A prototype protein nanocage minimized from carboxysomes with gated oxygen permeability.

Protein nanocages (PNCs) in cells and viruses have inspired the development of self-assembling protein nanomaterials for various purposes. Despite the successful creation of artificial PNCs, the de novo design of PNCs with defined permeability remains challenging. Here, we report a prototype oxygen-impermeable PNC (OIPNC) assembled from the vertex protein of the ß-carboxysome shell, CcmL, with quantum dots as the template via interfacial engineering. The structure of the cage was solved at the atomic scale by combined solid-state NMR spectroscopy and cryoelectron microscopy, showing icosahedral assembly of CcmL pentamers with highly conserved interpentamer interfaces. Moreover, a gating mechanism was established by reversibly blocking the pores of the cage with molecular patches. Thus, the oxygen permeability, which was probed by an oxygen sensor inside the cage, can be completely controlled. The CcmL OIPNC represents a PNC platform for oxygen-sensitive or oxygen-responsive storage, catalysis, delivery, sensing, etc.

Syntheses of three-dimensional catenanes under kinetic control.

Although catenanes comprising two ring-shaped components can be made in large quantities by templation, the preparation of three-dimensional (3D) catenanes with cage-shaped components is still in its infancy. Here, we report the design and syntheses of two 3D catenanes by a sequence of SN2 reactions in one pot. The resulting triply mechanically interlocked molecules were fully characterized in both the solution and solid states. Mechanistic studies have revealed that a suit[3]ane, which contains a threefold symmetric cage component as the suit and a tribromide component as the body, is formed at elevated temperatures. This suit[3]ane was identified as the key reactive intermediate for the selective formation of the two 3D catenanes which do not represent thermodynamic minima. We foresee a future in which this particular synthetic strategy guides the rational design and production of mechanically interlocked molecules under kinetic control.

Nanoscale Dodecahedral and Fullerene-Type Organoboroxine and Borazine Cages from Planar Building Units.

Boroxine- and borazine-cage analogs to C20, C60, and C70 were calculated and compared in terms of structure, strain indicators, and physical properties relevant to nanoscale applications. The results show C60 and C70 type cages are less strained than the smaller congener, primarily due to minimized bending in the B-arylene-B segments. The smallest cage calculated has a diameter of 2.4 nm, which increases up to 4.9 nm by either variation of the polyhedron (C20 < C60 < C70-type cage) or organic spacer elongation between boron centers. All calculated cages are porous (apertures ranging from 0.6 to 1.9 nm). Molecular electrostatic potential and Hirshfeld population analysis revealed both nucleophilic and electrophilic sites in the interior and exterior cage surfaces. HOMO-LUMO gaps range from 3.98 to 4.89 eV and 5.10-5.18 eV for the boroxine- and borazine-cages, respectively. Our findings provide insights into the design and properties of highly porous boroxine and borazine cages for nanoscience.

HDAC9 and miR-512 Regulate CAGE-Promoted Anti-Cancer Drug Resistance and Cellular Proliferation.

Histone deacetylase 9 (HDAC9) is known to be upregulated in various cancers. Cancer-associated antigens (CAGEs) are cancer/testis antigens that play an important role in anti-cancer drug resistance. This study aimed to investigate the relationship between CAGEs and HDAC9 in relation to anti-cancer drug resistance. AGSR cells with an anti-cancer drug-resistant phenotype showed higher levels of CAGEs and HDAC9 than normal AGS cells. CAGEs regulated the expression of HDAC9 in AGS and AGSR cells. CAGEs directly regulated the expression of HDAC9. Rapamycin, an inducer of autophagy, increased HDAC9 expression in AGS, whereas chloroquine decreased HDAC9 expression in AGSR cells. The downregulation of HDAC9 decreased the autophagic flux, invasion, migration, and tumor spheroid formation potential in AGSR cells. The TargetScan analysis predicted that miR-512 was a negative regulator of HDAC9. An miR-512 mimic decreased expression levels of CAGEs and HDAC9. The miR-512 mimic also decreased the autophagic flux, invasion, migration, and tumor spheroid forming potential of AGSR cells. The culture medium of AGSR increased the expression of HDAC9 and autophagic flux in AGS. A human recombinant CAGE protein increased HDAC9 expression in AGS cells. AGSR cells displayed higher tumorigenic potential than AGS cells. Altogether, our results show that CAGE-HDAC9-miR-512 can regulate anti-cancer drug resistance, cellular proliferation, and autophagic flux. Our results can contribute to the understanding of the molecular roles of HDAC9 in anti-cancer drug resistance.

