JACS Au最新文献

The external control of catalytic activity and substrate specificity of enzymes by light has aroused great interest in the fields of biocatalysis and pharmacology. Going beyond, we have attempted to photocontrol enzyme stereoselectivity on the example of phosphotriesterase (PTE), which is capable of hydrolyzing a wide variety of racemic organophosphorus substrates where one of two enantiomers is often highly toxic. To pursue this goal, the photocaged unnatural amino acid o-nitrobenzyl-l-tyrosine (ONBY) was incorporated by genetic code expansion at the large subsite of the active center, together with additional mutations at the small subsite. The stereoselectivities of the resulting PTE variants were tested with the achiral control substrate paraoxon and four different racemic substrates, which contained a p-nitrophenol leaving group in combination with either methyl-phenyl, ethyl-phenyl, methyl-cyclohexyl, or ethyl-cyclohexyl substituents. Comparison of the enantioselectivities (k_cat/K_M for S_p divided by k_cat/K_M for R_p) before and after decaging of ONBY using irradiation revealed the desired photoinduced inversion of enantioselectivity for three of the variants: PTE_I106A-H257ONBY exhibited a 43-fold stereoselectivity switch for the methyl-phenyl substrate, PTE_I106A-F132A-H257ONBY a 184-fold stereoselectivity switch for the methyl-cyclohexyl substrate, and PTE_I106A-F132A-S308A-H257ONBY a 52-fold and a 57-fold stereoselectivity switch for the methyl-cyclohexyl and the ethyl-cyclohexyl substrates. A computational analysis including molecular dynamics simulations and docking showed that a complicated interplay between steric constraints and specific enzyme–substrate interactions is responsible for the observed effects. Our findings significantly broaden the scope of possibilities for the spatiotemporal control of enantioselective transformations using light in biocatalytic systems.

Soil-release polymers (SRPs) are important components of fabric care formulations, performing important roles in the cleaning of synthetic fabrics. SRPs modify the surface of textiles and render materials resistant to staining, while offering environmental benefits by enabling effective cleaning using shorter, cooler wash cycles. Most SRPs used in formulations contain petroleum-sourced terephthalic acid, limiting the environmental benefits presented by the use of these key additives. Here, we have prepared SRPs using a selection of pyridine dicarboxylate monomers that can be accessed from biomass and assessed their ability to modify polyester surfaces. Interestingly, a wide range of surface deposition behavior was observed, with soil-release performance significantly impacted by the pyridine dicarboxylate component in use. The performance of polymers containing 2,5-pyridine dicarboxylate units exceeded or was comparable to that of current industry-standard SRPs, while polymers constructed using 2,4- or 2,6-pyridine dicarboxylate units displayed poor performance. Through a range of studies including dynamic light scattering, contact angle analysis, scanning electron microscopy, and molecular modeling we have explored the solution and interfacial behavior of SRPs and propose the observed changes in performance to arise from a combination of differences in solution self-assembly and variation in affinities for polyester surfaces. Our work highlights the potential of using biosourced starting materials in the replacement of petroleum-derived polymers within formulated consumer products and presents a rationale for the design of SRPs.

Mass spectrometry (MS) is a potentially powerful approach for the diagnostic detection of SARS-CoV-2 and other viruses. However, MS detection is compromised when viral antigens are present at low concentrations, especially in complex biological media. We hypothesized that viral receptors could be used for viral target capture to enable detection by MS under such conditions. This was tested using the extracellular domain of the SARS-CoV-2 receptor ACE2. To maximize recovery of the target protein, directed protein evolution was first used to increase the affinity of ACE2 for spike protein. This generated an evolved ACE2 with increased binding affinity for the spike protein receptor-binding domain (RBD). However, as with other affinity-enhanced evolved forms of ACE2, binding was sensitive to mutations in variant RBDs. As an alternative strategy to maximize capture, the native ACE2 extracellular domain was engineered for increased binding by the addition of an oligomerization scaffold to create pentameric ACE2. This bound extremely tightly to SARS-CoV-2 RBD, with an increase in apparent affinity of several thousand-fold over monomeric ACE2, and RBD retention of more than 8 h. Immobilization of multimeric ACE2 enabled quantitative enrichment of viral spike protein from saliva and increased the sensitivity of detection by MS. These data show that capture by engineered receptors combined with MS can be an effective, rapid method for detection and quantitation of target protein. A similar approach could be used for attachment proteins of other viruses or any target protein for which there are suitable receptors.

