with selective activity against receptor-containing cells. These compounds are hexestrol ethers with haloketone, halohydrin, or epoxide functions; 4-substituted deoxyhexestrols with nitro, azide, sulfonyl fluoride, or sulfonyl azide groups; and estradiol and hexestrol analogs incorporating benzyl halide functions ortho to the phenol or the corresponding methyl ether. The alkylating activity of the electrophilic derivatives was measured using the colorimetric reagent 4-(p-nitrobenzyl)pyridine, and the bromo derivatives were found to be consistently more reactive than the chloro ones. Their reversible binding to the lamb uterine estrogen receptor was measured by competitive binding assays, and their irreversible reaction with receptor was measured by exchange assays that determine the rate and extent of receptor inactivation. In general, etherification of hexestrol or substitution of deoxyhexestrol and estradiol produces compounds with relatively modest affinity for the estrogen receptor (0.3-10% that of estradiol). Most of the electrophilic derivatives are effective and rapid inactivators of receptor (24-44% inactivation within 0.5-5 hr at 25(DEGREES)C). Of the photosensitive derivatives, 4-azidodeoxyhexestrol appears to be the most efficient receptor inactivator (49%). The high estrogen receptor activity and the lack of interference by cellular nucleophiles suggests that these compounds may be useful as affinity labeling agents, or as selective cytotoxic agents in intact systems.","abstract_html":"A series of chemically-reactive derivatives of estradiol and the non-steroidal estrogen hexestrol have been synthesized as potential affinity labels for the uterine estrogen receptor, or as cytotoxic agents with selective activity against receptor-containing cells. These compounds are hexestrol ethers with haloketone, halohydrin, or epoxide functions; 4-substituted deoxyhexestrols with nitro, azide, sulfonyl fluoride, or sulfonyl azide groups; and estradiol and hexestrol analogs incorporating benzyl halide functions ortho to the phenol or the corresponding methyl ether. The alkylating activity of the electrophilic derivatives was measured using the colorimetric reagent 4-(p-nitrobenzyl)pyridine, and the bromo derivatives were found to be consistently more reactive than the chloro ones. Their reversible binding to the lamb uterine estrogen receptor was measured by competitive binding assays, and their irreversible reaction with receptor was measured by exchange assays that determine the rate and extent of receptor inactivation. In general, etherification of hexestrol or substitution of deoxyhexestrol and estradiol produces compounds with relatively modest affinity for the estrogen receptor (0.3-10% that of estradiol). Most of the electrophilic derivatives are effective and rapid inactivators of receptor (24-44% inactivation within 0.5-5 hr at 25(DEGREES)C). Of the photosensitive derivatives, 4-azidodeoxyhexestrol appears to be the most efficient receptor inactivator (49%). The high estrogen receptor activity and the lack of interference by cellular nucleophiles suggests that these compounds may be useful as affinity labeling agents, or as selective cytotoxic agents in intact systems.","abstract_has_math":false,"creators":["Mcgorrin, Robert Joseph, Jr."],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Chemistry","degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2014,"date_issued":"2014-12-13T20:11:05Z","date_published":"2014-12-13T20:11:05Z","updated_at":"2026-07-22T22:25:57Z","subjects":["Chemistry, Organic"],"languages":["eng"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["(UMI)AAI8108605"],"render_values":[{"text":"(UMI)AAI8108605","href":null,"code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/2142/67247","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Mcgorrin, Robert Joseph, Jr."]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2014-12-13T20:11:05Z","10000-01-01","1980"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Chemistry"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Chemistry, Organic"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/67247","(UMI)AAI8108605"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["A series of chemically-reactive derivatives of estradiol and the non-steroidal estrogen hexestrol have been synthesized as potential affinity labels for the uterine estrogen receptor, or as cytotoxic agents with selective activity against receptor-containing cells. These compounds are hexestrol ethers with haloketone, halohydrin, or epoxide functions; 4-substituted deoxyhexestrols with nitro, azide, sulfonyl fluoride, or sulfonyl