Cu(I)-Photosensitizer-Catalyzed Olefin-α-Amino Radical Metathesis/Demethylenative Cyclization of 1,7-Enynes.

A demethylenative En-Yne radical cyclization of 1,7-enynes has been successfully developed to chemoselectively afford 3,4-dihyroquinolin-2-ones or quinolin-2-ones under the catalysis of Cu(I) photosensitizers PS3 and PS6 with different redox potentials. The preliminary mechanistic experiments revealed that the reaction underwent an unprecedented olefin-α-amino radical metathesis-type process. A reasonable mechanism was proposed to illustrate the catalyst-controlled chemoselectivity of the reaction based on preliminary mechanistic experiments and DFT calculations.

Benzothiazole derivatives as histone deacetylase inhibitors for the treatment of autosomal dominant polycystic kidney disease.

Recent evidence suggests that histone deacetylases (HDACs) are important regulators of autosomal dominant polycystic kidney disease (ADPKD). In the present study, a series of benzothiazole-bearing compounds were designed and synthesized as potential HDAC inhibitors. Given the multiple participation of HDACs in ADPKD cyst progression, we embarked on a targeted screen using HeLa nuclear extracts to identify potent pan-HDAC inhibitors. Compound 26 emerged as the most efficacious candidate. Subsequent pharmacological characterization showed that compound 26 effectively inhibits several HDACs, notably HDAC1, HDAC2, and HDAC6 (IC50 < 150 nM), displaying a particularly high sensitivity towards HDAC6 (IC50 = 11 nM). The selected compound significantly prevented cyst formation and expansion in an in vitro cyst model and was efficacious in reducing cyst growth in both an embryonic kidney cyst model and an in vivo ADPKD mouse model. Our results provided compelling evidence that compound 26 represents a new HDAC inhibitor for the treatment of ADPKD.

Corrigendum: Double cross-linked graphene oxide hydrogel for promoting healing of diabetic ulcers.

[This corrects the article DOI: 10.3389/fchem.2024.1355646.].

Cepharanthine maintains integrity of the blood-brain barrier (BBB) in stroke via the VEGF/VEGFR2/ZO-1 signaling pathway.

Dysfunction of tight junctions such as zonula occludens protein-1 (ZO-1)-associated aggravation of blood-brain barrier (BBB) permeability plays an important role in the progression of stroke. Cepharanthine (CEP) is an extract from the plant Stephania cepharantha. However, the effects of CEP on stroke and BBB dysfunction have not been previously reported. In this study, we report that CEP improved dysfunction in neurological behavior in a middle cerebral artery occlusion (MCAO) mouse model. Importantly, CEP suppressed blood-brain barrier (BBB) hyperpermeability by increasing the expression of ZO-1. Notably, we found that CEP inhibited the expression of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 2 (VEGFR2) in the cortex of MCAO mice. Additionally, the results of in vitro experiments demonstrate that treatment with CEP ameliorated cytotoxicity of human bEnd.3 brain microvascular endothelial cells against hypoxia/reperfusion (H/R). Also, CEP attenuated H/R-induced aggravation of endothelial permeability in bEND.3 cells by restoring the expression of ZO-1. Further study proved that the protective effects of CEP are mediated by inhibition of VEGF-A and VEGFR2. Based on the results, we conclude that CEP might possess a therapeutic prospect in stroke through protecting the integrity of the BBB mediated by the VEGF/VEGFR2/ZO-1 axis.

Perimidocarbene-Based Tetradentate Platinum(II) Complexes with an Unexpectedly Negligible 3MLCT Character.

Two novel six-membered perimidocarbene (PIC)-based tetradentate Pt(II) complexes were designed and successfully synthesized. Systematical experimental and theoretical studies suggest that the PIC moiety greatly affects the frontier orbitals, as well as the photophysical and excited-state properties of the Pt(II) complexes. PtYK2 has a broad emission spectrum peaking at 576 nm with a shoulder band at 620 nm, along with a full width at half-maximum (FWHM) value of 100.0 nm at 77 K in 2-MeTHF; however, the emission spectrum is slightly red-shifted with a dominant peak at 610 nm and a FWHM value of 125.0 nm at room temperature in a poly(methyl methacrylate) (PMMA) film. Time-dependent-density functional theory and natural transition orbital analyses reveal that PtYK2 has a 3LC (3πPIC* → πPIC)-dominated character with an unexpectedly negligible contribution of 3MLCT transition (0.68%) in the T1 state, which results in a broad emission spectrum and a relatively low quantum efficiency of 7.4% in the PMMA film.

