Synergizing Steric Hindrance and Stacking Interactions to Facilitate the Controlled Assembly of Multiple 41 Metalla-Knots and Pseudo-Solomon Links.

In this work, a noncoplanar terphenyl served as building block to synthesize a novel 3,3'-substituted bipyridyl ligand (L1) which further reacted with binuclear half-sandwich units A/B, giving rise to two aesthetical 41 metalla-knots in high yields via coordination-driven self-assembly strategy. Furthermore, given the inherent compactness of the 41 metalla-knots, it creates favorable conditions for the emergence of steric repulsion. We focused on progressively introducing nitrogen atoms featuring lone pair electrons (LPEs) into ligand L1 to manipulate the balance of H···H/LPEs···LPEs steric repulsion during the assembly process, ultimately achieving controlled assembly from 41 metalla-knots to the pseudo-Solomon link and then to molecular tweezer-like assembly facilitated by stacking interactions. All the assemblies were well characterized by solution-state NMR techniques, ESI-TOF/MS, and single-crystal X-ray diffraction. The evolutionary process of topological architectures is equivalent to visualizing the synergistic effect of steric hindrance and stacking interactions on structural assembly, providing a new avenue for achieving the controlled synthesis of different topologies.

Formation and reactivity of a unique M⋯C-H interaction stabilized by carborane cages.

Broadening carborane applications has consistently been the goal of chemists in this field. Herein, compared to alkyl or aryl groups, a carborane cage demonstrates an advantage in stabilizing a unique bonding interaction: M⋯C-H interaction. Experimental results and theoretical calculations have revealed the characteristic of this two-center, two-electron bonding interaction, in which the carbon atom in the arene ring provides two electrons to the metal center. The reduced aromaticity of the benzene moiety, long distance between the metal and carbon atom in arene, and the upfield shift of the signal of M⋯C-H in the nuclear magnetic resonance spectrum distinguished this interaction from metal⋯C π interaction and metal-C(H) σ bonds. Control experiments demonstrate the unique electronic effects of carborane in stabilizing the M⋯C-H bonding interaction in organometallic chemistry. Furthermore, the M⋯C-H interaction can convert into C-H bond metallization under acidic conditions or via treatment with t-butyl isocyanide. These findings deepen our understanding regarding the interactions between metal centers and carbon atoms and provide new opportunities for the use of carboranes.

The codriven assembly of molecular metalla-links ([Formula: see text], [Formula: see text]) and metalla-knots ([Formula: see text], [Formula: see text]) via coordination and noncovalent interactions.

Although mechanically interlocked molecules (MIMs) display unique properties and functions associated with their intricate connectivity, limited assembly strategies are available for their synthesis. Herein, we presented a synergistic assembly strategy based on coordination and noncovalent interactions (π-π stacking and CH⋯π interactions) to selectively synthesize molecular closed three-link chains ([Formula: see text] links), highly entangled figure-eight knots ([Formula: see text] knots), trefoil knot ([Formula: see text] knot), and Borromean ring ([Formula: see text] link). [Formula: see text] links can be created by the strategic assembly of nonlinear multicurved ligands incorporating a furan or phenyl group with the long binuclear half-sandwich organometallic Cp*RhIII (Cp* = η5-pentamethylcyclopentadienyl) clip. However, utilizing much shorter binuclear Cp*RhIII units for union with the 2,6-naphthyl-containing ligand led to a [Formula: see text] knot because of the increased π-π stacking interactions between four consecutive stacked layers and CH⋯π interactions. Weakening such π-π stacking interactions resulted in a [Formula: see text] knot. The universality of this synergistic assembly strategy for building [Formula: see text] knots was verified by utilizing a 1,5-naphthyl-containing ligand. Quantitative conversion between the [Formula: see text] knot and the simple macrocycle species was accomplished by adjusting the concentrations monitored by NMR spectroscopy and electrospray ionization mass spectrometry (ESI-MS). Furthermore, increasing the stiff π-conjugated area of the binuclear unit afforded molecular Borromean ring, and this topology is a topological isomer of the [Formula: see text] link. These artificial metalla-links and metalla-knots were confirmed by single-crystal X-ray diffraction, NMR and ESI-MS. The results offer a potent strategy for building higher-order MIMs and emphasize the critical role that noncovalent interactions play in creating sophisticated topologies.