Mass spectrometry (MS) is a potentially powerful approach for the diagnostic detection of SARS-CoV-2 and other viruses. However, MS detection is compromised when viral antigens are present at low concentrations, especially in complex biological media. We hypothesized that viral receptors could be used for viral target capture to enable detection by MS under such conditions. This was tested using the extracellular domain of the SARS-CoV-2 receptor ACE2. To maximize recovery of the target protein, directed protein evolution was first used to increase the affinity of ACE2 for spike protein. This generated an evolved ACE2 with increased binding affinity for the spike protein receptor-binding domain (RBD). However, as with other affinity-enhanced evolved forms of ACE2, binding was sensitive to mutations in variant RBDs. As an alternative strategy to maximize capture, the native ACE2 extracellular domain was engineered for increased binding by the addition of an oligomerization scaffold to create pentameric ACE2. This bound extremely tightly to SARS-CoV-2 RBD, with an increase in apparent affinity of several thousand-fold over monomeric ACE2, and RBD retention of more than 8 h. Immobilization of multimeric ACE2 enabled quantitative enrichment of viral spike protein from saliva and increased the sensitivity of detection by MS. These data show that capture by engineered receptors combined with MS can be an effective, rapid method for detection and quantitation of target protein. A similar approach could be used for attachment proteins of other viruses or any target protein for which there are suitable receptors.

Lithium-ion batteries are among the most important energy-storage devices. In this regard, nickel–cobalt–manganese (NCM) cathodes are widely used because of their high energy density and stability. Cu on NCM can enhance the overall performance by aiding lithium-ion transport through cation mixing; however, it leads to issues, such as internal short circuits. The precipitation pH of Cu is high, making its chemical separation from the NCM challenging. Given the impacts and the challenge of separation, an accurate quantification of the residual Cu content in the NCM cathode is essential. Inductively coupled plasma methods struggle with the accurate quantification of trace impurities in NCM owing to the high contents of material elements, leading to instrument malfunction and time-consuming labor. In this study, the introduction of electrochemical methods significantly weakened the matrix effect and facilitated the pretreatment of the solution. In particular, a thin-film electrode (TFE) made of Rh allowed quantification of the Cu present in commercial NCM powder. Cyclic voltammetry and an electrochemical quartz crystal microbalance were used to confirm the formation of two types of underpotential deposition (UPD) Cu on the Rh TFE. Square-wave voltammetry was used to analyze the kinetic differences in Cu_upd and quantify trace amounts of Cu with high sensitivity. The results included a relative standard deviation of 2.54%, linear range of 13–450 ppb, and limit of detection of 3.9 ppb. The method was successfully applied to commercial NCM products, where the standard addition method determined Cu content in the range 40–60 ppb. This method provides standardized guidelines for both laboratory and industry for evaluating the effects of impurities across various NCM cathodes.

Axial chirality is the key physiochemical element, yet its chiroptical utilities have been largely limited to covalent synthesis and infinitely assembled systems so far. Here we report a new application of axially chiral binaphthyls for efficient, optical chirality enhancement and transfer upon noncovalent encapsulation by achiral aromatic micelles in water. The CD activities of dialkoxy binaphthyls are significantly enhanced (up to 7-fold) upon encapsulation by an anthracene-based aromatic micelle. Large emission enhancement (∼4-fold) and efficient guest-to-guest, optical chirality transfer are achieved through coencapsulation of the binaphthyls with achiral cycloparaphenylenes, in a guest-within-guest fashion, by the micelle. The observed unusual properties are derived from the tight inclusion of the chiral guests into the macrocyclic guests, efficiently generated only in the aromatic cavity. Moderate CPL can be observed from the coencapsulated macrocycles within the ternary composites. Furthermore, more than ∼4-fold enhanced guest-to-guest chiroptical transfer is demonstrated with a functionalized cycloparaphenylene through the present coencapsulation strategy.