Double cross-linked graphene oxide hydrogel for promoting healing of diabetic ulcers.

This study explores the synthesis and characterization of a novel double cross-linked hydrogel composed of polyvinyl alcohol (PVA), sodium alginate (SA), graphene oxide (GO), and glutathione (GSH), henceforth referred to as PVA/SA/GO/GSH. This innovative hydrogel system incorporates two distinct types of cross-linking networks and is meticulously engineered to exhibit sensitivity to high glucose and/or reactive oxygen species (ROS) environments. A sequential approach was adopted in the hydrogel formation. The initial phase involved the absorption of GSH onto GO, which was subsequently functionalized with boric acid and polyethylene glycol derivatives via a bio-orthogonal click reaction. This stage constituted the formation of the first chemically cross-linked network. Subsequently, freeze-thaw cycles were utilized to induce a secondary cross-linking process involving PVA and SA, thereby forming the second physically cross-linked network. The resultant PVA/SA/GO/GSH hydrogel retained the advantageous hydrogel properties such as superior water retention capacity and elasticity, and additionally exhibited the ability to responsively release GSH under changes in glucose concentration and/or ROS levels. This feature finds particular relevance in the therapeutic management of diabetic ulcers. Preliminary in vitro evaluation affirmed the hydrogel's biocompatibility and its potential to promote cell migration, inhibit apoptosis, and exhibit antibacterial properties. Further in vivo studies demonstrated that the PVA/SA/GO/GSH hydrogel could facilitate the healing of diabetic ulcer sites by mitigating oxidative stress and regulating glucose levels. Thus, the developed PVA/SA/GO/GSH hydrogel emerges as a promising candidate for diabetic ulcer treatment, owing to its specific bio-responsive traits and therapeutic efficacy.

An artificial intelligence platform for automated PFAS subgroup classification: A discovery tool for PFAS screening.

Since structural analyses and toxicity assessments have not been able to keep up with the discovery of unknown per- and polyfluoroalkyl substances (PFAS), there is an urgent need for effective categorization and grouping of PFAS. In this study, we presented PFAS-Atlas, an artificial intelligence-based platform containing a rule-based automatic classification system and a machine learning-based grouping model. Compared with previously developed classification software, the platform's classification system follows the latest Organization for Economic Co-operation and Development (OECD) definition of PFAS and reduces the number of uncategorized PFAS. In addition, the platform incorporates deep unsupervised learning models to visualize the chemical space of PFAS by clustering similar structures and linking related classes. Through real-world use cases, we demonstrate that PFAS-Atlas can rapidly screen for relationships between chemical structure and persistence, bioaccumulation, or toxicity data for PFAS. The platform can also guide the planning of the PFAS testing strategy by showing which PFAS classes urgently require further attention. Ultimately, the release of PFAS-Atlas will benefit both the PFAS research and regulation communities.

High-Performance Ultraviolet Organic Light-Emitting Diodes Enabled by Double Boron-Oxygen-Embedded Benzo[m]tetraphene Emitters.

Ultraviolet organic light-emitting diodes (UV OLEDs) have attracted increasing attention because of their promising applications in healthcare, industry, and agriculture; however, their development has been hindered by the shortage of robust UV emitters. Herein, we embedded double boron-oxygen units into nonlinear polycyclic aromatic hydrocarbons (BO-PAHs) to regulate their molecular configurations and excited-state properties, enabling novel bent BO-biphenyl (BO-bPh) and helical BO-naphthyl (BO-Nap) emitters with hybridized local and charge-transfer (HLCT) characteristics. They could be facilely synthesized in gram-scale amounts via a highly efficient two-step route. BO-bPh and BO-Nap showed strong UV and violet-blue photoluminescence in toluene with full width at half-maximum values of 25 and 37 nm, along with quantum efficiencies of 98 and 99%, respectively. A BO-bPh-based OLED showed high color purity UV electroluminescence peaking at 394 nm with Commission Internationale de l'Eclairage (CIE) coordinates of (0.166, 0.021). Moreover, the device demonstrated a record-high maximum external quantum efficiency (EQE) of 11.3%, achieved by successful hot exciton utilization. This work demonstrates the promising potential of double BO-PAHs as robust emitters for future UV OLEDs.

