One-Shot Construction of BN-Embedded Heptadecacene Framework Exhibiting Ultra-narrowband Green Thermally Activated Delayed Fluorescence.

BN-embedded nonacene, tridecacene, and heptadecacene frameworks were constructed using one-shot quadruple, sextuple, and octuple borylation reactions, respectively. The key to success is the judicious choice of borylating reagents and long-chain alkyl-substituted carbazolyl groups as boron-trapping groups, which suppressed the decrease in HOMO energy and insolubilization associated with borylation. Based on the product yields, each electrophilic C-H borylation proceeded in >99% yield, which is the best efficiency reported so far for C-H borylation reactions.

Theoretical Design of Blue-Color Phosphorescent Complexes for Organic Light-Emitting Diodes: Emission Intensities and Nonradiative Transition Rate Constants in Ir(ppy)(acac) Derivatives.

Theoretical calculations of phosphorescent spectra and nonradiative transition (NRT) rate constants for S ⇝ T, T ⇝ S, and S ⇝ S were carried out to determine the best candidate for a blue-color phosphorescent complex among several derivatives of bis(2-phenylpyridine)(acetylacetonate)iridium(III). The geometries of the ground state (S), the lowest triplet state (T), and the lowest excited singlet state (S) were optimized at the levels of density functional theory, in which B3LYP functionals and SBKJC+p basis sets were used. The NRT rate constants were derived by using a generating function method within the displaced harmonic oscillator model.

Design, synthesis, and biological evaluation of novel somatostatin receptor subtype-2 agonists: Optimization for potency and risk mitigation of hERG and phospholipidosis.

Somatostatin receptors are members of G-protein coupled receptor superfamily. Receptors can be classified into five subtypes, SSTR1 to 5. The highly potent and orally active SSTR2 agonist 7, which had been identified by our group, was found out to have toxicological liabilities such as hERG inhibition and phospholipidosis (PLD).

Prognostic Role of Tumor-Infiltrating Lymphocytes and Tumor Budding in Early Oral Tongue Carcinoma.

Objectives/hypothesis: Occult lymph metastasis is an important prognosticator for the treatment of early oral tongue squamous cell carcinoma (SCC). The objective of this study was to evaluate the prognostic significance of tumor-infiltrating lymphocytes (TILs) in early oral tongue SCC. The combination of the TIL subtype and intermediate- or high-grade budding scores was investigated as a prognostic marker for occult neck metastases.

Gestational dioxin exposure suppresses prolactin-stimulated nursing in lactating dam rats to impair development of postnatal offspring.

A number of epidemiological studies have implicated environmental chemicals including dioxins in the induction of negative effects on child development. To clarify the underlying mechanisms, almost all toxicologists have concentrated on effects on the offspring themselves. We examined an alternative hypothesis that gestational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a highly-toxic dioxin, targets factors related to maternal childcare to disturb offspring development.

Discovery and SAR Studies of Orally Active Somatostatin Receptor Subtype-2 (SSTR2) Agonists for the Treatment of Acromegaly.

Acromegaly is a disease caused by the oversecretion of growth hormone. It is currently treated by intravenous injection with cyclic peptide drugs that activate somatostatin receptor subtype 2 (SSTR2). Here, novel nonpeptidic, small-molecule, and orally active SSTR2 agonists were identified from a hit compound ().

Association between pathological invasion patterns and late lymph node metastases in patients with surgically treated clinical No early oral tongue carcinoma.

Background: This study evaluated the combination of tumor budding and depth (BD model) and worst pattern of invasion (WPOI) as histopathological prognostic factors in clinical N0 early oral tongue carcinoma.

Methods: Data from 62 patients were retrospectively analyzed. Associations between histopathological factors (differentiation, stage, lymphatic invasion, blood vessel invasion, WPOI, and BD model) and regional control (RC) or disease-free survival (DFS) were evaluated.

Vacuum-Level Shift at Al/LiF/Alq Interfaces: A First-Principles Study.

Work function changes, or vacuum-level shifts (Δ), in Al(001) surfaces by the adsorption of thin layers composed of tris(8-hydroxyquinolinato)aluminum (Alq) and/or LiF are theoretically investigated. First-principles calculations reasonably reproduce experimentally obtained Δ values, enabling us to discuss the underlying mechanism. Dipole moment of Alq and interfacial charge rearrangement (Pauli push-back effect) are the main reasons for Δ at Al(001)-Alq and Al(001)-LiF interfaces, respectively.

