ACS Central Science最新文献

The cellular uptake routes of peptides and proteins are complex and diverse, often handicapping therapeutic success. Understanding their mechanisms of internalization requires chemical derivatization with approaches that are compatible with wash-free and real-time imaging. In this work, we developed a new late-stage labeling strategy for unprotected peptides and proteins, which retains their biological activity while enabling live-cell imaging of uptake and intracellular trafficking. Benzo-2,1,3-thiadiazoles were selectively incorporated into Cys residues of both linear and cyclic peptides via Pd-mediated arylation with good yields and high purities. The resulting labeled peptides are chemically stable under physiological conditions and display strong fluorogenic character for wash-free imaging studies. We utilized this approach to prepare native-like analogues of cell-penetrating peptides and performed time-course analysis of their internalization routes in live cells by fluorescence lifetime imaging. Furthermore, we applied our strategy to label the chemokine protein mCCL2 and monitor its internalization via receptor-mediated endocytosis in live macrophages. This study provides a straightforward strategy for late-stage fluorogenic labeling of intact peptides and small proteins and direct visualization of dynamic intracellular events.

Late-stage labeling to prepare unprotected fluorogenic peptides/proteins via Cys arylation with minimal bioactivity perturbation and suitable optical properties for wash-free imaging in live cells.

The cellular uptake routes of peptides and proteins are complex and diverse, often handicapping therapeutic success. Understanding their mechanisms of internalization requires chemical derivatization with approaches that are compatible with wash-free and real-time imaging. In this work, we developed a new late-stage labeling strategy for unprotected peptides and proteins, which retains their biological activity while enabling live-cell imaging of uptake and intracellular trafficking. Benzo-2,1,3-thiadiazoles were selectively incorporated into Cys residues of both linear and cyclic peptides via Pd-mediated arylation with good yields and high purities. The resulting labeled peptides are chemically stable under physiological conditions and display strong fluorogenic character for wash-free imaging studies. We utilized this approach to prepare native-like analogues of cell-penetrating peptides and performed time-course analysis of their internalization routes in live cells by fluorescence lifetime imaging. Furthermore, we applied our strategy to label the chemokine protein mCCL2 and monitor its internalization via receptor-mediated endocytosis in live macrophages. This study provides a straightforward strategy for late-stage fluorogenic labeling of intact peptides and small proteins and direct visualization of dynamic intracellular events.

Photothermal conversion can promote plastic depolymerization (chemical recycling to a monomer) through light-to-heat conversion. The highly localized temperature gradient near the photothermal agent surface allows selective heating with spatial control not observed with bulk pyrolysis. However, identifying and incorporating practical photothermal agents into plastics for end-of-life depolymerization have not been realized. Interestingly, plastics containing carbon black as a pigment present an ideal opportunity for photothermal conversion recycling. Herein, we use visible light to depolymerize polystyrene plastics into styrene monomers by using the dye in commercial black plastics. A model system is evaluated by synthesizing polystyrene–carbon black composites and depolymerizing under white LED light irradiation, producing styrene monomer in up to 60% yield. Excitingly, unmodified postconsumer black polystyrene samples are successfully depolymerized to a styrene monomer without adding catalysts or solvents. Using focused solar irradiation, yields up to 80% are observed in just 5 min. Furthermore, combining multiple types of polystyrene plastics with a small percentage of black polystyrene plastic enables full depolymerization of the mixture. This simple method leverages existing plastic additives to actualize a closed-loop economy of all-colored plastics.

Simple light irradiation transforms postconsumer polystyrene products to a styrene monomer, using heat from the additives already found in many commercial products.

