Synthesis of a series of octaalkoxy-substituted cage silsesquioxanes catalyzed by zinc acetate.

Octaalkoxy-substituted polyhedral oligomeric silsesquioxane (8RO-POSS) is an attractive starting material for producing silicone resins. However, polymers derived from 8RO-POSS via the sol-gel process have seldom been reported owing to their synthetic difficulty. In this study, we attempted to use zinc acetate (Zn(OAc)2) as the catalyst for the synthesis of a series of 8RO-POSS from octahydrido-POSS (8H-POSS). The reaction conditions were optimized using heptaisobutyl monohydride-POSS (7iBu1H-POSS) as a model reaction. The desired product was obtained in 96% yield under optimized conditions. The alkoxylation of 8H-POSS was performed using methanol (MeOH), ethanol (EtOH), isopropyl alcohol (i-PrOH), and tert-butyl alcohol (t-BuOH) in the presence of Zn(OAc)2 as the catalyst. Although octamethoxy-POSS (8MeO-POSS) was isolated in the presence of a byproduct, octaethoxy-POSS (8EtO-POSS) and octaisopropoxy-POSS (8iPrO-POSS) were obtained in high yields. The degree of alkoxylation was 55% in the case of using t-BuOH. The structures of 8MeO-POSS, 8EtO-POSS, and 8iPrO-POSS were confirmed by FT-IR, 1H-, and 29Si-NMR and MALDI-TOF-MS analyses. Compared to the random silicate obtained by base-treated tetramethoxysilane (TMOS), base-treated 8EtO-POSS and 8iPrO-POSS showed that the cage structures were maintained even after the formation of condensed silicate structures via a condensation reaction.

Phenyl-Substituted Cage Silsesquioxane-Based Star-Shaped Giant Molecular Clusters: Synthesis, Properties, and Surface Segregation Behavior.

The crystallinity, solubility, and physical properties of polyhedral oligomeric silsesquioxane (POSS) compounds are highly dependent on their organic substituents. We previously synthesized a series of isobutyl-substituted star-shaped POSS derivatives with aliphatic chain linkers of different length. In this study, we prepared C3- and C6-linked phenyl-substituted star-shaped POSS derivatives (3Ph-C3 and 3Ph-C6) by the hydrosilylation of heptaphenylallyl- and hexenyl-POSS (1a and 1b) and octadimethylsiloxy-Q8-silsesquioxane (Q8M8H) (2), respectively, and their properties were compared with those of the corresponding isobutyl-substituted derivatives (5iBu-C3 and 5iBu-C6). Although 3Ph-C6 was only soluble in chloroform and insoluble in tetrahydrofuran (THF) and toluene, 3Ph-C3 was soluble even in THF and toluene, suggesting that the shorter linkers of the derivative afford a wider range of solvents for dissolution. Differential scanning calorimetry analysis showed that 3Ph-C3 exhibited a baseline shift at 190 °C and an endothermic peak at 316 °C. However, no clear baseline shift was observed for 3Ph-C6. Thermogravimetric analysis showed that the shorter linker in the phenyl-substituted star-shaped POSS derivative significantly increased the decomposition temperature compared with the longer linker. The annealed cast film of 3Ph-C3 at 340 °C above its melting temperature formed a transparent film even after cooling to room temperature. However, an opaque whitish film was formed in the case of 3Ph-C6. Poly(methyl methacrylate) (PMMA) films containing 2 wt % 3Ph-C3 and 3Ph-C6 were prepared by casting their chloroform solutions onto glass substrates overnight at room temperature. The static water contact angle measurements and XPS analysis for the castings film containing 3Ph-C3 and 3Ph-C6 suggested that degree of the segregation amount of 3Ph-C3 was larger than that of 3Ph-C6. The shorter linker length in the phenyl-substituted star-shaped POSS derivative, 3Ph-C3, with its greater predicted solubility in PMMA, exhibited entropy-driven surface segregation.

