A series of isostructural supramolecular cages with a rhombic dodecahedron shape have been assembled with distinct metal-coordination lability (M8 Pd6 -MOC-16, M=Ru2+ , Fe2+ , Ni2+ , Zn2+ ). The chirality transfer between metal centers generally imposes homochirality on individual cages to enable solvent-dependent spontaneous resolution of Δ8 /Λ8 -M8 Pd6 enantiomers; however, their distinguishable stereochemical dynamics manifests differential chiral phenomena governed by the cage stability following the order Ru8 Pd6 >Ni8 Pd6 >Fe8 Pd6 >Zn8 Pd6 . The highly labile Zn centers endow the Zn8 Pd6 cage with conformational flexibility and deformation, enabling intrigue chiral-Δ8 /Λ8 -Zn8 Pd6 to meso-Δ4 Λ4 -Zn8 Pd6 transition induced by anions. The cage stabilization effect differs from inert Ru2+ , metastable Fe2+ /Ni2+ , and labile Zn2+ , resulting in different chiral-guest induction. Strikingly, solvent-mediated host-guest interactions have been revealed for Δ8 /Λ8 -(Ru/Ni/Fe)8 Pd6 cages to discriminate the chiral recognition of the guests with opposite chirality. These results demonstrate a versatile procedure to control the stereochemistry of metal-organic cages based on the dynamic metal centers, thus providing guidance to maneuver cage chirality at a supramolecular level by virtue of the solvent, anion, and guest to benefit practical applications.
Molecular recognition lies at the heart of biological functions, which inspires lasting research in artificial host syntheses to mimic biomolecules that can recognize, process, and transport molecules with the highest level of complexity; nonetheless, the design principle and quantifying methodology of artificial hosts for multiple guests (≥4) remain a formidable task. Herein, we report two rhombic dodecahedral cages [(Zn/Fe)8Pd6-MOC-16], which embrace 12 adaptive pockets for multiguest binding with distinct conformational dynamics inherent in metal-center lability and are able to capture 4-24 guests to manifest a surprising complexity of binding scenarios. The exceptional high-order and hierarchical encapsulation phenomena suggest a wide host-guest dynamic-fit, enabling conformational adjustment and adaptation beyond the duality of induced-fit and conformational selection in protein interactions. A critical inspection of the host-guest binding events in solution has been performed by NMR and ESI-MS spectra, highlighting the importance of acquiring a reliable binding repertoire from different techniques and the uncertainty of quantifying the binding affinities of multiplying guests by an oversimplified method.
Biomimetics , Molecular Conformation
Supramolecular cage chemistry is of lasting interest because, as artificial blueprints of natural enzymes, the self-assembled cage structures not only provide substrate-hosting biomimetic environments but also can integrate active sites in the confined nanospaces for function synergism. Herein, we demonstrate a vertex-directed organic-clip chelation assembly strategy to construct a metal-organic cage Fe4L68+ (MOC-63) incorporating 12 imidazole proton donor-acceptor motifs and four redox-active Fe centers in an octahedral coordination nanospace. Different from regular supramolecular cages assembled with coordination metal vertices, MOC-63 comprises six ditopic organic-clip ligands as vertices and four tris-chelating Fe(Nâ©N)3 moieties as faces, thus improving its acid, base, and redox robustness by virtue of cage-stabilized dynamics in solution. Improved dehydrogenation catalysis of 1,2,3,4-tetrahydroquinoline derivatives is accomplished by MOC-63 owing to a supramolecular cage effect that synergizes multiple Fe centers and radical species to expedite intermediate conversion of the multistep reactions in a cage-confined nanospace. The acid-base buffering imidazole motifs play a vital role in modulating the total charge state to resist pH variation and tune the solubility among varied solvents, thereby enhancing reaction acceleration in acidic conditions and rendering a facile recycling catalytic process.