Axial chirality is the key physiochemical element, yet its chiroptical utilities have been largely limited to covalent synthesis and infinitely assembled systems so far. Here we report a new application of axially chiral binaphthyls for efficient, optical chirality enhancement and transfer upon noncovalent encapsulation by achiral aromatic micelles in water. The CD activities of dialkoxy binaphthyls are significantly enhanced (up to 7-fold) upon encapsulation by an anthracene-based aromatic micelle. Large emission enhancement (∼4-fold) and efficient guest-to-guest, optical chirality transfer are achieved through coencapsulation of the binaphthyls with achiral cycloparaphenylenes, in a guest-within-guest fashion, by the micelle. The observed unusual properties are derived from the tight inclusion of the chiral guests into the macrocyclic guests, efficiently generated only in the aromatic cavity. Moderate CPL can be observed from the coencapsulated macrocycles within the ternary composites. Furthermore, more than ∼4-fold enhanced guest-to-guest chiroptical transfer is demonstrated with a functionalized cycloparaphenylene through the present coencapsulation strategy.

Lithium-ion batteries are among the most important energy-storage devices. In this regard, nickel-cobalt-manganese (NCM) cathodes are widely used because of their high energy density and stability. Cu on NCM can enhance the overall performance by aiding lithium-ion transport through cation mixing; however, it leads to issues, such as internal short circuits. The precipitation pH of Cu is high, making its chemical separation from the NCM challenging. Given the impacts and the challenge of separation, an accurate quantification of the residual Cu content in the NCM cathode is essential. Inductively coupled plasma methods struggle with the accurate quantification of trace impurities in NCM owing to the high contents of material elements, leading to instrument malfunction and time-consuming labor. In this study, the introduction of electrochemical methods significantly weakened the matrix effect and facilitated the pretreatment of the solution. In particular, a thin-film electrode (TFE) made of Rh allowed quantification of the Cu present in commercial NCM powder. Cyclic voltammetry and an electrochemical quartz crystal microbalance were used to confirm the formation of two types of underpotential deposition (UPD) Cu on the Rh TFE. Square-wave voltammetry was used to analyze the kinetic differences in Cu_upd and quantify trace amounts of Cu with high sensitivity. The results included a relative standard deviation of 2.54%, linear range of 13-450 ppb, and limit of detection of 3.9 ppb. The method was successfully applied to commercial NCM products, where the standard addition method determined Cu content in the range 40-60 ppb. This method provides standardized guidelines for both laboratory and industry for evaluating the effects of impurities across various NCM cathodes.

Herein, we report a scalable and mild strategy for the monofluoroalkylation of a wide array of Giese acceptors via visible-light-mediated photoredox catalysis in continuous flow. The use of flow technology significantly enhances productivity and scalability, whereas mildness of conditions and functional group tolerance are ensured by leveraging 4CzIPN, a transition-metal-free organic photocatalyst. Structurally diverse secondary and tertiary monofluoroalkyl radicals can thus be accessed from readily available α-monofluorocarboxylic acids. Given the mild reaction conditions, this protocol is also amenable to the late-stage functionalization of biologically relevant molecules such as menthol, amantadine, bepotastine, and estrone derivatives, rendering it suitable for application to drug discovery programs, for which the introduction of fluorinated fragments is highly sought after. This method was also extended to enable a reductive multicomponent radical-polar crossover transformation to rapidly increase the complexity of the assembled fluorinated architectures in a single synthetic operation.

Herein, we report a scalable and mild strategy for the monofluoroalkylation of a wide array of Giese acceptors via visible-light-mediated photoredox catalysis in continuous flow. The use of flow technology significantly enhances productivity and scalability, whereas mildness of conditions and functional group tolerance are ensured by leveraging 4CzIPN, a transition-metal-free organic photocatalyst. Structurally diverse secondary and tertiary monofluoroalkyl radicals can thus be accessed from readily available α-monofluorocarboxylic acids. Given the mild reaction conditions, this protocol is also amenable to the late-stage functionalization of biologically relevant molecules such as menthol, amantadine, bepotastine, and estrone derivatives, rendering it suitable for application to drug discovery programs, for which the introduction of fluorinated fragments is highly sought after. This method was also extended to enable a reductive multicomponent radical-polar crossover transformation to rapidly increase the complexity of the assembled fluorinated architectures in a single synthetic operation.