Fluorescent sensors have found broad applications in determining the concentrations of diverse analytes by measuring specific sensor–analyte fluorescent responses. For a chiral substrate containing ...varying composition of two enantiomers, both the concentration and enantiomeric composition should greatly influence the fluorescent response of an enantioselective fluorescent sensor. Thus, multiple independent measurements are normally needed to determine both the concentration and enantiomeric composition of a chiral compound. In order to facilitate the application of the enantioselective fluorescent sensors, our laboratory has developed four strategies to simultaneously determine the concentration and enantiomeric composition of various chiral substrates by a single fluorescence measurement. A mixture of a chiral BINOL-based dialdehyde and an achiral compound salicylaldehyde in the presence of Zn2+ is used to interact with chiral diamines, amino alcohols, and amino acids. The fluorescence enhancement at λ1 = 447 nm due to the achiral sensor is mostly determined by the concentration of the substrates, and the fluorescence enhancement at λ2 > 500 nm due to the chiral sensor is highly enantioselective. A 3D graph combining the fluorescence intensities at λ1 and λ2 can be used to determine the enantiomeric composition. A chiral conjugated polymer containing the BINOL–dialdehyde units is shown to amplify the enantioselectivity of the small molecule sensor under the same conditions. Combination of the chiral polymer with salicylaldehyde allows simultaneous concentration and enantiomeric composition determination. In a pseudoenantiomeric sensor pair of the BINOL-based amino alcohols, one sensor shows greater fluorescence enhancement with one enantiomer of chiral α-hydroxy carboxylic acid at λ1 = 374 nm and another sensor shows greater fluorescence enhancement with another enantiomer at λ2 = 330 nm. Using a mixture of this sensor pair allows the determination of both concentration and enantiomeric composition with one fluorescence measurement. A BINOL-based trifluoromethyl ketone is found to exhibit dual emission responses toward a chiral diamine at λ1 = 370 nm and λ2 = 438 nm. The fluorescence enhancement at λ1 is mostly determined by the substrate concentration and that at λ2 is highly enantioselective. Thus, using one sensor with one measurement gives both parameters. A BINOL–naphthyl imine compound is designed to show two different fluorescent responses toward functional chiral amines in the presence of Zn2+. When the naphthylamine unit is displaced off the sensor by a chiral amine substrate via imine metathesis, the emission of naphthylamine is restored at λ1 = 427 nm, which allows determination of the substrate concentration. The fluorescence enhancement at λ2 > 500 nm due to the formation of the new chiral imine products is highly enantioselective. The work discussed here has provided convenient methods to obtain the two important parameters of a chiral molecule by a single fluorescence measurement. They should contribute to the development of analytical tools for the rapid assay of chiral compounds.
Fluorescent probes that can discriminate enantiomers of amino acids in organic media or aqueous solution are discussed. This Minireview focuses on recent progress in the studies of three classes of ...probes including those made of cyclodextrins, 1,1′‐binaphthyl compounds, and nanomaterials, and uses them to illustrate the design strategies, applications, and limitations in this area. These probes are potentially useful for rapid analysis of asymmetric reactions for amino acid synthesis as well as the real‐time imaging of amino acids in biological systems. The challenges in these applications are analyzed. Working in this field of enantioselective fluorescent recognition of amino acids offers great opportunities to make new scientific discoveries and to develop important practical applications.
Enantioselective fluorescent probes based on cyclodextrins, 1,1′‐binaphthyl‐based aldehydes, or nanomaterials for free amino acids are used to illustrate the design strategies, applications, and limitations in this area. The challenges and opportunities for using these probes for rapid analysis in the asymmetric synthesis of amino acids as well as enantioselective fluorescent imaging of amino acids in biological systems are discussed.
