A new auto‐inductive protocol employs a Meldrum's‐acid‐based conjugate acceptor (1) as a latent source of thiol for signal amplification, as well as optical detection of thiols. The auto‐induction is ...initiated by a thiol‐disulfide exchange that leads to the generation of β‐mercaptoethanol, which in turn decouples the conjugate acceptor to release more thiols, resulting in a self‐propagating cycle that continues until all the conjugate acceptor is consumed. Using 1 in a two‐step integrated protocol yields a rapid, sensitive, and precise diagnostic assay for the ultratrace quantitation of a thiophosphate nerve agent surrogate.
Thiol detection: Combining thiol‐disulfide exchange with decoupling of a conjugate acceptor (1), a new thiol auto‐inductive cascade was developed for signal amplification, as well as colorimetric and fluorometric detection of thiols. Using 1 in a two‐step protocol yields a rapid assay for the ultratrace quantitation of a thiophosphate nerve agent surrogate at ppb levels.
Dynamic assembly of macromolecules in biological systems is one of the fundamental processes that facilitates life. Although such assembly most commonly uses noncovalent interactions, a set of ...dynamic reactions involving reversible covalent bonding is actively being exploited for the design of functional materials, bottom‐up assembly, and molecular machines. This Minireview highlights recent implementations and advancements in the area of tunable orthogonal reversible covalent (TORC) bonds for these purposes, and provides an outlook for their expansion, including the development of synthetically encoded polynucleotide mimics.
TORC about: The utilization of tunable orthogonal reversible covalent (TORC) bonds is highlighted in this Minireview. The focus lies in the variety of different applications that are possible, including controlling molecular assembly, operating complex molecular machines, and designing dynamic, self‐healable polymer networks.
Chemical warfare agents (CWAs) are among the most prominent threats to the human population, our peace, and social stability. Therefore, their detection and quantification are of utmost importance to ...ensure the security and protection of mankind. In recent years, significant developments have been made in supramolecular chemistry, analytical chemistry, and molecular sensors, which have improved our capability to detect CWAs. Fluorescent and colorimetric chemosensors are attractive tools that allow the selective, sensitive, cheap, portable, and real-time analysis of the potential presence of CWAs, where suitable combinations of selective recognition and transduction can be integrated. In this review, we provide a detailed discussion on recently reported molecular sensors with a specific focus on the sensing of each class of CWAs such as nerve agents, blister agents, blood agents, and other toxicants. We will also discuss the current technology used by military forces, and these discussions will include the type of instrumentation and established protocols. Finally, we will conclude this review with our outlook on the limitations and challenges in the area and summarize the potential of promising avenues for this field.
This review highlights recently reported optical molecular sensors for the sensing of Chemical Warfare Agents (CWAs) including nerve agents, blister agents, blood agents, and other toxicants.
This Perspective highlights the advances of optical methods for asymmetric reaction discovery. Optical analysis allows for the determination of absolute configuration, enantiomeric excess and ...reaction yield that is amenable to high-throughput experimentation. Thus, the synthetic organic community is encouraged to incorporate the methods discussed to expedite the development of high-yielding, enantioselective transformations.
Indicator displacement assays (IDAs) offer a unique and innovative approach to molecular sensing. IDAs can facilitate the detection of a range of biologically/environmentally important species, ...provide a method for the detection of complex analytes or for the determination and discrimination of unknown sample mixtures. These attributes often cannot be achieved by traditional molecular sensors
i.e.
reaction-based sensors/chemosensors. The IDA pioneers Inouye, Shinkai, and Anslyn inspired researchers worldwide to develop various extensions of this idea. Since their early work, the field of indicator displacement assays has expanded to include: enantioselective indicator displacement assays (eIDAs), fluorescent indicator displacement assays (FIDAs), reaction-based indicator displacement assays (RIAs), DimerDye disassembly assays (DDAs), intramolecular indicator displacement assays (IIDAs), allosteric indicator displacement assay (AIDAs), mechanically controlled indicator displacement assays (MC-IDAs), and quencher displacement assays (QDAs). The simplicity of these IDAs, coupled with low cost, high sensitivity, and ability to carry out high-throughput automation analysis (
i.e.
, sensing arrays) has led to their ubiquitous use in molecular sensing, alongside the other common approaches such as reaction-based sensors and chemosensors. In this review, we highlight the various design strategies that have been used to develop an IDA, including the design strategies for the newly reported extensions to these systems. To achieve this, we have divided this review into sections based on the target analyte, the importance of each analyte and then the reported IDA system is discussed. In addition, each section includes details on the benefit of the IDAs and perceived limitations for each system. We conclude this Tutorial Review by highlighting the current challenges associated with the development of new IDAs and suggest potential future avenues of research.
Indicator displacement assays (IDAs) offer a unique and innovative approach to molecular sensing. This Tutorial review discusses the basic concepts of each IDA strategy and illustrates their use in sensing applications.
Information about chromogenic/fluorogenic ensemble chemosensing systems is presented. Topics discussed include two-component ensembles, three-component ensembles, multicomponent ensembles and ...inorganic-organic hybrid ensembles.
