Targeting the estrogen receptor with metal-carbonyl derivatives of estradiol.
ABSTRACT: As part of our program to develop new probes for the estrogen receptor binding domain, we prepared and evaluated a novel 17?-(rhenium tricarbonyl bipyridyl) vinyl estradiol complex. Preparation of the final compound was achieved using the Stille coupling between the preformed brominated rhenium tricarbonyl bipyridine complex and the tributylstannyl vinyl estradiol. Competitive receptor binding assays and stimulatory assays demonstrated that the final complex retained affinity and efficacy comparable to the corresponding pyridyl vinyl estradiol analog, but lower than that of the phenyl vinyl estradiol analog.
Project description:Heterogenization of homogenous catalysts on electrode surfaces provides a valuable approach for characterization of catalytic processes in operando conditions using surface selective spectroelectrochemistry methods. Ligand design plays a central role in the attachment mode and the resulting functionality of the heterogenized catalyst as determined by the orientation of the catalyst relative to the surface and the nature of specific interactions that modulate the redox properties under the heterogeneous electrode conditions. Here, we introduce new [Re(L)(CO)3Cl] catalysts for CO2 reduction with sulfur-based anchoring groups on a bipyridyl ligand, where L = 3,3'-disulfide-2,2'-bipyridine (SSbpy) and 3,3'-thio-2,2'-bipyridine (Sbpy). Spectroscopic and electrochemical analysis complemented by computational modeling at the density functional theory level identify the complex [Re(SSbpy)(CO)3Cl] as a multi-electron acceptor that combines the redox properties of both the rhenium tricarbonyl core and the disulfide functional group on the bipyridyl ligand. The first reduction at -0.85 V (vs. SCE) involves a two-electron process that breaks the disulfide bond, activating it for surface attachment. The heterogenized complex exhibits robust anchoring on gold surfaces, as probed by vibrational sum-frequency generation (SFG) spectroscopy. The binding configuration is normal to the surface, exposing the active site to the CO2 substrate in solution. The attachment mode is thus particularly suitable for electrocatalytic CO2 reduction.
Project description:Enantiomerically pure (S)-tributylstannyl[D1]methanol and (R)- and (S)-tributylstannyl[D1]methyl benzoates were Stille-coupled with bromobenzene and benzoyl chloride in 1,4-dioxane and toluene using [(Ph3P)4Pd] or [(Ph3P)2PdCl2] either alone or in combination with CuCN as cocatalyst at temperatures up to 80 °C. The products were found to be enantiomerically pure. (R)- and (S)-N-(tributylstannyl[D1]methyl)phthalimides gave enantiomerically pure products with benzoyl chloride, but with bromobenzene protected phenyl[D1]methylamines gave products of only 52-69?% ee depending on the solvent used. Tributyl(thio[D1]methyl)stannanes could not be Stille-coupled with benzoyl chloride or with bromobenzene. Similarly, dimethyl phenyl[D1]methylboronate underwent a Suzuki-Miyaura coupling with bromobenzene to give phenyl[D1]methylsilane with 99?% ee. All couplings followed a retentive course and, except in one case, the intermediate [XCHDPdL n ] complexes were found to be microscopically configurationally stable.
Project description:The synthesis and full characterization of two tetrathiafulvalene-appended azine ligands, namely 2-([2,2'-bi(1,3-dithiolylidene)]-4-yl)-6-((2,4-dinitrophenyl)hydrazono)methyl)pyridine (L1) and 5-([2,2'-bi(1,3-dithiolylidene)]-4-yl)-2-((2,4-dinitrophenyl)hydrazono)methyl)pyridine (L2) are described. The crystal structure of ligand L1 indicates that the ligand is completely planar with the presence of a strong intramolecular N3-H3···O1 hydrogen bonding. Titration experiments with inorganic anions showed that both ligands are suitable candidates for the sensing of fluoride anions. Ligand L2 was reacted with a Re(I) cation to yield the corresponding rhenium tricarbonyl complex 3. In the crystal structure of the newly prepared electroactive rhenium complex the TTF is neutral and the rhenium cation is hexacoordinated. The electrochemical behavior of the three compounds indicates that they are promising for the construction of crystalline radical cation salts.