The enantiomers of chiral amino acids play versatile roles in biological systems including humans. They are also very useful in the asymmetric synthesis of diverse chiral organic compounds. ...Therefore, identifying a specific amino acid and distinguishing it from its enantiomer are of great importance. Although significant progress has been made in the development of fluorescent probes for amino acids, most of them are not capable of conducting simultaneous chemoselective and enantioselective detection of a specific amino acid enantiomer. In this article, several fluorescent probes have been designed and synthesized for chemoselective as well as enantioselective recognition of certain amino acid enantiomers. (
S
)-
1
shows greatly enhanced fluorescence in the presence of
l
-glutamic acid and
l
-aspartic acid, but produces no or little fluorescence response toward their opposite enantiomers and other amino acids. (
R
)-
4
in combination with Zn
2+
shows greatly enhanced fluorescence in the presence of
l
-serine. (
S
)-
6
is designed for the selective recognition of histidine. Micelles made of an amphiphilic diblock copolymer are used to encapsulate the water-insoluble compound (
S
)-
8
which shows chemoselective as well as enantioselective fluorescence enhancement with
l
-lysine in the presence of Zn
2+
in aqueous solution. The same micelles are also used to encapsulate several (
S
)-1,1′-binaphthyl-based monoaldehydes (
S
)-
10
for the chemoselective and enantioselective fluorescence recognition of
l
-tryptophan in the presence of Zn
2+
in aqueous solution. These findings have demonstrated that highly selective fluorescence identification of a specific amino acid enantiomer can be achieved by incorporating certain functional groups at the designated locations of the 1,1′-binaphthyls. The binaphthyl core structure of these probes provides both a chirality source and highly tunable fluorescence properties. Matching the structure and chirality of these probes with those of the specific amino acid enantiomers can generate structurally rigid reaction products and give rise to greatly enhanced fluorescence. The strategies of this work can be further expanded to develop fluorescent probes for the specific identification of many amino acids of interest. This should facilitate the analysis of chiral amino acids in various applications. The outlook of this research and its comparison with other methods are also discussed.
Chiral fluorescent probes have been developed for chemoselective as well as enantioselective recognition of specific amino acid enantiomers including glutamic acid, aspartic acid, serine, histidine, lysine and tryptophan.
Chiral alcohols are ubiquitous in organic structures. One efficient method to generate chiral alcohols is the catalytic asymmetric addition of a carbon nucleophile to a carbonyl compound since this ...process produces a C–C bond and a chiral center simultaneously. In comparison with the carbon nucleophiles such as an organolithium or a Grignard reagent, an organozinc reagent possesses the advantages of functional group tolerance and more mild reaction conditions. Catalytic asymmetric reactions of aldehydes with arylzincs, vinylzincs, and alkynylzincs to generate functional chiral alcohols are discussed in this Account. Our laboratory has developed a series of 1,1′-bi-2-naphthol (BINOL)-based chiral catalysts for the asymmetric organozinc addition to aldehydes. It is found that the 3,3′-dianisyl-substituted BINOLs are not only highly enantioselective for the alkylzinc addition to aldehydes, but also highly enantioselective for the diphenylzinc addition to aldehydes. A one-step synthesis has been achieved to incorporate Lewis basic amine groups into the 3,3′-positions of the partially hydrogenated H8BINOL. These H8BINOL–amine compounds have become more generally enantioselective and efficient catalysts for the diphenylzinc addition to aldehydes to produce various types of chiral benzylic alcohols. The application of the H8BINOL–amine catalysts is expanded by using in situ generated diarylzinc reagents from the reaction of aryl iodides with ZnEt2, which still gives high enantioselectivity and good catalytic activity. Such a H8BINOL–amine compound is further found to catalyze the highly enantioselective addition of vinylzincs, in situ generated from the treatment of vinyl iodides with ZnEt2, to aldehydes to give the synthetically very useful chiral allylic alcohols. We have discovered that the unfunctionalized BINOL in combination with ZnEt2 and Ti(OiPr)4 can catalyze the terminal alkyne addition to aldehydes to produce chiral propargylic alcohols of high synthetic utility. The reaction was conducted by first heating an alkyne with ZnEt2 in refluxing toluene to generate an alkynylzinc reagent, which can then add to a broad range of aldehydes at room temperature in the presence of BINOL and Ti(OiPr)4 with high enantioselectivity. It was then found that the addition of a catalytic amount of dicyclohexylamine (Cy2NH) allows the entire process to be conducted at room temperature without the need to generate the alkynylzincs at elevated temperature. This BINOL–ZnEt2–Ti(OiPr)4–Cy2NH catalyst system can be used to catalyze the reaction of structurally diverse alkynes with a broad range of aldehydes at room temperature with high enantioselectivity and good catalytic activity. The work described in this Account demonstrates that BINOL and its derivatives can be used to develop highly enantioselective catalysts for the asymmetric organozinc addition to aldehydes. These processes have allowed the efficient synthesis of many functional chiral alcohols that are useful in organic synthesis.
