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The effect of the tert-alcohol reaction medium for nucleophilic fluorination with alkali metal fluorides is examined by studying various interactions among tert-alcohols, the alkali metal fluoride (CsF) and the sulfonyloxy substrate. The protic environment of the reaction medium, as well as hydrogen bonding between the tert-alcohol and reactive heteroatoms in the substrate, has reduced the side reactions such as eliminations, hydroxylations and intramolecular alkylations.

The synthesis of 2,2-bis-(4-hydroxyphenyl)-cyclopentanone via reductive coupling reaction of 4,4'-dihydroxybenzophenone and cyclobutanone with Ti[Cl.sub.4] and Zn is demonstrated.

Research has been conducted on the progesterone receptor high-affinity ligand, fluoro furanyl norprogesterone. The synthetic route developed for the synthesis of this ligand provides improvement in the yield of the fluoro furanyl norprogesterone.

The article examines a method to improve the diagnosing and staging of breast cancer. Development of imaging radiopharmaceuticals providing a determination of the estrogen receptor status in the tumor cells has been discussed.

The synthesis of 2-((super 18)F)fluoroestradiol, a potential diagnostic imaging compound for breast cancer, was described. The aim was to improve the pharmacokinetics of fluorine-18 labeled estrogens as receptor-based agents for diagnosis and staging of estrogen-receptor-positive breast carcinoma. The preparation of 2-((super 18)F)fluoroestradiol was performed via ((super 18)F)fluoride ion displacement of a trimethylammonium leaving group at the C-2 position of an estrogen.

Peptide ligands and protein receptors are crucial in the control of almost all biological processes but the identification of the fundamental elements required for recognition between a peptide ligand and its receptor at the molecular level remains a big challenge. Research conducted on the effort to create a beta-turn, dipeptide structural mimic of protein and peptide beta-turns are discussed.

Synthetic routes to (omega-(super 11)C)palmitic acid were improved through new tracer-level techniques. Three new synthetic approaches to (omega-(super 11)C)palmitic acid gave yields of 75%, 68% and 51% in 45, 55 and 65 min, respectively, from the end of target bombardment. These methods are the cross-coupling of a functionalized alkyl borane with a saturated primaryl alkyl iodide via a Suzuki reaction, the sulfone dianion approach and furan ozonolysis. The former two strategies have distinct advantages, but the Suzuki coupling is more convenient and efficient than the sulfone approach.

The influence of single-point mutated ligand binding domain of estrogen receptor on its ligand binding and its resistance to denaturants was investigated through ligand binding kinetic studies. It was shown that the mutant estrogen receptor, Y537S, had a slower rate of ligand binding and ligand dissociation. It was indicated that ligand binding induced a change in the conformation of the ligand binding pocket.

The synthesis and evaluation of the spectroscopic properties of two azatetrahydrochrysenes resulting from the inclusion of the (hydroxystyryl)pyridine and (hydroxystyryl)pyrimidine chromophores into the tetrahydrochrysene (THC) ring system, is reported. Absorbance and fluoresence properites relied strongly on solvent polarity and pH, due to the ionizable functionalities. Both systems have potential use as spectroscopic probes.

Oxometal(V) complexes are being developed as high affinity ligands for the estrogen receptor. The complexes could be used as imaging agents for estrogen receptor-positive breast tumors when labeled with technetium-99m, a radionuclide. The synthesis of a tetradentate oxorhenium(V) amino amido thioether thiol (AATT) complex, where metal replaces the CD ring of estradiol, is described. The stability of a new coordination scheme for oxorhenium(V) systems is established.

The syntheses and characterization of three isomeric 1,2-substituted-3,4-dihydronaphthalenes, pyrodine analogs of the antiestrogen desmethylnafoxidine, are presented. The isomers were prepared from alpha-(2-, 3-, and 4-pyridyl)acetophenone precursors. The results showed that all three isomers have high apparent binding affinity for estrogen receptor, and exhibited time-dependent irreversible inactivation.

