ABSTRACT
Sterically hindered naphthalene-substituted biphenyls and terphenyls were synthesized in good yields, by Michael addition of a conjugate base of core-substituted phenylacetones to substituted 2-oxo-2H-pyran-3-carbonitriles at room temperature under alkaline conditions. These diversely functionalized benzenes (1,2-teraryls or 1,3-teraryls), bearing naphthyl and substituted aryl rings, show the phenomenon of atropisomerism, with one or two stereogenic biaryl axes. The resolution of the respective four atropisomers of the naphthalene-substituted biphenyls and terphenyls bearing 1,2-type or 1,3-type chiral biaryl axes was achieved by HPLC on a chiral phase. The absolute stereostructures of 6a and 9a were determined by the combination of experimental electronic circular dichroism (ECD) investigations and quantum-chemical circular dichroism (QC-CD) calculations. For the atropisomerization of (1M,6M)-6a and (1M,5M)-9a to their (M,P)- and (P,M)-diastereomer, respectively, the possible transition states were investigated and the interconversion barriers (ΔG) were theoretically predicted. This study provides a general protocol for the synthesis, resolution, and stereochemical characterization of rotationally hindered naphthalene-substituted biphenyls and terphenyls. The strategy may be applied to investigate other, similarly hindered biaryl or teraryl systems either derived from natural sources or prepared through synthetic approaches.
ABSTRACT
The discovery of an iron(III)-selective ratiometric fluorescent probe to detect and visualize endogenous labile iron pools in living organisms at the molecular level has been long awaited. Herein we report the first dual colorimetric and ratiometric fluorescent probe naphtho[2,1-b][1,10]phenanthroline for selective and 'direct' visualization of labile iron(III) pools in a multicellular organism, Caenorhabditis elegans.
Subject(s)
Caenorhabditis elegans/chemistry , Colorimetry , Ferric Compounds/analysis , Fluorescent Dyes/chemistry , Heterocyclic Compounds, 4 or More Rings/chemistry , Animals , Fluorescent Dyes/chemical synthesis , Hep G2 Cells , Heterocyclic Compounds, 4 or More Rings/chemical synthesis , Humans , Molecular Structure , Quantum TheoryABSTRACT
A series of functionalized biaryl-4-carbonitriles was synthesized in three steps and evaluated for PTP-1B inhibitory activity. Among the synthesized compounds, four biaryls 6a-d showed inhibition (IC50 58-75 µM) against in vitro PTP-1B assay possibly due to interaction with amino acid residues Lys120, Tyr46 through hydrogen bonding and aromatic-aromatic interactions, respectively. Two biaryl-4-carbonitriles 6b and 6c showed improved glucose tolerance, fasting as well as postprandial blood glucose, serum total triglycerides, and increased high-density lipoprotein-cholesterol in SLM, STZ, STZ-S and C57BL/KsJ-db/db animal models. The bioanalysis of 4'-bromo-2,3-dimethyl-5-(piperidin-1-yl)biphenyl-4-carbonitrile (6b) revealed that like insulin, it increased 2-deoxyglucose uptake in skeletal muscle cells (L6 and C2C12 myotubes). The compound 6b significantly up-regulated the genes related to the insulin signaling pathways like AMPK, MAPK including glucose transporter-4 (GLUT-4) gene in muscle tissue of C57BL/KsJ-db/db mice. Furthermore, it was observed that the compound 6b up-regulated PPARα, UCP2 and HNF4α, which are key regulator of glucose, lipid, and fatty acid metabolism. Western blot analysis of the compound 6b showed that it significantly increased the phosphorylation of AMPK and p38 MAPK and ameliorated glucose uptake in C57BL/KsJ-db/db mice through the AMPK-p38 MAPK pathway.
Subject(s)
AMP-Activated Protein Kinases/metabolism , Diabetes Mellitus, Experimental/drug therapy , Hypoglycemic Agents/pharmacology , Nitriles/pharmacology , Signal Transduction/drug effects , p38 Mitogen-Activated Protein Kinases/metabolism , AMP-Activated Protein Kinases/genetics , Animals , Blood Glucose/metabolism , Cell Line , Cholesterol, HDL/blood , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Experimental/genetics , Diabetes Mellitus, Experimental/metabolism , Gene Expression Regulation , Glucose Transporter Type 4/genetics , Glucose Transporter Type 4/metabolism , Hepatocyte Nuclear Factor 4/genetics , Hepatocyte Nuclear Factor 4/metabolism , Hydrogen Bonding , Hydrophobic and Hydrophilic Interactions , Hyperglycemia , Hypoglycemic Agents/chemical synthesis , Insulin/metabolism , Ion Channels/genetics , Ion Channels/metabolism , Male , Mice , Mice, Inbred C57BL , Mitochondrial Proteins/genetics , Mitochondrial Proteins/metabolism , Models, Molecular , Muscle Fibers, Skeletal , Nitriles/chemical synthesis , PPAR alpha/genetics , PPAR alpha/metabolism , Rats , Streptozocin , Triglycerides/blood , Uncoupling Protein 2 , p38 Mitogen-Activated Protein Kinases/geneticsABSTRACT
A new series of thermally stable blue light-emitting nonplanar pyrenylarenes having an amine donor and a nitrile acceptor group was prepared from a ketene-S,S-acetal under conventional heating and/or microwave irradiation. The photophysical, electrochemical, and optical behavior of donor-acceptor pyrenylarenes are demonstrated. The performance of blue light-emitting pyrenylarenes was investigated by fabricating a multilayer device with the device configuration of ITO/PEDOT:PSS (40 nm)/NPB (30 nm)/pyrenylarene (55 nm)/BCP (8 nm)/LiF (0.6 nm)/Al (200 nm), which exhibited low turn-on voltage (5 V) with luminance efficiency of 0.8 Cd/A with nonaggregation behavior in both solution and solid state.
