Supramolecular assembly activated single-molecule phosphorescence resonance energy transfer for near-infrared targeted cell imaging.

Pure organic phosphorescence resonance energy transfer is a research hotspot. Herein, a single-molecule phosphorescence resonance energy transfer system with a large Stokes shift of 367 nm and near-infrared emission is constructed by guest molecule alkyl-bridged methoxy-tetraphenylethylene-phenylpyridines derivative, cucurbit[n]uril (n = 7, 8) and ß-cyclodextrin modified hyaluronic acid. The high binding affinity of cucurbituril to guest molecules in various stoichiometric ratios not only regulates the topological morphology of supramolecular assembly but also induces different phosphorescence emissions. Varying from the spherical nanoparticles and nanorods for binary assemblies, three-dimensional nanoplate is obtained by the ternary co-assembly of guest with cucurbit[7]uril/cucurbit[8]uril, accompanying enhanced phosphorescence at 540 nm. Uncommonly, the secondary assembly of ß-cyclodextrin modified hyaluronic acid and ternary assembly activates a single intramolecular phosphorescence resonance energy transfer process derived from phenyl pyridines unit to methoxy-tetraphenylethylene function group, enabling a near-infrared delayed fluorescence at 700 nm, which ultimately applied to mitochondrial targeted imaging for cancer cells.

Laponite-activated AIE supramolecular assembly with modulating multicolor luminescence for logic digital encryption and perfluorinated pollutant detection.

Recently, the non-covalently activated supramolecular scaffold method has become a prominent research area in the field of intelligent materials. Here, the inorganic clay (LP) promoted the AIE properties of 4,4',4″,4‴-(ethene-1,1,2,2-tetrayltetrakis(benzene-4,1-diyl))tetrakis(1-ethylpyridin-1-ium) (P-TPE), showing an astonishing 42-fold enhancement of the emission intensity of the yellow-green luminescence and a 34-fold increase of the quantum yield via organic-inorganic supramolecular strategy as well as the efficient light-harvesting properties (energy transfer efficiency up to 33 %) after doping with the dye receptor Rhodamine B. Furthermore, the full-color spectral regulation, including white light, was achieved by adjusting the ratio of the donor to the acceptor component and co-assembling with the carbon dots (CD). Interestingly, this TPE-based non-covalently activated full-color supramolecular light-harvesting system (LHS) could be achieved not only in aqueous media but also in the hydrogel and the solid state. More importantly, this panchromatic tunable supramolecular LHS exhibited the multi-mode and quadruple digital logic encryption property as well as the specific detection ability towards the perfluorobutyric acid and the perfluorobutanesulfonic acid, which are harmful to human health in drinking water. This result develops a simple, convenient and effective approach for the intelligent anti-counterfeiting and the pollutant sensing.

Density Functional Theory Study on the Mechanism of Nickel-Catalyzed 3,3-Dialkynylation of 2-Aryl Acrylamides Via Double Vinylic C-H Bond Activation.

The mechanisms of Ni-catalyzed 3,3-dialkynylation of 2-aryl acrylamide have been investigated by using density functional theory calculations. The result shows that this reaction includes double alkynylation, which involves sequential key steps of vinylic C-H bond activation, successive oxidative addition, and reductive elimination, with the second C-H bond activation being the rate-determining step. C-H and N-H bond activation occurs via the concerted metalation-deprotonation mechanism. The calculations show that no transition state exists in the first reductive elimination process, and a negative free energy barrier in the second reductive elimination process though a transition state is identified, indicating that the nickel-catalyzed vinylic C(sp2)-C(sp) bond formation does not require activation energy. Z-E isomerization is the prerequisite for the second alkynylation. In addition, our spin-flip TDDFT (SF-TDDFT) computational result discloses that the actual process of Z-E isomerization occurs on the potential energy surface of the first excited singlet state S1.

Density Functional Theory Study of the Mechanism of Ni-Catalyzed Carboxylation of Aryl C(sp2)-S Bonds with CO2: Computational Evidence for the Multifaceted Role of Additive Zn.