The synthesis of a bis-bidentate oxorhenium(V) complex, a close structural and stereochemical mimic of the androgen 5(alpha)-dihydrotestosterone, is described. Results of 2D-NMR analysis indicate that the N-methyl and oxo substituents are driven into the steroidal anti configuration (beta-N-methyl, alpha-oxo) by the beta-orientation of the methyl group equivalent to C-18. However, the oxometal mimic exhibited low stability and low lipophilicity, prohibiting its use in vivo.

Proteolysis of the ligand binding domain of the human estrogen receptor (hER-LBD) shows that the hormone binding domain possesses a protease-resistant N-terminus that attains more progressive but less localized cleavages from the C-terminus. The use of liquid chromatography/electrospray ionization mass spectrometry to analyze the proteolytic components and provide a significantly magnified conformational view of the hER-LBD is discussed.

A new N2S2 ligand system is designed and synthesized to obtain rhenium(V)oxo and technetium(V)oxo complexes. Such complexes are used in the manufacture of technetium- and rhenium-labeled steroids which are used for the therapy and diagnosis of breast cancer.

A number of synthetic routes to alpha- and beta-alkyl enol lactones, which may serve as mechanism-based inhibitors of human neutrophil elastase, are explored. Of these, the Eschenmoser-Tanabe approach proves to be a general method. The zinc-mediated alkylation of 3-ethoxy-2-cyclohexen-1-one is a simple way to give good to excellent yields of primary and secondary alkyl iodides. A four-step alkylation using 1,4-dibromobutane, on the other hand, is the most effective way towards alpha-alkyl-5-hexynoic acids. In subsequent assays, the alpha-alkyls prove to be better inhibitors than the beta-alkyls.

A study was conducted on the binding behavior and fluorescence characteristics of inherently fluorescent, high-affinity ligands for the estrogen receptor. The ligands are derivatives of 5,6,11, 12-tetrahydrochrysene (THC). The emissions of the observed donor-acceptor THCs was found to be highly solvatochromic and was observed to shift to longer wavelengths with increasing solvent polarity.

The utilization of an acyloin condensation-double cyclization procedure leads to the synthesis of 5,6,11,12-tetrahydrochrysenes from alpha-alkyl m-methoxyhydrocinnamate esters in quantitative amounts. Introduction of substituents at the C-5 and C-11 of the planar stilbene chromophore enhances the receptor binding affinity of the compound. The compounds exhibit a tetracyclic nature which makes them useful as fluorescent ligands for the estrogen receptor.

Molecular mechanics minimization and molecular dynamic simulation are used to investigate the possible conformations of the R and S beta-phenyl acyl enzymes and their deacylation tetrahedral intermediates. The studies show that the hydrogen bonding of the ketone carbonyl and the ester carbonyl slows down the deacylation rate of the R acyl enzyme by a factor of approximately 60 as compared to the S acyl enzyme. This difference is attributed to the less optimal stabilization of reactive intermediates in the case of the R enantiomer.

A one-donor/three-acceptor multicolor time-resolved fluorescence energy transfer (TR-FRET) system is developed and its use is exemplified by monitoring a ligand-regulated protein-protein exchange process in a four-component biological system. The studies have shown the power of a four-color TR-FRET experiment and have also shown that the overall process of estrogen receptor ligand exchange and coactivator binding is a dynamic but precisely coordinated process.

Several dual time-resolved fluorescence resonance energy transfer assays are developed to quantify the ligand-regulated binding of nuclear receptor corepressor and coactivator to the thyroid hormone receptor (TR). The key interactions that highly affect the ligand potency and efficacy of the TR are also discussed.

The study explains the dual nature of the fluorophore-doped nickel nitrilotriacetic acid-modified silica nanoparticles of combining histidine-tagged protein purification with site-specific fluorophore labeling. Tetramethylrhodamine (TMR)-doped silica nanoparticles are the commonly used example of such structures.

A racemic synthesis of 5,6-dihydro-5-fluorouracil (5-DHFU) from 5-fluorouracil (5-FU) or uracil by using p-methoxybenzyl protecting groups followed by L-selectride reduction is reported. 5-DHFU compound have a potential to find use in various biological applications.