The Topological Transformation of Trefoil Knots to Solomon Links via Diels-Alder Click Reaction.

The quest for more efficient, user-friendly, and less wasteful topological transformations remains a significant challenge in the realm of postassembly modifications. In this article, high yields of two molecular trefoil knots (Rh-1, Ir-1) were obtained using ligand 3,6-bis(3-(pyridin-4-yl)phenyl)-1,2,4,5-tetrazine (L1) with reactive tetrazine units and binuclear half-sandwich organometallic units [Cp*2M2(µ-TPPHZ)(OTf)2](OTf)2 (Rh-B, M = RhIII; Ir-B, M = IrIII). 2,5-Norbornadiene was used as an inducer of the Diels-Alder click reaction to modulate rapidly and efficiently the transformation of Trefoil knots to Solomon links. However, the key to achieving this topological structural change is the subtle increase in site steric of the pyridazine fragments (L2), which allows the molecular structures to spread and bend in three-dimensional space, as confirmed by single-crystal X-ray diffraction, ESI-TOF/MS, elementary analysis and detailed solution-state NMR techniques.

Selective B(3)-H Activation Affording Multinuclear Ir(III) Complexes with (o-Carboranyl)dithioester Ligands.

A method was developed to link two or three o-carborane moieties to form a series of carboranyl dithioester bridging ligands via in situ substitution of haloalkanes by tetraphenylphosphonium carboranyldithiocarboxylates. Based on these ligands, direct B-H activation without the assistance of Ag(I) and alkali was successfully achieved with half-sandwich Ir(III) substrate [Cp*IrCl2]2 to yield corresponding bimetallic or trimetallic complexes. Single crystal structure analyses of the B-H activated complexes and corresponding SnCl2-inserted derivatives confirm the selective B(3)-H activation in these complexes.

Efficient and Selective Construction of 41 2 Metalla-links Using Weak C-H⋠⋠⋠Halogen Interactions.

Through a coordination-driven self-assembly method, four 4 1 2 ${4_1^2 }$ metalla-links and one tetranuclear monocycle were constructed with high selectivity and yield by adjusting the substituent species of the building blocks, as evidenced using X-ray crystallographic analysis, electrospray ionization-time-of-flight/mass spectrometry (ESI-TOF/MS), elemental analysis and detailed solution-state nuclear magnetic resonance (NMR) spectroscopy. Based on X-ray crystallographic analysis and independent gradient model analysis, a significant factor leading to the formation of 4 1 2 ${4_1^2 }$ metalla-links was the introduction of F, Cl, Br and I atoms, which generated additional weak C-H⋅⋅⋅X (X=F, Cl, Br and I) interactions. Furthermore, the dynamic conversion of 4 1 2 ${4_1^2 }$ metalla-links to monocyclic rings in methanol solution was systematically investigated using quantitative 1H NMR techniques.

