Gold-Catalyzed C–O Cross-Coupling Reactions of Aryl Iodides with Silver Carboxylates

We have developed a C–O cross-coupling reaction of (hetero)aryl iodides with silver carboxylates via a AuI/AuIII catalytic cycle. The transformation featured exclusive chemoselectivity and moisture/air insensitivity. Aromatic and aliphatic (including primary, secondary, and tertiary) silver carboxylates are all suitable substrates. Moreover, this protocol worked well intermolecularly and intramolecularly. Most importantly, good yields were obtained regardless of the substrates’ electronic effect and steric hindrance

Divergent Synthesis of Sulfonyl Quinolines, Formyl Indoles, and Quinolones from Ethynyl Benzoxazinanones via Au^I Catalysis, Au^I‑ArI Co-Catalysis, and Silver Catalysis

The oxidative addition of AuI with aromatic iodide (Ar-I) may generate reactive yet functional group tolerant AuIII catalysts (Ar-AuIII-I) in situ. Ar-AuIII-I may show different reactivity compared to AuI catalysts and other transition metal catalysts. Our proof of concept application is the divergent synthesis of sulfonyl quinolines, formyl indoles, and quinolones from ethynyl benzoxazinanones via AuI catalysis, AuI-ArI co-catalysis, and silver catalysis. The chemo- and regioselectivity are good, and all the reactions can be conducted in the open air

Mild Base-Promoted Tandem Nucleophilic Substitution/Decarboxylation/Hydroamination: Access to 3‑Sulfonylindoles and 2‑Methyleneindophenols

We have developed an efficient construction of 3-sulfonylindoles and 2-methyleneindophenols via decarboxylative propargylation/hydroamination of ethynyl benzoxazinanones using sodium sulfonates and phenols as the nucleophiles. The reaction featured mild conditions (K2CO3), simple operation, and high chemoselectivity and was transition-metal-free. Our protocol could also be extended to other nucleophiles, including malonates, alcohols, and indoles. The broad substrate scope and scalability made this protocol practical for the synthesis of indole derivatives

Hydrogen Bond Donor and Unbalanced Ion Pair Promoter-Assisted Gold-Catalyzed Carbon–Oxygen Cross-Coupling of (Hetero)aryl Iodides with Alcohols

We have developed an efficient gold-catalyzed C–O cross-coupling reaction of (hetero)aryl iodides with primary and secondary alcohols via an AuI–AuIII catalytic cycle. This protocol featured moisture/air insensitivity, simple operation, and excellent functional group tolerance. Good yields were obtained regardless of steric hindrance and electronic factor (electron-rich or poor) of substrates, and the chirality of chiral alcohol starting materials could be preserved. Our protocol worked well for both intermolecular and intramolecular couplings. In addition, the RuPhos ligand was applied to gold-catalyzed cross-couplings. An unbalanced ion pair promoter and hydrogen bond donor solvent might be crucial in this transformation

Electrochemical Evaluation of Self-Disassociation of PKA upon Activation by cAMP

The allosteric reaction of protein kinase A (PKA) upon binding of cyclic AMP (cAMP) is revealed with an electrochemical technique through the redox current change of an electrochemically active marker. The different effect of cAMP's regulation at a distinct concentration level is obtained in this system. The influence of structural analogues is also examined with respect to the affinity and special selectivity. This study presents an electrochemical approach to the rapid and sensitive investigation of the protein−ligand interaction in the signal transduction networks

Electrochemical Evaluation of Self-Disassociation of PKA upon Activation by cAMP

The allosteric reaction of protein kinase A (PKA) upon binding of cyclic AMP (cAMP) is revealed with an electrochemical technique through the redox current change of an electrochemically active marker. The different effect of cAMP's regulation at a distinct concentration level is obtained in this system. The influence of structural analogues is also examined with respect to the affinity and special selectivity. This study presents an electrochemical approach to the rapid and sensitive investigation of the protein−ligand interaction in the signal transduction networks

Copper(I)-Catalyzed Oxyamination of β,γ-Unsaturated Hydrazones: Synthesis of Dihydropyrazoles

