Construction of Two-Dimensional Organometallic Coordination Networks with Both Organic Kagome and Semiregular Metal Lattices on Au(111).

Two-dimensional metal-organic networks (2D MONs) having heterogeneous coordination nodes (HCNs) could exhibit excellent performance in catalysis and optoelectronics because of the unbalanced electron distribution of the coordinating metals. Therefore, the design and construction of 2D MONs with HCNs are highly desirable but remain challenging. Here, we report the construction of 2D organometallic coordination networks with an organic Kagome lattice and a semiregular metal lattice on Au(111) via the in situ formation of HCNs. Using a bifunctional precursor 1,4-dibromo-2,5-diisocyanobenzene, the coordination of isocyano with Au adatom on a room-temperature Au(111) yielded metal-organic coordination chains with isocyano-Au-isocyano nodes. In contrast, on a high-temperature Au(111), a selective debromination/coordination cascade reaction occurred, affording 2D organometallic coordination networks with phenyl-Au-isocyano nodes. By combining scanning tunneling microscopy and density functional theory calculations, we determined the structures of coordination products and the nature of coordination nodes, demonstrating a thermodynamically favorable pathway for forming the phenyl-Au-isocyano nodes.

Two-Dimensional Nonbenzenoid Heteroacene Crystals Synthesized via In-Situ Embedding of Ladder Bipyrazinylenes on Au(111).

Precisely introducing topological defects is an important strategy in nanographene crystal engineering because defects can tune π-electronic structures and control molecular assemblies. The synergistic control of the synthesis and assembly of nanographenes by embedding the topological defects to afford two-dimensional (2D) crystals on surfaces is still a great challenge. By in-situ embedding ladder bipyrazinylene (LBPy) into acene, the narrowest nanographene with zigzag edges, we have achieved the precise preparation of 2D nonbenzenoid heteroacene crystals on Au(111). Through intramolecular electrocyclization of o-diisocyanides and Au adatom-directed [2+2] cycloaddition, the nonbenzenoid heteroacene products are produced with high chemoselectivity, and lead to the molecular 2D assembly via LBPy-derived interlocking hydrogen bonds. Using bond-resolved scanning tunneling microscopy, we determined the atomic structures of the nonbenzenoid heteroacene product and diverse organometallic intermediates. The tunneling spectroscopy measurements revealed the electronic structure of the nonbenzenoid heteroacene, which is supported by density functional theory (DFT) calculations. The observed distinct organometallic intermediates during progression annealing combined with DFT calculations demonstrated that LBPy formation proceeds via electrocyclization of o-diisocyanides, trapping of heteroarynes by Au adatoms, and stepwise elimination of Au adatoms.

Quantum Phase Transition in Magnetic Nanographenes on a Lead Superconductor.

Quantum spins, also known as spin operators that preserve SU(2) symmetry, lack a specific orientation in space and are hypothesized to display unique interactions with superconductivity. However, spin-orbit coupling and crystal field typically cause a significant magnetic anisotropy in d/f shell spins on surfaces. Here, we fabricate atomically precise S = 1/2 magnetic nanographenes on Pb(111) through engineering sublattice imbalance in the graphene honeycomb lattice. Through tuning the magnetic exchange strength between the unpaired spin and Cooper pairs, a quantum phase transition from the singlet to the doublet state has been observed, consistent with the quantum spin models. From our calculations, the particle-hole asymmetry is induced by the Coulomb scattering potential and gives a transition point about kBTk ≈ 1.6Δ. Our work demonstrates that delocalized π electron magnetism hosts highly tunable magnetic bound states, which can be further developed to study the Majorana bound states and other rich quantum phases of low-dimensional quantum spins on superconductors.

Two-Dimensional Crystal Transition from Radialene to Cumulene on Ag(111) via Retro-[2 + 1] Cycloaddition.