Regulatory mechanism of FCGR2A in macrophage polarization and its effects on intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) poses a significant health burden, necessitating a deeper understanding of its molecular underpinnings. Transcriptomic analysis reveals 485 differentially expressed genes (DEGs) associated with IDD, underscoring the importance of immune regulation. Weighted gene co-expression network analysis (WGCNA) identifies a yellow module strongly correlated with IDD, intersecting with 197 DEGs. Protein-protein interaction (PPI) analysis identifies ITGAX, MMP9 and FCGR2A as hub genes, predominantly expressed in macrophages. Functional validation through in vitro and in vivo experiments demonstrates the pivotal role of FCGR2A in macrophage polarization and IDD progression. Mechanistically, FCGR2A knockdown suppresses M1 macrophage polarization and NF-κB phosphorylation while enhancing M2 polarization and STAT3 activation, leading to ameliorated IDD in animal models. This study sheds light on the regulatory function of FCGR2A in macrophage polarization, offering novel insights for IDD intervention strategies. KEY POINTS: This study unveils the role of FCGR2A in intervertebral disc (IVD) degeneration (IDD). FCGR2A knockdown mitigates IDD in cellular and animal models. Single-cell RNA-sequencing uncovers diverse macrophage subpopulations in degenerated IVDs. This study reveals the molecular mechanism of FCGR2A in regulating macrophage polarization. This study confirms the role of the NF-κB/STAT3 pathway in regulating macrophage polarization in IDD.

Selective Construction and Structural Transformation of Homogeneous Linear Metalla[4]catenane and Metalla[2]catenane Assemblies.

Although the synthesis of mechanically interlocked molecules has been extensively researched, selectively constructing homogeneous linear [4]catenanes remains a formidable challenge. Here, we selectively constructed a homogeneous linear metalla[4]catenane in a one-step process through the coordination-driven self-assembly of a bidentate benzothiadiazole derivative ligand and a binuclear half-sandwich rhodium precursor. The formation of metalla[4]catenanes was facilitated by cooperative interactions between strong sandwich-type π-π stacking and non-classical hydrogen bonds between the components. Moreover, by modulating the aromatic substituents on the binuclear precursor, two homogeneous metalla[2]catenanes were obtained. The molecular structures of these metallacatenanes were unambiguously characterized by single-crystal X-ray diffraction analysis. Additionally, reversible structural transformation between metal-catenanes and the corresponding metallarectangles could be achieved by altering their concentration, as confirmed by mass spectrometry and NMR spectroscopy studies.

GAS5, a long noncoding RNA, contributes to annulus fibroblast osteogenic differentiation and apoptosis in intervertebral disk degeneration via the miR-221-3p/SOX11 axis.

miR-221-3p has been reported to attenuate the osteogenic differentiation of annulus fibrosus cells (AFs), which has been implicated in intervertebral disk degeneration (IVDD) development. This study aimed to elucidate miR-221-3p's role in osteogenic differentiation and apoptosis of AFs in an IVDD model. After successfully establishing an IVDD rat model by annulus fibrosus needle puncture, AFs were isolated. Bioinformatics, dual-luciferase reporter, and AGO2-RNA immunoprecipitation (RIP) assays predicted and confirmed the potential miR-221-3p lncRNA and gene target. Functional analyses were performed after AF transfection to explore the roles of the identified lncRNA and gene. Western blotting, Alkaline phosphatase (ALP), and Alizarin red and TUNEL staining were performed to investigate AF apoptosis and osteogenic differentiation with different transfections. Compared with AFs isolated from sham rats, IVDD-isolated Afs exhibited stronger osteogenic potential and higher apoptosis rates accompanied by miR-221-3p downregulation. The growth arrest-specific transcript 5 (GAS5) was identified as miR-221-3p's target lncRNA, which was highly expressed in IVDD. GAS5 overexpression facilitated AF apoptosis and osteogenic differentiation, whereas silencing GAS5 had the opposite effect. SRY box-related11 (SOX11) was identified as a downstream miR-221-3p target gene in IVDD. GASS silencing-induced suppression of AF apoptosis and osteogenic differentiation could be reversed by SOX11 overexpression. Our findings uncovered a lncRNA GAS5/miR-221-3p/SOX11 axis in Afs under IVDD, which may help implement novel IVDD therapeutic strategies.

Controllable Topological Transformations of 818 Molecular Metalla-knots by Oxidation of Thiazole-Based Ligands.