The mechanism of Ni-catalyzed carboxylation of aryl C(sp2)-S bonds with CO2 was studied for the first time by density functional theory calculations. We first proposed another possible reaction pathway in which CO2 insertion occurs prior to reduction. Then, we performed calculations on all proposed reaction pathways, and our calculation results show that the pathway in which reduction occurs prior to CO2 insertion is the favored pathway for this reaction. Additionally, our calculations disclose that additive Zn0 acts in multifaceted roles. (1) Zn0 acts as a reductant to reduce the NiI and NiII intermediates. (2) The simultaneously formed ZnIIBr2 can undergo transmetalation with NiI or NiII intermediates to produce an aryl reservoir by forming arylzinc species. (3) ZnIIBr2 can also coordinate to the CO2 to lower the energy barrier of the CO2 insertion step. Moreover, the calculation results suggest that CO2 insertion is the rate-determining step of the reaction, and CO2 is easier to insert into the NiI-Ph bond rather than into the NiII-Ph bond. These calculation results can improve our understanding of the mechanism of the carboxylation process and the multifaceted roles of metal additive Zn0 and provide theoretical guidance for improving the carboxylation reaction.

Structural deep multi-view clustering with integrated abstraction and detail.

Deep multi-view clustering, which can obtain complementary information from different views, has received considerable attention in recent years. Although some efforts have been made and achieve decent performances, most of them overlook the structural information and are susceptible to poor quality views, which may seriously restrict the capacity for clustering. To this end, we propose Structural deep Multi-View Clustering with integrated abstraction and detail (SMVC). Specifically, multi-layer perceptrons are used to extract features from specific views, which are then concatenated to form the global features. Besides, a global target distribution is constructed and guides the soft cluster assignments of specific views. In addition to the exploitation of the top-level abstraction, we also design the mining of the underlying details. We construct instance-level contrastive learning using high-order adjacency matrices, which has an equivalent effect to graph attention network and reduces feature redundancy. By integrating the top-level abstraction and underlying detail into a unified framework, our model can jointly optimize the cluster assignments and feature embeddings. Extensive experiments on four benchmark datasets have demonstrated that the proposed SMVC consistently outperforms the state-of-the-art methods.

Quantitative Analysis of Multimodal MRI Markers and Clinical Risk Factors for Cerebral Small Vessel Disease Based on Deep Learning.

Background: Cerebral small vessel disease lacks specific clinical manifestations, and extraction of valuable features from multimodal images is expected to improve its diagnostic accuracy. In this study, we used deep learning techniques to segment cerebral small vessel disease imaging markers in multimodal magnetic resonance images and analyze them with clinical risk factors. Methods and results: We recruited 211 lacunar stroke patients and 83 control patients. The patients' cerebral small vessel disease markers were automatically segmented using a V-shaped bottleneck network, and the number and volume were calculated after manual correction. The segmentation results of the V-shaped bottleneck network for white matter hyperintensity and recent small subcortical infarction were in high agreement with the ground truth (DSC>0.90). In small lesion segmentation, cerebral microbleed (average recall=0.778; average precision=0.758) and perivascular spaces (average recall=0.953; average precision=0.923) were superior to lacunar infarct (average recall=0.339; average precision=0.432) in recall and precision. Binary logistic regression analysis showed that age, systolic blood pressure, and total cerebral small vessel disease load score were independent risk factors for lacunar stroke (P<0.05). Ordered logistic regression analysis showed age was positively correlated with cerebral small vessel disease load score and total cholesterol was negatively correlated with cerebral small vessel disease score (P<0.05). Conclusion: Lacunar stroke patients exhibited higher cerebral small vessel disease imaging markers, and age, systolic blood pressure, and total cerebral small vessel disease score were independent risk factors for lacunar stroke patients. V-shaped bottleneck network segmentation network based on multimodal deep learning can segment and quantify various cerebral small vessel disease lesions to some extent.

Light and Heat-Driven Flexible Solid Supramolecular Polymer Displaying Phosphorescence and Reversible Photochromism.

