Microwave-assisted ketone-ketone rearrangement: an improved synthesis of 3-(4-alkoxyphenyl)-3- methylbutan-2-ones

[reaction: see text] A novel procedure for the preparation of 3-(4-alkoxyphenyl)-3-methylbutan-2-one in excellent yield is described via polymer-supported AlCl3-catalyzed rearrangement of 1-(4-ethoxyphenyl)-2,2-dimehtylpropan-1-one, followed by O-alkylation under microwave irradiation condition.     

Cholesterol-based dimeric liquid crystals: synthesis and mesomorphic behaviour

Chiral non-symmetric dimeric liquid crystals consisting of a cholesteryl ester moiety as chiral entity and a biphenyl aromatic core, interconnected through n-butyl (C₄) or n-pentyl (C₅) parity alkylene spacers, have been synthesized and investigated for their liquid crystalline properties. All the dimers exhibit enantiotropic mesophases. The first member of the dimers having the C₄ central spacer exhibit only the chiral nematic (N*) mesophase, while the higher homologues also show smectic A (SmA) and twist grain boundary (TGB) mesophases. The dimers of the other series containing the C₅ central spacer also have stable SmA, TGB and N* mesophases, except for the first which does not show the TGB phase. Both series of compounds show a weak odd-even effect with terminal alkyl chain substitution, while the spacer length has a marked influence on the phase transition temperatures.     

Label-Free Proteomic Identification of Endogenous,Insulin-Stimulated Interaction Partners of Insulin Receptor Substrate-1

Protein–protein interactions are key to most cellular processes. Tandem mass spectrometry (MS/MS)-based proteomics combined with co-immunoprecipitation (CO-IP) has emerged as a powerful approach for studying protein complexes. However, a majority of systematic proteomics studies on protein–protein interactions involve the use of protein overexpression and/or epitope-tagged bait proteins, which might affect binding stoichiometry and lead to higher false positives. Here, we report an application of a straightforward, label-free CO-IP-MS/MS method, without the use of protein overexpression or protein tags, to the investigation of changes in the abundance of endogenous proteins associated with a bait protein, which is in this case insulin receptor substrate-1 (IRS-1), under basal and insulin stimulated conditions. IRS-1 plays a central role in the insulin signaling cascade. Defects in the protein–protein interactions involving IRS-1 may lead to the development of insulin resistance and type 2 diabetes. HPLC-ESI-MS/MS analyses identified eleven novel endogenous insulin-stimulated IRS-1 interaction partners in L6 myotubes reproducibly, including proteins play an important role in protein dephosphorylation [protein phosphatase 1 regulatory subunit 12A, (PPP1R12A)], muscle contraction and actin cytoskeleton rearrangement, endoplasmic reticulum stress, and protein folding, as well as protein synthesis. This novel application of label-free CO-IP-MS/MS quantification to assess endogenous interaction partners of a specific protein will prove useful for understanding how various cell stimuli regulate insulin signal transduction.     

Giant Enhancement of Second Harmonic Generation Accompanied by the Structural Transformation of 7-Fold to 8-Fold Interpenetrated Metal–Organic Frameworks (MOFs)

Interpenetration in metal–organic frameworks (MOFs) is an intriguing phenomenon with significant impacts on their properties, and functional applications. Herein, we show that a 7-fold interpenetrated MOF ( 1 ) is transformed into an 8-fold interpenetrated MOF by the loss of DMF in a single-crystal-to-single-crystal manner. This is accompanied by a giant enhancement of the second harmonic generation (SHG ca. 125 times) and two-photon photoluminescence (ca. 14 times). The strengthened π–π interaction between the individual diamondoid networks and intensified oscillator strength of the molecules aid the augment of dipole moments and boost the nonlinear optical conversion efficiency. Large positive and negative thermal expansions of 1 occur at 30–150 °C before the loss of DMF. These results offer an avenue to manipulate the NLO properties of MOFs using interpenetration and provide access to tunable single-crystal NLO devices.     

