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The rational and controlled synthesis of metallo‐organic cages using polyaromatic ligands is well established in the literature. There is a strong interest to advance this field towards the use of chiral ligands capable of yielding cages in a stereoselective manner. Herein, we demonstrate that the classical approach for designing metallo‐organic cages can be translated to polyproline peptides, a biocompatible class of chiral ligands. We have successfully designed a series of polyprolines, which mimic the topology of ditopic polyaromatic ligands, to achieve the stereoselective synthesis of a novel Pd lantern cage. This cage exhibits excellent stability in water and demonstrates the stabilization of a highly reactive species in solution. This work will pave the way towards the stereospecific synthesis of more complex, functionalized peptide‐based metallo‐cages. The design principles used for the synthesis of classical metallo‐organic ligands have been successfully translated to polyproline peptides, a biocompatible class of chiral ligands. These peptide‐based ditopic ligands have been successfully used to stereoselectively synthesize a novel Pd lantern cage, which exhibits excellent stability in water and demonstrates the stabilization of a highly reactive species in solution.

The conformational preferences of N‐((6‐methylpyridin‐2‐yl)carbamothioyl)benzamide were studied in solution, the gas phase and the solid state via a combination of NMR, density functional theory (DFT) and single crystal X‐ray techniques. This acyl thiourea derivative can adopt two classes of low energy conformation, each stabilized by a different 6‐membered intramolecular hydrogen bond (IHB) pseudoring. Analysis in different solvents revealed that the conformational preference of this molecule is polarity dependent, with increasingly polar environments yielding a higher proportion of the minor conformer containing an NH⋅⋅⋅N IHB. The calculated barrier to interconversion is consistent with dynamic behaviour at room temperature, despite the propensity of 6‐membered IHB pseudorings to be static. This work demonstrates that introducing competitive IHB pathways can render static IHBs more dynamic and that such systems could have potential as chameleons in drug design. Giving molecules a choice: a small molecule with a choice of low energy conformations stabilized by intramolecular hydrogen bonding exhibits polarity‐driven conformational preferences and dynamic exchange.

The decontamination and remediation of sulfur mustard chemical warfare agents remains an ongoing challenge. Herein, we report the use of “off‐the‐shelf” metal salts alongside commercially available peroxides to catalyze the degradation of the simulant 2‐chloroethyl ethyl sulfide (CEES) in solution and encapsulated within a supramolecular gel. Two for the price of one: Innovative countermeasures are needed to combat the ongoing threat of chemical warfare agents. This work showcases a step‐change in the development of novel mustard agent (HD) remediation materials by combining supramolecular gels and transition‐metal catalysts to provide HD‐simulant (CEES) sequestration and remediation in a single system.

The Cover Feature celebrates the stereoselective synthesis of a peptide‐based palladium cage. The chiral, low‐symmetry peptide‐based ligand used to generate this Pd cage could theoretically yield up to four structural isomers. Remarkably, only a single isomeric cage is formed in solution, the thermodynamically stable one. The image represents the single isomer emerging into the spotlight from all the possible isomers, shown in different colours in the background. More information can be found in the Research Article by A. Palma and co‐workers (DOI: 10.1002/ceur.202400050).

The rational and controlled synthesis of metallo‐organic cages using polyaromatic ligands is well established in the literature. There is a strong interest to advance this field towards the use of chiral ligands capable of yielding cages in a stereoselective manner. Herein, we demonstrate that the classical approach for designing metallo‐organic cages can be translated to polyproline peptides, a biocompatible class of chiral ligands. We have successfully designed a series of polyprolines, which mimic the topology of ditopic polyaromatic ligands, to achieve the stereoselective synthesis of a novel Pd lantern cage. This cage exhibits excellent stability in water and demonstrates the stabilization of a highly reactive species in solution. This work will pave the way towards the stereospecific synthesis of more complex, functionalized peptide‐based metallo‐cages.

The rational and controlled synthesis of metallo-organic cages using polyaromatic ligands is well established in the literature. There is a strong interest to advance this field towards the use of chiral ligands capable of yielding cages in a stereoselective manner. Herein, we demonstrate that the classical approach for designing metallo-organic cages can be translated to polyproline peptides, a biocompatible class of chiral ligands. We have successfully designed a series of polyprolines, which mimic the topology of ditopic polyaromatic ligands, to yield the stereoselective synthesis of a novel Pd lantern cage. This work will pave the way towards the stereospecific synthesis of more complex, functionalized peptide cages.