Project description:The structures of two facially coordinated Group VII metal complexes are reported, namely: fac-bromido-[2-(2,2'-bipyridin-6-yl)benzoic acid-?2N,N']tricarbonyl-manganese(I) tetra-hydro-furan monosolvate, [MnBr(C17H12N2O2)(CO)3]·C4H8O, I, and fac-[2-(2,2'-bipyridin-6-yl)benzoic acid-?2N,N']tricarbonyl-chlorido-rhenium(I) tetra-hydro-furan monosolvate, [ReCl(C17H12N2O2)(CO)3]·C4H8O, II. In both complexes, the metal ion is coordinated by three carbonyl ligands, a halide ion, and a 2-(2,2'-bipyridin-6-yl)benzoic acid ligand, in a distorted octa-hedral geometry. In manganese complex I, the tetra-hydro-furan (THF) solvent mol-ecule could not be refined due to disorder. The benzoic acid fragment is also disordered over two positions, such that the carb-oxy-lic acid group is either positioned near to the bromide ligand or to the axial carbonyl ligand. In the crystal of I, the complex mol-ecules are linked by a pair of C-H?Br hydrogen bonds, forming inversion dimers that stack up the a-axis direction. In the rhenium complex II, there is hydrogen bonding between the benzoic acid moiety and a disordered co-crystallized THF mol-ecule. In the crystal, the mol-ecules are linked by C-H?Cl hydrogen bonds, forming layers parallel to (100) separated by layers of THF solvent mol-ecules.
Project description:The reaction of Re(CO)(3)(H(2)O)(3)(+) with hen egg lysozyme in aqueous solution results in a single covalent adduct; single crystal X-ray diffraction shows that the rhenium tricarbonyl cation binds to His15 in two significantly populated rotamer conformations.
Project description:We have developed shelf- and air-stable ortho-stannylated aniline reagents that can directly be coupled with alkenyl and aryl halides via Stille cross-coupling. We report i) the efficient preparation of o-(tributylstannyl)aniline (2a) and o-(trimethylstannyl)aniline (2b), ii) the comparison of the reactivities of 2a and 2b with those of related organostannanes in cross-coupling reaction with an alkenyl halide, and iii) the cross-coupling of 2a and 2b with a series of arylhalides and triflate.
Project description:We report the synthesis of a rigid phosphine-substituted, redox-active pincer ligand and its application to electrocatalytic CO2 reduction with first-row transition metal complexes. The tridentate ligand was prepared by Stille coupling of 2,8-dibromoquinoline and 2-(tributylstannyl)pyridine, followed by a palladium-catalyzed cross-coupling with HPPh2. Complexes were synthesized from a variety of metal precursors and characterized by NMR, high-resolution mass spectrometry, elemental analysis, and cyclic voltammetry. Formation of bis-chelated metal complexes, rather than mono-chelated complexes, was favored in all synthetic conditions explored. The complexes were assessed for their ability to mediate electrocatalytic CO2 reduction, where the cobalt complex was found to have the best activity for CO2-to-CO conversion in the presence of water as an added proton source.
Project description:An efficient, second-generation synthesis of the signature dioxabicyclo[3.2.1]octane core of (+)-sorangicin A (1), in conjunction with an effective, stereocontrolled protocol to arrive at the requisite (Z,Z,E)-triene acid system has been developed. Highlights of the core construction entail a three-component union, a KHMDS-promoted epoxide ring formation-ring opening cascade, a Takai olefination, and a chemoselective Sharpless dihydroxylation. Assembly of the triene acid system was then achieved via Stille cross-coupling with the ethyl ester of (Z,Z)-5-tributylstannyl-2,4-pentadienoic acid, followed by mild hydrolysis preserving the triene configuration.
Project description:A water-soluble PdCl?(NH?)?/cationic 2,2'-bipyridyl system was found to be a highly efficient catalyst for Stille coupling of aryl iodides and bromides with organostannanes. The coupling reaction was conducted at 110 °C in water, under aerobic conditions, in the presence of NaHCO? as a base to afford corresponding Stille coupling products in good to high yields. When aryltributylstannanes were employed, the reactions proceeded smoothly under a very low catalyst loading (as little as 0.0001 mol %). After simple extraction, the residual aqueous phase could be reused in subsequent runs, making this Stille coupling economical. In the case of tetramethylstannane, however, a greater catalyst loading (1 mol %) and the use of tetraethylammonium iodide as a phase-transfer agent were required in order to obtain satisfactory yields.
Project description:Transition met al catalysis has enabled the highly stereoselective and protecting group-free synthesis of the C14-C23 fragment of the apoptosis-inducing natural products biselyngbyolide A and B. A Pd-catalyzed Stille reaction between a vinyl stannane and a crotyl carbonate formed the skipped diene with complete control of the the trisubstituted bond and excellent control over the branched/linear products. A Cu-catalyzed Stahl oxidation was used to form the requisite aldehyde needed for a Ag-catalyzed asymmetric allylation. The latter provided the final fragment with excellent stereochemical control.