Cas12f possesses both cis- and trans-cleavage activities, with the former being extensively studied for its application in genome editing, while the latter remains less explored, particularly for diagnostic purposes, and is mostly focused on Un1Cas12f1. In this study, we conducted a comprehensive comparison of the trans-cleavage activities of four characterized Cas12f proteins, demonstrating that all four exhibit trans-DNase activity triggered by double-stranded DNA (dsDNA), single-stranded DNA (ssDNA), and single-stranded RNA (ssRNA). Additionally, we identified distinct base preferences for trans-cleavage substrates among these proteins. Our further investigation into the activities of Cas12f revealed the intricate relationship between cis- and trans-cleavage activities under various conditions. Our study provides a multifaceted characterization of the trans-cleavage features of Cas12f nucleases, offering new avenues for a deeper comprehension of the mechanisms underlying Cas12f's functionality.
RNA-protein interactions are crucial for regulating various cellular processes such as gene expression, RNA modification and translation. In contrast, undesirable RNA-protein interactions often cause dysregulated cellular activities associated with many human diseases. The RNA containing expanded GGGGCC repeats forms secondary structures that sequester various RNA binding proteins (RBPs), leading to the development of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, a gap persists in understanding the structural basis for GGGGCC repeat RNA binding to RBPs. Here, we resolve the first solution NMR structure of a natural GGGGCC repeat RNA containing a 2 × 2 GG/GG internal loop, and perform MD simulations and site-directed mutagenesis to elucidate the mechanism for GGGGCC repeat RNA binding to SRSF2, a splicing factor and key marker of nuclear speckles. We reveal that the R47/T51/R61 residues in RNA recognition motif of SRSF2 and the 2 × 2 GG/GG internal loop in GGGGCC repeat RNA are essential for binding. This work furnishes a valuable high-resolution structural basis for understanding the binding mechanism for GGGGCC repeat RNA and RBPs, and steers RNA structure-based drug design.
The lack of anion exchange membranes (AEMs) with good conductivity and alkaline stability has been one of the challenges for alkaline fuel cells. Introducing branched structure was a good strategy to promote conductivity and alkaline stability due to the bigger free volume of polymer and steric hindrance of cation. Herein, a series of branched AEMs with multiple arms (four and six) were successfully prepared. Multi-arm branched AEMs demonstrated obvious improvement of conductivity and alkaline stability because of the larger free volume and steric hindrance of multi-arm branched structures, respectively. Four-arm branched B4-QPPCTP-5 exhibited best comprehensive performance, including high conductivity of 242.2 mS·cm–1, a good alkaline stability of 2000 h with hardly degradation, and high mechanical property of >40 MPa. Single fuel cell based on multi-arm branched AEMs exhibited high power output of 1.2 W·cm–2. This work provides effective theoretical guidance for polymer structure design and preparation of branched AEMs.
This study explores the application of machine learning to predict the bond dissociation energies (BDEs) of metal-trifluoromethyl compounds. We constructed a dataset comprising 2219 metal-trifluoromethyl BDEs using density functional theory (DFT). Through a comparative analysis of various machine learning algorithms and molecular fingerprints, we determined that the XGBoost algorithm, when combined with MACCS and Morgan fingerprints, exhibited superior performance. To further enhance predictive accuracy, we integrated chemical descriptors alongside multiple fingerprints, achieving an R2 value of 0.951 on the test set. The model demonstrated excellent generalization capabilities when applied to synthesized metal-trifluoromethyl compounds, highlighting the critical role of chemical descriptors in improving predictive performance. This research not only establishes a robust predictive model for metal-trifluoromethyl BDEs but also underscores the value of incorporating chemical insights into machine learning workflows to enhance the prediction of chemical properties.
A novel method for the asymmetric synthesis of 1,7-annulated indazoles has been developed via bifunctional Brønsted base catalyzed cascade reaction. This process enabled the formation of multiple chiral centers including a quaternary carbon center in high yields with excellent diastereoselectivities and enantioselectivities. The reaction exhibited broad functional group tolerance and mild reaction conditions.
Herein, it is reported that the aryl radicals derived from aryl thianthrenium salts are used as coupling partner in the arylation reactions of isocyanides, simultaneously as initiators for the formation of alkyl and phosphoryl radicals from ethers and diarylphosphine oxides. This cascade cyclization reaction leads to diverse arylated, alkylated and phosphorylated heteroaromatic compounds. Notably, this transformation can be achieved without the aid of metals or photocatalysts, exhibiting a wide substrate applicability and operational simplicity. Mechanistic studies suggest the involvement of radical processes and electron donor-acceptor (EDA) complexes in this transformation.