Imidazoles , Metals , Catalysis , Imidazoles/chemistry , Ligands , Oxidation-Reduction , Solvents
BACKGROUND: Endothelial dysfunction, a hallmark of diabetes, is a critical and initiating contributor to the pathogenesis of diabetic cardiovascular complications. However, the underlying mechanisms are still not fully understood. Ferroptosis is a newly defined regulated cell death driven by cellular metabolism and iron-dependent lipid peroxidation. Although the involvement of ferroptosis in disease pathogenesis has been shown in cancers and degenerative diseases, the participation of ferroptosis in the pathogenesis of diabetic endothelial dysfunction remains unclear. AIM: To examine the role of ferroptosis in diabetes-induced endothelial dysfunction and the underlying mechanisms. METHODS: Human umbilical vein endothelial cells (HUVECs) were treated with high glucose (HG), interleukin-1ß (IL-1ß), and ferroptosis inhibitor, and then the cell viability, reactive oxygen species (ROS), and ferroptosis-related marker protein were tested. To further determine whether the p53-xCT (the substrate-specific subunit of system Xc-)-glutathione (GSH) axis is involved in HG and IL-1ß induced ferroptosis, HUVECs were transiently transfected with p53 small interfering ribonucleic acid or NC small interfering ribonucleic acid and then treated with HG and IL-1ß. Cell viability, ROS, and ferroptosis-related marker protein were then assessed. In addition, we detected the xCT and p53 expression in the aorta of db/db mice. RESULTS: It was found that HG and IL-1ß induced ferroptosis in HUVECs, as evidenced by the protective effect of the ferroptosis inhibitors, Deferoxamine and ferrostatin-1, resulting in increased lipid ROS and decreased cell viability. Mechanistically, activation of the p53-xCT-GSH axis induced by HG and IL-1ß enhanced ferroptosis in HUVECs. In addition, a decrease in xCT and the presence of de-endothelialized areas were observed in the aortic endothelium of db/db mice. CONCLUSION: Ferroptosis is involved in endothelial dysfunction and p53-xCT-GSH axis activation plays a crucial role in endothelial cell ferroptosis and endothelial dysfunction.
In patients undergoing percutaneous coronary intervention after acute myocardial infarction, hyperglycaemia on admission is associated with an increased risk of contrast-induced nephropathy (CIN). However, the effects of hyperglycaemia and elevated glycosylated haemoglobin (HbA1c) on CIN have remained to be fully elucidated. Therefore, a prospective cohort study was performed, comprising 258 patients who underwent coronary angiography between May 2017 and November 2017 at Zhongda Hospital affiliated with Southeast University (Nanjing, China). According to the diagnostic criteria for CIN (increase of serum creatinine by >44.2 µmol/l or by 25% within 48-72 h of using contrast agent), the patients were divided into two groups: CIN (45 cases) and non-CIN (213 cases). For all patients, the baseline data, medical history, laboratory parameters, medication history and intraoperative situation were recorded and assessed using single-factor analysis and multiple logistic regression analysis to analyse the risk factors of CIN. The incidence of CIN in the hyperglycaemia group (blood glucose on admission, >11.1 mmol/l) was 25%, compared with 13.8% in the non-hyperglycaemia group (P=0.026). Furthermore, the incidence of CIN in the elevated HbA1c group (HbA1c on admission, upper limit of normal) was 26.1%, compared with 14.3% in the group without elevated HbA1c (P=0.027). Hyperglycaemia was present on hospital admission in 84 of 258 patients (32.6%). The percentage of patients with elevated HbA1c was 26.7%. Age, estimated glomerular filtration rate, pre-operative blood cholesterol, hyperglycaemia on admission and elevated HbA1c were all identified to be associated with CIN. According to the multivariate logistic regression analysis, hyperglycaemia was an independent predictor of CIN (odds ratio, 2.815; 95% confidence interval, 1.042-4.581; P=0.029). In the acute coronary syndrome (ACS) and diabetes subgroups, hyperglycaemia was significantly associated with CIN. In the ACS subgroup, the incidence of CIN was 38.1%. It was indicated that hyperglycaemia is an independent risk factor for CIN, particularly in patients with ACS or diabetes. Trial registration no. ChiCTR-OOC-17011466.
Ischemic brain injury is the main cause of high mortality,high disability and high recurrence rates in ischemic stroke.The activation and differentiation of microglia are associated with inflammatory responses of ischemic brain injury,playing an important role in the occurrence,development and outcome of ischemic stroke.In addition,there is no effective treatment for ischemic stroke.Thus,it is of clinical significance to investigate regulatory mechanisms of microglia for ischemic stroke treatment.This review introduces the dual effect of microglia on ischemic stroke and research progress in associated treatment for ischemic stroke,hoping to provide new ideas for investigating targeted intervention therapies.
