Synthesis of 1H-benzo[g]indazole derivatives: propargyl–allenyl isomerization and 6π-electrocyclization involving two aromatic π-bonds

An efficient synthesis of 1H-benzo[g]indazoles starting from Morita–Baylis–Hillman (MBH) adducts is disclosed. The synthesis was carried out from MBH bromide via a sequential copper-catalyzed alkynylation, one-pot synthesis of pyrazole, propargyl–allenyl isomerization, and a 6π-electrocyclization involving two aromatic π-bonds and an allenyl π-bond.     

Therapeutic Targeting of Oncogenic K‐Ras by a Covalent Catalytic Site Inhibitor

We report the synthesis of a GDP analogue, SML‐8‐73‐1, and a prodrug derivative, SML‐10‐70‐1, which are selective, direct‐acting covalent inhibitors of the K‐Ras G12C mutant relative to wild‐type Ras. Biochemical and biophysical measurements suggest that modification of K‐Ras with SML‐8‐73‐1 renders the protein in an inactive state. These first‐in‐class covalent K‐Ras inhibitors demonstrate that irreversible targeting of the K‐Ras guanine‐nucleotide binding site is potentially a viable therapeutic strategy for inhibition of Ras signaling.     

An Off‐Pathway Folding Intermediate of an Acyl Carrier Protein Domain Coexists with the Folded and Unfolded States under Native Conditions

A protein can exist in multiple states under native conditions and those states with low populations are often critical to biological function and self‐assembly. To investigate the role of the minor states of an acyl carrier protein, NMR techniques were applied to determine the number of minor states and characterize their structures and kinetics. The acyl carrier protein from Micromonospora echinospora was found to exist in one major folded state (95.2 %), one unfolded state (4.1 %), and one intermediate state (0.7 %) under native conditions. The three states are in dynamic equilibrium and the intermediate state very likely adopts a native‐like structure and is an off‐pathway folding product. The intermediate state may mediate the formation of oligomers in vitro and play an important role in the recognition of partner enzymes in vivo.     

Guiding DC glow discharge in microchannels

This work describes the conditions, in terms of dimensions and geometry, to guide a dc glow discharge preferentially through a microchannel in simple networks. Two- and three-channel microfluidic structures were studied. A preference towards a wider channel, in a two-channel network, was observed when the difference in width was at least 18% and the length was at least 10 mm. In a three-channel structure, a change in glow discharge intensity was observed when the network was downscaled from a pathlength of 2 to 0.5 cm. While the intensity within the path with fewer turns decreased with a reduction in size, the intensity of the path with greater number of turns increased.     

Fabrication of microfluidic mixers and artificial vasculatures using a high-brightness diode-pumped Nd:YAG laser direct write method

This paper describes a direct write laser technology, which is fast and flexible, for fabricating multiple-level microfluidic channels. A high brightness diode-pumped Nd-YAG laser with slab geometry was used for its excellent beam quality. Channels with flat walls and staggered herringbone ridges on the floor have been successfully fabricated and their ability to perform passive mixing of liquid is discussed. Also, a multi-width multi-depth microchannel has been fabricated to generate biomimetic vasculatures whose channel diameters change according to Murray's law, which states that the cube of the radius of a parent vessel equals the sum of the cubes of the radii of the daughters. The multi-depth architecture allows for flow patterns to resemble physiological vascular systems with lower overall resistance and more uniform flow velocities throughout the network compared to planar patterning techniques which generate uniformly thin channels. The ability to directly fabricate multiple level structures using relatively straightforward laser technology enhances our ability to rapidly prototype complex lab-on-a-chip systems and to develop physiological microfluidic structures for tissue engineering and investigations in biomedical fluidics problems.     

