Discovery of Novel Bicyclic Pyrazoles as Potent PIP5K1C Inhibitors.

Phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) is generated by phosphatidylinositol 4-phosphate 5-kinases (PIP5Ks) from phosphatidylinositol 4-phosphate (PI4P). Structurally diverse and selective inhibitors against PIP5Ks are required to further elucidate the therapeutic potential for PIP5K inhibition, although the effects of PIP5K inhibition on various diseases and their symptoms, such as cancer and chronic pain, have been reported. Our medicinal chemistry efforts led to novel and potent PIP5K1C inhibitors.

Single-Layer Organic Light-Emitting Diode with Trap-Free Host Beats Power Efficiency and Lifetime of Multilayer Devices.

Organic light-emitting diodes (OLEDs) employing a single active layer potentially offer a number of benefits compared to multilayer devices; reduced number of materials and deposition steps, potential for solution processing, and reduced operating voltage due to the absence of heterojunctions. However, for single-layer OLEDs to achieve efficiencies approaching those of multilayer devices, balanced charge transport is a prerequisite. This requirement excludes many efficient emitters based on thermally activated delayed fluorescence (TADF) that exhibit electron trapping, such as the green-emitting bis(4-(9,9-dimethylacridin-10(9H)-yl)phenyl)methanone (DMAC-BP).

Photodissociative Modules that Control Dual-Emission Properties in Donor-π-Acceptor Organoborane Fluorophores.

Donor-π-acceptor fluorophores that consist of an electron-donating amino group and an electron-accepting triarylborane moiety generally exhibit substantial solvatochromism in their fluorescence while retaining high fluorescence quantum yields even in polar media. Herein, we report a new family of this compound class, which bears ortho-P(=X)R -substituted phenyl groups (X=O or S) as a photodissociative module. The P=X moiety that intramolecularly coordinates to the boron atom undergoes dissociation in the excited state, giving rise to dual emission from the corresponding tetra- and tricoordinate boron species.

Multiple resonance type thermally activated delayed fluorescence by dibenzo [1,4] azaborine derivatives.

We studied the photophysical and electroluminescent (EL) characteristics of a series of azaborine derivatives having a pair of boron and nitrogen aimed at the multi-resonance (MR) effect. The computational study with the STEOM-DLPNO-CCSD method clarified that the combination of a BN ring-fusion and a terminal carbazole enhanced the MR effect and spin-orbit coupling matrix element (SOCME), simultaneously. Also, we clarified that the second triplet excited state (T) plays an important role in efficient MR-based thermally activated delayed fluorescence (TADF).

Olefin-Borane Interactions in Donor-π-Acceptor Fluorophores that Undergo Frustrated-Lewis-Pair-Type Reactions.

Olefin-borane π-complexes have been postulated as intermediates for the addition of frustrated Lewis pairs (FLP) to olefins. In the present study, we have employed this weak interaction to modulate the electronic properties of boron-based π-electron materials. A series of donor-π-acceptor (D-π-A) fluorophores that contain an alkenyl-bridged diarylboryl group is synthesized.

Planarized Phenyldithienylboranes: Effects of the Bridging Moieties and π-Extension on the Photophysical Properties and Lewis Acidity.

Two kinds of planarized phenyldithienylboranes, which contain (CH ) C- or CH -bridging moieties, were synthesized. The difference of the bridging moieties affects their packing structures and photophysical properties. In particular, the (CH ) C-bridged derivative exhibits a large Stokes shift, unusual for such planarized compounds, that results from a large structural relaxation in the excited state.

Fluorescent Organic π-Radicals Stabilized with Boron: Featuring a SOMO-LUMO Electronic Transition.

We report on the fluorescence properties of a new class of emissive and stable π-radicals that contain a boron atom at a position distant from the radical center. A fully planarized derivative exhibited an intense red fluorescence with high fluorescence quantum yields (Φ >0.67) even in polar solvents.

Fully fused boron-doped polycyclic aromatic hydrocarbons: their synthesis, structure-property relationships, and self-assembly behavior in aqueous media.

Planarized triarylboranes are attracting increasing attention not only as models of boron-doped graphenes, but also as promising materials for organic optoelectronics. In particular, polycyclic aromatic hydrocarbon (PAH) skeletons with embedded boron atom(s) in the inner positions are of importance in light of their high chemical stability and π-stacking ability derived from their planar geometries. Herein, we disclose a robust synthesis of such fully fused boron-doped PAHs and their self-assembly behavior in aqueous media to explore their potential utility in biological applications.

