Hybridized plasmonic modes and Fabry-Perot effect in nanoscale bowtie aperture waveguide.

Based on Bethe's theory, light is hard to transmit through sub-wavelength apertures. However, a special designed sub-wavelength bowtie aperture is found to be able to transmit light with high efficiency. In this letter, modal analysis is used to study the hybridized plasmonic modes and Fabry-Perot effect of the nanoscale bowtie aperture waveguide. High frequency structure simulator (HFSS) simulations in perfect electrically conductor (PEC) and real metals are performed to calculate the fundamental mode, higher order mode, as well as their own cutoff wavelength. Mode analysis can give a better understanding of the intrinsic link between the plasmonic effects and Fabry-Perot effect. The TE10 and TE30 modes hybridize with channel plasmon polaritons (CPPs) modes and surface plasmon polaritons (SPPs) modes respectively. Experiments are carried out to verify the numerical results. These results are of great significance for understanding the internal mechanism of the bowtie aperture for coupling light to a sub-diffraction limited spot with high transmission efficiency.

40 nm thick photoresist-compatible plasmonic nanolithography using a bowtie aperture combined with a metal-insulator-metal structure.

In this Letter, 40 nm thick photoresist (PR)-compatible plasmonic nanolithography using a bowtie aperture incorporated with a metal-insulator-metal (MIM) structure is studied numerically and experimentally. The simulation results show that with a 20 nm index-matching layer, the light field that exits from the bowtie aperture penetrates into a 40 nm thick PR by using a MIM configuration. Imaging contrast calculations indicate that sub-45 nm resolution with an exposure depth in the order of tens of nanometers is achievable, which is confirmed by the experimental results. In addition, the ability to generate high-resolution, complex patterns using this technique via scanning is demonstrated. This brings plasmonic nanolithography using a bowtie aperture one step closer to practical applications.

Flexible devices fabricated by a plate-to-roll nanoimprint lithography system.

A plate-to-roll nanoimprint lithography (P2RNIL) system has been developed to realize a high-speed, large-scale and high-resolution nanoimprint process. Imprinted patterns have been achieved with a linewidth of less than 75 nm at a speed of 22 cm2 s-1 on flexible substrate. To improve the quality of the imprinted patterns, we have proposed a compliant mechanism which can realize passive alignment and minimize the lateral displacement between template and substrate. Finite element analysis of this compliant mechanism was carried out. By using the P2RNIL system, wire-grid polarizers (up to a 10 030:1 extinction ratio and up to 88% transmittance) and transparent metal electrodes whose performance is in good accordance with simulated results were successfully fabricated.

Resonant Effects in Nanoscale Bowtie Apertures.

Nanoscale bowtie aperture antennas can be used to focus light well below the diffraction limit with extremely high transmission efficiencies. This paper studies the spectral dependence of the transmission through nanoscale bowtie apertures defined in a silver film. A realistic bowtie aperture is numerically modeled using the Finite Difference Time Domain (FDTD) method. Results show that the transmission spectrum is dominated by Fabry-Pérot (F-P) waveguide modes and plasmonic modes. The F-P resonance is sensitive to the thickness of the film and the plasmonic resonant mode is closely related to the gap distance of the bowtie aperture. Both characteristics significantly affect the transmission spectrum. To verify these numerical results, bowtie apertures are FIB milled in a silver film. Experimental transmission measurements agree with simulation data. Based on this result, nanoscale bowtie apertures can be optimized to realize deep sub-wavelength confinement with high transmission efficiency with applications to nanolithography, data storage, and bio-chemical sensing.

Identification of a glycogen synthase kinase-3ß inhibitor that attenuates hyperactivity in CLOCK mutant mice.

Bipolar disorder is characterized by a cycle of mania and depression, which affects approximately 5 million people in the United States. Current treatment regimes include the so-called "mood-stabilizing drugs", such as lithium and valproate that are relatively dated drugs with various known side effects. Glycogen synthase kinase-3ß (GSK-3ß) plays a central role in regulating circadian rhythms, and lithium is known to be a direct inhibitor of GSK-3ß. We designed a series of second generation benzofuran-3-yl-(indol-3-yl)maleimides containing a piperidine ring that possess IC50 values in the range of 4 to 680 nM against human GSK-3ß. One of these compounds exhibits reasonable kinase selectivity and promising preliminary absorption, distribution, metabolism, and excretion (ADME) data. The administration of this compound at doses of 10 to 25 mg kg⁻¹ resulted in the attenuation of hyperactivity in amphetamine/chlordiazepoxide-induced manic-like mice together with enhancement of prepulse inhibition, similar to the effects found for valproate (400 mg kg⁻¹) and the antipsychotic haloperidol (1 mg kg⁻¹). We also tested this compound in mice carrying a mutation in the central transcriptional activator of molecular rhythms, the CLOCK gene, and found that the same compound attenuates locomotor hyperactivity in response to novelty. This study further demonstrates the use of inhibitors of GSK-3ß in the treatment of manic episodes of bipolar/mood disorders, thus further validating GSK-3ß as a relevant therapeutic target in the identification of new therapies for bipolar patients.