Further enhancement of the clickability of doubly sterically-hindered aryl azides by para-amino substitution.

Introduction of an amino group at the para position of doubly sterically-hindered aryl azides significantly enhances the reactivity with cyclooctynes. The distortability of the azido group is synergistically enhanced by the para-electron-donating group and two bulky ortho substituents, which increases the HOMO energy level and provoke the steric inhibition of resonance, respectively.

Anthracene-Based Organic Small-Molecule Electron-Injecting Material for Inverted Organic Light-Emitting Diodes.

A diphenylanthracene dimethylamine derivative (9-{3,5-di( N, N-dimethylaminoethoxy)phenyl}-10-phenyl-anthracene, DPAMA) was synthesized by the Suzuki-Miyaura cross-coupling reaction. Its ammonium salt, 9-{3,5-di(trimethylammonium ethoxy)phenyl}-10-phenyl-anthracene dichloride (DPAMA-Cl), was also synthesized as a reference material. DPAMA was characterized by UV-vis and fluorescence spectroscopy, cyclic voltammetry, photoelectron yield spectroscopy, and X-ray photoelectron spectroscopy to evaluate the work function-modifying ability of DPAMA on indium tin oxide (ITO) and ZnO.

Predictive Significance of Tumor Depth and Budding for Late Lymph Node Metastases in Patients with Clinical N0 Early Oral Tongue Carcinoma.

In clinical N0 early oral tongue carcinoma, treatment of occult lymph node metastasis is controversial. The purpose of this study was to assess the histopathological risk factors for predicting late lymph node metastasis in early oral tongue carcinoma. We retrospectively reviewed 48 patients with early oral tongue squamous cell carcinoma.

Thiazolobenzyne: a versatile intermediate for multisubstituted benzothiazoles.

Thiazolobenzyne, which is a benzyne species fused with a thiazole ring, was efficiently generated via an iodine-magnesium exchange reaction of an ortho-iodoaryl triflate-type precursor using a trimethylsilylmethyl Grignard reagent as an activator. A wide range of arynophiles reacted efficiently with the thiazolobenzynes generated by this method to afford various multisubstituted benzothiazoles.

Discovery of novel S1P2 antagonists, part 3: Improving the oral bioavailability of a series of 1,3-bis(aryloxy)benzene derivatives.

The structure of the S1P2 antagonist 1 has been modified with the aim of improving its oral bioavailability. The chemical modification of the alkyl chain and carboxylic acid moieties of 1 led to significant improvements in the oral exposure of compounds belonging to this series. The optimization of the ring size of the urea portion of these molecules also led to remarkable improvements in the oral exposure.

Discovery of novel S1P2 antagonists. Part 2: Improving the profile of a series of 1,3-bis(aryloxy)benzene derivatives.

Our initial lead compound 2 was modified to improve its metabolic stability. The resulting compound 5 showed excellent metabolic stability in rat and human liver microsomes. We subsequently designed and synthesized a hybrid compound of 5 and the 1,3-bis(aryloxy) benzene derivative 1, which was previously reported by our group to be an S1P2 antagonist.

Discovery of novel S1P2 antagonists. Part 1: discovery of 1,3-bis(aryloxy)benzene derivatives.

The structure-activity relationships of a novel series of sphingosine-1-phosphate receptor antagonists have been examined in detail. The initial hit compound 1 was modified through synthesis to improve its S1P2 activity. The synthesis of a series of analogs revealed that 1,3-bis(aryloxy)benzene derivatives, as represented by 22, are potent and selective S1P2 antagonists.

Furan fused V-shaped organic semiconducting materials with high emission and high mobility.

We report a facile synthetic protocol for preparation of dinaphtho[2,3-b:2',3'-d]furan (DNF-V) derivatives. DNF-V derivatives showed high emissive behaviour in solid. A solution-crystallized transistor based on alkylated DNF-V derivatives showed an excellent carrier mobility of up to 1.

V-shaped organic semiconductors with solution processability, high mobility, and high thermal durability.

V-shaped organic semiconductors have been designed and synthesized via a large-scale applicable synthetic route. Solution-crystallized films based on such molecules have demonstrated high-performance transistor properties with maximum mobilities of up to 9.5 cm(2) V(-1) s(-1) as well as pronounced thermal durability of up to 150 °C inherent in the V-shaped cores.