Towards high-performance nonlinear optical materials through embedding a D-A system into ß-ketoenamine-linked COFs.

Two covalent organic framework (COF) films supported by a glass substrate were obtained by solvothermal reaction of an electron donor with electron acceptor 1,3,5-triformylbenzene (TF) or 2,4,6-triformylphloroglucinol (TFP), respectively. The TFP-BD film exhibits a nonlinear absorption coefficient of -3.01 × 105 cm GW-1. The TFP-BD film can aggregate electrons around the connected monomer through the D-A effect due to its highly polar and electronegative carbonyl oxygen atoms, thereby modulating the electronic structure of the COFs. This work provides a novel approach for the structural modulation of optical materials with strong nonlinearity.

Double boron-oxygen-fused polycyclic aromatic hydrocarbons: skeletal editing and applications as organic optoelectronic materials.

An efficient one-pot strategy for the facile synthesis of double boron-oxygen-fused polycyclic aromatic hydrocarbons (dBO-PAHs) with high regioselectivity and efficient skeletal editing is developed. The boron-oxygen-fused rings exhibit low aromaticity, endowing the polycyclic aromatic hydrocarbons with high chemical and thermal stabilities. The incorporation of the boron-oxygen units enables the polycyclic aromatic hydrocarbons to show single-component, low-temperature ultralong afterglow of up to 20 s. Moreover, the boron-oxygen-fused polycyclic aromatic hydrocarbons can also serve as ideal n-type host materials for high-brightness and high-efficiency deep-blue OLEDs; compared to single host, devices using boron-oxygen-fused polycyclic aromatic hydrocarbons-based co-hosts exhibit dramatically brightness and efficiency enhancements with significantly reduced efficiency roll-offs; device 9 demonstrates a high color-purity (Commission International de l'Eclairage CIEy = 0.104), and also achieves a record-high external quantum efficiency (28.0%) among Pt(II)-based deep-blue OLEDs with Commission International de l'Eclairage CIEy < 0.20; device 10 achieves a maximum brightnessof 27219 cd/m2 with a peak external quantum efficiency of 27.8%, which representes the record-high maximum brightness among Pt(II)-based deep-blue OLEDs. This work demonstrates the great potential of the double boron-oxygen-fused polycyclic aromatic hydrocarbons as ultralong afterglow and n-type host materials in optoelectronic applications.

Tailoring Wavelength-Adaptive Visual Neuroplasticity Transitions of Synaptic Transistors Comprising Rod-Coil Block Copolymers for Dual-Mode Photoswitchable Learning/Forgetting Neural Functions.

The vision-inspired artificial neural network based on optical synapses has drawn a tremendous amount of attention for emulating biological senses. Although photoexcitation-induced synaptic functionalities have been widely studied, optical habituation via the photoinhibitory pathway is yet to be demonstrated for sophisticated biomimetic visual adaptive systems. Here, the first optical neuromorphic block copolymer (BCP) phototransistor is demonstrated as an all-optical operation responding to various wavelengths, fulfilling photoassisted dynamic learning/forgetting cycles via optical potentiation without gate bias. The polyfluorene BCPs were precisely designed to enable wavelength-adaptive responses, benefiting from interfacial semiconductor/electret morphology and the crystallinity/electron affinity of the BCPs. Notably, this is the first work to simultaneously exhibit fully light-controlled short- and long-term memory based on organic material systems. The device presents a high current contrast above 100-fold and long-term retention over 104 s. As a proof-of-concept for neural networks, a 6 × 6 array of photosynapses performed outstanding visual pattern learning/forgetting with high accuracy. This study exploits the design strategy of a conjugated BCP electret to unleash the full potential of wavelength-adaptive visual neuroplasticity transitions. It provides an effective architecture for designing high-performance and high-storage capacity required applications in next-generation neuromorphic systems.