Photothermal conversion can promote plastic depolymerization (chemical recycling to a monomer) through light-to-heat conversion. The highly localized temperature gradient near the photothermal agent surface allows selective heating with spatial control not observed with bulk pyrolysis. However, identifying and incorporating practical photothermal agents into plastics for end-of-life depolymerization have not been realized. Interestingly, plastics containing carbon black as a pigment present an ideal opportunity for photothermal conversion recycling. Herein, we use visible light to depolymerize polystyrene plastics into styrene monomers by using the dye in commercial black plastics. A model system is evaluated by synthesizing polystyrene-carbon black composites and depolymerizing under white LED light irradiation, producing styrene monomer in up to 60% yield. Excitingly, unmodified postconsumer black polystyrene samples are successfully depolymerized to a styrene monomer without adding catalysts or solvents. Using focused solar irradiation, yields up to 80% are observed in just 5 min. Furthermore, combining multiple types of polystyrene plastics with a small percentage of black polystyrene plastic enables full depolymerization of the mixture. This simple method leverages existing plastic additives to actualize a closed-loop economy of all-colored plastics.

Added electrons and holes in semiconducting (nano)materials typically occupy "trap states," which often determine their photophysical properties and chemical reactivity. However, trap states are usually ill-defined, with few insights into their stoichiometry or structure. Our laboratory previously reported that aqueous colloidal TiO₂ nanoparticles prepared from TiCl₄ + H₂O have two classes of electron trap states, termed Blue and Red. Herein, we show that the formation of Red from oxidized TiO₂ requires 1e ^- + 1H⁺, while Blue requires 1e ^- + 2H⁺. The two states are in a protic equilibrium, Blue ⇌ Red + H⁺, with K _eq = 2.65 mM. The Blue states in the TiO₂ NPs behave just like a soluble molecular acid with this K _eq as their K _a, as supported by solvent isotope studies. Because the trap states have different compositions, their population and depopulation occur with the making and breaking of chemical bonds and not (as commonly assumed) just by the movement of electrons. In addition, the direct observation of a 2H⁺/1e ^- trap state contradicts the emerging H atom transfer (1H⁺/1e ^-) paradigm for oxide/solution interfaces. Finally, this work emphasizes the importance of chemical stoichiometries, not just electronic energies, in understanding and directing the reactivity at solid/solution interfaces.

Added electrons and holes in semiconducting (nano)materials typically occupy “trap states,” which often determine their photophysical properties and chemical reactivity. However, trap states are usually ill-defined, with few insights into their stoichiometry or structure. Our laboratory previously reported that aqueous colloidal TiO₂ nanoparticles prepared from TiCl₄ + H₂O have two classes of electron trap states, termed Blue and Red. Herein, we show that the formation of Red from oxidized TiO₂ requires 1e^– + 1H⁺, while Blue requires 1e^– + 2H⁺. The two states are in a protic equilibrium, Blue ⇌ Red + H⁺, with K_eq = 2.65 mM. The Blue states in the TiO₂ NPs behave just like a soluble molecular acid with this K_eq as their K_a, as supported by solvent isotope studies. Because the trap states have different compositions, their population and depopulation occur with the making and breaking of chemical bonds and not (as commonly assumed) just by the movement of electrons. In addition, the direct observation of a 2H⁺/1e^– trap state contradicts the emerging H atom transfer (1H⁺/1e^–) paradigm for oxide/solution interfaces. Finally, this work emphasizes the importance of chemical stoichiometries, not just electronic energies, in understanding and directing the reactivity at solid/solution interfaces.

The two classes of trap states formed on reduction of colloidal TiO₂ nanoparticles contain 1e⁻/1H⁺ and 1e⁻/2H⁺, differing by a proton, providing a chemical view of trap states in oxide materials.