Enhanced clickability of doubly sterically-hindered aryl azides.

Steric character is one of the most fundamental factors to determine the reactivity of the substrate in organic synthesis. In bimolecular reaction, the sterically-bulky group situated close to the reactive center generally prevents the approach of the reaction partner retarding the bond formation. This report describes, to the contrary, significantly enhanced reactivity of 2,6-disubstituted phenyl azides observed in catalyst-free 1,3-dipolar cycloaddition with alkynes, unexpectedly reacting faster than unsubstituted phenyl azide and even more faster than unhindered alkyl azide, despite the steric hindrance adjacent to the reactive azido group.

Pyrrolo[1,2-b]pyridazines, pyrrolo[2,1-f]triazin-4(3H)-ones, and related compounds as novel corticotropin-releasing factor 1 (CRF₁) receptor antagonists.

To identify structurally novel corticotropin-releasing factor 1 (CRF(1)) receptor antagonists, a series of bicyclic core analogs pyrrolo[1,2-b]pyridazines and pyrrolo[2,1-f]triazin-4(3H)-ones, which were designed based on a monocyclic core antagonist, was synthesized and evaluated. Among the compounds tested, 2-difluoromethoxy-4-methylpyridin-5-yl analog 27 was found to show efficacy in a dose-dependent manner in an elevated plus maze test in rats. The discovery process and structure-activity relationship is presented.

Assessment of late cardiotoxicity of pirarubicin (THP) in children with acute lymphoblastic leukemia.

Background: Pirarubicin (tetrahydropyranyl-adriamycin: THP) is a derivative of doxorubicin with reportedly less cardiotoxicity in adults. However no studies of cardiotoxicity in children treated with THP have been reported. This study was performed to assess the THP-induced cardiotoxicity for children with acute lymphoblastic leukemia (ALL).

Strain-promoted double-click reaction for chemical modification of azido-biomolecules.

The strain-promoted "double-click" (SPDC) reaction using Sondheimer diyne, a novel convergent method conjugating three molecules spontaneously, has enabled us to readily modify an azido-biomolecule with a small reporter azido-molecule.

Minimal residual disease-based augmented therapy in childhood acute lymphoblastic leukemia: a report from the Japanese Childhood Cancer and Leukemia Study Group.

Background: The majority of minimal residual disease (MRD)-positive patients with acute lymphoblastic leukemia (ALL) have poor outcomes. The ALL2000 study was performed to evaluate the efficacy of augmented chemotherapy based on MRD-restratification in childhood ALL.

Procedure: Between 2000 and 2004, 305 eligible patients with precursor B or T-cell ALL were enrolled in the ALL2000 study.

Relativistic study on emission mechanism in palladium and platinum complexes.

The present study investigates the spin-orbit coupling (SOC) effects in the radiative processes from the electronically excited states of bis[-2-(2-thienyl)-pyridine] platinum (Pt(thpy)2) and palladium (Pd(thpy)2). The transition probabilities among the low-lying spin-mixed states in these complexes are estimated using the discrete variable representation (DVR) method based on the assumption that the system obeys Fermi's golden rule. It is revealed that the low-lying excited singlets and triplets are strongly mixed with each other by SOC in Pt(thpy)2 and, as a result, a fast nonradiative transition occurs to the low-lying excited spin-mixed states.

Theoretical study on mesogenic core structures of nematic liquid crystalline compounds.

The structures and intermolecular interaction energies of 10 dimers, included in the mesogenic core structures of typical liquid crystalline (LC) compounds, are obtained at the MP2/6-31G(d) level of theory. It is proved that the dispersion energy significantly contributes to the total interaction energy of these dimers. Even when bulky substituents are introduced into the core part, the interaction energy is still large.

Dissociation potential curves of low-lying states in transition metal hydrides. 3. Hydrides of groups 6 and 7.

The dissociation curves of low-lying spin-mixed states in monohydrides of groups 6 and 7 were calculated by using an effective core potential (ECP) approach. This approach is based on the multiconfiguration self-consistent field (MCSCF) method, followed by first-order configuration interaction (FOCI) calculations, in which the method employs an ECP basis set proposed by Stevens and co-workers (SBKJC) augmented by a set of polarization functions. Spin-orbit coupling (SOC) effects are estimated within the one-electron approximation by using effective nuclear charges, since SOC splittings obtained with the full Breit-Pauli Hamitonian are underestimated when ECP basis sets are used.