Two-dimensional (2D) crystal-to-crystal transition is an important method in crystal engineering because of its ability to directly create diverse crystal materials from one crystal. However, steering a 2D single-layer crystal-to-crystal transition on surfaces with high chemo- and stereoselectivity under ultra-high vacuum conditions is a great challenge because the transition is a complex dynamic process. Here, we report a highly chemoselective 2D crystal transition from radialene to cumulene with retention of stereoselectivity on Ag(111) via retro-[2 + 1] cycloaddition of three-membered carbon rings and directly visualize the transition process involving a stepwise epitaxial growth mechanism by the combination of scanning tunneling microscopy and non-contact atomic force microscopy. Using progression annealing, we found that isocyanides on Ag(111) at a low annealing temperature underwent sequential [1 + 1 + 1] cycloaddition and enantioselective molecular recognition based on C-H···Cl hydrogen bonding interactions to form 2D triaza[3]radialene crystals. In contrast, a higher annealing temperature induced the transformation of triaza[3]radialenes to generate trans-diaza[3]cumulenes, which were further assembled into 2D cumulene-based crystals through twofold N-Ag-N coordination and C-H···Cl hydrogen bonding interactions. By combining the observed distinct transient intermediates and density functional theory calculations, we demonstrate that the retro-[2 + 1] cycloaddition reaction proceeds via the ring opening of a three-membered carbon ring, sequential dechlorination/hydrogen passivation, and deisocyanation. Our findings provide new insights into the growth mechanism and dynamics of 2D crystals and have implications for controllable crystal engineering.

On-Surface Cross-Coupling Reactions.

On-surface synthesis, as a bottom-up synthetic method, has been proven to be a powerful tool for atomically precise fabrication of low-dimensional carbon nanomaterials over the past 15 years. This method relies on covalent coupling reactions that occur on solid substrates such as metal or metal oxide surfaces under ultra-high-vacuum conditions, and the achievements with this method have greatly enriched fundamental science and technology. However, due to the complicated reactivity of organic groups, distinct diffusion of reactants and intermediates, and irreversibility of covalent bonds, achieving the high selectivity of covalent coupling reactions on surfaces remains a great challenge. As a result, only a few on-surface covalent coupling reactions, mainly involving dehalogenation and dehydrogenation homocoupling, are frequently used in the synthesis of low-dimensional carbon nanosystems. In this Perspective, we focus on the development and synthetic applications of on-surface cross-coupling reactions, mainly Ullmann, Sonogashira, Heck, and divergent cross-coupling reactions.

Collective Quantum Magnetism in Nitrogen-Doped Nanographenes.

The emergence of quantum magnetism in nanographenes provides ample opportunities to fabricate purely organic devices for spintronics and quantum information. Although heteroatom doping is a viable way to engineer the electronic properties of nanographenes, the synthesis of doped nanographenes with collective quantum magnetism remains elusive. Here, a set of nitrogen-doped nanographenes (N-NGs) with atomic precision are fabricated on Au(111) through a combination of imidazole [2+2+2]-cyclotrimerization and cyclodehydrogenation reactions. High-resolution scanning probe microscopy measurements reveal the presence of collective quantum magnetism for nanographenes with three radicals, with spectroscopic features which cannot be captured by mean-field density functional theory calculations but can be well reproduced by Heisenberg spin model calculations. In addition, the mechanism of magnetic exchange interaction of N-NGs has been revealed and compared with their counterparts with pure hydrocarbons. Our findings demonstrate the bottom-up synthesis of atomically precise N-NGs which can be utilized to fabricate low-dimensional extended graphene nanostructures for realizing ordered quantum phases.

Synthesis of Dendronized Polymers on the Au(111) Surface.

Dendronized polymers (DPs) consist of a linear polymeric backbone with dendritic side chains. Fine-tuning of the functional groups in the side chains enriches the structural versatility of the DPs and imparts a variety of novel physical properties. Herein, the first on-surface synthesis of DPs is achieved via the postfunctionalization of polymers on Au(111), in which the surface-confinement-induced planar conformation and chiral configurations were unambiguously characterized. While the dendronized monomer was synthesized in situ on Au(111), the subsequent polymerization afforded only short, cross-linked DP chains owing to multiple side reactions. The postfunctionalization approach selectively produced brominated polyphenylene backbone moieties by the deiodination polymerization of 4-bromo-4″-iodo-5'-(4-iodophenyl)-1,1':3',1″-terphenyl on Au(111), which smoothly underwent divergent cross-coupling reactions with two different isocyanides to form two types of DPs as individual long chains.

On-Surface Synthesis of [3]Radialenes via [1+1+1] Cycloaddition.

