Turn conformations in a metallacyclictripeptide and a metallacyclictetrapeptide induced by tungsten-alkyne coordination

Tungsten-alkyne coordination was employed for the preparation of a metallacyclictripeptide and a metallacyclictetrapeptide. First, the dialkynyltripeptide 7 and the dialkynyltetrapeptide 9 were prepared using solution phase peptide synthesis. In both 7 and 9 the two alkynes were attached to the peptide at the N- and C-termini. Reaction of 7 with W(CO)₃(dmtc)₂ yielded the metallacyclictripeptide 10, while reaction of 9 with W(CO)₃(dmtc)₂ yielded the metallacyclictetrapeptide 11. The identities of 10 and 11 were established using ¹H NMR spectroscopy and positive ion electrospray mass spectrometry. The ¹H NMR spectra of 10 and 11 show that these species exist as a complex mixture of isomers that differ in how the ligands are arranged around the tungsten center. Interconversion between these isomers is slow at 23 °C, but the rate of interconversion increases as the temperature is raised. With 10, all the alkyne hydrogen signals coalesce at 95 °C. However, with 11 the alkyne hydrogen signals do not fully coalesce, even at 105 °C. Related to this is the behavior of 10 and 11 during HPLC analysis; 10 elutes as a single peak, but 11 elutes as two overlapping peaks. The overlapping peaks and the high isomer interconversion temperature of 11 as compared to 10 are attributed to the presence of additional intramolecular hydrogen bonding interactions between the two ends of the peptide in 11.     

Investigation of tyrosine nitration and nitrosylation of angiotensin II and bovine serum albumin with electrospray ionization mass spectrometry

Protein tyrosine nitration is one of the important regulatory mechanisms in various cellular phenomena such as cell adhesion, endo/exo-cytosis of cellular materials, and signal transduction. In the present study, electrospray ionization tandem mass spectrometry (ESI-MS/MS) with a linear ion-trap mass spectrometer was applied for identification of nitrated proteins and localization of the modified tyrosine residues. When angiotensin II(DRVYIHPF) was nitrated in vitro with tetranitromethane (TNM), the mass spectrum showed a shift of +45 Da which corresponded to tyrosine nitration. An additional +29 Da mass shift was also detected by ESI-MS. This differed from nitrated peptide analysis with matrix-associated laser desorption/ionization mass spectrometry (MALDI-MS), which showed oxygen neutral loss from the nitrated tyrosine residues upon laser irradiation. Hence the +29 Da mass shift of the nitrated peptide observed by ESI-MS suggested the introduction of an NO group for nitrosylation of tyrosine residues. To confirm this in vitro nitrosylation on the protein level, bovine serum albumin was in vitro nitrated with TNM and analyzed by ESI-MS/MS. As expected, +29 as well as +45 Da mass shifts were detected, and the +29 Da mass shift was found to correspond to the modification on tyrosine residues by NO. Although the chemical mechanism by which this occurs in ESI-MS is not clear, the +29 Da mass shift could be a new potential marker of nitrosylated peptides.     

Efficient Generation of Microdroplets Using Tail Breakup Induced with Multi-Branch Channels

In recent years, research on the application of microdroplets in the fields of biotechnology and chemistry has made remarkable progress, but the technology for the stable generation of single-micrometer-scale microdroplets has not yet been established. In this paper, we developed an efficient and stable single-micrometer-scale droplet generation device based on the fragmentation of droplet tails, called “tail thread mode”, that appears under moderate flow conditions. This method can efficiently encapsulate microbeads that mimic cells and chemical products in passively generated single-micrometer-scale microdroplets. The device has a simple 2D structure; a T-junction is used for droplet generation; and in the downstream, multi-branch channels are designed for droplet deformation into the tail. Several 1–2 µm droplets were successfully produced by the tail’s fragmentation; this continuous splitting was induced by the branch channels. We examined a wide range of experimental conditions and found the optimal flow rate condition can be reduced to one-tenth compared to the conventional tip-streaming method. A mold was fabricated by simple soft lithography, and a polydimethylsiloxane (PDMS) device was fabricated using the mold. Based on the 15 patterns of experimental conditions and the results, the key factors for the generation of microdroplets in this device were examined. In the most efficient condition, 61.1% of the total droplets generated were smaller than 2 μm.     

Syntheses of 1H-Indoles,Quinolines, and 6-Membered Aromatic N-Heterocycle-Fused Scaffolds via Palladium(II)-Catalyzed Aerobic Dehydrogenation under Alkoxide-Free Conditions

Aromatic N-heterocycle-fused scaffolds such as indoles and quinolines are important core structures found in various bioactive natural products and synthetic compounds. Recently, various dehydrogenation methods with the help of alkoxides, known to significantly promote dihydro- or tetrahydro-heterocycles to be oxidized, were developed for the heterocycle synthesis. However, these approaches are sometimes unsuitable due to resulting undesired side reactions such as reductive dehalogenation. Herein, expedient syntheses of 1H-indoles, quinolines, and 6-membered N-heterocycle-fused scaffolds from their hydrogenated forms through palladium(II)-catalyzed aerobic dehydrogenation under alkoxide-free conditions are reported. A total of 48 compounds were successfully synthesized with a wide range of functional groups including halogens (up to 99% yield). These methodologies provide facile routes for various privileged structures possessing aromatic N-heterocycles without the help of alkoxides, in highly efficient manners.     

