{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/20726"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/20726","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Tetrahydrochrysene and cyclofenil derivatives as fluorescent probes of the estrogen receptor","abstract":"We prepared tetrahydrochrysene (THC) derivatives IIIb-e as the first fluorescent estrogens, designed to satisfy the criteria for a direct fluorometric assay of the estrogen receptor in cells. The preparation of unsymmetrical chrysenes IIIb-e, containing ketone, ester, amide, and nitrile groups, was achieved efficiently under mild conditions, by the palladium-mediated arylcarbonylation of intermediate 15 as the key step. However, the RBA of compounds IIIb-e (RBA = 15-40%) is still sufficient for them to be studied as fluorescent probes for the estrogen receptor.","abstract_html":"We prepared tetrahydrochrysene (THC) derivatives IIIb-e as the first fluorescent estrogens, designed to satisfy the criteria for a direct fluorometric assay of the estrogen receptor in cells. The preparation of unsymmetrical chrysenes IIIb-e, containing ketone, ester, amide, and nitrile groups, was achieved efficiently under mild conditions, by the palladium-mediated arylcarbonylation of intermediate 15 as the key step. However, the RBA of compounds IIIb-e (RBA = 15-40%) is still sufficient for them to be studied as fluorescent probes for the estrogen receptor.","abstract_has_math":false,"creators":["Hwang, Kwang Jin"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Chemistry","degree_department":null,"school":null,"contributors":["Katzenellenbogen, John A."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2011,"date_issued":"2011-05-07T12:47:32Z","date_published":"2011-05-07T12:47:32Z","updated_at":"2026-07-22T22:25:16Z","subjects":["Chemistry, Organic","Chemistry, Pharmaceutical"],"languages":["eng"],"rights":["Copyright 1991 Hwang, Kwang Jin"],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["AAI9136623","(UMI)AAI9136623"],"render_values":[{"text":"AAI9136623","href":null,"code":true},{"text":"(UMI)AAI9136623","href":null,"code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/2142/20726","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Katzenellenbogen, John A."]},{"key":"dc:creator","label":"Author","values":["Hwang, Kwang Jin"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2011-05-07T12:47:32Z","10000-01-01","1991"]},{"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","Chemistry, Pharmaceutical"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 1991 Hwang, Kwang Jin"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["AAI9136623","(UMI)AAI9136623","http://hdl.handle.net/2142/20726"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["We prepared tetrahydrochrysene (THC) derivatives IIIb-e as the first fluorescent estrogens, designed to satisfy the criteria for a direct fluorometric assay of the estrogen receptor in cells. The preparation of unsymmetrical chrysenes IIIb-e, containing ketone, ester, amide, and nitrile groups, was achieved efficiently under mild conditions, by the palladium-mediated arylcarbonylation of intermediate 15 as the key step. However, the RBA of compounds IIIb-e (RBA = 15-40%) is still sufficient for them to be studied as fluorescent probes for the estrogen receptor.","Fluorescence emission of THC IIIb-e in TEA buffer was observed at 483-593 nm. This long wavelength emission reduces the overlap with cellular autofluorescence. When THC IIIb-e are bound to the estrogen receptor in lamb uterine cytosol ($\\sim$10$\\sp{-9}$ M), emissions were observed at 478-516 nm. The addition of a 100-fold excess of estradiol to block receptor binding of these compounds causes a blue-shift of 40-50 nm, with an increase in intensity.","The estrogen receptor binding site of ketone IIIb and ester IIIc was quite polar, similar to that of ethanol, whereas the receptor polarity at the binding site of amide IIId and nitrile IIIe was even more polar, similar to that of water.","Despite its considerable receptor binding affinity (RBA = 4.4%), nitrochrysene IIIf could not be used to assay the estrogen receptor because its emission is completely quenched in water.","The RBA of aziridine 63b nearly comparable to that of estradiol (RBA = 56%). This high apparent affinity is due to a rapid irreversible attachment of this ligand to the estrogen receptor. The superposition studies of the phenyl rings and the central carbons of the saturated and unsaturated cyclofenil derivatives (49 vs 58 and 61 vs 62) using a molecular graphics modeling program show that the second phenyl ring and aliphatic ring deviate each other considerably (1.07-1.44 A). Cyclofenil