[3]Radialenes are the smallest carbocyclic structures with unusual topologies and cross-conjugated π-electronic structures. Here, we report a novel [1+1+1] cycloaddition reaction for the synthesis of aza[3]radialenes on the Ag(111) surface, where the steric hindrance of the chlorine substituents guides the selective and orientational assembling of the isocyanide precursors. By combining scanning tunneling microscopy, non-contact atomic force microscopy, and time-of-flight secondary ion mass spectrometry, we determined the atomic structure of the produced aza[3]radialenes. Furthermore, two reaction pathways including synergistic and stepwise are proposed based on density functional theory calculations, which reveal the role of the chlorine substituents in the activation of the isocyano groups via electrostatic interaction.

Direct Access to Bridged Polycyclic Skeletons by Merging Oxidative C-H Annulation and Cascade [4 + 2] Cycloaddition.

We report a step-economic strategy for the direct synthesis of bridged polycyclic skeletons by merging oxidative C-H annulation and cascade cycloaddition. In the protocol, spiro[cyclopentane-1,3'-indoline]-2,4-dien-2'-ones were first synthesized by oxidative C-H annulation of ethylideneoxindoles with alkynes. Subsequent cascade [4 + 2] cycloaddition with dienophiles gave the bridged bicyclo[2.2.1]quinolin-2(1H)-ones and enabled the one-pot construction of two quaternary carbon centers and three C-C bonds. Mechanistic investigations of the latter suggest a cascade ring-opening, 1,5-sigmatropic rearrangement, and [4 + 2] cycloaddition process.

Steering Metal-Organic Network Structures through Conformations and Configurations on Surfaces.

Molecular adsorption conformations and arrangement configurations on surfaces are important structural aspects of surface stereochemistry, but their roles in steering the structures of metal-organic networks (MONs) remain vague and unexplored. In this study, we constructed MONs by the coordination self-assembly of isocyanides on Cu(111) and Ag(111) surfaces and demonstrated that the MON structures can be steered by surface stereochemistry, including the adsorption conformations of the isocyanide molecules and the arrangement configurations of the coordination nodes and subunits. The coordination self-assembly of 1,4-phenylene diisocyanobenzene afforded a honeycomb MON consisting of 3-fold (isocyano)3-Cu motifs on a Cu(111) surface. In contrast, geometrically different chevron-shaped 1,3-phenylene diisocyanobenzene (m-DICB) failed to generate a MON, which is ascribable to its standing conformation on the Cu(111) surface. However, m-DICB was adsorbed in a flat conformation on a Ag(111) surface, which has a larger lattice constant than a Cu(111) surface, and smoothly underwent coordination self-assembly to form a MON consisting of (isocyano)3-Ag motifs. Interestingly, only C3-Ag nodes with heterotactic configurations could grow into larger subunits; those subunits with heterotactic configurations further grew into Sierpinski triangle fractals (up to fourth order), while subunits with homotactic configurations afforded a triangular MON.

Mesenchymal stem cell therapy in pulmonary fibrosis: a meta-analysis of preclinical studies.

BACKGROUND: Pulmonary fibrosis (PF) is a devastating disease characterized by remodeling of lung architecture and abnormal deposition of fibroblasts in parenchymal tissue and ultimately results in respiratory failure and death. Preclinical studies suggest that mesenchymal stem cell (MSC) administration may be a safe and promising option in treating PF. The objective of our meta-analysis is to assess the efficacy of MSC therapy in preclinical models of PF. METHODS: We performed a comprehensive literature search in PubMed, EMBASE, Web of Science, and Cochrane Library databases from inception to March 17, 2021. Studies that assessed the efficacy of MSC therapy to animals with PF were included. The SYRCLE bias risk tool was employed to evaluate the bias of included studies. The primary outcomes included survival rate and pulmonary fibrosis scores. Meta-analysis was conducted via Cochrane Collaboration Review Manager (version 5.4) and Stata 14.0 statistical software. RESULTS: A total of 1120 articles were reviewed, of which 24 articles met inclusion criteria. Of these, 12 studies evaluated the survival rate and 20 studies evaluated pulmonary fibrosis scores. Compared to the control group, MSC therapy was associated with an improvement in survival rate (odds ratios (OR) 3.10, 95% confidence interval (CI) 2.06 to 4.67, P < 0.001, I2 = 0%) and a significant reduction in pulmonary fibrosis scores (weighted mean difference (WMD) 2.05, 95% CI -2.58 to -1.51, P < 0.001, I2 = 90%). CONCLUSIONS: MSC therapy is a safe and effective method that can significantly improve the survival and pulmonary fibrosis of PF animals. These results provide an important basis for future translational clinical studies.

