Tetrachlorophthalimides as Organocatalytic Acceptors for Electron Donor–Acceptor Complex Photoactivation

Excitation of photoactive electron donor–acceptor (EDA) complexes is an effective way to generate radicals. Applications in a catalytic regime typically use catalytic donors. Herein, we report that readily available electron-poor tetrachlorophthalimides can act as effective organocatalytic acceptors to trigger the formation of EDA complexes with a variety of radical precursors not amenable to previous catalytic methods. Excitation with visible light generates carbon radicals under mild conditions. The versatility of this EDA complex catalytic platform allowed us to develop mechanistically distinct radical reactions, including in combination with a cobalt-based catalytic system. Quantum yield measurements established that a closed catalytic cycle is operational, which hints at the ability of tetrachlorophthalimides to readily turn over and govern each catalytic cycle

Regioselective Sulfonylvinylation of the Unactivated C(sp³)–H Bond via a C‑Centered Radical-Mediated Hydrogen Atom Transfer (HAT) Process

Given the similarity of multiple sp3 C–H bonds in electronic properties and bond dissociation energy (BDE), regioselective sp3 C–H bond functionalization remains a paramount challenge. Here, we report a C-centered radical-mediated approach for site-specific sulfonylvinylation of the C­(sp3)–H bond via the hydrogen atom transfer (HAT) process. The reaction features mild conditions, broad substrate scope, and high regioselectivity and stereoselectivity, manifesting the nontrivial synthetic potential

Difunctional Microelectrode Arrays for Single-Cell Electrical Stimulation and pH Detection

Due to its direct effect on biomolecules and cells, electrical stimulation (ES) is now widely used to regulate cell proliferation, differentiation, and neurostimulation and is even used in the clinic for pain relief, treatment of nerve damage, and muscle rehabilitation. Conventional ES is mostly studied on cell populations, but the heterogeneity of cancer cells results in the inability to access the response of individual cells to ES. Therefore, detecting the extracellular pH change (ΔpHe) after ES at the single-cell level is important for the application of ES in tumor therapy. In this study, cellular ΔpHe after periodic impulse electrostimulation (IES) was monitored in situ by using a polyaniline (PANI)-modified gold microelectrode array. The PANI sensor had excellent sensitivity (53.68 mV/pH) and linear correlation coefficient (R2 = 0.999) over the pH range of 5.55–7.41. The cells showed different degrees of ΔpHe after the IES with different intervals and stimulation potential. A shorter pulse interval and a higher stimulation potential could effectively enhance stimulation and increase cellular ΔpHe. At 0.5 V potential stimulation, the cellular ΔpHe increased with decreasing pulse interval. However, if the pulse interval was long enough, even at a higher potential of 0.7 V, there was no significant additional ΔpHe due to the insufficient stimulus strength. Based on the above conclusions, the prepared PANI microelectrode arrays (MEAs) were capable of stimulating and detecting single cells, which contributed to the deeper application of ES in tumor therapy

Hyperbranched Tetraphenylethylene Derivatives with Low Non-specific Aggregation-Induced Emission for Fluorescence Recognition of Proteins with Hydrophobic Pockets

Proteins play an important role in the physiological process of many organisms, and their abnormal level often indicates the occurrence of some diseases. Therefore, protein analysis has important reference value and clinical significance for early diagnosis and therapy of disease. Using human serum albumin (HSA) as a model protein, a series of super-branched tetraphenylethylene (TPE) derivatives with different branching structures and terminal groups are reported herein for highly sensitive and specific recognition of proteins with hydrophobic cages. Benefiting from the hyperbranched structures, these probes showed much higher critical micelle concentrations (CMCs) than most linear TPE-based amphiphilic molecules since the hyperbranched structure not only improved their solubility but also amplified the steric hindrance effect and electrostatic repulsive force to prevent their aggregation. Dynamic light scattering experiments proved that these probes formed dense aggregates at CMC, and such aggregate structures would lead to a higher background fluorescence noise. Hence, a higher CMC is more conducive to the detection of the target with low backgrounds. Among them, P3-COOH with −COOH as the terminal unit and a relatively longer branch showed the highest CMC and the best signal to background ratio (S/N). Mechanism studies showed that P3-COOH was bound to HSA mainly through a hydrophobic force, resulting in a limited P3-COOH molecular movement and less attack from quenchers in solutions, thus leading to greatly enhanced fluorescence intensity. In addition, P3-COOH was also applied to the determination of HSA content in actual human serum samples

Photochemical Organocatalytic Synthesis of Thioethers from Aryl Chlorides and Alcohols

