Showing papers by "Gregory M. Anstead published in 1988"
TL;DR: Two 2,3-diphenylindene and -indenone systems, with potential fluorescent and photofluorogenic properties, were prepared and studied as ligands for the estrogen receptor.
Abstract: Two 2,3-diphenylindene and -indenone systems, with potential fluorescent and photofluorogenic properties, were prepared and studied as ligands for the estrogen receptor. The indene systems were prepared by Friedel-Crafts cyclization of appropriate alpha-benzyl desoxybenzoin systems, and the indenones either by oxidation of the indenes, by cyclization of alpha-benzoyl desoxybenzoins, or by acylium ion attack on tolan. Crystallographic analysis of the 2,3-diphenylindene and -indenone systems shows the phenyl substituents twisted out of the plane of the indene/indenone systems, with both torsional angles greater in the indenone than indene system; the phenyl attachment to the five-membered ring allows these systems to be considerably more planar than the related 1,2-diphenyl-3,4-dihydronaphthalene and the triarylethylene nonsteroidal estrogens. In contrast to the diphenyldihydronaphthalenes, the diarylindene and -indenone systems undergo photocyclization to phenanthrenes inefficiently. The estrogen receptor binding affinity of these systems is reasonably high (9-59% relative to estradiol), with the indenone systems having higher affinity than the indenes; additional hydroxyl substitution raises the affinity of the indenes but lowers that of the indenones. These trends can be rationalized by considering differences in molecular volumes or surface areas (related to torsional angles) and specific polar interactions.
52 citations
29 citations
TL;DR: Estrogen receptor binding affinity measurements on these compounds indicate that substituents that twist the pendant aryl rings (such as a 1-methyl group, or an o-methyl or trifluoromethyl group on the 2-phenyl ring) increase binding affinity.
Abstract: In an attempt to elucidate steric and electronic factors that affect the fluorescence and estrogen receptor binding properties of 2,3-diarylindenes, we have prepared and examined the behavior of 11 analogues bearing substituents on the 1-position or on the 2-aryl ring. These compounds were synthesized by alkylation of a 1,2-diarylethanone with 3-methoxybenzyl chloride, followed by cyclodehydration to the indene. The electronic spectra of those compounds without tau-electron accepting groups on the 2-aryl ring display the absorbance and fluorescence of a hindered stilbene system; those with nitro and cyano substituents on the 2-aryl ring show charge-transfer character, having a more bathochromic absorption and fluorescence. One bisphenolic nitroindene, in particular, shows a strong, long-wavelength absorption and an intense emission, with a large Stokes' shift that is highly sensitive to solvent polarity. Estrogen receptor binding affinity measurements on these compounds indicate that substituents that twist the pendant aryl rings (such as a 1-methyl group, or an o-methyl or trifluoromethyl group on the 2-phenyl ring) increase binding affinity. Bulky (4-bromo) or electron-withdrawing groups (3- and 4-nitro, 4-cyano) on the 2-phenyl group, or its replacement with a 3-pyridyl group, greatly reduce binding affinity, suggesting that the complementary region of the receptor is relatively intolerant of bulk and may have specific hydrogen-bonding requirements. This investigation of the concurrent effects of substituents on the fluorescence properties and receptor binding affinity of 2,3-diarylindenes should assist in the development of effective, inherently fluorescent ligands for the estrogen receptor.
21 citations
TL;DR: Two 2,3-diphenylindene and -indenone systems, with potential fluorescent and photofluorogenic properties, were prepared and studied as ligands for the estrogen receptor.
Abstract: Two 2,3-diphenylindene and -indenone systems, with potential fluorescent and photofluorogenic properties, were prepared and studied as ligands for the estrogen receptor. The indene systems were prepared by Friedel-Crafts cyclization of appropriate alpha-benzyl desoxybenzoin systems, and the indenones either by oxidation of the indenes, by cyclization of alpha-benzoyl desoxybenzoins, or by acylium ion attack on tolan. Crystallographic analysis of the 2,3-diphenylindene and -indenone systems shows the phenyl substituents twisted out of the plane of the indene/indenone systems, with both torsional angles greater in the indenone than indene system; the phenyl attachment to the five-membered ring allows these systems to be considerably more planar than the related 1,2-diphenyl-3,4-dihydronaphthalene and the triarylethylene nonsteroidal estrogens. In contrast to the diphenyldihydronaphthalenes, the diarylindene and -indenone systems undergo photocyclization to phenanthrenes inefficiently. The estrogen receptor binding affinity of these systems is reasonably high (9-59% relative to estradiol), with the indenone systems having higher affinity than the indenes; additional hydroxyl substitution raises the affinity of the indenes but lowers that of the indenones. These trends can be rationalized by considering differences in molecular volumes or surface areas (related to torsional angles) and specific polar interactions.
2 citations