Ladder Phenylenes Synthesized on Au(111) Surface via Selective [2+2] Cycloaddition.

Ladder phenylenes (LPs) composed of alternating fused benzene and cyclobutadiene rings have been synthesized in solution with a maximum length no longer than five units. Longer polymeric LPs have not been obtained so far because of their poor stability and insolubility. Here, we report the synthesis of linear LP chains on the Au(111) surface via dehalogenative [2+2] cycloaddition, in which the steric hindrance of the methyl groups in the 1,2,4,5-tetrabromo-3,6-dimethylbenzene precursor improves the chemoselectivity as well as the orientation orderliness. By combining scanning tunneling microscopy and noncontact atomic force microscopy, we determined the atomic structure and the electronic properties of the LP chains on the metallic substrate and NaCl/Au(111). The tunneling spectroscopy measurements revealed the charged state of chains on the NaCl layer, and this finding is supported by density functional theory calculations, which predict an indirect bandgap and antiferromagnetism in the polymeric LP chains.

Pd-Catalyzed Direct C-H Activation for the C5-Olefination of Methyleneindolinones.

The direct C-H activation without directing groups can realize the para-selectivity, which is a powerful and concise approach for functionalization of arenes. Utilizing the strategy, a C5-olefination of methyleneindolinones has been successfully developed by palladium-catalyzed direct C-H activation, which provides an expeditious access to 5-vinylindolin-2-ones with high regioselectivity. The protocol is distinguished by a mild reaction system avoiding ligand and high temperature. The kinetic isotope experiments indicate that the C-H bond cleavage is the rate-limiting step.

Post-Functionalization of Supramolecular Polymers on Surface and the Chiral Assembly-Induced Enantioselective Reaction.

Although post-functionalization is extensively used to introduce diverse functional groups into supramolecular polymers (SPs) in solution, post-functionalization of SPs on surfaces still remains unexplored. Here we achieved the on-surface post-functionalization of two SPs derived from 5,10,15-tri-(4-pyridyl)-20-bromophenyl porphyrin (Br-TPyP) via cross-coupling reactions on Au(111). The ladder-shaped, Cu-coordinated SPs preformed from Br-TPyP were functionalized through Heck reaction with 4-vinyl-1,1'-biphenyl. In the absence of Cu, Br-TPyP formed chiral SPs as two enantiomers via self-assembly, which were functionalized via divergent cross-coupling reaction with 4-isocyano-1,1'-biphenyl (ICBP). Surprisingly, this reaction was discovered as an enantioselective on-surface reaction induced by the chirality of SPs. Mechanistic analysis and DFT calculations indicated that after debromination of Br-TPyP and the first addition of ICBP, only one attack direction of ICBP to the chiral SP intermediate is permissive in the second addition step due to the steric hindrance, which guaranteed the high enantioselectivity of the reaction.

Dihydroartemisinin Inhibits the Proliferation, Colony Formation and Induces Ferroptosis of Lung Cancer Cells by Inhibiting PRIM2/SLC7A11 Axis.

OBJECTIVE: Lung cancer is the first leading cause of cancer-related deaths both worldwide and in China and threatens human health and quality of life. New drugs and therapeutic methods are urgently needed. Our study evaluated the roles of dihydroartemisinin (DHA) in lung cancer and further explored its underlying mechanisms. METHODS: CCK-8, colony formation and trypan blue exclusion assays were used to detect the cell viability, colony formation ability and cell death. qRT-PCR and Western blotting assays were applied to analyze the expressions of key molecules. RESULTS: DHA inhibited the proliferation and colony formation abilities and enhanced the cell death and induced ferroptosis of lung NCI-H23 and XWLC-05 cancer cells. DHA reduced PRIM2 expression and silencing PRIM2 mimicked the inhibitory roles on proliferation and colony formation and promotive roles on cell death and ferroptosis of DHA in lung NCI-H23 and XWLC-05 cancer cells. We further found that DHA treatment and loss of PRIM2 reduced the GSH level and increased the cellular lipid ROS and mitochondrial MDA levels, and further downregulated the expressions of SLC7A11 and ß-catenin in lung cancer cells, respectively. Exogenetic overexpression of PRIM2 recovered the inhibitory effects of DHA on proliferation and colony formation in lung NCI-H23 cancer cells, meanwhile loss of PRIM2 sensitizes NCI-H23 cells to DHA therapy. In vivo experiment further showed that DHA treatment significantly suppressed the tumor growth and downregulated PRIM2 and SLC7A11. CONCLUSION: Our study suggested that DHA inhibited the proliferation, colony formation and enhanced cell death and induced ferroptosis of lung cancer cells by inactivating PRIM2/SLC7A11 axis. Loss of PRIM2 induced ferroptosis might developed to be a novel therapeutic method in lung cancer therapy.