By exploiting coordination-driven self-assembly, high yields of two 818 molecular metalla-knots could be obtained using a thiazole-moiety-containing asymmetric dipyridyl ligand 2-(pyridin-4-yl)-5-(pyridin-4-ylethynyl)benzo[d]thiazole (L1 ), as confirmed using X-ray crystallographic analysis, electrospray ionization-time-of-flight/mass spectrometry (ESI-TOF/MS), and detailed liquid-state nuclear magnetic resonance (NMR) spectroscopy. To modulate the self-assembled structures, m-chloroperbenzoic acid (m-CPBA) was utilized to oxidize thiazole-based ligand L1 to N-thiazole-oxide-based ligand 2-(pyridin-4-yl)-5-(pyridin-4-ylethynyl)benzo[d]thiazole 3-oxide (L2 ), which enabled the selective construction of the corresponding tetranuclear macrocycles. Notably, two molecular metalla-knots could be topologically transformed from 818 knots to simple monocycles because the L1 alkyne bond was inert toward m-CPBA, as confirmed by liquid-state NMR spectroscopy, ESI-TOF/MS, and elemental analysis.

Supramolecular Architectures Bearing Half-Sandwich Iridium- or Rhodium-Based Carboranes: Design, Synthesis, and Applications.

The utilization of carboranes in supramolecular chemistry has attracted considerable attention. The unique spatial configuration and weak interaction forces of carboranes can help to explore the properties of supramolecular complexes, particularly via host-guest chemistry. Additionally, certain difficulties encountered in carborane development─such as controlled B-H bond activation─can be overcome by judiciously selecting metal centers and their adjacent ligands. However, few studies are being conducted in this nascent research area. With advances in this field, novel carborane-based supramolecular complexes will likely be prepared, structurally characterized, and intrinsically investigated. To expedite these efforts, we present major findings from recent studies, including π-π interactions, host-guest associations, and steric effects, which have been leveraged to implement a regioselective process for activating B(2,9)-, B(2,8)-, and B(2,7)-H bonds of para-carboranes and B(4,7)-H bonds of ortho-carboranes. Future studies should clarify the unique weak interactions of carboranes and their potential for enhancing the utility of supramolecular complexes. Although carboranes exhibit several unique weak interactions (such as dihydrogen-bond [Bδ+-Hδ-···Hδ+-Cδ-], Bδ+-Hδ-···M+, and Bδ+-Hδ-···π interactions), the manner in which they can be utilized remains unclear. Supramolecular complexes, particularly those based on host-guest chemistry, can be utilized as a platform for demonstrating potential applications of these weak interactions. Owing to the importance of alkane separation, applications related to the recognition and separation of alkane isomers via dihydrogen-bond interactions are primarily summarized. Advances in the research of unique weak interactions in carboranes will certainly lead to more possibilities for supramolecular chemistry.

"Cage Walking" Synthetic Strategy for Unusual Unsymmetrical Supramolecular Cages.

Developing novel assembly methods for supramolecular compounds has long been a research challenge. Herein, we describe how to integrate the B-C coupling reaction and "cage walking" process into coordination self-assembly to construct supramolecular cages. In this strategy, dipyridine linkers containing alkynes react with the metallized carborane backbone through B-C coupling and then "cage walking" resulting in metallacages. However, dipyridine linkers without alkynyl groups can form only metallacycles. We can regulate the size of metallacages based on the length of the alkynyl bipyridine linkers. When tridentate-pyridine linkers participate in this reaction, a new type of ravel is formed. The metallization of carboranes, the B-C coupling reaction, and especially the "cage walking" process of carborane cages play a vital role in this reaction. This work provides a promising principle for the synthesis of metallacages and opens up a novel opportunity in the supramolecular field.

Selective Synthesis and Structural Transformation of a 4-Ravel Containing Four Crossings and Featuring Cp*Rh/Ir Fragments.

