Latest ArticlesDeveloping efficient photosensitizers for C–P bond construction is highly important and remains a challenge due to the urgently needed for the synthesis of modified nucleosides, nucleotides, and other phosphine-containing ligands. Herein, two pyrene-tethered bismoviologen derivatives (Py-BiV2+) were designed and synthesized for visible-light-induced C–P bonds formation. The photochemical and electrochemical properties of Py-BiV2+ were studied systemically, certifying fine-tunable opto-electronic properties through the number of pyrene groups (4, n = 1; 6, n = 2). The prepared Py-BiV2+ showed strong light absorption, while retaining good redox features and chromic response features that were inherent to viologens. 4 exhibited accelerated photoinduced electron transfer in the presence of the electron donor (pyrene) and the generated 4' (radical cation) showed higher stability. Accordingly, Py-BiV2+ directly served as photosensitizers for the first time in the visible-light-induced C(sp3)–P and C(sp2)–P bonds formation. As expected, these novel viologen derivatives exhibited good catalytic performance and good substrate expansibility under ambient conditions.
Bacterial antimicrobial resistance (AMR) is a severe threat to global health and development. Under the stimulation of antibiotics, bacterial cells can undergo filamentation and generate daughter cells with stronger AMR. The current research on bacterial AMR mechanism is mainly conducted with a population of cells. However, bacterial cells exhibit heteroresistance, making the study at population level not reliable. Herein, we developed single bacterial cell metabolic profiling by mass spectrometry (MS) to study bacterial AMR at single-cell level. By utilizing a microprobe controlled by a microoperation platform, single filamentous extended spectrum beta-lactamase (ESBL) producing Escherichia coli (ESBL-E. coli) cells generated by ceftriaxone sodium stimulation can be extracted and spray-ionized for MS analysis. Heterogeneous among ESBL-E. coli cells under the same antibiotic stimulus condition was observed from mass spectra as well as cell morphology. The metabolic profiles by MS of different individual cells can be clustered into subgroups well in accordance with bacterial cell length. Metabolic pathways including arginine and proline metabolism, as well as cysteine and methionine metabolism were disclosed to play an important role in the bacterial SOS-associated filamentation against antibiotics. The microprobe electrospray ionization-MS-based single bacterial cell analysis method is promising in the study of various bacterial AMR mechanism and can reveal the heterogeneity of bacterial AMR from-cell-to-cell.
Proteolysis targeting chimeras (PROTACs) are bifunctional degrader molecules via hijacking the ubiquitin-proteasome system (UPS) to specifically eliminate targeted proteins. PROTACs have gained momentum as a new modality of attractive technologies in the drug discovery landscape, since it allows to degrade disease-related proteins effectively. Although some PROTACs drugs reached the clinical research, they are still facing some bottlenecks and challenges that should not be neglected, such as poor oral bioavailability and potential toxic side effects. To overcome these limitations, herein, we provide an overview of recent strategies for improving the durability of PROTACs by enhancing cell permeability and reducing toxic side effects. Meanwhile, the impact of these strategies on improving oral bioavailability as well as their advantages and drawbacks will also be discussed. This review will give a useful reference toolbox for PROTACs design and further promote its clinical application.
As one of the top global health problems, the effective treatment of cancer is one of the most urgent clinical challenges. Currently, the main treatments for cancer include surgery, chemotherapy, radiotherapy, and gene therapy etc. Chemotherapy is one of the most commonly used treatments, however it has limitations such as highly toxic side effects and low drug utilization rate that limit its application. Gene therapy, as an emerging cancer treatment, has limitations such as drug instability, off-target effects and low internalization efficiency. Poly(amino acid)s carriers with good biocompatibility, degradability and multifunctionality as drug carriers have received much attention, as they can reduce the toxic side effects of chemotherapy, improve drug utilization, and enhance the internalization efficiency and utilization of gene drugs. However, little attention has been paid to the nature of the carriers themselves. This paper reviews the immunomodulatory, anti-inflammatory, antioxidant, internalization-promoting and apoptosis-promoting functions of poly(amino acid)s drug carriers in tumor therapy to provide a theoretical basis for different carrier-drug-adapted synergistic therapies.
