On the Precise Determination of Molar Mass and Dispersity in Controlled Chain-Growth Polymerization: A Distribution Function-Based Strategy

Accurate information for the molar mass of polymers is a critical item in polymerization kinetic investigation and precision polymer synthesis. Size exclusion chromatography (SEC) is an irreplaceable technique to determine molar mass averages based on conventional calibration, which may nonetheless lead to inaccurate results due to the dissimilarity between the sample and the standard polymer. Herein, a facile distribution function-based strategy was proposed for the precise determination of molar mass average properties, aiming at rectifying the deviation of the standard-equivalent results from the true values. The number-average molar mass (Mn) can be recalculated involving the contribution of each molar mass component beyond the fundamental Mark–Houwink–Sakurada relation. In addition, the as-developed strategy is capable of converting the dispersity from the apparent to the true value, thereby re-estimating the uniformity of the rectified molar mass distribution. The strategy was successfully applied to the linear polymers with medium and low dispersities obtained by two well-controlled chain-growth polymerizations: reversible addition-fragmentation chain transfer polymerization and ring-opening metathesis polymerization, respectively. The rectified Mn closely match the benchmarks (i.e., absolute/theoretical Mn), showing a much higher accuracy than those conventionally calibrated SEC results. Attributing to the consideration of dispersity, the errors of the rectified results can be as low as zero. This work reduces the risk of experimental bias caused by conventionally calibrated SEC analysis to acquire precise mechanism insight and realistic polymerization process details

Unraveling the Compounded Interplay of Weakly and Strongly Coordinating Ligands in G3-Catalyzed Living Metathesis Polymerization: toward Well-Defined Polynorbornene at Ambient Temperature

Ambient temperature ring-opening metathesis polymerization (ROMP) of unhindered cycloolefins is crucial for industrial applications from a sustainable perspective. However, balancing the reactivity of propagating species and polymer molecular structure remains a challenge due to competing secondary metathesis at ambient temperature. We report a facile ligand-competition strategy for achieving excellent control over 3-bromopyridine-coordinated Grubbs’ third-generation catalyst (3-bropyr-G3)-catalyzed ROMP of unsubstituted norbornene (NB). The addition of external pyridine with a strong coordinating affinity to regulate the catalytic metathesis activity is capable of tuning polymerization rates. Importantly, our strategy allows well-controlled ROMP of NB at both low (i.e., −20 °C) and ambient (i.e., 20 °C) temperatures, yielding PNB with quantitative Mn and low D̵ (≤1.07). Synergetic experimental and computational investigations suggest that stably coordinated pyridine can prevent the Ru center from attacking the backbone CC double bonds by breaking the interaction between the original weakly coordinating ligand and Ru carbene and thus mitigates the intermolecular chain transfer. This study guides the design of new G3-catalyzed ROMP systems to regulate the balance of metathesis reactivity and polymer molecular structures

Di- and Tetranuclear Dysprosium Single-Molecule Magnets Bridged by Unprecedentedly Disassembled Nitrogen-Enriched Tetrazine Derivatives

A series of di- and tetranuclear lanthanide complexes with the formulas [Dy2bmzch­(tmhd)5 (CH3OH)]·CH3OH (1), [Dy2bmzch­(dbm)4 (CH3O)­(CH3OH)]·0.5CH3OH·0.5H2O (2), and Dy4bmzch­(btfa)10 (3), where tmhd = 2,2,6,6-tetramethyl-3,5-heptanedionate, dbm = dibenzoylmethane, btfa = benzoyltrifluoroacetone, and bmzch = (Z)-N-[(E)-pyrimidin-2-ylmethylene]­pyrimidine-2-carbohydrazonate, were structurally and magnetically characterized. More strikingly, although the nitrogen-enriched bridged ligand 3,6-di­(pyrimidin-2-yl)-1,2,4,5-tetrazine (bmtz) was initially adopted, the structures of the complexes obtained indicated that bmtz underwent unprecedented asymmetric ring opening and generated a new ligand bmzch. Combined with different β-diketonates, di- and tetranuclear dysprosium complexes were constructed in which the structural patterns are very sensitive to the selected β-diketonates. In view of this, the bilateral and unilateral dinuclear Dy2 complexes 1 and 2 and tetranuclear Dy4 complex 3 were obtained by choosing different β-diketonates. Magnetic test results reveal that both complexes 1 and 3 showcase typical slow magnetic relaxation behavior without an external direct-current field and the effective energy barrier of the latter is almost twice that of the former, while complex 2 only displays in-field single-molecule-magnetic behavior. Also of note is that these are the first tetrazine-type dysprosium-based single-molecule-magnets undergoing in situ asymmetric ring-opening reaction of this ligand that are formed

Chiral Carbon Quantum Dots Encapsulated in ZIF‑8 Nanoparticles for Turn-On Recognition of Chiral Folic Acid and Nitrofurazone and Applications as Fluorescent Inks

