The Development of 2,3-Diarylindenes as Integrated Fluorescent Estrogens
Anstead, Gregory Michael
This item is only available for download by members of the University of Illinois community. Students, faculty, and staff at the U of I may log in with your NetID and password to view the item. If you are trying to access an Illinois-restricted dissertation or thesis, you can request a copy through your library's Inter-Library Loan office or purchase a copy directly from ProQuest.
Permalink
https://hdl.handle.net/2142/70406
Description
Title
The Development of 2,3-Diarylindenes as Integrated Fluorescent Estrogens
Author(s)
Anstead, Gregory Michael
Issue Date
1988
Doctoral Committee Chair(s)
Katzenellenbogen, John A.
Department of Study
Chemistry
Discipline
Chemistry
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(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.
Use this login method if you
don't
have an
@illinois.edu
email address.
(Oops, I do have one)
IDEALS migrated to a new platform on June 23, 2022. If you created
your account prior to this date, you will have to reset your password
using the forgot-password link below.