8-Phenylquinoline-Based Tetradentate 6/6/6 Platinum(II) Complexes for Near-Infrared Emitters.

A series of novel tetradentate 6/6/6 Pt(II) complexes containing an 8-phenylquinoline-benzo[d]imidazole-carbazole ligand was designed; the Pt(II) complexes could be synthesized by metalizing the corresponding ligand with K2PtCl4 in high isolated yields of 60-90%. Experimental and theoretical studies suggested that the ligand modification of the quinoline moieties of the Pt(II) complexes could tune their electrochemical, photophysical, and excited-state properties. Notably, all the Pt(II) complexes exhibited highly electrochemical stabilities with reversible redox processes except the quasi-reversible reduction of PtYL3. The large π-conjugation of the ligand together with increased metal-to-ligand charge-transfer (3MLCT) characters in T1 states enabled the Pt(II) complexes to show broad Gaussian-type NIR emission spectra with high photoluminescence quantum efficiencies of 1.2-1.5% and short τ of 0.8-1.5 µs in dichloromethane at room temperature. This work should provide a valuable reference for the design and development of monomer NIR emitters.

Mechanistic Investigation of Ni-Catalyzed Reductive Cross-Coupling of Alkenyl and Benzyl Electrophiles.

Mechanistic investigations of the Ni-catalyzed asymmetric reductive alkenylation of N-hydroxyphthalimide (NHP) esters and benzylic chlorides are reported. Investigations of the redox properties of the Ni-bis(oxazoline) catalyst, the reaction kinetics, and mode of electrophile activation show divergent mechanisms for these two related transformations. Notably, the mechanism of C(sp3) activation changes from a Ni-mediated process when benzyl chlorides and Mn0 are used to a reductant-mediated process that is gated by a Lewis acid when NHP esters and tetrakis(dimethylamino)ethylene is used. Kinetic experiments show that changing the identity of the Lewis acid can be used to tune the rate of NHP ester reduction. Spectroscopic studies support a NiII-alkenyl oxidative addition complex as the catalyst resting state. DFT calculations suggest an enantiodetermining radical capture step and elucidate the origin of enantioinduction for this Ni-BOX catalyst.

Molecular Dynamics of Iron Porphyrin-Catalyzed C-H Hydroxylation of Ethylbenzene.

Quasi-classical molecular dynamics (MD) simulations were carried out to study the mechanism of iron porphyrin-catalyzed hydroxylation of ethylbenzene. The hydrogen atom abstraction from ethylbenzene by iron-oxo species is the rate-determining step, which generates the radical pair of iron-hydroxo species and the benzylic radical. In the subsequent radical rebound step, the iron-hydroxo species and benzylic radical recombine to form the hydroxylated product, which is barrierless on the doublet energy surface. In the gas-phase quasi-classical MD study on the doublet energy surface, 45% of the reactive trajectories lead directly to the hydroxylated product, and this increases to 56% in implicit solvent model simulations. The percentage of reactive trajectories leading to the separated radical pair is 98-100% on high-spin (quartet/sextet) energy surfaces. The low-spin state reactivity dominates in the hydroxylation of ethylbenzene, which is dynamically both concerted and stepwise, since the time gap between C-H bond cleavage and C-O bond formation ranges from 41 to 619 fs. By contrast, the high-spin state catalysis is an energetically stepwise process, which has a negligible contribution to the formation of hydroxylation products.

Predicting band gaps of MOFs on small data by deep transfer learning with data augmentation strategies.

Porphyrin-based MOFs combine the unique photophysical and electrochemical properties of metalloporphyrins with the catalytic efficiency of MOF materials, making them an important candidate for light energy harvesting and conversion. However, accurate prediction of the band gap of porphyrin-based MOFs is hampered by their complex structure-function relationships. Although machine learning (ML) has performed well in predicting the properties of MOFs with large training datasets, such ML applications become challenging when the training data size of the materials is small. In this study, we first constructed a dataset of 202 porphyrin-based MOFs using DFT computations and increased the training data size using two data augmentation strategies. After that, four state-of-the-art neural network models were pre-trained with the recognized open-source database QMOF and fine-tuned with our augmented self-curated datasets. The GCN models predicted the band gaps of the porphyrin-based materials with the lowest RMSE of 0.2767 eV and MAE of 0.1463 eV. In addition, the data augmentation strategy rotation and mirroring effectively decreased the RMSE by 38.51% and MAE by 50.05%. This study demonstrates that, when proper transfer learning and data augmentation strategies are applied, machine learning models can predict the properties of MOFs using small training data.