Ab initio investigation of excited state charge transfer pathways in differently capped bithiophene cages.

The electronic excitations of conformationally constrained bithiophene cage systems as previously investigated by Lewis et al. (J. Am. Chem. Soc. 143, 18548 (2021)) are revisited, employing the correlated ab initio Scaled Opposite-Spin Algebraic Diagrammatic Construction Second Order electronic structure method. Quantitative descriptors are determined to assess the extent of charge transfer between the bithiophene moieties and the capping domains, represented by either phenyl or triazine groups. The investigation substantiates intrinsic differences in the photophysical behavior of these two structural variants and reveals the presence of lower-energy excited states characterized by noteworthy charge transfer contributions in the triazine cage system. The manifestation of this charge transfer character is discernible even at the Franck-Condon geometry, persisting throughout the relaxation of the excited state. By examining isolated monomer building blocks, we confirm the existence of analogous charge transfer contributions in their excitations. Employing this methodological approach facilitates the prospective identification of potential wall/cap chromophore pairs, wherein charge transfer pathways can be accessed within the energetically favorable regime.

Chiral Self-Sorting, Spontaneous Resolution, and Hierarchical Self-Assembly in Metal-Organic Cages.

The ability to collectively program chiral recognition and the hierarchical self-assembly of molecular and supramolecular building blocks into complex higher-order superstructures is a significant goal in supramolecular chemistry. Metal-organic cages are excellent model systems to examine chiral self-sorting and build hierarchical self-assembly. Herein, details on how limiting the conformational flexibility and incorporating hydrogen bonding functional groups in the ligands can influence chiral self-sorting and hierarchical self-assembly of metal-organic cages are reported. The urea-functionalized axially chiral bis-pyridyl ligands afford high-fidelity in chiral self-sorting in Pd2L4 cages, when they have fewer conformations. Ligand L1, with more conformations, affords mixture of heterochiral and homochiral cages (≈70:30). Among them, the heterochiral cage adopts unusual twisted conformation and self-assembles into 2D sheets, linked by anion coordination between urea and nitrate. Ligand L2, with fewer conformations, affords homochiral cages via high-fidelity chiral self-sorting. The choice of counter anions influences further self-sorting in the solid state: racemate with PF6 - and spontaneously resolves conglomerate with BF4 -. Urea-BF4 hydrogen bonding directs hierarchical self-assembly of the Pd2L4 metal-organic cages into super-cubic networks. The study introduces a new approach in hierarchical self-assembly of metal-organic cages into higher-order networks aided by hydrogen bonding anion coordination with functional ligands.

Unlocking High Porosity: Post-Synthetic Solvothermal Treatment of Cu-Paddlewheel Based Metal-Organic Cages.

Metal-organic cages (MOCs) have garnered significant attention due to their unique discrete structures, intrinsic porosity, designability, and tailorability. However, weak inter-cage interactions, such as van der Waals forces and hydrogen bonding can cause solid-state MOCs to lose structural integrity during desolvation, leading to the loss of porosity. In this work, a novel strategy to retain the permanent porosity of Cu-paddlewheel-based MOCs, enabling their use as heterogeneous catalysts is presented. Post-synthetic solvothermal treatments in non-coordinating solvents, mesitylene, and p-xylene, effectively preserve the packing structures of solvent-evacuated MOCs while preventing cage agglomeration. The resulting MOCs exhibit an exceptional N2 sorption capacity, with a high surface area (SBET = 1934 m2 g-1 for MOP-23), which is among the highest reported for porous MOCs. Intriguingly, while the solvothermal treatment reduced Cu(II) to Cu(I) in the Cu-paddlewheel clusters, the MOCs with mixed-valenced Cu(I)/Cu(II) maintained their crystallinity and permanent porosity. The catalytic activities of these MOCs are successfully examined in copper(I)-catalyzed hydrative amide synthesis, highlighting the prospect of MOCs as versatile reaction platforms.

