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We showcase the successful combination of photochemistry and kinetic target‐guided synthesis (KTGS) for rapidly pinpointing enzyme inhibitors. KTGS is a fragment‐based drug discovery (FBDD) methodology in which the biological target (BT) orchestrates the construction of its own ligand from fragments featuring complementary reactive functionalities. Notably, fragments interacting with the protein binding sites leverage their spatial proximity, facilitating a preferential reaction. Consequently, the resulting bivalent ligand exhibits heightened affinity. Within the realm of KTGS strategies, in situ click chemistry stands out as the most widely used to identify potent protein binders. This approach requires significant protein contributions, such as binding interactions and appropriate orientations of fragments, to overcome high activation barriers. This leads to prolonged incubation times and the potential for generating false negatives, thereby limiting this strategy to proteins that are stable enough in buffer. We herein unveil the possibility to integrate photochemistry into the realm of KTGS, accelerating the ligation reaction between fragments to a time scale of minutes. This approach should significantly expand the narrow reactivity window of traditional KTGS reactions, paving the way for the exploration and development of novel photo‐KTGS reactions. [ABSTRACT FROM AUTHOR]

The constant need for high‐performance aniline‐ or phenol‐based fluorophores suitable for the construction of activity‐based fluorescent probes, led us to study both synthesis and photophysics of C3‐N‐methylpyridinium‐4‐yl substituted 7‐(dialkylamino)/7‐hydroxycoumarins. Indeed, in the field of photoactive organic molecules, the positively charged N‐alkylpyridinium‐4‐yl groups are often used as acceptor units to dramatically impact spectral features through promoting intramolecular charge transfer (ICT) processes. They are also known as effective water‐solubilizing and mitochondria targeting moieties. The poor fluorescence efficiency of cationic 7‐hydroxycoumarin derivatives in aqueous physiological conditions was highlighted and rationalized by the predominance of a neutral quinonoid form in such buffer medium. The ability of the excited singlet state (S1) of this neutral species to undergo intersystem crossing (ISC) to triplet state (T1) was partly supported by phosphorescence measurements of singlet oxygen. We also took advantage of green‐emissive properties of 7‐(diethylamino)‐3‐(N‐methylpyridinium‐4‐yl)coumarin to successfully design and validate a novel small‐molecule fluorescent probe for the detection of alkaline phosphatase (ALP), based on the "covalent‐assembly" principle. A practical use of ortho‐formylated 7‐hydroxy‐3‐(N‐methylpyridinium‐4‐yl)coumarin was next considered with the synthesis of a Fe(III)‐salen complex whose the potential as a "molecular disassembly" probe for fluorogenic sensing of pyrophosphate (PPi) anion was assessed. [ABSTRACT FROM AUTHOR]

This communication introduces a highly efficient, safe and sustainable flow protocol for the oxidative neutralization of sulfur-based chemical warfare agent simulants using ozone. The methodology employs preliminary in silico mechanistic studies and chemical analogy studies with DFT to scout reaction profiles and kinetics. It unveils crucial parameters that guide selectivity and prevent the formation of undesirable overoxidized by-products. This computational foundation is seamlessly translated into real-world neutralization experiments conducted under flow conditions, yielding remarkably swift neutralization rates under mild conditions. Full oxidative neutralization of CWA simulants with ozone is achieved within a second, without the need for additives or catalysts, in an EtOH/water mixture. This convergence of computational insights and experimental validation provides a promising avenue toward new neutralization protocols, foreseeing transformative possibilities with low waste generation and high safety. [ABSTRACT FROM AUTHOR]

Photophysical properties of quinoxalin‐2(1H)‐ones have long been neglected, in particular compared with those of coumarins, their oxygenated counterparts, despite their complementarity in terms of absorbance and fluorescence windows. This review provides first an overview of the synthesis of quinoxalin‐2(1H)‐ones, focusing on the most recent contributions. Fluorescence properties of quinoxalin‐2(1H)‐ones and of their π‐extended derivatives are tackled through the description of a series of examples and applications, including chemosensing and biosensing. [ABSTRACT FROM AUTHOR]

This report describes a concept in which an immunoassay is used indirectly to quantify a nonantigenic very low molecular weight compound participating in a chemical reaction with a haptenic reporter. The detection limit of each reagent is, therefore, governed only by the affinity of the antibodies toward the reporter. Fluoride was used as a model, and silylated estradiol was used as a reporter. Upon silylation with N-O-bis(trimethyisilyl)trifluoroacetamide (BSTFA) or N-O-bis(dimethylterbutylsilyl) trifluoroacetamide (MTBSTFA), estradiol is no longer recognized by antibodies specific to estradiol. After reaction with hydrofluoric acid (HF) or fluoride salts (KF, CsF, NaF), its immunoreactivity is restored, and native estradiol is formed and is detected by immunoassay. The level of synthesized estradiol is dependent on the concentration of fluoride. A fluoride detection limit of 0.3 [micro]g/L (15 nM) is obtained. Potential interference with other acids has been eliminated by choosing the silyl group (trimethylsilyl vs tert-butyldimethylsilyl) and by selecting optimal reaction conditions for the desilylation. The method has been applied to the detection of fluoride salts in natural waters (range 0.28-9.0 mg/L) and in an atmosphere artificially contaminated with HF between 8 and 160 [micro]g/[m.sup.3] in the parts-per-billion range. This indirect immunoassay combines simplicity and high sensitivity and, therefore, can be used in field monitoring. Finally, the extension of the concept to other chemicals is discussed.

Research has been conducted on the acetylcholinestrase, the enzyme regulating neurotransmission. The activity of this enzyme has been investigated and the description of the 1,3-dioxetane chemiluminescent probe generated in search for a sensitive detection assay is presented.