Stimuli-responsive organic luminescent materials exhibit significant sensitivity to various external stimuli, among which their excellent photosensitivity is particularly prominent. This unique feature gives them great potential for applications. Herein, five organic small molecule emitters based on triphenylamine derivatives have been synthesized via Suzuki-coupling reaction. These small molecules have excellent fluorescence properties with fluorescence quantum yields (Φ) all reaching over 90%. When irradiated with a 365 nm UV lamp, interesting photochromic phenomena occurred in their chloroform solutions. This phenomenon has been studied intensively by UV-vis absorption and fluorescence spectroscopy, EPR measurements, and density functional theory calculations, and finally, the triphenylamine group was used as a photoinitiation precursor and electron donor, and the photo-induced charge transfer complex (PCTC) initiated by the donor molecule was successfully constructed.
Presented herein is a condition-controlled selective synthesis of CF3-chromene and CF3-benzofuran based on the reaction of N-phenoxyacetamide and CF3-ynone. When the reaction is carried out in MeOH under the catalysis of Rh(III), CF3-chromene is formed via C—H metalation-initiated alkenylation, acetamide group migration and intramolecular oxo-nucleophilic addition. On the other hand, when the reaction is run in DMSO under the promotion of CsOAc, CF3-benzofuran is generated via aza-Michael addition-initiated [3,3]-σ rearrangement, intramolecular oxo-nucleophilic addition and water elimination. To our knowledge, this is the first report on the selective construction of chromene or benzofuran scaffold along with introduction of a CF3 unit from the same starting materials. The methodology was scalable and the products could be readily transformed into other valuable products. Moreover, the products thus obtained possess decent anticancer activity.
Non-π-conjugated groups have recently emerged as excellent fundamental building blocks (FBUs) for UV nonlinear optical (NLO) crystals, due to their ability to achieve wide transparency. However, their generally high crystallographic symmetry often results in limited optical anisotropy, making few resultant crystals phase-matchable in the UV wavelength range. In this work, we introduce the polar [NH(CH2SO3)2]2− dimer as a novel non-π-conjugated FBU, and synthesize the first NLO iminodimethanesulfonate crystal, namely Cs2NH(CH2SO3)2·H2O. Experimental results demonstrate that this crystal exhibits second-harmonic generation (SHG) responses with 0.8 times of KDP, moderate birefringence of 0.044@550 nm, and broad UV transparency (< 200 nm), enabling phase-matchable SHG at the key UV wavelength of 266 nm. First-principles calculations confirm that polar [NH(CH2SO3)2]2− dimers contribute to the optical properties of Cs2NH(CH2SO3)2·H2O. This work highlights an excellent UV NLO-active FBU for exploring high-performance UV NLO crystals.
Traditional fluorescent probes typically display blueshifted emission in rigidifying media; however, a newly developed class of rigidochromic fluorophores derived from phenanthridine demonstrates remarkable redshifted emission under similar conditions. Pyridine, with similar N-heterostructure to those of phenanthridine group, is considered a promising candidate for achieving comparable rigidity-induced redshift behavior. In this work, we synthesized eight organic fluorophores featuring diverse functional units and substitutes by systematically combining pyridine with carbazole, triazatruxene (TAT), and tetraphenylethylene (TPE), respectively. These molecules exhibit significant emission redshifts (up to 225 nm, a record high value ever reported) or notable emission intensity changes as the rigidity of the polymer matrix increases, along with unique acid responsiveness. The differences in polar-π interactions between fluorophores and polymers diversify the emission behavior, advancing the development of secure printing and intelligent optical materials. By embedding these fluorophores into polymer films with helical phase structures, redshifted emission with tunable chirality was achieved. Notably, leveraging the acid-responsive properties of these fluorophores, a time-dependent light-controlled dynamic encryption system was constructed, successfully enabling multi-level information encryption. This research greatly expands the scope of rigidochromic fluorophores, and their applications in anti-counterfeiting and information storage.
UiO-66, a prototypical and stable zirconium-based metal-organic framework (MOF), consists of zirconium-oxide clusters (Zr6O4(OH)4) and benzene-1,4-dicarboxylate (BDC) organic linkers. It exhibits abundant active sites, a high specific surface area, a tunable pore structure, and exceptional chemical and thermal stability, making it highly advantageous for various practical applications. The integration of functional components within UiO-66 has been shown to optimize its electronic properties and coordination environment, thereby enhancing its multifunctionality and catalytic performance. This review highlights the analysis of structural characteristics of UiO-66, explores various modification strategies such as the introduction of functional organic linkers, selection of metal nodes, defect engineering, and doping with external functional components, and discusses its applications in environmental remediation and energy-related fields.
Recent progress in nanotechnology and synthetic biology has demonstrated the potential of DNA coacervates for biomimetic and biological applications. DNA coacervates are micron-scale, membrane-free, spherical structures formed by liquid-liquid phase separation of DNA materials. They uniquely combine the programmability of DNA with the fluidic properties of coacervates, allowing for controlled modulation of their structures, biomimetic and biological functions, and dynamic behaviors through rational sequence design. This review summarizes methods for the formation of different DNA coacervates and explores their extensive applications in biomimicry, biosensing and therapeutics. Limitations and prospects of DNA coacervates are also discussed.