Photobase-Driven Excited-State Intramolecular Proton Transfer (ESIPT) in a Strapped π-Electron System.

We report a new design strategy for an excited-state intramolecular proton transfer (ESIPT) fluorophore that can be used in acidic media. A photobasic pyridine-centered donor-acceptor-donor-type fluorophore is combined with a basic trialkylamine "strap". In the presence of an acid, protonation occurs predominantly at the amine moiety in the ground state.

Electron-Deficient Heteroacenes that Contain Two Boron Atoms: Near-Infrared Fluorescence Based on a Push-Pull Effect*.

Electron-deficient heteroacenes that contain two tricoordinate boron atoms in their acene skeletons and planarized phenyl ether moieties at their periphery were synthesized via the borylation of silicon-bridged precursors. X-ray crystallographic analysis revealed quinoidal structures, which give rise to two-step reversible redox processes for both the reduction and oxidation. These compounds exhibit intense absorption and sharp fluorescence bands with vibronic structures in the near-infrared (NIR) region.

Boron-Doped Polycyclic π-Electron Systems with an Antiaromatic Borole Substructure That Forms Photoresponsive B-P Lewis Adducts.

Heteroatom doping is a powerful strategy to alter the electronic structure of polycyclic aromatic hydrocarbons (PAHs). Especially boron doping endows PAH scaffolds with electron-accepting character and Lewis acidic centers. Herein, we report that embedding a five-membered borole ring into a polycyclic skeleton imparts the π-system with antiaromatic character and thereby induces unique properties and behavior.

Dual Trapping of a Metastable Planarized Triarylborane π-System Based on Folding and Lewis Acid-Base Complexation for Seeded Polymerization.

We report the kinetically controlled supramolecular polymerization of boron-containing π-conjugated molecules, which was enabled by a seeding method based on dual trapping of a metastable state by synergistic intramolecular hydrogen bonding and Lewis acid-based complexation. Planarized triarylborane-based , which bears a diamide chain with chiral alkyl groups, was synthesized. Upon cooling, the solution of monomer afforded a supramolecular polymerization in a cooperative manner to form helical supramolecular nanostructures with intense J-type aggregate emission.

Twofold C-H Activation Enables Synthesis of a Diazacoronene-Type Fluorophore with Near Infrared Emission Through Isosteric Replacement.

The synthesis and photophysical properties of a soluble amide-embedded coronene is reported. The key step in this synthesis is the twofold C-H activation of diazaperylene by a rhodium(III)Cp* catalyst. This unprecedented structural motif shows intense fluorescence in the near infrared region with a small Stokes shift and a distinct vibronic structure, which exhibits a slight extent of negative solvatochromism.

Prenatal clinical manifestations in individuals with variants.

Background: Variants in the type IV collagen gene () cause early-onset cerebrovascular diseases. Most individuals are diagnosed postnatally, and the prenatal features of individuals with variants remain unclear.

Methods: We examined in 218 individuals with suspected /2-related brain defects.

Multistep Photoisomerization of Dimesitylboron-Functionalized Stilbene Analogues.

Dimesitylboron-functionalized stilbene derivatives have been found to undergo an unusual regioselective photoisomerization upon irradiation at 365 nm. Using NMR to follow the photoreaction, the structures of key reaction intermediates and the final products were established. This photoisomerization occurs in four steps: isomerization, Diels-Alder reaction, di-π-methane rearrangement, and ring opening with [1,3]-H migration.

Near-infrared fluorescein dyes containing a tricoordinate boron atom.

Bora-fluoresceins (s), fluorescein analogues containing a tricoordinate boron atom instead of an oxygen atom at the 10-position of the fluorescein skeleton, were synthesized as a new family of fluorescein analogues. The deprotonated s exhibited absorption and fluorescence in the near-infrared region, which were significantly red-shifted relative to those of hitherto-known heteroatom-substituted fluorescein analogues on account of the orbital interaction between the tricoordinate boron atom and the fluorescein skeleton. s also showed multi-stage changes resulting from a Lewis acid-base equilibrium at the boron center in combination with a Brønsted acid-base equilibrium at the phenolic hydroxy group.

Investigation of the Effective Concentration of Ozonated Water for Disinfection in the Presence of Protein Contaminants.

Ozonated water (OW) is presently used as a chemical disinfectant in many fields, due to its versatile antimicrobial properties. As ozone rapidly decomposes to oxygen, especially in the presence of organic matter, it is important to estimate the authentic antimicrobial activity of OW in the presence of contaminants. However, the effect of contaminants on the antimicrobial activity of OW has not been fully investigated.