Highly Efficient and Thermally Durable Luminescence of 1D Eu3+ Coordination Polymers with Arsenic Bridging Ligands.

In this work, bisarsine oxides were evaluated as novel bridging ligands, aiming to develop practical and efficient luminescent lanthanide coordination polymers. We have synthesized one-dimensional (1D) Eu3+ coordination polymers that incorporate bisarsine oxide bridging ligands and hexafluoroacetylacetonate anions. These polymers exhibited a denser packing of chains compared to analogous polymers bridged with bisphosphine oxides. The coordination polymers demonstrated exceptional thermal stability and substantial emission quantum yields. Additionally, the bisarsine oxides induced a pronounced polarization effect, facilitating a sensitive electric dipole transition that yields considerably narrow band red emission. Remarkably, the Eu3+ coordination polymers with bisarsine oxides maintained intense emission even at 550 K. A distinctive feature of these polymers is their heating-induced emission enhancement observed when the temperature was increased from 300 K to 400 K.

Extending BioMASS to construct mathematical models from external knowledge.

Motivation: Mechanistic modeling based on ordinary differential equations has led to numerous findings in systems biology by integrating prior knowledge and experimental data. However, the manual curation of knowledge necessary when constructing models poses a bottleneck. As the speed of knowledge accumulation continues to grow, there is a demand for a scalable means of constructing executable models. Results: We previously introduced BioMASS-an open-source, Python-based framework-to construct, simulate, and analyze mechanistic models of signaling networks. With one of its features, Text2Model, BioMASS allows users to define models in a natural language-like format, thereby facilitating the construction of large-scale models. We demonstrate that Text2Model can serve as a tool for integrating external knowledge for mathematical modeling by generating Text2Model files from a pathway database or through the use of a large language model, and simulating its dynamics through BioMASS. Our findings reveal the tool's capabilities to encourage exploration from prior knowledge and pave the way for a fully data-driven approach to constructing mathematical models. Availability and implementation: The code and documentation for BioMASS are available at https://github.com/biomass-dev/biomass and https://biomass-core.readthedocs.io, respectively. The code used in this article are available at https://github.com/okadalabipr/text2model-from-knowledge.

Breathing Metal-Organic Frameworks Supported by an Arsenic-Bridged 4,4'-Bipyridine Ligand.

Bent ligands bridged by heteroatoms have drawn significant interest as supramolecular coordination architectures. Traditionally, divalent group 16 elements are preferred over trivalent group 15 elements because of the anticipated steric hindrance. In this study, we explore metal-organic frameworks (MOFs) based on dipyridinoarsoles (DPAs), 4,4'-bipyridines bridged with an arsenic atom. An MOF with methyl-substituted DPA collapsed upon solvent removal, whereas that with phenyl-substituted DPA demonstrated breathing behavior due to guest molecule adsorption/desorption. In contrast, MOFs using the phosphorus analogue dipyridinophosphole exhibit inferior adsorption and lack breathing behavior. This is the first study to investigate the interplay among substituents, bridging elements, and dynamic behavior in MOFs using bent group 15 ligands.

Synthesis, structures, and photophysical properties of π-extended arsaborins.

In this study, various (hetero)arene-fused arsaborins were synthesized. All the synthesized arsaborins were stable under ambient conditions and allowed for the chemical modification of the lone pair of the arsenic atom. Experimental and computational studies revealed that these compounds possessed planar structures and weak anti-aromatic properties. Fluorescence with large Stokes shifts was observed due to drastic structural relaxation at 298 K, whereas intense phosphorescence due to the heavy-atom effect of arsenic was observed at 77 K. Furthermore, a thiophene-fused derivative demonstrated a temperature-dependent emission color change in the solid state, attributable to the gradual alteration in the ratio of monomer fluorescence, excimer fluorescence, and phosphorescence.

