Pd-catalyzed cross-coupling reactions that form C–N bonds have become useful methods to synthesize anilines and aniline derivatives, an important class of compounds throughout chemical research. A key factor in the widespread adoption of these methods has been the continued development of reliable and versatile catalysts that function under operationally simple, user-friendly conditions. This review provides an overview of Pd-catalyzed N-arylation reactions found in both basic and applied chemical research from 2008 to the present. Selected examples of C–N cross-coupling reactions between nine classes of nitrogen-based coupling partners and (pseudo)aryl halides are described for the synthesis of heterocycles, medicinally relevant compounds, natural products, organic materials, and catalysts.

Applications of Palladium-Catalyzed C–N Cross-Coupling Reactions

Reactive oxygen (ROS) and nitrogen (RNS) species cause oxidative and nitrosative stresses, respectively. These stresses are implicated not only in diverse physiological processes but also in various pathological processes, including cancer and neurodegenerative disorders. In addition, some ROS and RNS in the environment are pollutants that threaten human health. As a consequence of these effects, sensitive methods, which can be employed to selectively monitor ROS and RNS in live cells, tissues and organisms as well as in environmental samples, are needed so that their biological roles can be understood and their concentrations in environmental samples can be determined. In this review, fluorescent, luminescent and colorimetric ROS and RNS probes, which have been developed since 2011, are comprehensively discussed.

Recent progress in the development of fluorescent, luminescent and colorimetric probes for detection of reactive oxygen and nitrogen species

A type III protein secretion system encoded by Salmonella pathogenicity island 2 (SPI2) has been found to be required for virulence and survival within macrophages. Here, SPI2 was shown to allow Salmonella typhimurium to avoid NADPH oxidase-dependent killing by macrophages. The ability of SPI2-mutant bacteria to survive in macrophages and to cause lethal infection in mice was restored by abrogation of the NADPH oxidase-dependent respiratory burst. Ultrastructural and immunofluorescence microscopy demonstrated efficient localization of the NADPH oxidase in the proximity of vacuoles containing SPI2-mutant but not wild-type bacteria, suggesting that SPI2 interferes with trafficking of oxidase-containing vesicles to the phagosome.

Salmonella Pathogenicity Island 2—Dependent Evasion of the

Peroxynitrite (ONOO–) is a kind of reactive oxygen species (ROS) with super activity of oxidization and nitration, and overproduction of ONOO– is associated with pathogenesis of many diseases. Thus, accurate detection of ONOO– with high sensitivity and selectivity is imperative for elucidating its functions in health or disease states. Herein we for the first time present a new two-photon ratiometric fluorescent ONOO– probe (MITO-CC) based on FRET mechanism by combining rational design strategy and dye-screening approach. MITO-CC, with fast response rate (within 20 s), excellent sensitivity (detection limit = 11.30 nM) and outstanding selectivity toward ONOO–, was successfully applied to ratiometric detection of endogenous ONOO– produced by HepG2/RAW264.7 cells and further employed for imaging oxidative stress in an inflamed mouse model. Therefore, probe MITO-CC could be a potential biological tool to explore the roles of ONOO– under different physiological and pathological settings.

Selective Visualization of the Endogenous Peroxynitrite in an Inflamed Mouse Model by a Mitochondria-Targetable Two-Photon Ratiometric Fluorescent Probe

Traditional biochemical methods for enzyme detection are mainly based on antibody-based immunoassays, which lack the ability to monitor the spatiotemporal distribution and, in particular, the in situ activity of enzymes in live cells and in vivo. In this review, we comprehensively summarize recent progress that has been made in the development of small-molecule as well as material-based fluorogenic probes for sensitive detection of the activities of enzymes that are related to a number of human diseases. The principles utilized to design these probes as well as their applications are reviewed. Specific attention is given to fluorogenic probes that have been developed for analysis of the activities of enzymes including oxidases and reductases, those that act on biomacromolecules including DNAs, proteins/peptides/amino acids, carbohydrates and lipids, and those that are responsible for translational modifications. We envision that this review will serve as an ideal reference for practitioners as well as beginners in relevant research fields.

Fluorogenic probes for disease-relevant enzymes.

Peroxynitrite (ONOO–), the product of a radical combination reaction of nitric oxide and superoxide, is a potent biological oxidant involved in a broad spectrum of physiological and pathological processes Herein we report the development, characterization, and biological applications of a new fluorescent probe, HKGreen-4, for peroxynitrite detection and imaging HKGreen-4 utilizes a peroxynitrite-triggered oxidative N-dearylation reaction to achieve an exceptionally sensitive and selective fluorescence turn-on response toward peroxynitrite in chemical systems and biological samples We have thoroughly evaluated the utility of HKGreen-4 for intracellular peroxynitrite imaging and, more importantly, demonstrated that HKGreen-4 can be efficiently employed to visualize endogenous peroxynitrite generated in Escherichia coli-challenged macrophages and in live tissues from a mouse model of atherosclerosis This probe should serve as a powerful molecular imaging tool to explore peroxynitrite biology under a vari

Molecular Imaging of Peroxynitrite with HKGreen-4 in Live Cells and Tissues

Page 11728. Derek Hoi-Hang Ho, at his request and with the agreement of all co-authors, is removed as an author of this article. Page 11733. It should be noted that, in Figure 5, we display only the target tissues (i.e., smooth muscles of the aortic root) that are of relevance and interest to the atherosclerosis model for comparison of peroxynitrite levels. Although the surrounding tissues (i.e., cardiac muscles) have greater fluorescence than the tissues of interest (i.e., smooth muscles), they may not be relevant to the atherosclerosis model reported. The original uncropped images of Figure 5 are included as Figure S20 in the revised Supporting Information. Supporting Information. Similarly, in Figure S16, only the target tissues (i.e., smooth muscles) are displayed and compared, whereas surrounding tissues are cropped out for simple illustration. The original uncropped images of Figure S16 are included as Figure S21 in the revised Supporting Information.

https://pubs.acs.org/doi/pdf/10.1021/jacs.7b13132

Yee-Kwan Chan

Papers

Molecular Imaging of Peroxynitrite with HKGreen-4 in Live Cells and Tissues

Correction to “Molecular Imaging of Peroxynitrite with HKGreen-4 in Live Cells and Tissues”