Poly(triazine imide) or PTI is an ordered graphitic carbon nitride hosting Å‐scale pores attractive for selective molecular transport. AA’‐stacked PTI layers are synthesized by ionothermal route ...during which ions occupy the framework and occlude the pores. Synthesis of ion‐free PTI hosting AB‐stacked layers has been reported, however, pores in this configuration are blocked by the neighboring layer. The unavailability of open pore limits application of PTI in molecular transport. Herein, we demonstrate acid treatment for ion depletion which maintains AA’ stacking and results in open pore structure. We provide first direct evidence of ion‐depleted open pores by imaging with the atomic resolution using integrated differential phase‐contrast scanning transmission electron microscopy. Depending on the extent of ion‐exchange, AA’ stacking with open channels and AB stacking with closed channels are obtained and imaged for the first time. The accessibility of open channels is demonstrated by enhanced proton transport through ion depleted PTI.
Poly(triazine imide) or PTI is an ordered graphitic carbon nitride with nanoporous framework. However, pores in PTI are blocked by Li+ and halide ions, and a complete removal of ions leads to an impermeable AB stacking. We report an ion‐exchange route which tunably opens pore channels while maintaining the AA′ configuration leading to an improved proton conductivity.
Understanding the structure and dynamics of newcomer optoelectronic materials - lead halide perovskites APbX
A = Cs, methylammonium (CH
NH
, MA), formamidinium (CH(NH
)
, FA); X = Cl, Br, I - has ...been a major research thrust. In this work, new insights could be gained by using
Pb solid-state nuclear magnetic resonance (NMR) spectroscopy at variable temperatures between 100 and 300 K. The existence of scalar couplings
J
of ca. 400 Hz and
J
of ca. 2.3 kHz could be confirmed for MAPbX
and CsPbX
. Diverse and fast structure dynamics, including rotations of A-cations, harmonic and anharmonic vibrations of the lead-halide framework and ionic mobility, affect the resolution of the coupling pattern.
Pb NMR can therefore be used to detect the structural disorder and phase transitions. Furthermore, by comparing bulk and nanocrystalline CsPbBr
a greater structural disorder of the PbBr
-octahedra had been confirmed in a nanoscale counterpart, not readily captured by diffraction-based techniques.
Abstract The stability of hybrid organic–inorganic halide perovskite semiconductors remains a significant obstacle to their application in photovoltaics. To this end, the use of low‐dimensional (LD) ...perovskites, which incorporate hydrophobic organic moieties, provides an effective strategy to improve their stability, yet often at the expense of their performance. To address this limitation, supramolecular engineering of noncovalent interactions between organic and inorganic components has shown potential by relying on hydrogen bonding and conventional van der Waals interactions. Here, the capacity to access novel LD perovskite structures that uniquely assemble through unorthodox S‐mediated interactions is explored by incorporating benzothiadiazole‐based moieties. The formation of S‐mediated LD structures is demonstrated, including one‐dimensional (1D) and layered two‐dimensional (2D) perovskite phases assembled via chalcogen bonding and S–π interactions, through a combination of techniques, such as single crystal and thin film X‐ray diffraction, as well as solid‐state NMR spectroscopy, complemented by molecular dynamics simulations, density functional theory calculations, and optoelectronic characterization, revealing superior conductivities of S‐mediated LD perovskites. The resulting materials are applied in n‐i‐p and p‐i‐n perovskite solar cells, demonstrating enhancements in performance and operational stability that reveal a versatile supramolecular strategy in photovoltaics.
The optimization of a material functionality requires both the rational design and precise engineering of its structural and chemical parameters. In this work, we show how colloidal chemistry is an ...excellent synthetic choice for the synthesis of novel ternary nanostructured chalcogenides, containing exclusively noble metals, with tailored morphology and composition and with potential application in the energy conversion field. Specifically, the Ag-Au-Se system has been explored from a synthetic point of view, leading to a set of Ag2Se-based hybrid and ternary nanoparticles, including the room temperature synthesis of the rare ternary Ag3AuSe2 fischesserite phase. An in-depth structural and chemical charac-terization of all nanomaterials has been performed, which proofed especially useful for unravelling the reaction mecha-nism behind the formation of the ternary phase in solution. The work is complemented with the thermal and electric characterization of a ternary Ag-Au-Se nanocomposite with promising results: we found that the use of the ternary nano-composite represents a clear improvement in terms of thermoelectric energy conversion as compared to a binary Ag-Se nanocomposite analogue.
Objectives
To compare the performance of standard and simulated short gadoxetic acid-enhanced MRI protocols for the detection of colorectal liver metastases (CRLM).