Thioethers, often found in pharmaceuticals and natural compounds, typically involve metal cross-coupling reactions, high temperatures, and the use of disagreeable thiols for their synthesis. Here we present a straightforward, thiol-free organocatalytic protocol that uses mild conditions to stitch together inexpensive alcohols and aryl chlorides, yielding a diverse array of aryl alkyl thioethers. Central to this approach was the discovery that tetramethylthiourea can serve as a simple sulfur source upon intercepting photochemically generated aryl radicals. To form radicals, we used a readily available indole thiolate organocatalyst that, when excited with 405 nm light, gained a strongly reducing power, enabling the activation of typically unreactive aryl chlorides via single-electron transfer. Radical trapping by the thiourea, followed by an alcohol attack via a polar path, resulted in the formation of thioether products

Promising Mercaptobenzoic Acid-Bridged Charge Transfer for Electrochemiluminescence from CuInS₂@ZnS Nanocrystals via Internal Cu⁺/Cu²⁺ Couple Cycling

Screening novel electrochemiluminescence (ECL) systems with less inherent interference is strongly anticipated for ECL evolution. Herein, near-infrared ECL (∼730 nm) with an ultralow triggering potential of 0.45 V (vs Ag/AgCl) is achieved under physiological conditions with 4-mercaptobenzoic acid (MBA) and citrate capped CuInS2@ZnS (CIS@ZnS) nanocrystals (NCs), which is promising for less autofluorescence and electrochemical interference. Cu+ species within the CIS@ZnS NCs can be electrochemically oxidized at 0.45 V to form internal Cu2+ defects, while the capping agent MBA can bridge a direct charge transfer between the oxidized NCs and the traditional coreactant tripropylamine (TPrA) for weak ECL at 0.45 V. When hydrazine hydrate is adopted as coreactant, CIS@ZnS NCs/hydrazine hydrate exhibits 8k-fold enhanced oxidative-reduction ECL via the internal Cu+/Cu2+ couple cycling at 0.45 V in comparison to CIS@ZnS NCs/TPrA. This work opens a way to enhance the radiative charge transfer of NCs

Data_Sheet_1_Amyloid beta-correlated plasma metabolite dysregulation in Alzheimer's disease: an untargeted metabolism exploration using high-resolution mass spectrometry toward future clinical diagnosis.PDF

IntroductionAlzheimer's disease (AD) is a leading cause of dementia, and it has rapidly become an increasingly burdensome and fatal disease in society. Despite medical research advances, accurate recognition of AD remains challenging. Epidemiological evidence suggests that metabolic abnormalities are tied to higher AD risk.MethodsThis study utilized case-control analyses with plasma samples and identified a panel of 27 metabolites using high-resolution mass spectrometry in both the Alzheimer's disease (AD) and cognitively normal (CN) groups. All identified variables were confirmed using MS/MS with detected fragmented ions and public metabolite databases. To understand the expression of amyloid beta proteins in plasma, ELISA assays were performed for both amyloid beta 42 (Aβ42) and amyloid beta 40 (Aβ40).ResultsThe levels of plasma metabolites PAGln and L-arginine were found to significantly fluctuate in the peripheral blood of AD patients. In addition, ELISA results showed a significant increase in amyloid beta 42 (Aβ42) in AD patients compared to those who were cognitively normal (CN), while amyloid beta 40 (Aβ40) did not show any significant changes between the groups. Furthermore, positive correlations were observed between Aβ42/Aβ40 and PAGln or L-arginine, suggesting that both metabolites could play a role in the pathology of amyloid beta proteins. Binary regression analysis with these two metabolites resulted in an optimal model of the ROC (AUC = 0.95, p DiscussionThis study highlights the potential of advanced high-resolution mass spectrometry (HRMS) technology for novel plasma metabolite discovery with high stability and sensitivity, thus paving the way for future clinical studies. The results of this study suggest that the combination of PAGln and L-arginine holds significant potential for improving the diagnosis of Alzheimer's disease (AD) in clinical settings. Overall, these findings have important implications for advancing our understanding of AD and developing effective approaches for its future clinical diagnosis.</p

Table_1_Amyloid beta-correlated plasma metabolite dysregulation in Alzheimer's disease: an untargeted metabolism exploration using high-resolution mass spectrometry toward future clinical diagnosis.xlsx

