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Excited-state intramolecular proton transfer (ESIPT) molecules, which feature large Stokes shifts to avoid self-absorption, play an essential role in photoluminescent bioimaging probes. Herein, we report the development of an ESIPT molecule 3-(3-hydroxypyridin-2-yl)isoquinolin-4-ol (PiQ). PiQ not only undergoes a distinct ESIPT process unlike the symmetrical 2,2'-bipyridyl-3,3'-diol but also exhibits aggregation-induced emission (AIE) characteristics. PiQ self-assembles into aggregates with an average size of 241.0±51.9 nm in aqueous solutions, leading to significantly enhanced photoluminescence. On the basis of the ESIPT and AIE characteristics of PiQ, the latter is functionalized with a hydrogen peroxide-responsive 4-pinacoratoborylbenzyl group (B) and a carboxylesterase-responsive acetyl group (A) to produce a photoluminescent probe B-PiQ-A. The potential of PiQ for applications in bioimaging and chemical sensing is underscored by its efficient detection of both endogenous and exogenous hydrogen peroxide in living cells., (© 2024 Wiley-VCH GmbH.)

Turn-on fluorescence probes can visualize the enzyme activity with high contrast. We have established a new turn-on mechanism, activator-induced nucleophilic quencher detachment (AiQd), and developed AiQd-based turn-on fluorescence probes for the detection of enzymes. Herein, we demonstrate that the precise steric control efficiently quenches the fluorescence of AiQd-based turn-on probes before the enzymatic transformation. Theoretical calculation appropriately predicted the ratio of the fluorescence-quenched closed-ring form of probes. βC5S-A, which has a sterically demanding methyl group at the β-position of a fluorescence-quenching nucleophilic mercapto group, showed a low background signal. βC5S-A responded to aldehyde dehydrogenase 1A1 (ALDH1A1) with high selectivity, thereby enabling high-contrast live imaging of cancer stem cells (signal-to-noise ratio >10). The ALDH1A1-responsiveness of βC5S-A was not significantly affected by amino acids and biological thiols, such as cysteine and glutathione., (© 2022 Wiley-VCH GmbH.)