LncRNA SATB2-AS1 overexpression represses the development of hepatocellular carcinoma through regulating the miR-3678-3p/GRIM-19 axis.

Hepatocellular carcinoma (HCC) is a malignancy worldwide with one of the worst prognoses. Emerging studies have revealed that long noncoding RNAs (lncRNAs) contribute to HCC progression. This research probes the expression and regulatory effect of lncRNA SATB2-AS1 on HCC development. Reverse transcription-polymerase chain reaction (RT-PCR) was applied to measure the SATB2-AS1 profile in HCC tissues and adjacent non-tumor tissues. The impact of SATB2-AS1, miR-3678-3p, or GRIM-19 on HCC cell proliferation, growth, migration, invasion, and apoptosis was determined by gain- and loss-of-function experiments. The results revealed that SATB2-AS1 was downregulated in HCC tissues, and its lower levels were related to higher tumor staging and poorer prognosis of HCC patients. SATB2-AS1 overexpression repressed HCC cell proliferation, induced G1 arrest, and apoptosis, and inhibited migration, invasion, and epithelial-mesenchymal transition (EMT). Mechanistically, SATB2-AS1 inactivated STAT3/HIF-1α and strengthened GRIM-19 expression. After knocking down GRIM-19 with small interfering RNA (siRNA), the malignant phenotypes of HCC cells were enhanced. Further bioinformatics analysis showed that miR-3678-3p was targeted by SATB2-AS1. The dual-luciferase reporter assay, RNA immunoprecipitation (RIP) experiment, and Fluorescence in situ Hybridization (FISH) test confirmed that SATB2-AS1 sponged miR-3678-3p and the latter targeted GRIM-19. The rescue experiments showed that miR-3678-3p aggravated the malignant behaviors of HCC cells, whereas SATB2-AS1 overexpression reversed miR-3678-3p-mediated effects. Inhibition STAT3 promoted SATB2-AS1 and GRIM-19 expression, and reduced miR-3678-3p level. Activation STAT3 exerted opposite effects. Overall, this study confirmed that SATB2-AS1 is a potential prognostic biomarker for HCC and regulates HCC devolvement by regulating the miR-3678-3p/GRIM-19/STAT3/HIF-1α pathway.

Deep transfer learning for predicting frontier orbital energies of organic materials using small data and its application to porphyrin photocatalysts.

Machine learning (ML) models have received increasing attention as a new approach for the virtual screening of organic materials. Although some ML models trained on large databases have achieved high prediction accuracy, the application of ML to certain types of organic materials is limited by the small amount of available data. On the other hand, metalloporphyrins and porphyrins (MpPs) have received increasing attention as potential photocatalysts, and recent studies have found that both HOMO/LUMO energy levels and energy gaps are important factors controlling the MpP photocatalysts. Since the training data of MpPs are insufficient and limited to porphyrin-based dyes, in this study, we proposed a deep transfer learning approach to rapidly predict the HOMO/LUMO energy levels and energy gaps of MpPs. To complement the open-source Porphyrin-based Dyes Database (PBDD), we curated a new database, the Metalloporphyrins and Porphyrins Database (MpPD), in which MpPs were specifically designed as potential photocatalysts and the HOMO/LUMO energies were calculated by advanced DFT functionals. We proposed PorphyBERT, a BERT-based regression model that was pre-trained with PBDD and fine-tuned with MpPD. The model performed satisfactorily in predicting HOMO and LUMO energies and energy gap with RMSEs of 0.0955, 0.0988, and 0.0787 eV and MAEs of 0.0774, 0.0824, and 0.0549 eV. Furthermore, due to its unique unsupervised pre-training phase, the model is not affected by the difference in computational functionals between pre-training and fine-tuning databases. Finally, we recommended 12 MpPs as potential photocatalysts for CO2 reduction with out-of-sample model predictions of energy gaps close to the values calculated by DFT.