IntroductionAlzheimer's disease (AD) is a leading cause of dementia, and it has rapidly become an increasingly burdensome and fatal disease in society. Despite medical research advances, accurate recognition of AD remains challenging. Epidemiological evidence suggests that metabolic abnormalities are tied to higher AD risk.MethodsThis study utilized case-control analyses with plasma samples and identified a panel of 27 metabolites using high-resolution mass spectrometry in both the Alzheimer's disease (AD) and cognitively normal (CN) groups. All identified variables were confirmed using MS/MS with detected fragmented ions and public metabolite databases. To understand the expression of amyloid beta proteins in plasma, ELISA assays were performed for both amyloid beta 42 (Aβ42) and amyloid beta 40 (Aβ40).ResultsThe levels of plasma metabolites PAGln and L-arginine were found to significantly fluctuate in the peripheral blood of AD patients. In addition, ELISA results showed a significant increase in amyloid beta 42 (Aβ42) in AD patients compared to those who were cognitively normal (CN), while amyloid beta 40 (Aβ40) did not show any significant changes between the groups. Furthermore, positive correlations were observed between Aβ42/Aβ40 and PAGln or L-arginine, suggesting that both metabolites could play a role in the pathology of amyloid beta proteins. Binary regression analysis with these two metabolites resulted in an optimal model of the ROC (AUC = 0.95, p DiscussionThis study highlights the potential of advanced high-resolution mass spectrometry (HRMS) technology for novel plasma metabolite discovery with high stability and sensitivity, thus paving the way for future clinical studies. The results of this study suggest that the combination of PAGln and L-arginine holds significant potential for improving the diagnosis of Alzheimer's disease (AD) in clinical settings. Overall, these findings have important implications for advancing our understanding of AD and developing effective approaches for its future clinical diagnosis.</p

PDA–PEI-Copolymerized Nanodots with Tailorable Fluorescence Emission and Quenching Properties for the Sensitive Ratiometric Fluorescence Sensing of miRNA in Serum

Dopamine and polyethyleneimine (PEI) copolymerized nanodots (PDA–PEI nanodots) with both fluorescence emission and quenching features were synthesized by a simple one-step reaction at room temperature. By adjusting the dopamine and PEI ratio as well as the chain length of PEI, the fluorescence emission and quenching properties of PDA–PEI nanodots can be controlled well. Under optimal conditions, the nanodots showed strong green fluorescence emission with an absolute quantum yield of 1–2% and a quenching efficiency of more than 99% to several fluorophores with emission wavelengths ranging from blue to red light regions. The nanodots with a large number of functional groups also showed strong affinity to nucleic acid strands, excellent solubility in aqueous solution, long-term stability, and uniform size distribution. Integrating these attractive features with the specific enzymatic digestion reaction of the DSN enzyme, a highly sensitive ratiometric fluorescence nanoprobe for miRNA analysis was developed. Aminomethylcoumarin acetate (AMCA), which possesses the same excitation wavelength but a well-resolved blue fluorescence emission with PDA–PEI nanodots, was selected as the signal-reporting unit for capture probe labeling, while the inherent green fluorescence of PDA–PEI nanodots served as the reference. According to the ratiometric fluorescence signal, the ratiometric fluorescence nanoprobes showed high sensitivity and good accuracy for the miRNA assay. Because of the high and universal quenching efficiency, stable fluorescence emission, easily assembled interface, and uniform morphology, the nanodots may have great application prospects to serve as a universal nanoplatform for the fabrication of ratiometric fluorescence nanoprobes

Revealing Adsorption Mechanism of <i>p</i>‑Mercaptobenzoic Acid with TiO₂ Surfaces Using Electric Field-Enhanced Semiconductor SERS

p-Mercaptobenzoic acid (4-MBA) is a typical molecular probe for a surface-enhanced Raman scattering (SERS) study of the enhancement performance of semiconductor nanoparticles. Understanding the molecular adsorption mechanism of 4-MBA on a semiconductor surface is crucial to reveal the enhancement mechanism of semiconductor SERS. Herein, two types of submicrometer-sized TiO2 particles with amorphous (denoted as a-TiO2) and anatase structures (denoted as c-TiO2) were fabricated, and their potential as SERS-active substrates with high electric-field enhancement was explored based on the near-field scattering theory and finite-element method simulation. The electric field-enhanced semiconductor SERS provide a better vision for us to study the adsorption modes of molecules on the TiO2 surface. On this basis, adsorption behaviors of 4-MBA on a-TiO2 and c-TiO2 particles were systematically studied by the semiconductor SERS and density functional theory. The results demonstrated that the adsorption mechanism of 4-MBA with TiO2 surfaces is highly dependent on the exposure of acid sites of TiO2 surfaces. 4-MBA adsorbs preferentially on Brønsted acid sites of a-TiO2 through a carboxyl group, in contrast on Lewis acid sites of c-TiO2 through a sulfhydryl group. Furthermore, 4-MBA molecules may form multilayer adsorption on TiO2 surfaces through the hydrogen bond and/or π–π stacking interaction. Research results not only provide a new insight to re-evaluate the chemical enhancement mechanism for TiO2–4-MBA systems but also provide a theoretical guidance for the modification of TiO2 surface with organic molecules containing carboxyl and sulfhydryl groups