A Combination of Conformation-Specific RAF Inhibitors Overcome Drug Resistance Brought about by RAF Overexpression.

Cancer cells often adapt to targeted therapies, yet the molecular mechanisms underlying adaptive resistance remain only partially understood. Here, we explore a mechanism of RAS/RAF/MEK/ERK (MAPK) pathway reactivation through the upregulation of RAF isoform (RAFs) abundance. Using computational modeling and in vitro experiments, we show that the upregulation of RAFs changes the concentration range of paradoxical pathway activation upon treatment with conformation-specific RAF inhibitors. Additionally, our data indicate that the signaling output upon loss or downregulation of one RAF isoform can be compensated by overexpression of other RAF isoforms. We furthermore demonstrate that, while single RAF inhibitors cannot efficiently inhibit ERK reactivation caused by RAF overexpression, a combination of two structurally distinct RAF inhibitors synergizes to robustly suppress pathway reactivation.

Parallel synthesis of donor-acceptor π-conjugated polymers by post-element transformation of organotitanium polymer.

The donor-acceptor type π-conjugated polymers having heterole units were prepared by the reaction of a regioregular organometallic polymer having both reactive titanacyclopentadiene and electron-donor thiophene-2,5-diyl units in the main chain with electrophiles such as diphenyltin dichloride, dichlorophenylphosphine, and diiodophenylarsine. For example, a polymer having electron-accepting phosphole unit was obtained in 54% yield whose number-average molecular weight (Mn) and molecular weight distribution (Mw/Mn) were estimated as 3,000 and 1.9, respectively. The obtained polymer exhibits a high highest occupied molecular orbital (HOMO) and low lowest unoccupied molecular orbital (LUMO) energy levels (-5.13 eV and -3.25 eV, respectively) due to the electron-donating thiophene and electron-accepting phosphole units. Reflecting upon the alternating structure of thiophene and phosphole, the polymer exhibits a band gap energy level (Eg) of 1.78 eV which is narrower than that of a derivative of poly(thiophene) (Eg = 2.25 eV).

Robust and highly emissive copper(I) halide 1D-coordination polymers with triphenylarsine and a series of bridging N-heteroaromatic co-ligands.

Various 1D-coordination polymers with dinuclear rhombic {Cu2X2} cores (X = Br, I) were synthesized using a spontaneous evaporation method employing triphenylarsine (AsPh3) and six types of bidentate N-heteroaromatic co-ligands. The coordination polymers exhibited intense emission even at 298 K (quantum yield: up to 0.60), and their emission color was dependent on the N-heteroaromatic co-ligand. The emission efficiencies of these coordination polymers were higher than those of the discrete complexes with AsPh3 and monodentate N-heteroaromatic co-ligands reported in our previous work. In addition, the luminescence of these coordination polymers was more resistant to mechanical stimuli than that of the discrete ones.

Steric and electronic effects of arsa-Buchwald ligands on Suzuki-Miyaura coupling reaction.

The Suzuki-Miyaura coupling (SMC) reaction is one of the most commonly used cross-coupling reactions. Bulky biaryldialkyl monophosphine ligands, i.e., Buchwald ligands, are beneficial for the SMC reaction. We recently developed a synthetic procedure for arsa-Buchwald ligands, arsenic analogs of Buchwald ligands, and found that these ligands are effective for sterically hindered substrates because of facilitating the transmetalation step owing to the longer arsenic-palladium bond. However, the relationship between the structure and steric/electronic properties of the arsa-Buchwald ligands has not yet been studied in detail. In this study, a series of arsa-Buchwald ligands with various alkyl substituents were synthesized. The cyclopentyl group afforded the highest catalytic activity for the SMC reaction, particularly with sterically hindered substrates. Furthermore, the steric/electronic properties of the arsa-Buchwald ligands were computationally analyzed.

Pnictogen-Bridged Diphenyl Sulfones as Photoinduced Pnictogen Bond Forming Emission Motifs.