Tuning Vinylethylene Carbonates into [4 + 2] Cycloaddition via Silylation and Vinylogous Peterson Elimination.

Vinylethylene carbonates have been extensively used to trigger [3 + n] or [5 + n] cycloaddition via the formation of η3-allylic intermediates, while the important [4 + n] cycloaddition has not been explored yet. Here, we report a new strategy to convert vinylethylene carbonates into 4-(trimethylsilyl)but-2-en-1-ols, which can readily undergo [4 + 2] cycloaddition by in situ formation of 1,3-dienes. This novel reaction involves [PdII]-catalyzed decarboxylative silylation, [FeIII]-catalyzed vinylogous Peterson elimination, and subsequent [4 + 2] cycloaddition to afford a multisubstituted cyclohexa-1,4-diene skeleton.

Construction of multiple bonds via a domino reaction of trifluoroacetimidoyl nitriles with in situ generated bis-nucleophiles.

A transition-metal-free double addition/double rearrangement domino reaction affording CF3-substituted pyrimidines was developed, which enables the one-pot construction of five new bonds, namely three C-C bonds and two C-N bonds. The keys to achieve this highly efficient reaction include the delicate design of the bis-nucleophiles in situ generated from the dimerization of alkyl nitriles and the use of trifluoroacetimidoyl nitriles containing C[double bond, length as m-dash]N, C[triple bond, length as m-dash]N, and CF3 groups as the reactant. The mechanistic studies by the experiments and DFT calculations reveal that the transformation involves two addition and two unprecedented rearrangement processes.

On-surface synthesis of planar dendrimers via divergent cross-coupling reaction.

Dendrimers are homostructural and highly branched macromolecules with unique dendritic effects and extensive use in multidisciplinary fields. Although thousands of dendrimers have been synthesized in solution, the on-surface synthetic protocol for planar dendrimers has never been explored, limiting the elucidation of the mechanism of dendritic effects at the single-molecule level. Herein, we describe an on-surface synthetic approach to planar dendrimers, in which exogenous palladium is used as a catalyst to address the divergent cross-coupling of aryl bromides with isocyanides. This reaction enables one aryl bromide to react with two isocyanides in sequential steps to generate the divergently grown product composed of a core and two branches with high selectivity and reactivity. Then, a dendron with four branches and dendrimers with eight or twelve branches in the outermost shell are synthesized on Au(111). This work opens the door for the on-surface synthesis of various planar dendrimers and relevant macromolecular systems.

Direct access to substituted benzo[b]carbazoles through cascade annulation of 2-vinylbenzaldehydes with indoles.

A highly efficient palladium-catalyzed cascade annulation of 2-vinylbenzaldehydes with indoles has been achieved to afford 6-(3-indolyl)benzo[b]carbazoles under mild conditions in good yield and with excellent regioselectivity. Mechanistic investigations reveal that the reaction proceeds via double addition of indoles, unexpected intramolecular 1,4-aryl and 1,2-hydrogen migrations, and oxidative aromatization.

On-surface reactions of aryl chloride and porphyrin macrocycles via merging two reactive sites into a single precursor.

The reaction of aryl chloride and porphyrin macrocycles, which are merged into a single precursor, has been achieved on Cu(111). Scanning tunneling microscopy analysis of the oligomer products showed that the adjacent porphyrin moieties linked mainly by the phenyl group with the porphyrin macrocycle.