Methods
From 2008 to 2017, 67 ...patients (44 men (66%); mean age 65 ± 11 years old) who underwent gadoxetic acid-enhanced MRI during the initial work-up for colorectal cancer were included. Exams were independently reviewed by two readers blinded to clinical data in two reading sessions: (1) all acquired sequences (standard “long” protocol) and (2) only T2-weighted, diffusion-weighted, and hepatobiliary phase images (simulated “short” protocol). Readers characterized detected lesions using a 5-point scale (1—certainly benign to 5—certainly malignant). A lesion was considered a CRLM when the score was ≥ 3. The reference standard was histopathology or 12-month imaging follow-up. Chi-square, Student’s
t
, and McNemar tests were used for comparisons.
Results
A total of 486 lesions including 331 metastases (68%) were analyzed. The metastasis detection rate was 86.1% (95% CI 82–89.4)–86.7% (82.6–90) and 85.8% (81.6–89.2)–87% (82.9–90.2) with the short and long protocols, respectively (
p
> 0.99). Among detected lesions, 92.1% (89.1–94.4)–94.8% (92.2–96.6) and 84.6% (80.8–87.7)–88.8% (85.4–91.5) were correctly classified with the short and long protocols, respectively (
p
= 0.13 and
p
= 0.10). The results remained unchanged when lesions scored ≥ 4 were considered as CRLM.
Conclusion
The diagnostic performance of a simulated short gadoxetic enhanced-MR protocol including T2-weighted, diffusion-weighted, and hepatobiliary phase appears similar to that of a standard long protocol including dynamic phase images. Since this protocol shortens the duration of MR examination, it could facilitate the evaluation of patients with colorectal liver metastases.
Key Points
•
The detection rate of colorectal metastases with a simulated, short, MRI protocol was similar to that of a standard protocol.
•
The performance of both protocols for the differentiation of metastases and benign lesions appears to be similar.
•
A short MR imaging protocol could facilitate the evaluation of patients with colorectal liver metastases.
Metallo-β-lactamases (MBLs) contribute to the resistance of Gram-negative bacteria to carbapenems, last-resort antibiotics at hospital, and MBL inhibitors are urgently needed to preserve these ...important antibacterial drugs. Here, we describe a series of 1,2,4-triazole-3-thione-based inhibitors displaying an α-amino acid substituent, which amine was mono- or disubstituted by (hetero)aryl groups. Compounds disubstituted by certain nitrogen-containing heterocycles showed submicromolar activities against VIM-type enzymes and strong NDM-1 inhibition (K i = 10–30 nM). Equilibrium dialysis, native mass spectrometry, isothermal calorimetry (ITC), and X-ray crystallography showed that the compounds inhibited both VIM-2 and NDM-1 at least partially by stripping the catalytic zinc ions. These inhibitors also displayed a very potent synergistic activity with meropenem (16- to 1000-fold minimum inhibitory concentration (MIC) reduction) against VIM-type- and NDM-1-producing ultraresistant clinical isolates, including Enterobacterales and Pseudomonas aeruginosa. Furthermore, selected compounds exhibited no or moderate toxicity toward HeLa cells, favorable absorption, distribution, metabolism, excretion (ADME) properties, and no or modest inhibition of several mammalian metalloenzymes.
PEGylation of therapeutic agents is known to improve the pharmacokinetic behavior of macromolecular drugs and nanoparticles. In this work, we performed the conjugation of polyethylene glycols ...(220–5000 Da) to a series of non-steroidal small agonists of the bile acids receptor TGR5. A suitable anchoring position on the agonist was identified to retain full agonistic potency with the conjugates. We describe herein an extensive structure–properties relationships study allowing us to finely describe the non-linear effects of the PEG length on the physicochemical as well as the in vitro and in vivo pharmacokinetic properties of these compounds. When appending a PEG of suitable length to the TGR5 pharmacophore, we were able to identify either systemic or gut lumen-restricted TGR5 agonists.
Endoplasmic reticulum aminopeptidase 2 (ERAP2) is a key enzyme involved in the trimming of antigenic peptides presented by Major Histocompatibility Complex class I. It is a target of growing interest ...for the treatment of autoimmune diseases and in cancer immunotherapy. However, the discovery of potent and selective ERAP2 inhibitors is highly challenging. Herein, we have used kinetic target‐guided synthesis (KTGS) to identify such inhibitors. Co‐crystallization experiments revealed the binding mode of three different inhibitors with increasing potency and selectivity over related enzymes. Selected analogues engage ERAP2 in cells and inhibit antigen presentation in a cellular context. 4 d (BDM88951) displays favorable in vitro ADME properties and in vivo exposure. In summary, KTGS allowed the discovery of the first nanomolar and selective highly promising ERAP2 inhibitors that pave the way of the exploration of the biological roles of this enzyme and provide lead compounds for drug discovery efforts.
Kinetic target‐guided synthesis and optimisation led to the first nanomolar ERAP2 inhibitors with outstanding selectivity. The binding modes of the most potent inhibitors were elucidated by X‐ray crystallography. Our frontrunners engage target in cells and display good in vitro and in vivo pharmacokinetic properties.
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