derivative 67 with a model fluorophore BODIPY may prove to be the first the fluorophore-ligand conjugate potentially useful for the assay of the estrogen receptor, due to its relatively high binding affinity (RBA = 5%) and long emission wavelength (511 nm in ethanol). (Abstract shortened with permission of author.)","Made available in DSpace on 2011-05-07T12:47:32Z (GMT). No. of bitstreams: 2 license.txt: 4922 bytes, checksum: 910b249b4beec47e7ab768910c8f966f (MD5) 9136623.pdf: 5031677 bytes, checksum: 727eddc35c997e1c665dccff41c85954 (MD5) Previous issue date: 1991","Item marked as restricted to the 'UIUC Users [automated]' Group (id=2) by Howard Ding (hding2@illinois.edu) on 2011-05-07T14:45:51Z Item is restricted indefinitely.","Restriction data tranferred 2014-07-01T11:20:23-05:00 Original Data Group with Access UIUC Users [automated] Release Date: none Reason: ETDs are only available to UIUC Users without author permission","ETDs are only available to UIUC Users without author permission","U of I Only"]},{"key":"dc:title","label":"Title","values":["Tetrahydrochrysene and cyclofenil derivatives as fluorescent probes of the estrogen receptor"]}]}],"canonical_facts":{"dc:contributor":["Katzenellenbogen, John A."],"dc:creator":["Hwang, Kwang Jin"],"dc:date":["2011-05-07T12:47:32Z","10000-01-01","1991"],"dc:description":["We prepared tetrahydrochrysene (THC) derivatives IIIb-e as the first fluorescent estrogens, designed to satisfy the criteria for a direct fluorometric assay of the estrogen receptor in cells. The preparation of unsymmetrical chrysenes IIIb-e, containing ketone, ester, amide, and nitrile groups, was achieved efficiently under mild conditions, by the palladium-mediated arylcarbonylation of intermediate 15 as the key step. However, the RBA of compounds IIIb-e (RBA = 15-40%) is still sufficient for them to be studied as fluorescent probes for the estrogen receptor.","Fluorescence emission of THC IIIb-e in TEA buffer was observed at 483-593 nm. This long wavelength emission reduces the overlap with cellular autofluorescence. When THC IIIb-e are bound to the estrogen receptor in lamb uterine cytosol ($\\sim$10$\\sp{-9}$ M), emissions were observed at 478-516 nm. The addition of a 100-fold excess of estradiol to block receptor binding of these compounds causes a blue-shift of 40-50 nm, with an increase in intensity.","The estrogen receptor binding site of ketone IIIb and ester IIIc was quite polar, similar to that of ethanol, whereas the receptor polarity at the binding site of amide IIId and nitrile IIIe was even more polar, similar to that of water.","Despite its considerable receptor binding affinity (RBA = 4.4%), nitrochrysene IIIf could not be used to assay the estrogen receptor because its emission is completely quenched in water.","The RBA of aziridine 63b nearly comparable to that of estradiol (RBA = 56%). This high apparent affinity is due to a rapid irreversible attachment of this ligand to the estrogen receptor. The superposition studies of the phenyl rings and the central carbons of the saturated and unsaturated cyclofenil derivatives (49 vs 58 and 61 vs 62) using a molecular graphics modeling program show that the second phenyl ring and aliphatic ring deviate each other considerably (1.07-1.44 A). Cyclofenil derivative 67 with a model fluorophore BODIPY may prove to be the first the fluorophore-ligand conjugate potentially useful for the assay of the estrogen receptor, due to its relatively high binding affinity (RBA = 5%) and long emission wavelength (511 nm in ethanol). (Abstract shortened with permission of author.)","Made available in DSpace on 2011-05-07T12:47:32Z (GMT). No. of bitstreams: 2 license.txt: 4922 bytes, checksum: 910b249b4beec47e7ab768910c8f966f (MD5) 9136623.pdf: 5031677 bytes, checksum: 727eddc35c997e1c665dccff41c85954 (MD5) Previous issue date: 1991","Item marked as restricted to the 'UIUC Users [automated]' Group (id=2) by Howard Ding (hding2@illinois.edu) on 2011-05-07T14:45:51Z Item is restricted indefinitely.","Restriction data tranferred 2014-07-01T11:20:23-05:00 Original Data Group with Access UIUC Users [automated] Release Date: none Reason: ETDs are only available to UIUC Users without author permission","ETDs are only available to UIUC Users without author permission","U of I Only"],"dc:identifier":["AAI9136623","(UMI)AAI9136623","http://hdl.handle.net/2142/20726"],"dc:language":["eng"],"dc:rights":["Copyright 1991 Hwang, Kwang Jin"],"dc:subject":["Chemistry, Organic","Chemistry, Pharmaceutical"],"dc:title":["Tetrahydrochrysene and cyclofenil derivatives as fluorescent probes of the estrogen receptor"],"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":"2026-07-22T22:25:16Z"}