azide groups; and estradiol and hexestrol analogs incorporating benzyl halide functions ortho to the phenol or the corresponding methyl ether. The alkylating activity of the electrophilic derivatives was measured using the colorimetric reagent 4-(p-nitrobenzyl)pyridine, and the bromo derivatives were found to be consistently more reactive than the chloro ones. Their reversible binding to the lamb uterine estrogen receptor was measured by competitive binding assays, and their irreversible reaction with receptor was measured by exchange assays that determine the rate and extent of receptor inactivation. In general, etherification of hexestrol or substitution of deoxyhexestrol and estradiol produces compounds with relatively modest affinity for the estrogen receptor (0.3-10% that of estradiol). Most of the electrophilic derivatives are effective and rapid inactivators of receptor (24-44% inactivation within 0.5-5 hr at 25(DEGREES)C). Of the photosensitive derivatives, 4-azidodeoxyhexestrol appears to be the most efficient receptor inactivator (49%). The high estrogen receptor activity and the lack of interference by cellular nucleophiles suggests that these compounds may be useful as affinity labeling agents, or as selective cytotoxic agents in intact systems.","Made available in DSpace on 2014-12-13T20:11:05Z (GMT). No. of bitstreams: 1 8108605.pdf: 10064913 bytes, checksum: e34ce42719ec10de05f7808810c859ad (MD5) Previous issue date: 1980","Embargo set by: Seth Robbins for item 67425 Lift date: Forever Reason: Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs","Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs","U of I Only","319 p.","Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1980."]},{"key":"dc:title","label":"Title","values":["Estrogens Containing Alkylating Substituents: The Synthesis and Estrogen Receptor Interactions of Estradiol and Hexestrol Affinity Labels"]}]}],"canonical_facts":{"dc:creator":["Mcgorrin, Robert Joseph, Jr."],"dc:date":["2014-12-13T20:11:05Z","10000-01-01","1980"],"dc:description":["A series of chemically-reactive derivatives of estradiol and the non-steroidal estrogen hexestrol have been synthesized as potential affinity labels for the uterine estrogen receptor, or as cytotoxic agents with selective activity against receptor-containing cells. These compounds are hexestrol ethers with haloketone, halohydrin, or epoxide functions; 4-substituted deoxyhexestrols with nitro, azide, sulfonyl fluoride, or sulfonyl azide groups; and estradiol and hexestrol analogs incorporating benzyl halide functions ortho to the phenol or the corresponding methyl ether. The alkylating activity of the electrophilic derivatives was measured using the colorimetric reagent 4-(p-nitrobenzyl)pyridine, and the bromo derivatives were found to be consistently more reactive than the chloro ones. Their reversible binding to the lamb uterine estrogen receptor was measured by competitive binding assays, and their irreversible reaction with receptor was measured by exchange assays that determine the rate and extent of receptor inactivation. In general, etherification of hexestrol or substitution of deoxyhexestrol and estradiol produces compounds with relatively modest affinity for the estrogen receptor (0.3-10% that of estradiol). Most of the electrophilic derivatives are effective and rapid inactivators of receptor (24-44% inactivation within 0.5-5 hr at 25(DEGREES)C). Of the photosensitive derivatives, 4-azidodeoxyhexestrol appears to be the most efficient receptor inactivator (49%). The high estrogen receptor activity and the lack of interference by cellular nucleophiles suggests that these compounds may be useful as affinity labeling agents, or as selective cytotoxic agents in intact systems.","Made available in DSpace on 2014-12-13T20:11:05Z (GMT). No. of bitstreams: 1 8108605.pdf: 10064913 bytes, checksum: e34ce42719ec10de05f7808810c859ad (MD5) Previous issue date: 1980","Embargo set by: Seth Robbins for item 67425 Lift date: Forever Reason: Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs","Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs","U of I Only","319 p.","Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1980."],"dc:identifier":["http://hdl.handle.net/2142/67247","(UMI)AAI8108605"],"dc:language":["eng"],"dc:subject":["Chemistry, Organic"],"dc:title":["Estrogens Containing Alkylating Substituents: The Synthesis and Estrogen Receptor Interactions of Estradiol and Hexestrol Affinity Labels"],"dc:type":["text"],"thesis:degree_discipline":["Chemistry"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois at Urbana-Champaign"]},"updated_at":"2026-07-22T22:25:57Z"}