Identification, synthesis, and pharmacological evaluation of tetrahydroindazole based ligands as novel antituberculosis agents.

The resurgence of tuberculosis (TB), the incidence of drug-resistant strains of Mycobacterium tuberculosis (MTB), and the coinfection between TB and HIV have led to serious infections, high mortality, and a global health threat, resulting in the urgent search for new classes of antimycobacterial agents. Herein, we report the identification of a novel class of tetrahydroindazole based compounds as potent and unique inhibitors of MTB. Compounds 6a, 6m, and 6q exhibited activity in the low micromolar range against replicating Mycobacterium tuberculosis (R-TB) phenotype, with minimum inhibitory concentrations (MICs) of 1.7, 1.9, and 1.9 muM, respectively, while showing no toxicity to Vero Ccells. Moreover, studies aimed to assess the in vitro metabolic stability of 6a and 6m in mouse liver microsomes and in vivo pharmacokinetic profiles in plasma levels gave satisfactory results. This research suggests that tetrahydroindazole based anti-TB compounds can serve as a promising lead scaffold in developing new drugs to combat tuberculosis infections.

Natural product leads for drug discovery: isolation, synthesis and biological evaluation of 6-cyano-5-methoxyindolo[2,3-a]carbazole based ligands as antibacterial agents.

Indolo[2,3-a]carbazole based inhibitors were synthesized from readily available indigo via a seven-step linear synthetic sequence with a moderate overall yield. The inhibitors were selectively and readily functionalized at the nitrogen on the indole portion of the carbazole unit. The synthesized analogs displayed moderate inhibitory activities toward Bacillus anthracis and Mycobacterium tuberculosis, indicating that indolo[2,3-a]carbazoles could serve as promising leads in the development of new drugs to combat anthrax and tuberculosis infections.

From a natural product lead to the identification of potent and selective benzofuran-3-yl-(indol-3-yl)maleimides as glycogen synthase kinase 3beta inhibitors that suppress proliferation and survival of pancreatic cancer cells.

Recent studies have demonstrated that glycogen synthase kinase 3beta (GSK-3beta) is overexpressed in human colon and pancreatic carcinomas, contributing to cancer cell proliferation and survival. Here, we report the design, synthesis, and biological evaluation of benzofuran-3-yl-(indol-3-yl)maleimides, potent GSK-3beta inhibitors. Some of these compounds show picomolar inhibitory activity toward GSK-3beta and an enhanced selectivity against cyclin-dependent kinase 2 (CDK-2). Selected GSK-3beta inhibitors were tested in the pancreatic cancer cell lines MiaPaCa-2, BXPC-3, and HupT3. We determined that some of these compounds, namely compounds 5, 6, 11, 20, and 26, demonstrate antiproliferative activity against some or all of the pancreatic cancer cells at low micromolar to nanomolar concentrations. We found that the treatment of pancreatic cancer cells with GSK-3beta inhibitors 5 and 26 resulted in suppression of GSK-3beta activity and a distinct decrease of the X-linked inhibitor of apoptosis (XIAP) expression, leading to significant apoptosis. The present data suggest a possible role for GSK-3beta inhibitors in cancer therapy, in addition to their more prominent applications in CNS disorders.

Amino acid and peptide synthesis and functionalization by the reaction of thioacids with 2,4-dinitrobenzenesulfonamides.

Readily prepared amino thioacids react at room temperature in DMF in the presence of cesium carbonate with 2,4-dinitrobenzenesulfonamides to give amides. When the sulfonamide is derived from an amino acid the method results in peptide bond formation, whereas the use of carbohydrate derived sulfonamides gives neoglycoconjugates.

Addition of amines to the triple bond in alpha,alpha,alpha-trichloromethylpropargyl mesylate: synthesis of alpha,alpha-dichloromethylenaminones and preparation of 2-phenyl-4-dichloromethylquinolines.

[reaction: see text] Addition of amines to the triple bond in alpha,alpha,alpha-trichloromethylpropargyl mesylate to give alpha,alpha-dichloromethylenaminones and its use in the preparation of 2-phenyl-4-dichloromethylquinolines in good yields are reported.