Conspectus The advent of high-throughput screening (HTS) for chiral catalysts has encouraged the development of fast methods for determining enantiomeric excess (ee). Traditionally, chromatographic ...methods such as chiral HPLC have been used for ee determination in HTS. These methods, however, are not optimal because of high duty cycle. Their long analysis time results in a bottleneck in the HTS process. A more ideal method for HTS that requires less analysis time such as chiroptical methods are thus of interest. In this Account, we summarize our efforts to develop host–guest systems for ee determination. The first part includes our enantioselective indicator displacement assays (eIDAs), and the second part focuses on our circular dichroism based host–guest systems. Our first eIDA utilizes chiral boronic acid receptors, along with prescreened indicators, to determine ee for chiral α-hydroxyacids and vicinal diols with ±7% average error (AE). To further the practicality for this system, a HTS protocol was developed. Our second eIDA uses diamino chiral ligands and CuII as the receptor for the ee determination of α-amino acids. The system reported ±12% AE, and a HTS protocol was developed for this system. Our first CD based host–guest system uses metal complexes composed of CuI or PdII with enantiopure 2,2′-diphenylphosphino-1,1′-binaphthyl (BINAP) as host to determine the ee of chiral vicinal diamines (±4% AE), primary amines (±17% AE), and cyclohexanones (±7% AE). Primary amines and cyclohexanones were derivatized to form chiral imines or chiral hydrazones to allow coordination with the metal complex. Upon coordination of chiral analytes, the metal-to-ligand (BINAP) charge transfer band was modulated, thus allowing the discrimination of chiral analytes. As an effort to improve the accuracy for chiral primary amine ee determination, a system with a host composed of o-formylphenyl boronic acid (FPBA) and enantiopure 1,1′-bi-2-naphthol (BINOL) was used to reduce the AE to ±5.8%. In the presence of amines, the FPBA–BINOL host forms an imine-coordinated boronic ester, thus affecting the CD signal of the boron complex. Another chiral primary amine ee determination system was developed with FeII and 3-hydroxy-2-pyridinecarbaldehyde. The chiral imines, formed by the pyridinecarbaldehyde and chiral amines, would coordinate to the FeII ion yielding exciton-coupled circular dichroism (ECCD) active metal complexes. This system was able to determine the ee of chiral amines with ±5% AE. Furthermore, this imine–FeII complex system also successfully determined the ee of α-chiral aldehydes with ±5% AE. Other ECCD based hosts were subsequently developed; one with bisquinolylpyridylamine and CuII for chiral carboxylates and amino acids and another multicomponent system with pyridine chromophores for chiral secondary alcohol ee determination. Both of the systems were able to determine ee of the chiral analytes with ±3% AE. Overall, our group has developed ee determining host–guest systems that target various functionalities. To date, we are able to determine the ee of vicinal diols, α-hydroxyacids, vicinal diamines, cyclohexanones, amines, α-chiral aldehydes, carboxylates, amino acids, and secondary alcohols with ±7% or lower average error. Future development will involve improving the average error and employing the current systems to analyze real-life samples resulting from parallel syntheses.
A fluorescent turn-on sensor for the selective and sensitive detection of sulfur mustard simulants in water that uses a metal-ion indicator displacement assay (IDA) has been devised. In this IDA ...approach, a sulfur mustard simulant (the analyte) is allowed to react with a dithiol (1) to form a podand (2). This podand has a strong affinity to bind with Cd2+ and displaces an indicator (4-methylesculetin, ME) from a Cd2+–indicator complex (8) to give a turn-on of fluorescence. The detection is rapid and highly selective, as we did not observe any interference from other electrophiles, even from the oxygen analogue of the mustard simulant. The protocol was successfully used for the detection of the simulant present on surfaces and in soil samples.
Different mechanisms for the emission turn-on of ortho-aminomethylphenylboronic acids with appended fluorophores in response to saccharide binding in aqueous media have been postulated, such as ...photoinduced electron transfer (PET), “pK a switch”, and disaggregation. However, none of the hypotheses is consistent with all the data for boronic acid–based sensors. To create a unifying theory that can explain the data, we performed a series of experiments to explore the origin of the emission turn-on with several boronic-acid based sensors upon binding fructose. First, we showed that the receptors and their complexes with fructose are solvent-inserted, with no B–N interactions. Second, we verified that the sensors are not aggregated. Third, in pure methanol, that exchanges −B(OH)2 to −B(OMe)2 groups, we found no fluorescence response upon binding fructose. We propose this occurs via lessening of internal conversion mechanisms. To investigate this proposal further, we performed a solvent isotope effect study. The fluorescence of the probes in D2O (−B(OH)2 → −B(OD)2) does not change upon fructose binding. It is well accepted that −OD oscillators are less efficient energy acceptors due to their lower frequency vibrational modes. Thus, our studies reveal that modulating the −B(OH)2-induced internal conversion (an example of a “loose bolt effect”) explains how potentially all ortho-aminomethylphenylboronic acid-based fluorescence sensors signal the presence of sugars.
Nature has inspired an emergent supramolecular field of synthetic receptor arrays and assays for the pattern-based recognition of various bioanalytes and metal species. The synthetic receptors are ...not necessarily selective for a particular analyte, but the combined signal response from the array is diagnostic for the analyte. This tutorial review describes recent work in the literature for this emerging supramolecular field and details basic array and assay design principles. We review the analytes targeted, signaling types used, and pattern recognition. Developing specific receptors for the solution-based analysis of complex analytes and mixtures is a daunting task. A solution to this difficult task has been inspired by nature's use of arrays of receptors in the senses of taste and smell. An emerging field within supramolecular chemistry is the use of synthetic and readily available receptors in array formats for the detection of analytes in solution. Each receptor in a differential array does not necessarily have selectivity for a particular analyte, but the combined fingerprint response can be extracted as a diagnostic pattern visually, or using chemometric tools. This new genre of molecular recognition is advancing rapidly with several groups developing novel array platforms and receptors.
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