Molecular template growth of organic heterojunctions to tailor visual neuroplasticity for high performance phototransistors with ultralow energy consumption.

The optical and charge transport properties of organic semiconductors are strongly influenced by their morphology and molecular structures. Here we report the influence of a molecular template strategy on anisotropic control via weak epitaxial growth of a semiconducting channel for a dinaphtho[2,3-b:2',3'-f]thieno[3,2-b]thiophene (DNTT)/para-sexiphenyl (p-6P) heterojunction. The aim is to improve charge transport and trapping, to enable tailoring of visual neuroplasticity. The proposed phototransistor devices, comprising a molecular heterojunction with optimized molecular template thickness, exhibited an excellent memory ratio (ION/IOFF) and retention characteristics in response to light stimulation, owing to the enhanced orientation/packing of DNTT molecules and a favorable match between the LUMO/HOMO levels of p-6P and DNTT. The best performing heterojunction exhibits visual synaptic functionalities, including an extremely high pair-pulse facilitation index of ∼206%, ultralow energy consumption of 0.54 fJ, and zero-gate operation, under ultrashort pulse light stimulation to mimic human-like sensing, computing, and memory functions. An array of heterojunction photosynapses possess a high degree of visual pattern recognition and learning, to mimic the neuroplasticity of human brain activities through a rehearsal learning process. This study provides a guide to the design of molecular heterojunctions for tailoring high-performance photonic memory and synapses for neuromorphic computing and artificial intelligence systems.

Computational Exploration of Dirhodium Complex-Catalyzed Selective Intermolecular Amination of Tertiary vs. Benzylic C-H Bonds.

The mechanism and origins of site-selectivity of Rh2(S-tfpttl)4-catalyzed C(sp3)-H bond aminations were studied using density functional theory (DFT) calculations. The synergistic combination of the dirhodium complex Rh2(S-tfpttl)4 with tert-butylphenol sulfamate TBPhsNH2 composes a pocket that can access both tertiary and benzylic C-H bonds. The nonactivated tertiary C-H bond was selectively aminated in the presence of an electronically activated benzylic C-H bond. Both singlet and triplet energy surfaces were investigated in this study. The computational results suggest that the triplet stepwise pathway is more favorable than the singlet concerted pathway. In the hydrogen atom abstraction by Rh-nitrene species, which is the rate- and site-selectivity-determining step, there is an attractive π-π stacking interaction between the phenyl group of the substrate and the phthalimido group of the ligand in the tertiary C-H activation transition structure. By contrast, such attractive interaction is absent in the benzylic C-H amination transition structure. Therefore, the DFT computational results clearly demonstrate how the synergistic combination of the dirhodium complex with sulfamate overrides the intrinsic preference for benzylic C-H amination to achieve the amination of the nonactivated tertiary C-H bond.

A new class of transformable kirigami metamaterials for reconfigurable electromagnetic systems.

The rapid development of radio frequency (RF) components requires smart multifunctional materials that can adapt their physical shapes and properties according to the environment. While most current reconfigurable systems provide limited flexibility with high manufacturing cost, this research proposes to harness the transformable properties of kirigami-inspired multistable mechanical metasurfaces that can repeatedly deform and lock into different configurations to realize a novel class of low-cost reconfigurable electromagnetic structures with a broad design space. The metasurfaces are formed by designing kinematic-based unit cells with metallised coating that can provide adjustable resonant electromagnetic (EM) properties while rotating with respect to each other. Tailoring the cut length and geometry parameters of the patterns, we demonstrate programming of the topologies and shapes of different configurations. The influence of critical parameters on the structural multistability is illustrated by means of both a simplified energy model and finite element simulations. As examples of the reconfigurable electromagnetic devices that can be realized, we report the development of a tuneable half-wave dipole and two frequency selective surface (FSS) designs featuring isotropic and anisotropic responses. While the kirigami dipole can be tuned by mechanically stretching its arms, the FSSs exhibit distinct transmittance and reflectance spectra in each of the kirigami patterns stable states. The functionality of these kirigami devices is validated both by full-wave EM simulations and experiments. The proposed transformable structures can be mechanically actuated to tune the EM response in frequency or induce anisotropies for wave propagation.