In this study, pnictogen (Pn)-bridged diphenyl sulfones were synthesized as motifs for photoinduced dynamic rearrangement. The newly synthesized sulfones exhibited dual fluorescence at 298 K. Density functional theory calculations revealed that the longer-wavelength fluorescence was derived from the geometries after structural relaxation through photo-driven pnictogen bond formation between the O atom lone pair of the sulfonyl moiety and the antibonding orbital of the Pn-C bond. This is the first report on emission dynamics driven by pnictogen bond formation upon photoexcitation.

Synthetic Strategy for AB2-Type Arsines via Bidentate Dithiolate Leaving Groups.

Despite their potential for several transition-metal-catalyzed reactions, arsenic ligands are poorly diversified. In this work, we developed an efficient synthetic methodology for AB2-type ligands, which is a typical motif in phosphorus systems, for example, in Buchwald ligands. The introduction of 1,2-benzenedithiol to tribromoarsine reduces the reactivity of two of the three reaction sites. After the substitution reaction with the first nucleophile involving the elimination of bromide, the substitution reaction with the second nucleophile produced AB2-type arsines through the elimination of the dithiolate anion. Among the various types of obtained AB2-type arsines, the arsa-Buchwald ligands, which are arsenic analogues of Buchwald ligands, were applied to the Suzuki-Miyaura cross-coupling reaction. Some of the arsa-Buchwald ligands showed activity comparable to that of the well-known Buchwald ligand, SPhos. Furthermore, the arsenic analogue of SPhos showed higher activity and stability than SPhos under open-air conditions.

Emission Properties of Eu(III) Complexes Containing Arsine and Phosphine Ligands with Annulated Structures.

In this study, we synthesized Eu3+ complexes containing arsine and phosphine oxides with annulated structures as the antenna ligands. The type of bridging in the annulated structures controlled the energy level of the triplet excited state and the intersystem crossing efficiency, leading to different emission properties. Eu3+ complexes bearing the arsine oxides showed a higher intensity ratio of electric/magnetic dipole transitions and energy-transfer efficiency than the complexes with the corresponding phosphine oxides.

1,2,5-Triarylcycloalka[c]arsoles: Structural Effects of Fused-cycloalkanes on Stability and Photophysical Properties.

Herein, we have synthesized a variety of cycloalkane-fused arsoles. Cyclopentane and cyclohexane were incorporated into the cycloalkane-fused arsoles. Surprisingly, cyclohexane-fused arsole 2 a gradually decomposed via oxidative ring-opening under ambient conditions, while cyclopentane-fused 1 a was stable. In addition, the Stokes shift of 2 a (7766 cm-1 ) is larger than that of 1 a (5120 cm-1 ). The effects of the fused cycloalkane on the stability and photophysical properties were attributed to the distortion of the cycloalkane. Computational calculations demonstrated that the cyclohexane moiety in 2 a was frustrated upon being incorporated into the rigid arsole ring, while the cyclopentane moiety in 1 a was much less distorted.

Protocol for stratification of triple-negative breast cancer patients using in silico signaling dynamics.

Personalized kinetic models can predict potential biomarkers and drug targets. Here, we provide a step-by-step approach for building an executable mathematical model from text and integrating transcriptomic datasets. We additionally describe the steps to personalize the mechanistic model and to stratify patients with triple-negative breast cancer (TNBC) based on in silico signaling dynamics. This protocol can also be applied to any signaling pathway for patient-specific modeling. For complete details on the use and execution of this protocol, please refer to Imoto et al. (2022).

Tetrachlorocatecholates of triarylarsines as a novel class of Lewis acids.