We synthesized the liquid crystal dimer and trimer members of a series of flexible linear oligomers and characterized their microscopic and nanoscopic properties using resonant soft X-ray scattering and a number of other experimental techniques. On the microscopic scale, the twist–bend phases of the dimer and trimer appear essentially identical. However, while the liquid crystal dimer exhibits a temperature-dependent variation of its twist–bend helical pitch varying from 100 to 170 Å on heating, the trimer exhibits an essentially temperature-independent pitch of 66 Å, significantly shorter than those reported for other twist–bend forming materials in the literature. We attribute this to a specific combination of intrinsic conformational bend of the trimer molecules and a sterically favorable intercalation of the trimers over a commensurate fraction (two-thirds) of the molecular length. We develop a geometric model of the twist–bend phase for these materials with the molecules arranging into helical chain structures, and we fully determine their respective geometric parameters.

In many different cell types, pro-inflammatory agonists induce the expression of cyclooxygenase 2 (COX-2), an enzyme that catalyzes rate-limiting steps in the conversion of arachidonic acid to a variety of lipid signaling molecules, including prostaglandin E 2 (PGE 2 ). PGE 2 has key roles in many early inflammatory events, such as the changes of vascular function that promote or facilitate leukocyte recruitment to sites of inflammation. Depending on context, it also exerts many important anti-inflammatory effects, for example increasing the expression of the anti-inflammatory cytokine interleukin 10 (IL-10), and decreasing that of the pro-inflammatory cytokine tumor necrosis factor (TNF). The tight control of both biosynthesis of, and cellular responses to, PGE 2 are critical for the precise orchestration of the initiation and resolution of inflammatory responses. Here we describe evidence of a negative feedback loop, in which PGE 2 augments the expression of dual specificity phosphatase 1, impairs the activity of mitogen-activated protein kinase p38, increases the activity of the mRNA-destabilizing factor tristetraprolin, and thereby inhibits the expression of COX-2. The same feedback mechanism contributes to PGE 2 -mediated suppression of TNF release. Engagement of the DUSP1-TTP regulatory axis by PGE 2 is likely to contribute to the switch between initiation and resolution phases of inflammation.

ObjectivesFibroblasts in synovium include fibroblast-like synoviocytes (FLS) in the lining and Thy1+ connective-tissue fibroblasts in the sublining. We aimed to investigate their developmental origin and relationship with adult progenitors.MethodsTo discriminate between Gdf5-lineage cells deriving from the embryonic joint interzone and other Pdgfrα-expressing fibroblasts and progenitors, adult Gdf5-Cre;Tom;Pdgfrα-H2BGFP mice were used and cartilage injury was induced to activate progenitors. Cells were isolated from knees, fibroblasts and progenitors were sorted by fluorescence-activated cell-sorting based on developmental origin, and analysed by single-cell RNA-sequencing. Flow cytometry and immunohistochemistry were used for validation. Clonal-lineage mapping was performed using Gdf5-Cre;Confetti mice.ResultsIn steady state, Thy1+ sublining fibroblasts were of mixed ontogeny. In contrast, Thy1-Prg4+ lining fibroblasts predominantly derived from the embryonic joint interzone and included Prg4-expressing progenitors distinct from molecularly defined FLS. Clonal-lineage tracing revealed compartmentalisation of Gdf5-lineage fibroblasts between lining and sublining. Following injury, lining hyperplasia resulted from proliferation and differentiation of Prg4-expressing progenitors, with additional recruitment of non-Gdf5-lineage cells, into FLS. Consistent with this, a second population of proliferating cells, enriched near blood vessels in the sublining, supplied activated multipotent cells predicted to give rise to Thy1+ fibroblasts, and to feed into the FLS differentiation trajectory. Transcriptional programmes regulating fibroblast differentiation trajectories were uncovered, identifying Sox5 and Foxo1 as key FLS transcription factors in mice and humans.ConclusionsOur findings blueprint a cell atlas of mouse synovial fibroblasts and progenitors in healthy and injured knees, and provide novel insights into the cellular and molecular principles governing the organisation and maintenance of adult synovial joints.