Herein, a type of light- and heat-driven flexible supramolecular polymer with reversibly long-lived phosphorescence and photochromism is constructed from acrylamide copolymers with 4-phenylpyridinium derivatives containing a cyano group (P-CN, P-oM, P-mM), sulfobutylether-ß-cyclodextrin (SBCD), and polyvinyl alcohol (PVA). Compared to their parent solid polymers, these flexible supramolecules based on the non-covalent cross-linking of copolymers, SBCD, and PVA efficiently boost the phosphorescence lifetimes (723.0 ms for P-CN, 623.0 ms for P-oM, 945.8 ms for P-mM) through electrostatic interaction and hydrogen bonds. The phosphorescence intensity/lifetime, showing excellent responsiveness to light and heat, sharply decreased after irradiation with a 275 nm flashlight or sunlight and gradually recovered through heating. This is accompanied by the occurrence and fading of visible photochromism, manifesting as dark green for P-CN and pink for P-oM and P-mM. These reversible photochromism and phosphorescence behaviors are mainly attributed to the generation and disappearance of organic radicals in the 4-phenylpyridinium derivatives with a cyano group, which can guide tunable luminescence and photochromism.

Selective Access to Silacyclopentanes and Homoallylsilanes by La-Catalyzed Hydrosilylations of 1-Aryl Methylenecyclopropanes.

Methylenecyclopropanes (MCPs) have emerged as versatile building blocks in synthetic chemistry because of their unique reactivity. However, metal-catalyzed hydrosilylation of MCPs has met with very limited successes. In this paper, catalytic selective hydrosilylations of MCPs with some primary silanes using an ene-diamido lanthanum ate complex as the catalyst were described. The catalytic reactions resulted in the selective formation of silacyclopentanes and (E)-homoallylsilanes, respectively, depending on the substituents on MCPs. The formation of silacyclopentanes via a catalytic cascade inter- and intramolecular hydrosilylation mechanism is strongly supported by the control and deuteration-labeling experiments and DFT calculations. The unique reactivity and selectivity could be attributed to the large lanthanum ion and ate structure of the catalyst.

Bile acids inhibit ferroptosis sensitivity through activating farnesoid X receptor in gastric cancer cells.

BACKGROUND: Gastric cancer (GC) is associated with high mortality rates. Bile acids (BAs) reflux is a well-known risk factor for GC, but the specific mechanism remains unclear. During GC development in both humans and animals, BAs serve as signaling molecules that induce metabolic reprogramming. This confers additional cancer phenotypes, including ferroptosis sensitivity. Ferroptosis is a novel mode of cell death characterized by lipid peroxidation that contributes universally to malignant progression. However, it is not fully defined if BAs can influence GC progression by modulating ferroptosis. AIM: To reveal the mechanism of BAs regulation in ferroptosis of GC cells. METHODS: In this study, we treated GC cells with various stimuli and evaluated the effect of BAs on the sensitivity to ferroptosis. We used gain and loss of function assays to examine the impacts of farnesoid X receptor (FXR) and BTB and CNC homology 1 (BACH1) overexpression and knockdown to obtain further insights into the molecular mechanism involved. RESULTS: Our data suggested that BAs could reverse erastin-induced ferroptosis in GC cells. This effect correlated with increased glutathione (GSH) concentrations, a reduced GSH to oxidized GSH ratio, and higher GSH peroxidase 4 (GPX4) expression levels. Subsequently, we confirmed that BAs exerted these effects by activating FXR, which markedly increased the expression of GSH synthetase and GPX4. Notably, BACH1 was detected as an essential intermediate molecule in the promotion of GSH synthesis by BAs and FXR. Finally, our results suggested that FXR could significantly promote GC cell proliferation, which may be closely related to its anti-ferroptosis effect. CONCLUSION: This study revealed for the first time that BAs could inhibit ferroptosis sensitivity through the FXR-BACH1-GSH-GPX4 axis in GC cells. This work provided new insights into the mechanism associated with BA-mediated promotion of GC and may help identify potential therapeutic targets for GC patients with BAs reflux.

DFT Study on Mechanism of Ni-Al Bimetallic-Catalyzed C-H Cyclization to Construct Tricyclic Imidazoles: Roles of NHC Ligand and AlMe3.

