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Title:The Development of 2,3-Diarylindenes as Integrated Fluorescent Estrogens
Author(s):Anstead, Gregory Michael
Doctoral Committee Chair(s):Katzenellenbogen, John A.
Department / Program:Chemistry
Degree Granting Institution:University of Illinois at Urbana-Champaign
Subject(s):Chemistry, Organic
Chemistry, Pharmaceutical
Abstract:A series of hydroxylated 2,3-diarylindenes were prepared and evaluated as fluorescent ligands for the estrogen receptor. A practical fluorescent estrogen would allow cell-by-cell quantitation of the estrogen receptor in breast tumors, providing a prognostic tool for the clinical differentiation of hormone-responsive and unresponsive tumors. The 2,3-diarylindenes and -indenones were inefficient as photofluorogenic estrogens due to geometric considerations and competition from fluorescence and intersystem crossing. Crystallography indicated more planar topography for the indenes and indenones as compared to other triarylethylenes. The estrogen receptor binding affinities of the indenes, indenones, and other triarylethylenes were related to the torsional and valence angles at the double bond. The intrinsic fluorescence of the 2,3-diarylindenes was found at too short of a wavelength (420 nm) to be useful in biological studies. However, a long emission wavelength and high environmental sensitivity was attained by affixing an acceptor nitro auxochrome to the 2-aryl ring. In the p-position, the nitro group produced a quasi-planar intramolecular charge transfer state, with emission from 490 nm in heptane to 672 nm in acetonitrile. In the m-position, a nitro group produces a twisted intramolecular charge transfer (TICT) state with emission up to 690 nm in chloroform. A nitro group in the m-position or a nitro, bromo, or cyano group in the p-position of the 2-ring all greatly reduce estrogen receptor binding affinity. A hydroxy group in the p-position of the 2-ring enhances binding affinity. Methylation of C-1 produces a modest enhancement in binding affinity. Ortho-substitution of the 2-ring by methyl or trifluoromethyl groups produces significant increase in the estrogen receptor binding affinity. Recommendations for the future development of fluorescent estrogens are made.
Issue Date:1988
Description:149 p.
Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1988.
Other Identifier(s):(UMI)AAI8823074
Date Available in IDEALS:2014-12-15
Date Deposited:1988

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