Two fluoro steroids, 7[alpha]-(fluoromethyl)dihydrotestosterone and 7[alpha]-(fluoromethyl)nortestosterone, are synthesized in order to examine the role of sex hormone binding globulin (SHBG) in prostate tumor uptake of positron emission tomography (PET) imaging agents. These two fluoro steroids are well matched in terms of their site of fluorine labeling, structure and equivalent androgen receptor (AR) and hence they can be used as agents for evaluating the role of SHBG binding in the target tissue uptake of AR PET imaging agents in humans.

The Estrogen receptors ER alpha and ER beta are ligand-regulated transcription factors of the Nuclear Receptor (NR). The preparation of protein microarrays of ER alpha and ER beta ligand-binding domains on glass slides, is presented.

Research has been conducted on 2-hydrazinopyridines. The authors have investigated these compounds as ligands for technetium and rhenium via the study of the palladium-catalyzed reactions of halo-pyridine substrates with di-tert-butyl hydrazodiformate.

Research into the preparation of substituted cyclopentadienyl and indenyltricarbonyl rhenium is described. The paper reports the synthesis in a one-pot method of CpRe(CO)3 and InTR utilizing in situ generated enyl-stannane.

The interaction of estrogens with the estrogen receptor is investigated. A quantitative structure activity relationship (QSAR) database was built which contained 12,500 examples of interactions between estrogen receptors and its ligands. The experiments used different receptor preparations and different ligands. The results showed that a common feature of the QSAR equations was the lack of a positive hydrophobic parameter. The interactions between the receptors and the substituents of the ligands can be quantitatively explained by electronic and steric parameters.

A novel approach for synthesizing halo-, carbonyloxy- and hydroxy-substituted CpRe(CO)3 complexes by a one-pot reaction of diazocyclopentadiene (C5H4N2), a rhenium(I) tricarbonyl species and a nucleophile was described. The synthetic approach was found to demonstrate rapidity and simplicity, making it ideal for labeling biologically interesting compounds with Re-186, Re-188 and Tc-99m radionuclides. Boronic acids were used to extend the three-component reaction toward the preparation of the CpRe(CO)3 complexes.

The synthesis of halo-, carbonyl-, oxy- and hydroxy-substituted cyclopentadienyl tricarbonyl rhenium complexes using a 'one pot/three component assembly' reaction is described. Results showed that under mild conditions and shorter reaction times the method develops nucleophile, Cp and Re precursors that resulted in substituted CpRe-(CO)3 complexes. The development of new types of rhenium- and technetium-labeled radiopharmaceuticals cane be accomplished using the method.

A 1,3-dipolar cycloaddition reaction between an azomethine ylide and dipolarophile was performed to synthesize trifluoromethyl ketones (TFMK) via 4-trifluoromethyl-substituted delta(sup 3)-imidazolines. The latter, which acts as a protected form of TFMKs, were incorporated into peptides through standard Fmoc-peptide synthesis methods using Carpino's carbamate-protected amino acid fluorides. This was followed by hydrolization with mild acid to produce the desired TFMKs.

X-ray crystallographic studies of the structure of the rhenium complex bis(amido)bis(thilato)oxorhenium(V) indicate that this complex is in anionic form and possesses a symmetrical structure where the nitrogens are in the sp2 hybridization state. This complex reacts with silica gel-derived calcium to yield a methanol-solvated salt and the Ca counterion possesses high density as a result of a dication.

Rhenium complexes, characterized by a chelate molecule which donates four heteroatoms to an oxometal core, is prepared in solution by the substitution reaction of oxotrichlorobis(triphenylphosphine)rhenium (1, Cl3ReO(PPh3)2) in the presence of a coordinating ligand. The ligands 1-(4'-methoxyphenyl)amino-2-methyl-propane-2-thiol and pyridine-2-methanethiol are added to 1 in 2 milliliters of one mole of NaOAc in methanol and the resulting mixture is heated. Subsequent cooling yields a brownish purple precipitate which is recrystallized from MeOH/CHCl3. A quantitative yield of crystalline (N(2-mercapto-2-methylpropyl)-N-(4'-methoxyphenyl)aminato)oxorhenium (mercapt omethylpyridinato)oxorhenium is obtained.