Intricately interwoven topologies are continually being synthesized and are ultimately equally versatile and significant at the nanoscale level; however, reports concerning ravel structures, which are highly entwined new topological species, are extremely rare and fraught with tremendous synthesis challenges. To solve the synthesis problem, a tetrapodontic pyridine ligand L1 with two types of olefinic bond units and two Cp*M-based building blocks (E1, M=Rh; E2, M=Ir) featuring large conjugated planes was prepared to perform the self-assembly. Two unprecedented [5+10] icosanuclear molecular 4-ravels containing four crossings were obtained by parallel-displaced π⋅⋅⋅π interactions in a single-step strategy. Remarkably, reversible structural transformations between the 4-ravel and the corresponding metallocage could be realized by concentration changes and solvent- and guest-induced effects. X-ray crystallographic data and NMR spectroscopy provide full confirmation of these phenomena.

Selective Construction of Molecular Borromean Rings and [2]Catenane Utilizing Ether Bipyridyl Ligands.

A series of Cp* Rh-based discrete architectures was constructed by selecting four ether bipyridyl ligands and three half-sandwich rhodium(III) bimetallic construction units, respectively. This study demonstrates a strategy for making the transition from a binuclear D-shaped ring to a tetranuclear [2]catenane by adjusting the length of bipyridyl ligands. In addition, changing the position on the naphthyl group of the bipyridyl ligand from 2,6- to 1,5-position substitution can realize the selective synthesis of [2]catenane and Borromean rings under similar conditions. The above-mentioned constructions have been determined via X-ray crystallographic analysis, detailed NMR techniques, electrospray ionization-time-of-flight/mass spectrometry analysis, and elemental analysis.

Metal-Backboned Polymers with Well-Defined Lengths.

Constructing the backbones of polymers with metal atoms is an attractive strategy to develop new functional polymeric materials, but it has yet to be studied due to synthetic challenges. Here, metal atoms are interconnected as the backbones of polymers to yield metal-backboned polymers (MBPs). Rational design of multidentate ligands synthesized via an efficient iterative approach leads to the successful construction of a series of nickel-backboned polymers (NBPs) with well-defined lengths and up to 21 nickel atoms, whose structures are systematically confirmed. These NBPs exhibit strong and length-depended absorption with narrow band gaps, offering promising applications in optoelectronic devices and semiconductors. We also demonstrate the high thermal stability and solution processsability of such nickel-backboned polymers. Our results represent a new opportunity to design and synthesize a variety of new metal-backboned polymers for promising applications in the future.

Organometallic Borromean Rings and [2]Catenanes Featuring Di-NHC Ligands.

We report herein a series of organometallic Borromean rings (BRs) and [2]catenanes prepared from benzobiscarbene ligands. The reaction of dinickel complexes of the benzobiscarbenes 1 a-1 c with a thiazolothiazole bridged bipyridyl ligand L2 led by self-assembly to a series of organometallic BRs. Solvophobic effects played a crucial role in the formation and stability of the interlocked species. The stability of BRs is related to the N-alkyl substituents at the precursors 1 a-1 c, where longer alkyl substitutes improve stability and inter-ring interactions. Solvophobic effects are also important for the stability of [2]catenanes prepared from 1 a-1 c and a flexible bipyridyl ligand L3 . In solution, an equilibrium between the [2]catenanes and their macrocyclic building blocks was observed. High proportions of [2]catenanes were obtained in concentrated solutions or polar solvents. The proportion of [2]catenanes in solution could be further enhanced by lengthening of the N-alkyl substitutes.

Cation-Templated Assembly of 613 and 623 Metalla-Links.