Angle-strained alkyne-containing π-conjugated macrocycles are attractive compounds both in functional materials chemistry and biochemistry. Their interesting reactivity as well as photophysical and supramolecular properties have been revealed in the past three decades. This review highlights the recent advances in angle-strained alkyne-containing π-conjugated macrocycles, especially their synthetic methods, the bond angles of alkynes (∠ sp at C≡C-C), and their functions. The theoretical and experimental research on cyclo[n]carbons and para-cyclophynes consisting of ethynylenes and para-phenylenes are mainly summarized. Related macrocycles bearing other linkers, such as ortho-phenylenes, meta-phenylenes, heteroaromatics, biphenyls, extended aromatics, are also overviewed. Bond angles of strained alkynes in π-conjugated macrocycles, which are generable, detectable, and isolable, are summarized at the end of this review., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Carbon-based double helicates consisting of two anthracene-containing oligo(p-phenyleneethynylene) units and two flexible chiral 1,1'-binaphthyl units or two rigid chiral 9,9'-spirobifluorene units were developed. The curved oligo(p-phenyleneethynylene) fragments in the double helicates were successfully constructed by tin-mediated reductive aromatization. Helical oligo(p-phenyleneethynylene) double strands fixed by two rigid spirobifluorene units showed little structural change under photoirradiation, thereby emitting circularly polarized luminescence (CPL) in the visible region with a high quantum yield (Φ PL =0.93). In contrast, flexible binaphthyl units induced dynamic structural change of the oligo(p-phenyleneethynylene) luminophores under photoirradiation, leading to strong CPL (|g lum |=1.1×10 -2 ) in the near-infrared (NIR) region. UV/Vis, circular dichroism (CD), CPL and NMR spectroscopic analyses of the binaphthyl-hinged double helicate suggested excimer formation between two π-conjugated strands in the excited state. Theoretical calculations highlight the importance of the tightly interlocked excimer structure of the carbon-based double helicate in controlling the angle between the electric and magnetic transition dipole moments for strong NIR CPL generation., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Nitrene-transfer reactions are powerful synthetic tools for the direct incorporation of nitrogen atoms into organic molecules. The discovery of novel nitrene-transfer reactions has been dominantly supported not only by improvements in transition-metal catalysts but also by the employment of novel precursors of nitrenoids. Since pioneering work involving the use of organic azides and iminoiodinanes as practical synthetic tools for nitrogen-containing compounds was reported, a new approach using various N-heterocycles containing strain energy or a weak bond has emerged. In this review, we briefly summarize the history of nitrene-transfer chemistry from the viewpoint of its precursors. In particular, the use of N-heterocycles such as 2H-azirines, 1,4,2-dioxazol-5-ones, 1,2,4-oxadiazol-5-ones, isoxazol-5(4H)-ones, and isoxazoles is comprehensively described, showing the recent remarkable progress in this chemistry., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Carbon nanotubes (CNTs) interlocked by cyclic compounds through supramolecular interaction are promising rotaxane-like materials applicable as 2D and 3D networks of nanowires and disease-specific theranostic agents having multifunctionalities. Supramolecular complexation of CNTs with cyclic compounds in a "ring toss'' manner is a straightforward method to prepare interlocked CNTs; however, to date, this has not been reported on. Here, the "ring toss" method to prepare interlocked CNTs by using π-conjugated carbon nanorings: [8]-, [9]-, and [10]cycloparaphenyleneacetylene (CPPA) is reported. CPPAs efficiently interact with CNTs to form CNT@CPPA complexes, while uncomplexed CPPAs can be recovered without decomposition. CNTs, which tightly fit in the cavities of CPPAs through convex-concave interaction, efficiently afford "tube-in-ring"-type CNT@CPPA complexes. "Tube-in-ring"-type and "ring-on-tube"-type complexation modes are successfully distinguished by spectroscopic, thermogravimetric, and microscopic analyses., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Intermolecular C-H alkylation of simple arenes in the presence of an iron catalyst has been achieved in a cascade manner with an aminative cyclization triggered by N-O bond cleavage of an alkene-tethered oxime ester. Various arenes, including electron-rich and electron-poor arenes, and heteroarenes can be employed in the reaction system. Regioselectivity and radical trapping experiments support the involvement of alkyl radical species, which undergo a homolytic aromatic substitution (HAS) to afford the arylation products., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Highly strained 2H-azirines with a tetrasubstituted stereocenter were synthesized by the enantioselective isomerization of isoxazoles with a chiral diene-rhodium catalyst system. The effect of ligands and the coordination behavior support the proposed catalytic cycle in which the coordination site is fixed in favor of efficient enantiodiscrimination by a bulky substituent of the ligand. In silico studies also support the existence of a rhodium-imido complex as a key intermediate for enantiodiscrimination., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The reaction of an oxime ester with [Ru(PPh 3 ) 3 X 2 ] proceeded smoothly at room temperature to afford a stable Ru IV ketimido complex as oxidative adduct. The structure of the complex was unambiguously determined by X-ray crystallographic analysis, which showed an almost linear Ru-N-C array. The electronic properties of the nitrogen atom were estimated by DFT calculations, and the results suggested double-bond character of the Ru-N bond. Kinetic studies and consideration of the substituent effect on the oxime ester led to the proposal of a reaction mechanism involving oxidative addition, which could proceed by N,O-chelating coordination to the Ru center prior to N-O bond cleavage. The obtained Ru ketimido complex could be transformed into a ruthenacycle by C-H activation by a concerted metalation-deprotonation mechanism in dichloromethane/methanol. Ru ketimido complexes with a tethered alkyne or alkene moiety underwent chloroamination of unsaturated C-C bonds followed by C-H activation, which resulted in the formation of a ruthenacycle. Considering the LUMO of an isolated Ru ketimido complex, the chloroamination should proceed by a synchronous 1,3-dipolar cycloaddition-type mechanism. Insight into the character and reactivity of Ru ketimido complexes will be helpful for developments in the catalytic transformation of oxime esters., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A phosphine-free iridium-catalyzed reaction of isoxazol-5(4H)-ones (isoxazolones) has been developed, and affords 2H-azirines through decarboxylation and ring contraction. This method provides an efficient and environmentally benign protocol which could replace the conventional approaches used to synthesize 2H-azirines., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The Sc(OTf)3-catalyzed [3+2] cycloaddition of allylsilanes to β-silyl-α,β-unsaturated ketones (β-silylenones) has been developed to form five-membered syn-1,3-disilylketones diastereoselectively through the rearrangement of the silicon substituents on the allylsilane. Stabilization of the carbocation intermediates by a double silicon effect plays a key role in directing the course of the reaction to favor the [3+2] cycloaddition pathway over simple allylation., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In this study, amphiphilic Janus-type polymers were synthesized via ring-opening metathesis polymerization (ROMP), multiple vicinal diol formation, and grafting of poly(ethylene glycol) monomethyl ether (mPEG). These amphiphilic polymers formed self-assemblies, which were a mixture of micelles and multimicellar aggregates, in water. By choosing suitable Janus-type polymers and irradiating an aqueous solution of polymers using a sonicator, either small micelles or large multimicellar aggregates were obtained selectively. Hydrophobic substituents controlled the aggregation-disaggregation behavior, leading to the formation of metastable self-assemblies by sonication. The formation of self-assemblies with a uniform size was affected by ultrasonic frequency, rather than power. In vivo optical tumor imaging revealed that the large-size multimicellar aggregates persisting for a long time in blood circulation slowly accumulated in tumor tissues. In contrast, the tumor site was rapidly, clearly visualized using the small-size micelles., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

This paper describes the development of a palladium-catalyzed decarboxylative inter- and intramolecular condensation reaction of isoxazol-5(4 H)-ones with carbonyl compounds in the presence of PPh3 , giving various 2-azabuta-1,3-dienes or pyrroles in moderate to high yields., (Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