Optically Biaxial,Re‐entrant and Frustrated Mesophases in Chiral,Non‐symmetric Liquid Crystal Dimers and Binary Mixtures

Sixteen optically active, non‐symmetric dimers, in which cyanobiphenyl and salicylaldimine mesogens are interlinked by a flexible spacer, were synthesized and characterized. While the terminal chiral tail, in the form of either (R)‐2‐octyloxy or (S)‐2‐octyloxy chain attached to salicylaldimine core, was held constant, the number of methylene units in the spacer was varied from 3 to 10 affording eight pairs of (R & S) enantiomers. They were probed for their thermal properties with the aid of orthoscopy, conoscopy, differential scanning calorimetry and X‐ray powder diffraction. In addition, the binary mixture study was carried out using chiral and achiral dimers with the intensions of stabilizing optically biaxial phase/s, re‐entrant phases and important phase sequences. Notably, one of the chiral dimers as well as some mixtures exhibited a biaxial smectic A (SmA_b) phase appearing between a uniaxial SmA and a re‐entrant uniaxial SmA phases. The mesophases such as chiral nematic (N*) and frustrated phases viz., blue phases (BPs) and twist grain boundary (TGB) phases, were also found to occur in most of the dimers and mixtures. X‐ray diffraction studies revealed that the dimers possessing oxybutoxy and oxypentoxy spacers show interdigitated (SmA_d) phase where smectic periodicity is over 1.4 times the molecular length; whereas in the intercalated SmA (SmA_c) phase formed by a dimer having oxydecoxy spacer the periodicity was found to be approximately half the molecular length. The handedness of the helical structure of the N* phases formed by two enantiomers was examined with the aid of CD measurements; as expected, these enantiomers showed optical activities of equal magnitudes but with opposite signs. Overall, it appears that the chiral dimers and mixtures presented herein may serve as model systems in design and developing novel materials exhibiting the apolar SmA_b phase possessing D_2h symmetry and nematic‐type biaxiality.     

Deciphering the Role of MicroRNAs in Neuroblastoma

Neuroblastoma (NB) is a type of peripheral sympathetic nervous system cancer that most commonly affects children. It is caused by the improper differentiation of primitive neural crest cells during embryonic development. Although NB occurs for 8% of paediatric cancers, it accounts for 15% of cancer-related deaths. Despite a considerable increase in cytotoxic chemo- and radiotherapy, patients in advanced stages remain virtually incurable. Therefore, there is a desperate necessity for new treatment strategies to be investigated. Accumulating evidence suggested that microRNAs (miRNAs) are a class of non-coding RNAs with 19–25 nucleotides lengths and play a central role in the development of NB carcinogenesis. Fascinatingly, miRNA inhibitors have an antisense property that can inhibit miRNA function and suppress the activity of mature miRNA. However, many studies have addressed miRNA inhibition in the treatment of NB, but their molecular mechanisms and signalling pathways are yet to be analysed. In this study, we impart the current state of knowledge about the role of miRNA inhibition in the aetiology of NB.     

A dianionic oxy-cope rearrangement route to benzotropones - part XII

The divinyl carbinols $\text{3}$ and $\text{6}$ furnished the benzotropones $\text{4}$ and $\text{7}$ respectively, when treated with base.     

Specially Structured Precedence Constraints in Three-Dimensional Bottleneck Assignment Problems

A three-dimensional, time-minimizing (bottleneck) assignment problem consists of assigning n jobs to n workers to be performed on n machines under different forms of feasibility conditions so that the different functions of the individual times taken by a worker to finish a job on a given machine are minimized. The usual assumption made in such a problem is that all the jobs can be commenced simultaneously. In this paper, two specially structured precedence constraints on jobs are considered, which necessitate modifications in this assumption. Further, the main purpose here is to develop branch-and-bound-type algorithms for solving the corresponding problems and to illustrate them by a numerical example.