The mechanism of the Ni-Al bimetallic-catalyzed C-H cyclization to construct tricyclic imidazoles is investigated using density functional theory calculations. The calculation result shows that the reaction mechanism involves sequential steps of substrate coordination, ligand-to-ligand hydrogen transfer (LLHT), and C-C reductive elimination to produce the final product tricyclic imidazole. The LLHT step is calculated to be the rate-determining step. The oxidative addition of the benzimidazole C-H bond to the Ni center and the insertion of the alkene into the Ni-H bond occur concertedly in the LLHT step. The effects of N-heterocyclic carbene (NHC) ligands and AlMe3 on the reactivity and regioselectivity were also analyzed. These calculation results shed light on some ambiguous suggestions from experiments.

Theory and experiment: The synthesis and drug application of "ON-OFF-ON" fluorescent probes for copper and biothiols detection.

Abnormal copper ions (Cu2+) and biothiols have potential impacts on environmental pollution and human health, so the detection of these substances with high selectivity and sensitivity has become an important research topic. In this study, we designed and synthesized two fluorescent probes (L1 and L2) based on naphthalene and anthracene derivatives that could specifically detect Cu2+ and biothiols. Owing to the paramagnetic effect of Cu2+, the strong fluorescent intensity was quenched after the addition of Cu2+. When biothiols were added to the solution (L-Cu2+), the fluorescence intensity was significantly enhanced and recovered. So, the interaction process was accompanied with "ON-OFF-ON" phenomenon in fluorescent intensity. Two complexes (L-Cu2+) showed low limit of detection for biothiols (Cys was 3.4 ×10-5 M and GSH was 2.0 ×10-5 M) and weak cytotoxicity (< 150 µg/mL). Theoretical investigation analysis revealed that the intramolecular hydrogen bond existed in the structure of probes and the roles of molecular frontier orbitals in molecular interplay. In addition, two probes also showed good applicability in actual drug Atomolan. The GSH content in the tested Atomolan reached over 99.9% of the labeling which was accord with the percentage of pharmacopoeia. Therefore, two probes have the real application value in the detection of Cu2+, biothiols and drug efficacy in various environments.

DFT Study on the Mechanism of the Palladium-Catalyzed [3 + 2] Annulation of Aromatic Amides with Maleimides via Benzylic and meta-C-H Bond Activation: Role of the External Ligand Ac-Gly-OH.

The mechanism of the Ac-Gly-OH-assisted palladium-catalyzed [3 + 2] annulation of aromatic amides with maleimides is investigated using density functional theory calculations. The results show that the reaction undergoes the sequential steps of N-H bond deprotonation, first benzylic C-H bond activation, maleimide insertion, second meta-C-H bond activation, reductive elimination, and oxidation. The external ligand Ac-Gly-OH acts as the internal base for hydrogen abstraction in the first benzylic C-H bond activation. The maleimide insertion step is found to be the rate-determining step. Based on the nearly same energetic span of the two pathways to generate the enantio products, the computational results are consistent with the experimental observation that the terminal [3 + 2] annulation products are racemic when using an achiral ligand. These calculation results disclose the detailed reaction mechanism and shed light on some experimental ambiguities.

Structure-aware deep clustering network based on contrastive learning.

Recently, deep clustering has been extensively employed for various data mining tasks, and it can be divided into auto-encoder (AE)-based and graph neural networks (GNN)-based methods. However, existing AE-based methods fall short in effectively extracting structural information, while GNN suffer from smoothing and heterophily. Although methods that combine AE and GNN achieve impressive performance, there remains an inadequate balance between preserving the raw structure and exploring the underlying structure. Accordingly, we propose a novel network named Structure-Aware Deep Clustering network (SADC). Firstly, we compute the cumulative influence of non-adjacent nodes at multiple depths and, thus, enhance the adjacency matrix. Secondly, an enhanced graph auto-encoder is designed. Thirdly, the latent space of AE is endowed with the ability to perceive the raw structure during the learning process. Besides, we design self-supervised mechanisms to achieve co-optimization of node representation learning and topology learning. A new loss function is designed to preserve the inherent structure while also allowing for exploration of latent data structure. Extensive experiments on six benchmark datasets validate that our method outperforms state-of-the-art methods.

