BET Bromodomain Inhibitors with One-Step Synthesis Discovered from Virtual Screen.

Chemical inhibition of epigenetic regulatory proteins BrdT and Brd4 is emerging as a promising therapeutic strategy in contraception, cancer, and heart disease. We report an easily synthesized dihydropyridopyrimidine pan-BET inhibitor scaffold, which was uncovered via a virtual screen followed by testing in a fluorescence anisotropy assay. Dihydropyridopyimidine 3 was subjected to further characterization and is highly selective for the BET family of bromodomains.

Synthesis of a quinolone library from ynones.

A library of 72 quinolones was synthesized from substituted anthranilic acids, using ynone intermediates. These masked β-dicarbonyl synthons allowed cyclization under milder conditions than previously reported quinolone syntheses.

SERS detection of indirect viral DNA capture using colloidal gold and methylene blue as a Raman label.

An indirect capture model assay using colloidal Au nanoparticles is demonstrated for surface enhanced Raman scattering (SERS) spectroscopy detection of DNA. The sequence targeted for capture was derived from the West Nile Virus (WNV) RNA genome and selected on the basis of exhibiting minimal secondary structure formation. Upon incubation with colloidal Au, hybridization complexes containing the WNV target sequence, a complementary capture oligonucleotide conjugated to a strong tethering group and a complementary reporter oligonucleotide conjugated to methylene blue (MB), a Raman label, anchors the resultant ternary complex to Au nanoparticles and positions MB within the required sensing distance for SERS enhancement.

Mechanistic studies on the photochromism of [e]-annelated dimethyldihydropyrenes.

The photochemistry of several photochromic arene [e]-annelated dimethyldihydropyrenes (DHPs) was studied. These compounds have much larger photochemical ring opening quantum yields than the simple DHPs, making them potentially more useful as building blocks for photoswitchable materials.

Synthesis and photochromic properties of molecules containing [e]-annelated dihydropyrenes. Two and three way pi-switches based on the dimethyldihydropyrene-metacyclophanediene valence isomerization.

The syntheses of several new simple negative, a simple positive, and multiple negative photochromes containing the dihydropyrene-cyclophanediene photochromic system are described. The photo-openings of the negative photochromes, the [e]-annelated benzo (7), naphtho (9), anthro (11), furano (19), and triphenyleno (15) derivatives of the parent 2,7-di-tert-butyl-trans-10b,10c-dimethyl-dihydropyrene (5), as well as its 4,5-dibromo derivative (13), are described to give the corresponding cyclophanedienes, as well as their photoclosures and thermal closures back to the dihydropyrenes. These are compared to the results obtained for the positive photochrome dibenzo[e,l]dihydropyrene (21) and to the bis(dihydropyreno)chrysene (44) and the (dihydropyrenobenzo)(benzo)metacyclophanediene (47) photochromes, which have more than one photochromic switch present and thus have more than a simple "on-off" state.

Dimethyldihydropyrene-dehydrobenzoannulene hybrids: studies in aromaticity and photoisomerization.

The synthesis and study of dehydrobenzoannulene (DBA)-dimethyldihydropyrene (DDP) hybrids as models for the investigation of aromaticity in weakly diatropic systems is reported. Three new monofused DBA-DDP hybrids have been synthesized, and their NMR spectra are discussed with regard to quantifying the aromaticity remaining in multibenzene-fused DBAs. Nucleus-independent chemical shifts, determined at a series of locations for each compound, bond lengths, and (1)H and (13)C NMR chemical shifts were calculated and used to probe the aromaticity of these hybrids.

A theoretical and experimental scale of aromaticity. The first nucleus-independent chemical shifts (NICS) study of the dimethyldihydropyrene nucleus.

Nucleus-independent chemical shift (NICS) values were calculated at several locations for a series of dimethyldihydropyrenes (DDPs). These NICS values were used to assess the relative aromaticities of the dimethyldihydropyrene nucleus (DDPN) of these DDPs and to construct a NICS scale of aromaticity. The NICS and experimentally determined relative aromaticities of these DDPNs are in complete agreement, verifying that NICS can be used not only to classify a compound as aromatic but also to determine the degrees of aromaticity of structurally related systems.