Encasing Few-Layer MoS2 within 2D Ordered Cubic Graphitic Cages to Smooth Trapping-Conversion of Lithium Polysulfides for Dendrite-Free Lithium-Sulfur Batteries.

The industrialization of lithium-sulfur (Li-S) batteries faces challenges due to the shuttling effect of lithium polysulfides (LiPSs) and the growth of lithium dendrites. To address these issues, a simple and scalable method is proposed to synthesize 2D membranes comprising a single layer of cubic graphitic cages encased with few-layer, curved MoS2. The distinctive 2D architecture is achieved by confining the epitaxial growth of MoS2 within the open cages of a 2D-ordered mesoporous graphitic framework (MGF), resulting in MoS2@MGF heterostructures with abundant sulfur vacancies. The experimental and theoretical studies establish that these MoS2@MGF membranes can act as a multifunctional interlayer in Li-S batteries to boost their comprehensive performance. The inclusion of the MoS2@MGF interlayer facilitates the trapping and conversion kinetics of LiPSs, preventing their shuttling effect, while simultaneously promoting uniform lithium deposition to inhibit dendrite growth. As a result, Li-S batteries with the MoS2@MGF interlayer exhibit high electrochemical performance even under high sulfur loading and lean electrolyte conditions. This work highlights the potential of designing advanced MoS2-encased heterostructures as interlayers, offering a viable solution to the current limitations plaguing Li-S batteries.

Ligand Conformation Controls Assembly of a Helicate/Mesocate, Heteroleptic [Pd2L2L'2] Cages and a Six-Jagged [Pd6L12] Ring.

Molecular building blocks, capable of adopting several strongly deviating conformations, are of particular interest in the development of stimuli-responsive self-assemblies. The pronounced structural flexibility of a short acridone-based bridging ligand, equipped with two monodentate isoquinoline donors, is herein exploited to assemble a surprisingly diverse series of coordination-driven Pd(II) architectures. First, it can form a highly twisted Pd2L4 helicate, transformable into the corresponding mesocate, controlled by temperature, counter anion and choice of solvent. Second, it also allows the formation of heteroleptic cages, either from a mix of ligands with Pd(II) cations or by cage-to-cage transformation from homoleptic assemblies. Here, the acridone-based ligand tolerates counter ligands that carry their donors either in a diverging or converging arrangement, as it can rotate its own coordination sites by 90° and structurally adapt to both situations via shape complementarity. Third, by a near 180° rotation of only one of its arms, the ligand can adopt an S-shape conformation and form an unprecedented C6h-symmetric Pd6L12 saw-toothed six-membered ring.

Synthesis of Calix[4]arene-Based Porous Organic Cages and Their Gas Adsorption.