The application of fluorescent probes for in vivo retinal imaging is of great importance, which could provide direct and crucial imaging evidence for a better understanding of common eye diseases. Herein, a group of bright organic luminogens with typical electron-donating (D) and electron-accepting (A) structures (abbreviated as LDs-BDM, LDs-BTM, and LDs-BHM) was synthesized through a simple single-step reaction. They were found to be efficient solid-state emitters with high fluorescence quantum yields of above 70% (e.g., 83.7% for LDs-BTM). Their light-emission properties could be tuned by the modulation of π-conjugation effect with methoxy groups at different substituent positions. Their resulting fluorescent nanoparticles (NPs) were demonstrated as specific lipid droplets (LDs) targeting probes with high brightness, good biocompatibility, and satisfactory photostability. LDs-BTM NPs with a large two-photon absorption cross section (σ2 = 249 GM) were further utilized as ultrabright two-photon fluorescence (2PF) nanoprobes for in vivo retina imaging of live zebrafish by NIR excitation at an ultralow concentration (0.5 µmol/L). Integrated histological structures at the tissue level and corresponding fine details at the cellular level of the embryonic retina of live zebrafish were clearly demonstrated. This is the first report of using ultrabright LDs-targeting nanoprobes to accurately measure fine details in the retina with 2PF microscopic technique. These good results are anticipated to open up a new avenue in the development of efficient 2PF emitters for non-invasive bioimaging of living animals.
Cardiovascular disease (CVD) is a global health problem and is thought to be responsible for almost half of all deaths in the world. Nevertheless, currently available diagnostic methods for CVD are strongly depended on clinical observation and monitoring, which commonly result in false diagnosis. Herein, an attractive strategy of a metal-organic framework (MOF) nanofilm-based laser desorption/ionization mass spectrometry (LDI-MS) was developed for enhancing serum metabolic profiling, which could provide precise diagnosis and molecular subtyping of CVD. The porous MOF nanofilm fabricated on indium-tin oxide (ITO) glass possessed enhanced ionization efficiency and size-exclusion effect, which endowed it as substrate with high sensitivity and selectivity for serum metabolites. Furthermore, the MOF nanofilm with uniform surface and high orientation provided high-quality and high-reproducibility serum metabolic profiles (SMPs) without any tedious pretreatment. Further analysis of extracted serum metabolic fingerprints could successfully distinguish patients with CVD from healthy controls and also differentiate two major subtypes of CVD. This work not only extends the application of MOF nanofilm as an attractive MS probe, but also provide an alternative way for precise diagnosis of CVD in molecular level.
Benzimidazole amino acid derivatives behave as supramolecular hosts to include organic acids via complementary hydrogen bonding whereby supramolecular chirality and chiroptical properties could be manipulated. Organic acids enhanced the chiral assembly that showed tunable circularly polarized luminescence with high dissymmetry g-factors at 10-2 grade.
Developing an efficient Zn-based catalyst modified with Trifluoromethanesulfonic acid (TfOH) ligand is extremely desirable for the acetylene hydration reaction. In this paper, with the use of a simple impregnation method, a series of Zn-TfOH/AC catalysts were synthesized, and the Zn-1.5TfOH/AC catalyst demonstrated the optimal catalytic performance with 96% acetylene conversion in the hydration of acetylene. The X-ray absorption fine structure (XAFS) spectra of the fresh Zn-1.5TfOH/AC catalysts demonstrated the establishment of the Zn-O4 coordination structure. According to the characterization results, TfOH ligands effectively inhibited carbon accumulation and Zinc loss, improved acidic sites and the dispersion of active metal, and produced more catalytic active site. Furthermore, the hydration reaction mechanism of Zn-TfOH/AC catalyst with Zn(OTf)2, TfO-ZnCl, and TfO-ZnOH complex configurations was explored by the Density Functional Theory (DFT) method, which showed that the activation barrier increased sequentially TfO-ZnOH < Zn(OTf)2 < TfO-ZnCl. Importantly, the OH− in TfO-ZnOH is involved in the reaction and regenerated by the dissociation of H2O, which lowers the energy barrier. This will provide a reference to design more efficient nonmercury catalysts for acetylene hydration.
Metal-based catalysis, including homogeneous and heterogeneous catalysis, plays a significant role in the modern chemical industry. Heterogeneous catalysis is widely used due to the high efficiency, easy catalyst separation and recycling. However, the metal-utilization efficiency for conventional heterogeneous catalysts needs further improvement compared to homogeneous catalyst. To tackle this, the pursing of heterogenizing homogeneous catalysts has always been attractive but challenging. As a recently emerging class of catalytic material, single-atom catalysts (SACs) are expected to bridge homogeneous and heterogeneous catalytic process in organic reactions and have arguably become the most active new frontier in catalysis field. In this review, a brief introduction and development history of single-atom catalysis and SACs involved organic reactions are documented. In addition, recent advances in SACs and their practical applications in organic reactions such as oxidation, reduction, addition, coupling reaction, and other organic reactions are thoroughly reviewed. To understand structure-property relationships of single-atom catalysis in organic reactions, active sites or coordination structure, metal atom-utilization efficiency (e.g., turnover frequency, TOF calculated based on active metal) and catalytic performance (e.g., conversion and selectivity) of SACs are comprehensively summarized. Furthermore, the application limitations, development trends, future challenges and perspective of SAC for organic reaction are discussed.