Metal–organic frameworks (MOFs) are a kind of nanoporous coordination materials, which have the advantages of high crystallinity and tunable functionalization. Carbon dots (CDs) are zero-dimensional luminescent carbon nanomaterials, which combine the advantages of small organic molecules such as fluorophores and conventional semiconductors such as inorganic quantum dots. Chiral quantum dots are appealing for detection of chiral substances due to their unique chirality. In this work, chiral CDs can be loaded into zeolitic imidazolate framework-8 (ZIF-8) via an in situ encapsulation method, forming the chiral composite hybrid material CCQDs/ZIF-8 (1). The framework structure and luminescent property of 1 can be maintained after being soaked in water and ethanol for 24 h as confirmed by PXRD characterization. A luminescent experiment demonstrated that 1 can be utilized as a highly sensitive and selective “turn-on” fluorescent probe of d-folic acid (KBH 9.82 × 104 M–1 and detection limit 0.31 μM) and l-folic acid (KBH 2.99 × 104 M–1 and detection limit 4.36 μM). 1 also shows good cycling detection performance for d-folic acid (94.96%) and l-folic acid (93.69%). Enantioselective identification between d-folic acid and l-folic acid (KD/KL = 3.28) can be carried out. Furthermore, simultaneously, 1 can be used as an efficient turn-on fluorescence probe to detect the antibiotic nitrofurazone (NFZ; KBH 3.29 × 104 M–1 and detection limit 3.06 μM). Further, 1 can be utilized to detect folic acid and NFZ in real samples. The results demonstrated that 1 can be used as a highly efficient turn-on detection platform for folic acid and NFZ. Further, 1 with these targeted objects can be successfully applied as a fluorescent ink; a mixed-matrix membrane based on 1 has been prepared. The detection mechanism of composite material 1 for recognition of folic acid and NFZ is also investigated and discussed

An <i>o</i>-Aminoanilide Analogue of 1α,25-Dihydroxyvitamin D₃ Functions as a Strong Vitamin D Receptor Antagonist

Vitamin D receptor (VDR) antagonists have therapeutic potential in treatment of allergic conditions and hypercalcemia driven by granulomatous diseases. We have identified an o-aminoanilide analogue of the hormonal form of vitamin D with a dienyl side chain that functions as a strong VDR antagonist. Modeling studies indicate that antagonism arises from side chain rigidity, when compared to a more flexible saturated analogue, which interferes with H12 folding/alignment

Preclinical Investigations on Anti-fibrotic Potential of Long-Term Oral Therapy of Sodium Astragalosidate in Animal Models of Cardiac and Renal Fibrosis

In traditional Chinese medicine, Radix Astragali has played a vital role in treating progressive fibrotic diseases. One of its main active components, astragaloside IV, is a promising anti-fibrotic treatment despite its extremely low bioavailability. Our study aimed to optimize sodium astragalosidate (SA) by salt formation to improve solubility and oral absorption for anti-fibrotic therapy in vivo. Isoproterenol-induced myocardial fibrosis rat models and obese BKS-db mice presenting diabetic kidney fibrosis were used in this study. Daily oral administration of SA (20 mg/kg) for 14 days ameliorated cardiac fibrosis by reducing collagen accumulation and fibrosis-related inflammatory signals, including TNF-α, IL-1β, and IL-6. In db/db mice, SA (5,10, and 20 mg/kg per day for 8 weeks) dose-dependently alleviated lipid metabolism impairment and renal dysfunction when administered orally. Furthermore, Western blot and immunohistochemistry analyses demonstrated that SA treatment inhibited renal fibrosis by suppressing TGF-β1/Smads signaling. Taken together, our findings provide the oral-route medication availability of SA, which thus might offer a novel lead compound in preclinical trial-enabling studies for developing a long-term therapy to treat and prevent fibrosis

DataSheet1_Lipophilic Constituents in Salvia miltiorrhiza Inhibit Activation of the Hepatic Stellate Cells by Suppressing the JAK1/STAT3 Signaling Pathway: A Network Pharmacology Study and Experimental Validation.docx

Liver fibrosis is currently a global health challenge with no approved therapy, with the activation of hepatic stellate cells being a principal factor. Lipophilic constituents in Salvia miltiorrhiza (LS) have been reported to improve liver function and reduce the indicators of liver fibrosis for patients with chronic hepatitis B induced hepatic fibrosis. However, the pharmacological mechanisms of LS on liver fibrosis have not been clarified. In this study, 71 active compounds, 342 potential target proteins and 22 signaling pathways of LS were identified through a network pharmacology strategy. Through text mining and data analysis, the JAK1/STAT3 signaling pathway was representatively selected for further experimental validation. We firstly confirmed the protective effect of LS on liver fibrosis in vivo by animal experiments. Hepatic stellate cells, which proliferated and displayed a fibroblast-like morphology similar to activated primary stellate cells, were applied to evaluate its underlying mechanisms. The results showed that LS could inhibit the cell viability, promote the cell apoptosis, decrease the expression of liver fibrosis markers, and downregulate the JAK1/STAT3 signaling pathway. These results demonstrated that LS could exert anti-liver-fibrosis effects by inhibiting the activation of HSCs and regulating the JAK1/STAT3 signaling pathway, which is expected to benefit its clinical application.</p

Co-culture with SAECs does not enhance autophagy in <i>Mtb</i>-infected macrophages.

<p>(<b>A</b>) Representative bright-field microscopy of infected macrophages cultured in the absence or presence of 1,25D and/or a transwell containing SAECs. Cells were fixed and probed with an antibody against <i>Mtb</i>, LC3, and the nuclear stain DAPI. (<b>B</b>) Percent of <i>Mtb</i> that colocalized with LC3 signal under each condition as determined by counting populations of infected macrophages across at least 10 confocal images, with at least two infected cells per image. Statistical significance was determined by a two-tailed Fisher's exact test (**P<0.01). (<b>C</b>) 3-dimensional rendering of confocal stacks of infected macrophages treated with 1,25D to demonstrate colocalization of LC3 and <i>Mtb</i> signal.</p

Amino acid mutations in the light chain of the 1-17-2 mAb.

<p>Amino acid mutations in the light chain of the 1-17-2 mAb.</p

Amino acid mutations in the heavy chain of 1-17-2 mAb.

<p>Amino acid mutations in the heavy chain of 1-17-2 mAb.</p