Two crystalline large-sized porous organic cages (POCs) based on conical calix[4]arene (C4A) were designed and synthesized. The four-jaw C4A unit tends to follow the face-directed self-assembly law with the planar triangular building blocks such as tris(4-aminophenyl)amine (TAPA) or 1,3,5-tris(4-aminophenyl)benzene (TAPB) to generate a predictable cage with a stoichiometry of [6+8]. The formation of the large cages is confirmed through their relative molecular mass measured using MALDI-TOF/TOF spectra. The protonated molecular ion peaks of C4A-TAPA and C4A-TAPB were observed at m/z 5109.0 (calculated for C336H240O24N32: m/z 5109.7) and m/z 5594.2 (calculated for C384H264O24N24: m/z 5598.4). C4A-POCs exhibit I-type N2 adsorption-desorption isotherms with the BET surface areas of 1444.9 m2 ⋅ g-1 and 1014.6 m2 ⋅ g-1. The CO2 uptakes at 273 K are 62.1 cm3 ⋅ g-1 and 52.4 cm3 ⋅ g-1 at a pressure of 100 KPa. The saturated iodine vapor static uptakes at 348 K are 3.9 g ⋅ g-1 and 3.5 g ⋅ g-1. The adsorption capacity of C4A-TAPA for SO2 reaches to 124.4 cm3 ⋅ g-1 at 298 K and 1.3 bar. Additionally, the adsorption capacities of C4A-TAPA for C2H2, C2H4, and C2H6 were evaluated.

Predisposition in Dynamic Covalent Chemistry: The Role of Non-Covalent Interactions in the Assembly of Tetrahedral Boronate Cages.

Directional bonding strategies guide the design of complex molecular architectures, yet challenges arise due to emergent behavior. Rigid structures face geometric constraints and sensitivity to mismatches, hindering the efficient assembly of molecular organic cages (MOCs). Harnessing intramolecular non-covalent interactions offers a promising solution, broadening geometrical possibilities and enhancing adaptability to boost assembly yields. However, identifying these interactions remains challenging, with their full potential sometimes latent until final assembly. This study explores these challenges by synthesizing boronic acid tripods with varied oxygen positions at the tripodal feet and investigating their role in assembling tetrahedral boronate MOCs. Our results reveal substantial differences in the assembly efficiency among tripods. While the building blocks with oxygen in the benzylic position relative to the central aromatic ring form the MOCs in high yields, those with the oxygen atom directly bound to the central aromatic ring, only yield traces. Through X-ray crystallography and DFT analyses, we elucidate how intramolecular interactions profoundly influence the geometry of the building blocks and cages in a relay-like fashion, highlighting the importance of considering intramolecular interactions in the rational design of (supra)molecular architectures.

Metal-Organic Frameworks (MOFs) and Metal-Organic Cages (MOCs) for Photocatalytic Hydrogen Production.

Metal-organic frameworks (MOFs) and metal-organic cages (MOCs) have garnered significant attention as promising photocatalysts due to their tunable chemical structures and integrated multifunctionality. To increase the photocatalytic efficiency, strategies like ligand functionalization, introducing additional catalytic sites, and doping or encapsulating photosensitizers have been explored for both MOFs and MOCs. This concept review focuses on recent advancements in utilizing MOFs and MOCs for photocatalytic hydrogen production, highlighting their unique characteristics and introducing their respective mechanisms in this field. Moreover, it outlines the current challenges and prospects faced by MOFs and MOCs, offering an outlook on their future in this domain.

Water-Soluble Triazolium Covalent Cages for ATP Sensing.

Water-soluble organic cages are attractive targets for their molecular recognition and sensing features of biologically relevant molecules. Here, we have successfully designed and synthesized a pair of water-soluble cationic cages employing click reaction as the fundamental step followed by the N-methylation of the triazole rings. The rigid and shape-persistent 3D hydrophobic cavity, positively charged surface, H-bonding triazolium rings, and excellent water solubility empower both cages to exhibit a superior affinity and selectivity for binding with adenosine-5'-triphosphate (ATP) compared to cyclophanes and other macrocyclic receptors. Both cage molecules (PCC⋅Cl and BCC⋅Cl) can bind a highly emissive dye HPTS (8-hydroxypyrene-1,3,6-trisulfonic acid trisodium salt) to form non-fluorescent complexes. The addition of ATP resulted in the stronger cage⊂ATP complexes with the retention of HPTS emission upon its displacement. The resultant indicator-displacement assay system can efficiently sense and quantify ATP in nanomolar detection limits in buffer solutions and human serum matrix. Spectroscopic and theoretical studies revealed the synergistic effect of π⋅⋅⋅π stacking interaction between the aromatic moiety of the cationic cages and the adenine moiety of ATP, as well as the electrostatic and hydrogen bonding interaction between the phosphate anion of ATP and triazole protons of cages, played the pivotal roles in the sensing process.