New tricks, old reaction: The title reaction proceeds under mild and transition-metal-free conditions (see scheme; Tf=trifluoromethanesulfonyl). Various combinations of substrates are applicable to the synthesis of γ,δ-unsaturated ketones by employing silicon substituents at the β-position of the enones. The silicon substituents play a key role in stabilization of the cationic intermediate by hyperconjugation., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In this study, amphiphilic brush-like copolymers conjugated with short alkyl or long polymeric chains of various lengths are synthesized using ring-opening metathesis polymerization (ROMP) of substituted norbornadiene monomers followed by chemical transformations. These amphiphilic copolymers form spherical self-assemblies in aqueous media with diameters of 132-244 nm. The low critical aggregation concentration of these assemblies (2.5 × 10(-3) -1.4 × 10(-5) g/L) indicates that they are quite stable in dilute conditions. An appropriate length of polymer side chain that conjugates the polymer backbone with a hydrophobic ICG (indocyanine green) moiety enhanced the fluorescence intensities of these self-assemblies in aqueous solution as well as in tumor-bearing mice. A longer side chain conjugated with tumor targeting agents could significantly affect the tumor specificity of self-assemblies to a greater extent. The self-assemblies bearing hydrophilic tumor targeting agents, such as a glucosamine molecule and a cyclic RGD (arginine-glycine-asparatic acid) peptide, accumulated in tumor tissues with high selectivity, while those having a hydrophobic targeting agent, such as folate moieties, accumulated in tumor sites with low selectivity. The results demonstrated here unambiguously indicate that the fluorescence intensity and tumor specificity of self-assemblies are strongly affected by the length of side chains that conjugate with dyes and targeting agents., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Recently, 1,2-dehydropyrrolizidine alkaloid (PA) ester alkaloids, found predominantly as their N-oxides (PANOs, pyrrolizidine N-oxides), have been reported in both honey and in pollen obtained directly from PA plants and pollen loads collected by bees, raising the possibility of health risks for consumers of these products. We confirm these findings in regard to floral pollen, using pollen collected directly from flowers of the known PA plants Senecio jacobaea, S. vernalis, Echium vulgare and pollinia of Phalaenopsis hybrids, and we extend analyses of 1,2-unsaturated PAs and 1,2-unsaturated PANOs to include bee-pollen products currently being sold in supermarkets and on the Internet as food supplements. PA content of floral pollen ranged from 0.5 to 5 mg/g. The highest values were observed in pollen obtained from Senecio species. Up to 95% of the PAs are found as PANOs. Detailed studies with S. vernalis revealed unique PA patterns in pollen and flowers. While seneciphylline was the most prominent PA in S. vernalis pollen, the flowers were dominated by senecionine. To analyze trace amounts of 1,2-unsaturated PAs in pollen products, our previously elaborated method consisting of strong cation exchange-SPE, two reduction steps followed by silylation and subsequent capillary high-resolution GC-MS using SIM mode was applied. In total, 55 commercially available pollen products were analyzed. Seventeen (31%) samples contained 1,2-unsaturated PAs in the range from 1.08 to 16.35 microg/g, calculated as retronecine equivalents. The 1,2-unsaturated PA content of pollen products is expressed in terms of a single sum parameter and no background information such as foraged plants, pollen analysis, etc. was needed to analyze the samples. The detection limit of overall procedure and the reliable quantitation limit were 0.003 and 0.01 microg/g, respectively.

Recently, contamination of honey with pyrrolizidine alkaloids (PA) has been reported as potential health risk. Therefore, it was of interest to develop a reliable tool for selective and quantitative determination of PA in honey. Sample preparation of the novel method comprises strong cation exchange SPE (SCX-SPE), followed by two reduction steps using zinc and LiAlH(4), as well as subsequent silylation. During this procedure the separated PA are converted into the necin backbone, the common structural feature of PA toxicity, which is analyzed by GC-MS in the SIM mode. The procedure was validated using PA from extracts of Senecio vernalis as well as authentic PA standards including their corresponding N-oxides. The PA content of honey samples was quantified with heliotrine as internal standard. The method was applied to generate a dataset in order to evaluate the potential risk of PA contamination especially for retail honeys available on the German/European market. No selection criteria in terms of floral or geographical origin were applied on the samples before analysis. In total, 216 commercially available floral honey samples were analyzed. Among them 19 samples contained PA, in the range of 0.019-0.120 microg/g, calculated as retronecine equivalents. The reported method facilitates the selective determination of PA without the need to identify each individual PA independently. The PA contamination of honey is expressed in terms of a single sum parameter and no background information such as foraged plants and pollen analysis is necessary. The LOQ is 0.01 ppm with a S/N of 7:1.

Up to 99 % de is obtained in the imidation of diaryl sulfides bearing a chiral oxazolinyl moiety at the ortho position. The corresponding N-p-tosylsulfimides are produced upon use of chloramine T trihydrate in the presence of Cu(OTf) 2 as catalyst [Eq. (1)]. OTf=trifluoromethanesulfonate; Ts=toluenesulfonyl., (© 1999 WILEY-VCH Verlag GmbH, Weinheim, Fed. Rep. of Germany.)