An efficient aerobic copper­(I)-catalyzed oxyamination of β,γ-unsaturated hydrazones has been developed. The methodology provides effective access to dihydropyrazole derivatives in a one-pot process utilizing dioxygen as a sustainable sacrificial oxidant. Mechanistic studies have been performed and are suggestive of an aerobic manifold via single electron transfer

Comprehensive analysis of the RSK gene family in acute myeloid leukemia determines a prognostic signature for the prediction of clinical prognosis and treatment responses

The prognosis of acute myeloid leukemia (AML) remains poor although the basic and translational research has been highly productive in understanding the genetics and pathopoiesis of AML and a plethora of targeted therapies have been developed. Consequently, it is crucial to deepen the knowledge of molecular pathogenesis underlying AML for the advancement of new treatment options. A RSK gene family-related signature was constructed to investigate whether RSK gene family members were useful in predicting the prognosis of AML patients. The relationship between the RSK gene family-related signature and the infiltration of immune cells was further assessed using the CIBERSORT algorithm. The ‘oncoPredict’ package was used to analyze relationships between the RSK gene family-related signature and the sensitivity to drugs or small molecules. Patients were classified into two groups using the RSK gene family-related signature following the median risk score. Overall survival (OS) was significantly longer in patients with low-risk scores than that in patients with high-risk scores as showed by both training and validation datasets. Moreover, the signature was helpful in predicting 1-year, 3-year, and 5-year OS in training and validation datasets. In addition, it was identified that low-risk patients exhibited greater sensitivity to 20 drugs or small molecules and that high-risk patients had higher sensitivity to 38 drugs or small molecules. RSK gene family members, particularly RPS6KA1 and RPS6KA4, may help to predict prognosis for AML patients. Furthermore, RPS6KA1 may serve as a novel drug target for AML.</p

Dynamic Interface-Assisted Rapid Self-Assembly of DNA Origami-Framed Anisotropic Nanoparticles

The ordered arrangement of nanoparticles can generate unique physicochemical properties, rendering it a pivotal direction in the field of nanotechnology. DNA-based chemical encoding has emerged as an unparalleled strategy for orchestrating precise and controlled nanoparticle assemblies. Nonetheless, it is often time-consuming and has limited assembly efficiency. In this study, we developed a strategy for the rapid and ordered assembly of DNA origami-framed nanoparticles assisted by dynamic interfaces. By assembling Au nanoparticles (AuNPs) onto DNA origami with different sticky ends in various directions, we endowed them with anisotropic specific affinities. After assembling DNA origami-framed AuNPs onto supported lipid bilayers with freely diffusing single-stranded DNA via DNA hybridization, we found that DNA origami-framed AuNPs could form larger ordered assemblies than those in 3D solution within equivalent time frames. Furthermore, we also achieved rapid and ordered assembly of liposome nanoparticles by employing the aforementioned strategy. Our work provides a novel avenue for efficient and rapid assembly of nanoparticles across two-dimensional interfaces, which is expected to promote the application of ordered nanoparticle assemblies in sensor and biomimetic system construction

Triplex DNA Nanoswitch for pH-Sensitive Release of Multiple Cancer Drugs

A DNA-based stimulus-responsive drug delivery system for synergetic cancer therapy has been developed. The system is built on a triplex-DNA nanoswitch capable of precisely responding to pH variations in the range of ∼5.0–7.0. In extracellular neutral pH space, the DNA nanoswitch keeps a linear conformation, immobilizing multiple therapeutics such as small molecules and antisense compounds simultaneously. Following targeted cancer cell uptake via endocytosis, the nanoswitch inside acidic intracellular compartments goes through a conformational change from linear to triplex, leading to smart release of the therapeutic combination. This stimuli-responsive drug delivery system does not rely on artificial responsive materials, making it biocompatible. Furthermore, it enables simultaneous delivery of multiple therapeutics for enhanced efficacy. Using tumor-bearing mouse models, we show efficient gene silencing and significant inhibition of tumor growth upon intravenous administration of the smart nanoswitch, providing opportunities for combinatorial cancer therapy