An efficient regiospecific co-assembly (RSCA) strategy is developed for general synthesis of mesoporous metal oxides with pore walls precisely decorated by highly dispersed noble metal nanocrystals with customized parameters (diameter and composition). It features the rational utilization of the specific interactions between hydrophilic molecular precursors, hydrophobic noble metal nanocrystals, and amphiphilic block copolymers, to achieve regiospecific co-assembly as confirmed by molecular dynamics simulations. Through this RSCA strategy, we achieved a controllable synthesis of a variety of functional mesoporous metal oxide composites (e.g., WO₃, ZrO₂, TiO₂) with in-pore walls precisely decorated by various noble metal nanocrystals of tailored components (Au, Ag, Pt, Pd and their nanoalloys) and sizes (3.0-8.5 nm). As an example, the obtained mesoporous 0.5-Ag/WO₃ material has a highly interconnected mesoporous structure and uniform 6.5 nm Ag nanocrystals confined in the mesopores, showing superior NO sensing performances with high sensitivity, good selectivity, and stability at low working temperature (127 °C). In situ spectroscopy study indicates that the NO sensing process involves a unique gas-solid reaction, where NO molecules are converted into chemisorbed NO _x species over the sensitive materials, inducing a remarkable change of resistance and outputting a dramatic response signal.

An efficient regiospecific co-assembly (RSCA) strategy is developed for general synthesis of mesoporous metal oxides with pore walls precisely decorated by highly dispersed noble metal nanocrystals with customized parameters (diameter and composition). It features the rational utilization of the specific interactions between hydrophilic molecular precursors, hydrophobic noble metal nanocrystals, and amphiphilic block copolymers, to achieve regiospecific co-assembly as confirmed by molecular dynamics simulations. Through this RSCA strategy, we achieved a controllable synthesis of a variety of functional mesoporous metal oxide composites (e.g., WO₃, ZrO₂, TiO₂) with in-pore walls precisely decorated by various noble metal nanocrystals of tailored components (Au, Ag, Pt, Pd and their nanoalloys) and sizes (3.0–8.5 nm). As an example, the obtained mesoporous 0.5-Ag/WO₃ material has a highly interconnected mesoporous structure and uniform 6.5 nm Ag nanocrystals confined in the mesopores, showing superior NO sensing performances with high sensitivity, good selectivity, and stability at low working temperature (127 °C). In situ spectroscopy study indicates that the NO sensing process involves a unique gas–solid reaction, where NO molecules are converted into chemisorbed NO_x species over the sensitive materials, inducing a remarkable change of resistance and outputting a dramatic response signal.

A facile regiospecific co-assembly strategy enables the obtained mesoporous WO₃ materials with precisely decorated Ag nanocrystals and rich oxygen vacancies to show superior NO sensitivity.

Prodrug-based nanoassemblies are promising platforms for cancer therapy. Prodrugs typically consist of three main components: drug modules, intelligent response modules, and modification modules. However, the available modification modules are usually hydrophobic aliphatic side chains, which affect the activation efficiency of the prodrugs. Herein, hydrophilic ethylene glycol fragments were inserted between the modification modules and the response modules, and the important effects of hydrophilic fragments on the assembly, drug release, and therapeutic index of the prodrugs were investigated. Notably, the introduction of hydrophilic fragments affected the intermolecular forces of the prodrugs and increased the interaction of hydrogen bonding. In addition, hydrophilic fragments significantly improved the redox drug release profiles, which affected the therapeutic index of the prodrug nanoassemblies. PTX-SS-OA NPs with hydrophilic fragments exhibited increased redox sensitivity, enhanced cytotoxicity, and superior antitumor efficacy. In comparison, PTX-SS-OAL NPs without hydrophilic fragments showed limited redox sensitivity and cytotoxicity but displayed better safety. Overall, the hydrophilic fragment is a critical determinant in modulating the therapeutic index of the prodrug nanoassemblies, which contributes to the development of advanced prodrug nanodelivery systems.

Hydrophilic ethylene glycol fragment is a critical determinant in modulating the therapeutic index of the paclitaxel prodrug nanoassemblies.

User-friendly software that allows scientists to design, print, test, and iterate upon reactors enables key reactor parameters to be optimized for electrochemical reactions.