Unimolecular Chiral Stepping Inversion Machine.

Intelligent molecular machines that are driven by light, electricity, and temperature have attracted considerable interest in the fields of chemistry, materials, and biology. Herein, a unimolecular chiral stepping inversion molecular machine (SIMM) was constructed by a coupling reaction between dibromo pillar[5]arene and a tetrathiafulvalene (TTF) derivative (PT3 and PT5). Compared with the longer aliphatic linker PT5, PT3 with a shorter aliphatic linker shows chiral stepping inversion, achieving chiral inversion under a two-electron redox potential. Benefiting from the successive reversible two-electron redox potential of TTF, the self-exclusion and self-inclusion conformational transformations of SIMM can proceed in two steps under redox, leading to the chirality step inversion in the pillar[5]arene core. Electrochemical experiments and circular dichroism (CD) spectra show that the redox processes can cause SIMM CD signaling to reversibly switch. More importantly, as the oxidant Fe(ClO4)3 was increased from 0.1 to 1 equiv, the CD spectral signal of SIMM disappeared at 1 equiv, and further addition of Fe(ClO4)3 resulted in the CD signal reversed from positive to negative at 309 nm, indicating that the chirality was reversed after chemical oxidation and reached a negative maximum with the addition of 2 equiv Fe(ClO4)3; thus, redox-triggered chiral stepping inversion was achieved. Furthermore, the chiral inversion can be restored to its original state after the addition of 2 equiv of reducing agent, sodium ascorbate. This work demonstrates unimolecular chiral stepping inversion, providing a new perspective on stimulus-responsive chirality in molecular machines.

Hydrogen-bonded Complex-based Frameworks for Stable Lithium Storage.

Metal-complex-based materials for lithium storage have attracted great interest due to their highly designable structures with multiple active sites and well-defined lithium transport pathways. Their cycling and rate performances, however, are still constrained by structural stability and electrical conductivity. Herein, we present two hydrogen-bonded complex-based frameworks with excellent lithium storage capability. Multiple hydrogen bonds among the mononuclear molecules result in three-dimensional frameworks that are stable in electrolyte. The origin of the remarkable lithium storage performance of this family was revealed through kinetic analysis and DFT calculations.

Computational Study of Iron-Catalyzed Intramolecular [2 + 2] Cycloaddition and Cycloisomerization of Enyne Acetates: Mechanism and Selectivity.

The mechanism of iron-catalyzed intramolecular [2 + 2] cycloaddition and cycloisomerization of enyne acetates has been investigated with DFT computations. Both mechanisms start the catalytic cycle from the stepwise 1,2-acyloxy migration to afford the iron carbene. The [2 + 2] cycloaddition mechanism involves subsequent key steps of [2 + 2] cycloaddition, 1,2-acyloxy migration, and reductive elimination to generate the azabicyclo [3.2.0] heptane product, with the reductive elimination being the rate-determining step. The cycloisomerization mechanism involves subsequent key steps of [2 + 2] cycloaddition, stepwise 1,4-acyloxy migration to produce the allenylpyrrolidine product, with the 1,4-acyloxy migration being the rate-determining step. Reaction potential energy surfaces for two model substrates that have or do not have alkene-terminal substituents have been investigated and the origins of the selectivities have been disclosed. Moreover, energy profiles with three possible spin states (SFe = 0, 1, 2) have been considered. The reaction is suggested to occur mainly on the singlet potential energy surface with a few spin crossovers between singlet and triplet states involved, which indicates that this reaction should have two-state reactivity (TSR).

Efficient Recognition and Removal of Persistent Organic Pollutants by a Bifunctional Molecular Material.