Planarized B,N-phenylated dibenzoazaborine with a carbazole substructure: electronic impact of the structural constraint.

A B,N-diphenyl-5,10-dihydro-dibenzo-1,4-azaborine, in which both phenyl groups on the boron and nitrogen atoms are planarized to generate a carbazole substructure, was synthesized. The structral constraint around the boron and nitrogen atoms alters the π-conjugation mode and thus the photophysical and electrochemical properties. Specifically, this structurally constrained dibenzoazaborine showed an intense blue emission with a narrow full width at half maximum.

A novel homozygous missense mutation in the SH3-binding motif of STAMBP causing microcephaly-capillary malformation syndrome.

Microcephaly-capillary malformation syndrome is a congenital and neurodevelopmental disorder caused by biallelic mutations in the STAMBP gene. Here we identify the novel homozygous mutation located in the SH3 binding motif of STAMBP (NM_006463.4) (c.

A planarized B-phenyldibenzoborepin: impact of structural constraint on its electronic properties and Lewis acidity.

A B-phenyldibenzo[b,f]borepin planarized with two methylene bridges was synthesized. The structural constraint on the B-phenyl group resulted in a bathochromic shift of the absorption and fluorescence properties as well as enhanced Lewis acidity. A donor-π-acceptor type derivative based on this scaffold exhibited intense fluorescence irrespective of the solvent polarity.

A de novo p.Arg756Cys mutation in ATP1A3 causes a distinct phenotype with prolonged weakness and encephalopathy triggered by fever.

Patients with a mutation at Arg756 in ATP1A3 have been known to exhibit a distinct phenotype, characterized by prolonged weakness and encephalopathy, triggered by febrile illness. With only eight reports published to date, more evidence is required to correlate clinical features with a mutation at Arg756. Here we report an additional case with an Arg756Cys mutation in ATP1A3.

Boron-Stabilized Planar Neutral π-Radicals with Well-Balanced Ambipolar Charge-Transport Properties.

Organic neutral π-monoradicals are promising semiconductors with balanced ambipolar carrier-transport abilities, which arise from virtually identical spatial distribution of their singly occupied and unoccupied molecular orbitals, SOMO(α) and SOMO(β), respectively. Herein, we disclose a boron-stabilized triphenylmethyl radical that shows outstanding thermal stability and resistance toward atmospheric conditions due to the substantial spin delocalization. The radical is used to fabricate organic Mott-insulator transistors that operate at room temperature, wherein the radical exhibits well-balanced ambipolar carrier transport properties.

Photochemical Intramolecular C-H Addition of Dimesityl(hetero)arylboranes through a [1,6]-Sigmatropic Rearrangement.

A new reaction mode for triarylboranes under photochemical conditions was discovered. Photoirradiation of dimesitylboryl-substituted (hetero)arenes produced spirocyclic boraindanes, where one of the C-H bonds in the ortho-methyl groups of the mesityl substituents was formally added in a syn fashion to a C-C double bond of the (hetero)aryl group. Quantum chemical calculations and laser flash photolysis measurements indicated that the reaction proceeds through a [1,6]-sigmatropic rearrangement.

Defects in autophagosome-lysosome fusion underlie Vici syndrome, a neurodevelopmental disorder with multisystem involvement.

Vici syndrome (VICIS) is a rare, autosomal recessive neurodevelopmental disorder with multisystem involvement characterized by agenesis of the corpus callosum, cataracts, cardiomyopathy, combined immunodeficiency, developmental delay, and hypopigmentation. Mutations in EPG5, a gene that encodes a key autophagy regulator, have been shown to cause VICIS, however, the precise pathomechanism underlying VICIS is yet to be clarified. Here, we describe detailed clinical (including brain MRI and muscle biopsy) and genetic features of nine Japanese patients with VICIS.

A combination of genetic and biochemical analyses for the diagnosis of PI3K-AKT-mTOR pathway-associated megalencephaly.

Background: Constitutive activation of the PI3K-AKT-mTOR pathway (mTOR pathway) underlies megalencephaly in many patients. Yet, prevalence of the involvement of the PI3K-AKT-mTOR pathway in patients with megalencephaly remains to be elucidated, and molecular diagnosis is challenging. Here, we have successfully established a combination of genetic and biochemical methods for diagnosis of mTOR pathway-associated megalencephaly, and have attempted to delineate the clinical characteristics of the disorder.