Ratiometric Fluorescence Assay for Nitroreductase Activity: Locked-Flavylium Fluorophore as a NTR-Sensitive Molecular Probe

Nitroreductases belong to a member of flavin-containing enzymes that can reduce nitroaromatic compounds to amino derivatives with NADH as an electron donor. NTR activity is known to be elevated in the cancerous environment and is considered an advantageous target in therapeutic prodrugs for the treatment of cancer. Here, we developed a ratiometric fluorescent molecule for observing NTR activity in living cells. This can provide a selective and sensitive response to NTR with a distinct increase in fluorescence ratio (FI₅₃₀/FI₆₃₀) as well as color changes. We also found a significant increase in NTR activity in cervical cancer HeLa and lung cancer A549 cells compared to non-cancerous NIH3T3. We proposed that this new ratiometric fluorescent molecule could potentially be used as a NTR-sensitive molecular probe in the field of cancer diagnosis and treatment development related to NTR activity.     

An efficient organic additive to control the crystallization rate of aliphatic polyketone: A non-isothermal crystallization kinetics study

Three types of organic compounds—two carboxylic acids and an anhydride, were used as additives for polyketone(PK). The effect of the additive structure and their feed ratios on the melting temperature, crystallization temperature, and crystallization rate of PK were studied. We found that the crystallization temperature could be reduced significantly by introducing a small quantity of organic additive, in particular, an anhydride. On addition of 1 phr of anhydride, the crystallization temperature was reduced by 10.7 ℃. Therefore, the non-isothermal crystallization kinetics of aliphatic PK/anhydride blends with various feed ratios was investigated using DSC. The results were analyzed by various theoretical models, such as Avrami, Ozawa and combined Avrami-Ozawa models.     

Large-Scale Structured Sparsity via Parallel Fused Lasso on Multiple GPUs

We present a massively parallel algorithm for the fused lasso, powered by a multiple number of graphics processing units (GPUs). Our method is suitable for a class of large-scale sparse regression problems on which a two-dimensional lattice structure among the coefficients is imposed. This structure is important in many statistical applications, including image-based regression in which a set of images are used to locate image regions predictive of a response variable such as human behavior. Such large datasets are increasingly common. In our study, we employ the split Bregman method and the fast Fourier transform, which jointly have a high data-level parallelism that is distinct in a two-dimensional setting. Our multi-GPU parallelization achieves remarkably improved speed. Specifically, we obtained as much as 433 times improved speed over that of the reference CPU implementation. We demonstrate the speed and scalability of the algorithm using several datasets, including 8100 samples of 512 × 512 images. Compared to the single GPU counterpart, our method also showed improved computing speed as well as high scalability. We describe the various elements of our study as well as our experience with the subtleties in selecting an existing algorithm for parallelization. It is critical that memory bandwidth be carefully considered for multi-GPU algorithms. Supplementary material for this article is available online.     

Synthesis of N-unsubstituted 1,2,3-triazoles via aerobic oxidative N-dealkylation using copper(II) acetate

A copper-catalyzed aerobic oxidative CN bond cleavage reaction was developed for the synthesis of 4-substituted-NH-1,2,3-triazoles. Diverse β-ketotriazoles derivatives, which are the starting materials for the aerobic oxidative CN bond cleavage reaction, were prepared from nine aryl and seven alkyl alkynes and α-azidoacetophenone by a copper(I)-catalyzed [3 + 2]cycloaddition reaction. The aerobic oxidation of α-(1,2,3-triazol-1-yl)acetophenones using a catalytic amount of copper(II) acetate in the presence oxygen under neutral conditions gave the title compounds in high yield.     

Catalyst-free synthesis of 4-alkynylazobenzenes from quinols

A catalyst-free and environmently benign synthesis of highly conjugated 4-alkynylazoaromatic compounds from quinols having an alkyne is described. Formation of hydrazones by preferential condensation of quinols bearing many sensitive functional groups with mono-substituted hydrazines followed by dehydration under mild reaction conditions is the key to success of this method.     

Simple liquid crystal display backlight unit comprising only a single-sheet micropatterned polydimethylsiloxane (PDMS) light-guide plate

A simple liquid crystal display (LCD) backlight unit (BLU) comprising only a single-sheet polydimethylsiloxane (PDMS) light-guide plate (LGP) has been developed. The PDMS LGP, having micropatterns with an inverse-trapezoidal cross section, was fabricated by backside 3-D diffuser lithography followed by PDMS-to-PDMS replication. The fabricated BLU showed an average luminance of 2878 cd/m(2) with 73.3% uniformity when mounted in a 5.08 cm backlight module with four side view 0.85cd LEDs. The developed BLU can greatly reduce the cost and thickness of LCDs, and it can be applied to flexible displays as a flexible light source due to the flexible characteristic of the PDMS itself.