Pnictogen-mediated Lewis acidity is an emerging research subject in organic chemistry, supramolecular chemistry, etc. In contrast to the extensive studies on phosphorus and antimony, the diversity of arsenic-Lewis acids was quite limited. Herein, tetrachlorocatecholates of triarylarsines were newly synthesized. Their structures, electronic properties, and Lewis acidities were experimentally and computationally examined and compared with the corresponding phosphorus and antimony analogs. This is the first systematic study on the relationship between the structure and Lewis acidity of arsenic-mediated Lewis acids.

4-Aryldithieno[3,2-b:2',3'-d]arsoles: effects of the As-substituent on the structure, photophysical properties, and stability.

Dithieno[3,2-b:2',3'-d]arsole (DTA) is one of the representative arsenic-containing conjugated units. In this work, the effects of the As-substituent on the structure, photophysical properties, and stability were investigated. Surprisingly, the As-substituent affected the structural relaxation and stability in the photo-excited state, while there was negligible effect in the ground state. Bulky substituents resulted in red-shifted emissions due to the relaxation of steric repulsion upon photo-excitation. In addition, the crystal structure highly affected the photo-degradation behaviors.

Systematic Study of Pnictogen-Fused Heterofluorenes.

Heteroatom-fused π-conjugated molecules have attracted considerable attention, and various elements for such fusion have been investigated. Herein, we focused on pnictogen-fused heterofluorenes. The structures, reactivity with O2 and I2, coordination ability to AuCl, and photophysical properties were systematically studied to better understand the effects of pnictogen atoms on the nature of π-conjugated molecules.

A text-based computational framework for patient -specific modeling for classification of cancers.

Patient heterogeneity precludes cancer treatment and drug development; hence, development of methods for finding prognostic markers for individual treatment is urgently required. Here, we present Pasmopy (Patient-Specific Modeling in Python), a computational framework for stratification of patients using in silico signaling dynamics. Pasmopy converts texts and sentences on biochemical systems into an executable mathematical model. Using this framework, we built a model of the ErbB receptor signaling network, trained in cultured cell lines, and performed in silico simulation of 377 patients with breast cancer using The Cancer Genome Atlas (TCGA) transcriptome datasets. The temporal dynamics of Akt, extracellular signal-regulated kinase (ERK), and c-Myc in each patient were able to accurately predict the difference in prognosis and sensitivity to kinase inhibitors in triple-negative breast cancer (TNBC). Our model applies to any type of signaling network and facilitates the network-based use of prognostic markers and prediction of drug response.

Unsymmetric Dumbbell-Shaped Polyhedral Oligomeric Silsesquioxane (POSS) Compound as a Single-Component POSS Hybrid.

Dumbbell-shaped polyhedral oligomeric silsesquioxane (POSS) derivatives, in which two POSS units are linked through a bridge, have attracted attention in the last decade. Here, we prepared an unsymmetric dumbbell-shaped POSS derivative (3Ph-iBu) in which isobutyl- and phenyl-substituted POSS units are linked by a disiloxane unit and compared its thermal properties with those of the corresponding symmetric isobutyl- and phenyl-substituted dumbbell-shaped POSS derivatives (3iBu-iBu and 3Ph-Ph, respectively). The symmetric isobutyl- and phenyl-substituted dumbbell-shaped POSS derivatives, 3iBu-iBu and 3Ph-Ph, were almost completely phase-separated during a mixing process. This phase separation is due to the limited solubility of phenyl-substituted POSS compounds, which are only soluble in tetrahydrofuran (THF) and insoluble in hydrocarbons such as n-hexane and toluene, while the isobutyl-substituted POSS derivatives exhibit a wider spectrum of soluble solvents. The unsymmetric dumbbell-shaped POSS, 3Ph-iBu, showed hybrid properties of solubility in solvents and thermal behaviors. Differential scanning calorimetric (DSC) analysis showed that enthalpy of the phase transition of 3Ph-iBu was significantly lower than those of the mixture of 3iBu-iBu and 3Ph-Ph. No apparent melting behavior was observed above the phase transition. The thermal degradation of the weakest isobutyl substituents improves in the present single-component hybrid structure.