Persistent organic pollutants (POPs) exist widely in the environment and place significant impact on human health by bioaccumulation. Efficient recognition of POPs and their removal are highly challenging tasks because their specific structures interact often very weakly with the capture materials. Herein, a molecular nanocage (1) is studied as an efficient sensing and sorbent material for POPs, which is demonstrated by a representative and stable perfluorooctane sulfonate (PFOS) substrate containing a hydrophilic sulfonic group and a hydrophobic fluoroalkyl chain. A highly sensitive and unusual turn-on fluorescence response within 10 s and a 97% total removal of PFOS from water in 20 min have been achieved owing to the strong host-guest interactions between 1 and PFOS. The binding constant of 1 to PFOS is 2 orders of magnitude higher than state-of-the-art adsorbents for PFOS and thus represents a new benchmark material for the recognition and removal of PFOS. The host-guest interaction has been elucidated by solid-state NMR spectroscopy and single-crystal X-ray diffraction, which provide key insights at a molecular level for the design of new advanced sensing/sorbent materials for POPs.

C3-Cyanation of Pyridines: Constraints on Electrophiles and Determinants of Regioselectivity.

Methods for C-H cyanation of pyridines are rare. Here, we report a method for C3-selective cyanation of pyridines by a tandem process with the reaction of an in situ generated dihydropyridine with a cyano electrophile as the key step. The method is suitable for late-stage functionalization of pyridine drugs. The low reduction potential of the electrophile and effective transfer of the nitrile group were found to be essential for the success of this method. We studied the reaction mechanism in detail by means of control experiments and theoretical calculations and found that a combination of electronic and steric factors determined the regioselectivity of reactions involving C2-substituted pyridines.

A tunable full-color lanthanide noncovalent polymer based on cucurbituril-mediated supramolecular dimerization.

The construction of lanthanide multicolor luminescent materials with tunable photoluminescence properties has been developed as one of the increasingly significant topics and shown inventive applications in miscellaneous fields. However, fabricating such materials based on synergistically assembly-induced emission rather than simple blending of different fluorescent dyes together still remains a challenge. Herein, we report a europium-based noncovalent polymer with tunable full-color emission, which is constructed from the 2,6-pyridinedicarboxylic acid-bearing bromophenylpyridinium salt. This rationally designed bifunctional component can concurrently serve as a guest molecule and a chelating ligand to associate with cucurbit[8]uril and europium ions, thus leading to the formation of a trichromatic (red-green-blue, RGB) photoluminescent polypseudorotaxane-type noncovalent polymer in aqueous solution. Meanwhile, the full-color emission enclosed within the RGB color triangle could be readily produced by simply tuning the molar ratio of cucurbit[8]uril and europium ions. The lanthanide supramolecular polymer featuring tricolor emission, long lifetime, high photoluminescence efficiency and low cytotoxicity could be further applied in multicolor imaging in a cellular environment. These results provide a new and feasible strategy for the construction of full-color single lanthanide self-assembled nanoconstructs.

Application of Diffusion Tensor Imaging Based on Automatic Fiber Quantification in Alzheimer's Disease.

BACKGROUND: Neuroimaging suggests that white matter microstructure is severely affected in Alzheimer's disease (AD) progression. However, whether alterations in white matter microstructure are confined to specific regions and whether they can be used as potential biomarkers to distinguish normal control (NC) from AD are unknown. METHODS: In this cross-sectional study, 33 cases of AD and 25 cases of NC were recruited for automatic fiber quantification (AFQ). A total of 20 fiber bundles were equally divided into 100 segments for quantitative assessment of fractional anisotropy (FA), mean diffusivity (MD), volume and curvature. In order to further evaluate the diagnostic value, the maximum redundancy minimum (mRMR) and LASSO algorithms were used to select features, calculate the Radscore of each subject, establish logistic regression models, and draw ROC curves, respectively, to assess the predictive power of four different models. RESULTS: There was a significant increase in the MD values in AD patients compared with healthy subjects. The differences were mainly located in the left cingulum hippocampus (HCC), left uncinate fasciculus (UF) and superior longitudinal fasciculus (SLF). The point-wise level of 20 fiber bundles was used as a classification feature, and the MD index exhibited the best performance to distinguish NC from AD. CONCLUSION: These findings contribute to the understanding of the pathogenesis of AD and suggest that abnormal white matter based on DTI-based AFQ analysis is helpful to explore the pathogenesis of AD.