UoC-10: Exploring the Packings of Chiral Copper(II) Paddle-Wheel Based Metal-Organic Cages (MOCs).

The fluorination of the central ring of 1,3,5-benzene-tris-(meta-benzoate) (referred to as BTMB) leads to a twisted tritopic linker which reacts with copper(II) ions to assemble into octahedral (pseudospherical) metal-organic cages (MOCs) with paddle-wheel units at their vertices. In this work, the different sphere packings of these MOCs are explored in detail together with their material properties, which closely resemble those of copper-based metal-organic frameworks (MOFs). Theoretical investigations of the linkers are carried out to analyze the energetic barrier imposed by the fluorine substituents to form the observed atropisomers.

Exploring the differences in radiologic and clinical outcomes of transforaminal lumbar interbody fusion with single- and bi-planar expandable cages: a systematic review and meta-analysis.

Transforaminal lumbar interbody fusion (TLIF) is a universal surgical technique used to achieve lumbar fusion. Traditionally static cages have been used to restore the disc space after discectomy. However, newer technological advancements have brought up uniplanar expandable cages (UECs) and more recently bi-planar expandable cages (BECs), the latter with the hope of reducing the events of intra- or postoperative subsidence compared to UECs. However, since BECs are relatively new, there has been no comparison to UECs. In this PRISMA-compliant systematic review, we sought to identify all Medline and Embase reports that used UECs and/or BECs for TLIF or posterior lumbar interbody fusion. Primary outcomes included subsidence and fusion rates. Secondary outcomes included VAS back pain score, VAS leg pain score, ODI, and other complications. A meta-analysis of proportions was the main method used to evaluate the extracted data. Bias was assessed using the ROBINS-I tool. A total of 15 studies were pooled in the analysis, 3 of which described BECs. There were no studies directly comparing the UECs to BECs. A statistically significant difference in fusion rates was found between UECs and BECs (p = 0.04). Due to lack of direct comparative literature, definitive conclusions cannot be made about differences between UECs and BECs. The analysis showed a statistically higher fusion rate for BECs versus UECs, but this should be interpreted cautiously. No other statistically significant differences were found. As more direct comparative studies emerge, future meta-analyses may clarify potential differences between these cage types.

Porous Metal Augments Have Comparable Outcomes to Other Constructs for Severe Acetabular Bone Loss at Mid-Term Follow-up.

BACKGROUND: Acetabular reconstruction options in the setting of severe bone loss remain limited, with few comparative studies published to date. The purpose of this study was to compare the outcomes of revision total hip arthroplasty (THA) for severe bone loss using porous metal augments to cup cage and triflange prostheses. METHODS: We reviewed a consecutive series of 180 patients who had Paprosky 3A or 3B acetabular defects and underwent revision THA. Patients treated with porous augments (n = 141) were compared with those who received cup cages or triflange constructs (n = 39). Failure of the acetabular construct was defined as undergoing acetabular revision surgery or radiographic evidence of loosening. RESULTS: There was no difference in acetabular component survivorship in patients undergoing revision THA with porous augments or a cage or triflange prosthesis (92.2 versus 87.2%, P = .470) at a mean follow-up of 6.6 ± 3.4 years. Overall, survivorship free from any revision surgery was comparable between the 2 groups (78.7 versus 79.5%, P = .720). There was also no difference in dislocation (5.7 versus 10.3%, P = .309) or periprosthetic joint infection rates (7.8 versus 10.3%, P = .623). In a subgroup analysis of patients who had pelvic discontinuity (n = 47), survivorship free from any revision surgery was comparable between the 2 groups (79.5 versus 72.2%, P = .543). CONCLUSIONS: Porous metal augments in the setting of severe acetabular bone loss demonstrated excellent survivorship at intermediate-term (mean 6.6 years follow-up, even in cases of pelvic discontinuity, with comparable outcomes to cup cages and triflanges. Instability and infection remain major causes of failure in this patient population, and long-term follow-up is needed.