Wuhan was the first epicentre of COVID-19 in the world, accounting for 80% of cases in China during the first wave. We aimed to assess household transmissibility of severe acute respiratory syndrome ...coronavirus 2 (SARS-CoV-2) and risk factors associated with infectivity and susceptibility to infection in Wuhan.
This retrospective cohort study included the households of all laboratory-confirmed or clinically confirmed COVID-19 cases and laboratory-confirmed asymptomatic SARS-CoV-2 infections identified by the Wuhan Center for Disease Control and Prevention between Dec 2, 2019, and April 18, 2020. We defined households as groups of family members and close relatives who did not necessarily live at the same address and considered households that shared common contacts as epidemiologically linked. We used a statistical transmission model to estimate household secondary attack rates and to quantify risk factors associated with infectivity and susceptibility to infection, accounting for individual-level exposure history. We assessed how intervention policies affected the household reproductive number, defined as the mean number of household contacts a case can infect.
27 101 households with 29 578 primary cases and 57 581 household contacts were identified. The secondary attack rate estimated with the transmission model was 15·6% (95% CI 15·2–16·0), assuming a mean incubation period of 5 days and a maximum infectious period of 22 days. Individuals aged 60 years or older were at a higher risk of infection with SARS-CoV-2 than all other age groups. Infants aged 0–1 years were significantly more likely to be infected than children aged 2–5 years (odds ratio OR 2·20, 95% CI 1·40–3·44) and children aged 6–12 years (1·53, 1·01–2·34). Given the same exposure time, children and adolescents younger than 20 years of age were more likely to infect others than were adults aged 60 years or older (1·58, 1·28–1·95). Asymptomatic individuals were much less likely to infect others than were symptomatic cases (0·21, 0·14–0·31). Symptomatic cases were more likely to infect others before symptom onset than after (1·42, 1·30–1·55). After mass isolation of cases, quarantine of household contacts, and restriction of movement policies were implemented, household reproductive numbers declined by 52% among primary cases (from 0·25 95% CI 0·24–0·26 to 0·12 0·10–0·13) and by 63% among secondary cases (from 0·17 0·16–0·18 to 0·063 0·057–0·070).
Within households, children and adolescents were less susceptible to SARS-CoV-2 infection but were more infectious than older individuals. Presymptomatic cases were more infectious and individuals with asymptomatic infection less infectious than symptomatic cases. These findings have implications for devising interventions for blocking household transmission of SARS-CoV-2, such as timely vaccination of eligible children once resources become available.
National Natural Science Foundation of China, Fundamental Research Funds for the Central Universities, US National Institutes of Health, and US National Science Foundation.
Lin Pu summarizes the activity of the enantioselective fluorescent recognition studies. Studying the chiral discrimination of organic fluorophores began with the work on their fluorescent responses ...to chiral amines and amino alcohols.