Thermodynamics of phase transitions in langmuir monolayers observed by vibrational sum frequency spectroscopy

Vibrational sum-frequency spectroscopy (VSFS) was used to study gauche defects in octadecylamine (ODA) monolayers at the air/water interface. The VSFS spectra provide unique insights into phase transitions that occur as a result of changes in the structure of the monolayer's hydrophobic region. These changes can be attributed to the increased presence of gauche conformers in the ODA alkyl chains during the monolayer's transition from the solid to liquid phase. Temperature-dependent spectra from monolayers at several different pressures were used to assign the phase transition temperature based on the observed changes in microscopic structure. Through application of a two-dimensional form of the Clapeyron equation, the first in situ measurements of the entropy and enthalpy changes associated with gauche conformers in a monolayer were made.     

Surface‐Independent and Oriented Immobilization of Antibody via One‐Step Polydopamine/Protein G Coating: Application to Influenza Virus Immunoassay

For the construction of high‐performance biosensor, it is important to interface bioreceptors with the sensor surface densely and in the optimal orientation. Herein, a simple surface modification method that can optimally immobilize antibodies onto various kinds of surfaces is reported. For the surface modification, a mixture of polydopamine (PDA) and protein G was employed. PDA is a representative mussel‐inspired polymer, and protein G is an immunoglobulin‐binding protein that enables an antibody to have an optimal orientation. The surface characteristics of PDA/Protein G mixture‐coated substrates are analyzed and the PDA/protein G ratio is optimized to maximize the antibody binding efficiency. Moreover, the antibody‐immobilized substrates are applied to the detection of influenza viruses with the naked eye, providing a detection limit of 2.9 × 10³ pfu mL^‐1. Importantly, the several substrates (glass, SiO₂, Si, Al₂O₃, polyethylene terephthalate, polyethylene, polypropylene, and paper) can be modified by simple incubation with the mixture of PDA/protein G, and then the anti‐influenza A H1N1 antibodies can be immobilized on the substrates successfully. Regardless of the substrate, the influenza viruses are detectable after the sandwich immunoreaction and silver enhancement procedure. It is anticipated that the developed PDA/protein G coating method will extend the range of applicable materials for biosensing.     

Rational Molecular Design Overcoming the Long Delayed Fluorescence Lifetime and Serious Efficiency Roll-Off in Blue Thermally Activated Delayed Fluorescent Devices

Blue thermally activated delayed fluorescent (TADF) devices with short excited-state lifetime, high reverse intersystem crossing rate, and low-efficiency roll-off were developed by managing the molecular structure of donor–acceptor-type blue emitters. Three isomers of blue TADF emitters with a diphenyltriazine acceptor and three carbazole donors were synthesized. The position of the donor moieties in the phenyl linker connecting the donor and acceptor moieties was controlled to devise compounds with a short delayed fluorescence lifetime. A blue TADF emitter with three carbazole donors at 2-, 3-, and 4- positions of a phenyl linker shortened the excited state lifetime to 4.1 μs, showed a high external quantum efficiency of 20.4 %, and low efficiency roll-off of less than 10 % at 1000 cd m⁻². Therefore, a molecular design distorting the donors by aligning them in a consecutive way is useful to resolve the issues of long delayed fluorescence lifetime and efficiency roll-off of blue TADF devices.     

Indium-mediated regioselective mono-allylation of 1,5-dicarbonyl compounds and dehydrative cyclization to 2,3-dihydro-4H-pyran-4-ones and 3,4-dihydro-2H-[1,4]oxazines

An indium-mediated Barbier type mono-allylation of 1,5-dicarbonyl compounds and a subsequent acid-catalyzed dehydrative cyclization afforded 2,3-dihydro-4H-pyran-4-ones and 3,4-dihydro-2H-[1,4]oxazines.     

Palladium-catalyzed arylation of α,β-unsaturated Weinreb amides

Palladium-catalyzed arylation of α,β-unsaturated Weinreb amides has been examined to obtain β-aryl-α,β-unsaturated Weinreb amides. The chelation between the palladium center of an alkylpalladium intermediate and Weinreb amide moiety facilitated both coordination and insertion steps.