Locking Patterned Carbon Nanotube Cages by Nanofibrous Mats to Construct Cucurbituril[n]-Based Ultrapermselective Dye/Salt Separation Membranes.

Surface patterning is a promising strategy to overcome the trade-off effect of separation membranes. Herein, a bottom-up patterning strategy of locking micron-sized carbon nanotube cages (CNCs) onto a nanofibrous substrate is developed. The strongly enhanced capillary force triggered by the abundant narrow channels in CNCs endows the precisely patterned substrate with excellent wettability and antigravity water transport. Both are crucial for the preloading of cucurbit[n]uril (CB6)-embeded amine solution to form an ultrathin (∼20 nm) polyamide selective layer clinging to CNCs-patterned substrate. The CNCs-patterning and CB6 modification result in a 40.2% increased transmission area, a reduced thickness, and a lowered cross-linking degree of selective layer, leading to a high water permeability of 124.9 L·m-2 h-1 bar-1 and a rejection of 99.9% for Janus Green B (511.07 Da), an order of magnitude higher than that of commercial membranes. The new patterning strategy provides technical and theoretical guidance for designing next-generation dye/salt separation membranes.

Water-Soluble Molecular Cages for Biological Applications.

The field of molecular cages has attracted increasing interest in relation to the development of biological applications, as evidenced by the remarkable examples published in recent years. Two key factors have contributed to this achievement: First, the remarkable and adjustable host-guest chemical properties of molecular cages make them highly suitable for biological applications. This allows encapsulating therapeutic molecules to improve their properties. Second, significant advances have been made in synthetic methods to create water-soluble molecular cages. Achieving the necessary water solubility is a significant challenge, which in most cases requires specific chemical groups to overcome the inherent hydrophobic nature of the molecular cages which feature the organic components of the cage. This can be achieved by either incorporating water-solubilizing groups with negative/positive charges, polyethylene glycol chains, etc.; or by introducing charges directly into the cage structure itself. These synthetic strategies allow preparing water-soluble molecular cages for diverse biological applications, including cages' anticancer activity, anticancer drug delivery, photodynamic therapy, and molecular recognition of biological molecules. In the review we describe selected examples that show the main concepts to achieve water solubility in molecular cages and some selected recent biological applications.

Recent Advances in Carborane-Based Crystalline Porous Materials.

The field of carborane research has witnessed continuous development, leading to the construction and development of a diverse range of crystalline porous materials for various applications. Moreover, innovative synthetic approaches are expanding in this field. Since the first report of carborane-based crystalline porous materials (CCPMs) in 2007, the synthesis of carborane ligands, particularly through innovative methods, has consistently posed a significant challenge in discovering new structures of CCPMs. This paper provides a comprehensive summary of recent advances in various synthetic approaches for CCPMs, along with their applications in different domains. The primary challenges and future opportunities are expected to stimulate further multidisciplinary development in the field of CCPMs.

Biomedical Applications of Sulfonylcalix[4]arene-Based Metal-Organic Supercontainers.

Coordination cages sustained by metal-ligand interactions feature polyhedral architectures and well-defined hollow structures, which have attracted significant attention in recent years due to a variety of structure-guided promising applications. Sulfonylcalix[4]arenes-based coordination cages, termed metal-organic supercontainers (MOSCs), that possess unique multi-pore architectures containing an endo cavity and multiple exo cavities, are emerging as a new family of coordination cages. The well-defined built-in multiple binding domains of MOSCs allow the efficient encapsulation of guest molecules, especially for drug delivery. Here, we critically discuss the design strategy, and, most importantly, the recent advances in research surrounding cavity-specified host-guest chemistry and biomedical applications of MOSCs.