Patients with critical illness due to infection with the 2019 coronavirus disease (COVID-19) show rapid disease progression to acute respiratory failure. The study aimed to screen the most useful ...predictive factor for critical illness caused by COVID-19.
The study prospectively involved 61 patients with COVID-19 infection as a derivation cohort, and 54 patients as a validation cohort. The predictive factor for critical illness was selected using LASSO regression analysis. A nomogram based on non-specific laboratory indicators was built to predict the probability of critical illness.
The neutrophil-to-lymphocyte ratio (NLR) was identified as an independent risk factor for critical illness in patients with COVID-19 infection. The NLR had an area under receiver operating characteristic of 0.849 (95% confidence interval CI, 0.707 to 0.991) in the derivation cohort and 0.867 (95% CI 0.747 to 0.944) in the validation cohort, the calibration curves fitted well, and the decision and clinical impact curves showed that the NLR had high standardized net benefit. In addition, the incidence of critical illness was 9.1% (1/11) for patients aged ≥ 50 and having an NLR < 3.13, and 50% (7/14) patients with age ≥ 50 and NLR ≥ 3.13 were predicted to develop critical illness. Based on the risk stratification of NLR according to age, this study has developed a COVID-19 pneumonia management process.
We found that NLR is a predictive factor for early-stage prediction of patients infected with COVID-19 who are likely to develop critical illness. Patients aged ≥ 50 and having an NLR ≥ 3.13 are predicted to develop critical illness, and they should thus have rapid access to an intensive care unit if necessary.
A wealth of data has elucidated the mechanisms by which sensory inputs are encoded in the neocortex, but how these processes are regulated by the behavioral relevance of sensory information is less ...understood. Here, we focus on neocortical layer 1 (L1), a key location for processing of such top-down information. Using Neuron-Derived Neurotrophic Factor (NDNF) as a selective marker of L1 interneurons (INs) and in vivo 2-photon calcium imaging, electrophysiology, viral tracing, optogenetics, and associative memory, we find that L1 NDNF-INs mediate a prolonged form of inhibition in distal pyramidal neuron dendrites that correlates with the strength of the memory trace. Conversely, inhibition from Martinotti cells remains unchanged after conditioning but in turn tightly controls sensory responses in NDNF-INs. These results define a genetically addressable form of dendritic inhibition that is highly experience dependent and indicate that in addition to disinhibition, salient stimuli are encoded at elevated levels of distal dendritic inhibition.
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•NDNF is a selective marker for neocortical layer 1 interneurons•NDNF interneurons mediate prolonged inhibition of distal pyramidal neuron dendrites•Inhibition from Martinotti cells tightly controls NDNF interneuron responses•Dendritic inhibition by NDNF interneurons is highly experience dependent
Using a selective marker for neocortical layer 1 interneurons, Abs, Poorthuis, et al. identify these little-understood cells as a powerful, highly experience-dependent source of inhibition in pyramidal neuron dendrites that is in turn controlled by activity in the local circuit.
Metal–organic frameworks (MOFs) have demonstrated great potentials toward catalysis, particularly in the establishment of structure–property relationships. Herein, an unusual OOP (out-of-plane) ...porphyrin-based MOF, synthesized by controlling the metal ion release with an unprecedented In(OH)3 precursor, possesses high stability and exhibits unexpectedly high photocatalytic hydrogen production activity, far surpassing the isostructural in-plane porphyrin-based MOF counterparts. In the MOF structure, indium ions not only form indium–oxo chains but also metalate the porphyrin rings in situ, locating above the porphyrin plane instead of fitting in a coplanar fashion into the cavity and affording an unusual OOP porphyrin. Control experiments demonstrate that the OOP In(III) ions readily detach from the porphyrin rings under light excitation, avoiding the fast back electron transfer and thus greatly improving electron–hole separation efficiency and photocatalytic performance. To our knowledge, this is an unprecedented report on boosting MOF photocatalysis on the basis of special metalloporphyrin behavior.
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