Facilitated by multiple stacking interactions between components, two kinds of metalla-links containing molecular Borromean rings (623 links) and head-to-tail cyclic [3]catenanes (613 links), as isomers, were constructed in high yield by introducing tri-µ-methoxyl-dinuclear complexes [(Cp*M)2(µ-OCH3)3][OTf] (M = RhIII or IrIII, Cp* = η5-pentamethylcyclopentadienyl, OTf = triflate) as unusual cationic guests during coordination-driven assembly. The topology of these intricate structures was controlled by strategically selecting two dipyridyl ligands that differ in their coordination orientations, as evidenced by X-ray crystallography and electrospray ionization-time-of-flight/mass spectrometry analysis. The behavior of the abovementioned metalla-links in solution was monitored and further studied by the detailed NMR techniques.

Stereoselective Construction of Chiral Linear [3]Catenanes and [2]Catenanes.

We have successfully constructed a chiral linear [3]catenane stereoselectively by coordination-driven self-assembly using a ditopic monodentate ligand containing l-valine residues with a binuclear half-sandwich organometallic rhodium(III) unit. Furthermore, by increasing the steric hindrance of the amino acid residues in the ligand, a chiral [2]catenane was obtained, which can be regarded as the factor catenane of the chiral linear [3]catenane from a topological viewpoint. Notably, the resulting molecular catenanes all exhibit complex coconformational mechanical helical chirality and planar chirality ascribed to the point chirality of the ligands. Linear [3]catenanes and [2]catenanes with the opposite chirality can be obtained by using ligands containing the corresponding d-amino acid residues, which have been confirmed by single-crystal X-ray diffraction, NMR, mass spectrometry, and circular dichroism spectroscopy.

Synthesis of Carborane-Backbone Metallacycles for Highly Selective Capture of n-Pentane.

The specific recognition and separation of alkanes with similar molecular structures and close boiling points face significant scientific challenges and industrial demands. Here, rectangular carborane-based metallacycles were designed to selectively encapsulate n-pentane from n-pentane, iso-pentane, and cyclo-pentane mixtures in a simple-to-operate and more energy-efficient way. Metallacycle 1, bearing 1,2-di(4-pyridyl) ethylene, can selectively separate n-pentane from these three-component mixtures with a purity of 97%. The selectivity is ascribed to the capture of the preferred guest with matching size, C-H···π interactions, and potential B-Hδ-···Hδ+-C interactions. Besides, the removal of n-pentane gives rise to original guest-free carborane-based metallacycles, which can be recycled without losing performance. Considering the variety of substituted carborane derivatives, metal ions, and organic linkers, these new carborane-based supramolecular coordination complexes (SCCs) may be broadly applicable to other challenging recognition and separation systems with good performance.

Highly selective synthesis and near-infrared photothermal conversion of metalla-Borromean ring and [2]catenane assemblies.

Although the selective synthesis of complicated supramolecular architectures has seen significant progress in recent years, the exploration of the properties of these complexes remains a fascinating challenge. Herein, a series of new supramolecular topologies, metalla[2]catenanes and Borromean ring assemblies, were constructed based on appropriate Cp*Rh building blocks and two rigid alkynyl pyridine ligands (L1, L2) via coordination-driven self-assembly. Interestingly, minor differences between the two rigid alkynyl pyridine ligands with/without organic substituents led to products with dramatically different topologies. Careful structural analysis showed that π-π stacking interactions play a crucial role in stabilizing these [2]catenanes and Borromean ring assemblies, while also promoting nonradiative transitions and triggering photothermal conversion in both the solution and the solid states. These results were showcased through comparative studies of the NIR photothermal conversion efficiencies of the Borromean ring assemblies, [2]catenanes and metallarectangles, which exhibited a wide range of photothermal conversion efficiencies (12.64-72.21%). The influence of the different Cp*Rh building blocks on the NIR photothermal conversion efficiencies of their assemblies was investigated. Good photothermal conversion properties of the assemblies were also found in the solid state. This study provides a new strategy to construct valuable half-sandwich-based NIR photothermal conversion materials while also providing promising candidates for the further development of materials science.