588-73-8Relevant articles and documents
On the planarity of styrene and its derivatives: The molecular structures of styrene and (Z)-β-bromostyrene as determined by ab initio calculations and gas-phase electron diffraction
Cochran, John C.,Hagen, Kolbjorn,Paulen, Gunnar,Shen, Quang,Tom, Samson,Traetteberg, Marit,Wells, Christopher
, p. 313 - 326 (1997)
The molecular structures of styrene and (Z)-β-bromostyrene have been studied in the gas phase at nozzle temperatures of 303 and 338 K respectively. For both molecules the electron diffraction data were consistent with the results from ab initio calculatio
Illuminatinganti-hydrozirconation: controlled geometric isomerization of an organometallic species
Gilmour, Ryan,Hostmann, Theresa,Nevesely, Tomá?
, p. 10643 - 10648 (2021/08/20)
A general strategy to enable the formalanti-hydrozirconation of arylacetylenes is reported that mergescis-hydrometallation using the Schwartz Reagent (Cp2ZrHCl) with a subsequent light-mediated geometric isomerization atλ= 400 nm. Mechanistic delineation of thecontra-thermodynamic isomerization step indicates that a minor reaction product functions as an efficientin situgenerated photocatalyst. Coupling of theE-vinyl zirconium species with an alkyne unit generates a conjugated diene: this has been leveraged as a selective energy transfer catalyst to enableE→Zisomerization of an organometallic species. Through anUmpolungmetal-halogen exchange process (Cl, Br, I), synthetically useful vinyl halides can be generated (up toZ?:?E= 90?:?10). This enabling platform provides a strategy to access nucleophilic and electrophilic alkene fragments in both geometric forms from simple arylacetylenes.
Chemical validation of a druggable site on Hsp27/HSPB1 using in silico solvent mapping and biophysical methods
Makley, Leah N.,Johnson, Oleta T.,Ghanakota, Phani,Rauch, Jennifer N.,Osborn, Delaney,Wu, Taia S.,Cierpicki, Tomasz,Carlson, Heather A.,Gestwicki, Jason E.
, (2021/02/09)
Destabilizing mutations in small heat shock proteins (sHsps) are linked to multiple diseases; however, sHsps are conformationally dynamic, lack enzymatic function and have no endogenous chemical ligands. These factors render sHsps as classically “undruggable” targets and make it particularly challenging to identify molecules that might bind and stabilize them. To explore potential solutions, we designed a multi-pronged screening workflow involving a combination of computational and biophysical ligand-discovery platforms. Using the core domain of the sHsp family member Hsp27/HSPB1 (Hsp27c) as a target, we applied mixed solvent molecular dynamics (MixMD) to predict three possible binding sites, which we confirmed using NMR-based solvent mapping. Using this knowledge, we then used NMR spectroscopy to carry out a fragment-based drug discovery (FBDD) screen, ultimately identifying two fragments that bind to one of these sites. A medicinal chemistry effort improved the affinity of one fragment by ~50-fold (16 μM), while maintaining good ligand efficiency (~0.32 kcal/mol/non-hydrogen atom). Finally, we found that binding to this site partially restored the stability of disease-associated Hsp27 variants, in a redox-dependent manner. Together, these experiments suggest a new and unexpected binding site on Hsp27, which might be exploited to build chemical probes.