Insight into Regioselective Control in Aerobic Oxidative C-H/C-H Coupling for C3-Arylation of Benzothiophenes: Toward Structurally Nontraditional OLED Materials.

The installation of (benzo)thiophene-containing biaryls via coupling reactions has become a staple in designing photoelectric materials. Undeniably, C-H/C-H cross-coupling reactions between two (hetero)aromatics would be a shortcut toward these structural fragments. While more reliable cross-coupling technologies are well-established to provide C2-arylated (benzo)thiophenes, efficient methods that arylate the C3-position remain underdeveloped. Herein we provide insight into the factors that determine regioselectivity switching for these cross-coupling reactions. X-ray crystallographic analysis gives solid evidence for the key roles of triflate in regioselective dearomatization and acetate in base-assisted anti-ß-deprotonated rearomatization. The first isolation and X-ray characterization of a medium-sized dearomatized cyclometalated adduct involving both substrates provide extra insight into aerobic oxidative Ar-H/Ar-H cross-coupling reactions. The mechanistic breakthrough incubates the first example, enabling C-H/C-H-type C3-arylation of benzothiophenes. Finally, this chemistry is used to design blue-emitting thermally activated delayed fluorescence (TADF) materials with a helicene conformation that exhibit a high maximum external quantum efficiency of 25.4% in OLED.

Switchable cascade C-H annulation to polycyclic pyryliums and pyridiniums: discovering mitochondria-targeting fluorescent probes.

Disclosed herein is a counterion additive-switched rhodium-catalyzed cascade triple C-H annulation of 4-hydroxy-1-naphthaldehydes with alkynes, in which six chemical bonds are formed in one-pot. This reaction enables the rapid assembly of diverse polycyclic pyrylium and pyridinium fluorophores, which leads to two specific mitochondria-labeling reagents with low cytotoxicity and superior photostability.

Regioselective addition/annulation of ferrocenyl thioamides with 1,3-diynes via a sulfur-transfer rearrangement to construct extended π-conjugated ferrocenes with luminescent properties.

Herein a regioselective addition/annulation strategy of ferrocenyl (Fc) thioamides with alkynes to construct thienylferrocene (ThienylFc) structures, involving a rhodium-catalyzed C-H activation, an unusual C2-selective addition of 1,3-diyne, and an unexpected intramolecular sulfur-transfer rearrangement process is described. In this protocol, thioamide not only serves as a directing group to activate the ortho-C-H bond of the ferrocene, but also as a sulfur source to form the thiophene ring. The resulting carboxylic ester group after sulfur transfer can act as a linkage to construct extended π-conjugated ferrocenes (OCTFc) with luminescent properties. ThienylFc displays effective fluorescence quenching due to the photoinduced electron transfer (PET) from the Fc unit to the excited luminophore, which turns out to be a promising type of redox molecular switch. OCTFc exhibit relatively strong emission owing to their intramolecular charge transfer (ICT) characteristics. The ring-fused strategy is herein employed for the first time to construct luminescent materials based on ferrocenes, which provides inspiration for the development of novel organic optoelectronic materials, such as electroluminescent materials based on ferrocenes.

Molecular engineering enabling reversible transformation between helical and planar conformations by cyclization of alkynes.

Molecular engineering enabling reversible transformation between helical and planar conformations is described herein. Starting from easily available 2-(pyridin-2-yl)anilines and alkynes, a one-pot strategy is set up for the synthesis of aza[4]helicenes via two successive rhodium-catalyzed C-H activation/cyclizations. Helical pyrrolophenanthridiziniums can be transformed into planar conformations through the cleavage of acidic pyrrole N-H, leading to turn-off fluorescence. NMR spectra, single crystal X-ray diffraction and DFT calculations demonstrate that the formation of an intramolecular C-H⋯N hydrogen bond is beneficial to stabilize the pyrrole nitrogen anion of the planar molecule and provide increased planarity. The reversible conformation transformations can be finely adjusted by the electron-donating and -withdrawing groups on the π+-fused pyrrole skeleton in the physiological pH range, thus affording an opportunity for pH-controlled intracellular selective fluorescence imaging. Pyrrolophenanthridiziniums show turn-on fluorescence in lysosomes owing to the acidic environment of lysosomes and turn-off fluorescence out of lysosomes, indicating the occurrence of the deprotonation reaction outside lysosomes and the corresponding transformation from helical to planar conformations.

Oxidative C-H/C-H Cross-Coupling of [1,2,4]Triazolo[1,5- a]pyrimidines with Indoles and Pyrroles: Discovering Excited-State Intramolecular Proton Transfer (ESIPT) Fluorophores.

A highly efficient Rh(III)-catalyzed oxidative C-H/C-H cross-coupling of [1,2,4]triazolo[1,5- a]pyrimidines (TAP) with indoles and pyrroles has been developed, which provides an opportunity to rapidly assemble a large library of novel excited-state intramolecular proton transfer (ESIPT) fluorophores. The resulting 7-(pyrrol-2-yl)TAPs only show the enol-form emission, while 7-(indol-2-yl)TAPs would undergo an ESIPT process and mainly exhibit the keto-form emission. In highly polar solvents, the enol-form emission of 7-(indol-2-yl)TAPs is enhanced significantly, thus showing the dual emission of enol and keto forms.

Molecular Engineering of Mechanochromic Materials by Programmed C-H Arylation: Making a Counterpoint in the Chromism Trend.

The development of facile methods for screening organic functional molecules through C-H bond activation is a revolutionary trend in materials research. The prediction of mechanochromism as well as mechanochromic trends of luminogens is an appealing yet challenging puzzle. Here, we present a strategy for the design of mechanochromic luminogens based on the dipole moment of donor-acceptor molecules. For this purpose, a highly efficient route to 2,7-diaryl-[1,2,4]triazolo[1,5-a]pyrimidines (2,7-diaryl-TAPs) has been established through programmed C-H arylation, which unlocks a great opportunity to rapidly assemble a library of fluorophores for the discovery of mechanochromic regularity. Molecular dipole moment can be employed to explain and further predict the mechanochromic trends. The 2,7-diaryl-TAPs with electron-donating groups on the 2-aryl and electron-withdrawing groups on the 7-aryl possess a relatively small dipole moment and exhibit a red-shifted mechanochromism. When the two aryls are interchanged, the resulting luminogens have a relatively large dipole moment and display a blue-shifted mechanochromism. Seven pairs of isomers with opposite mechanochromic trends are presented as illustrative examples. The aryl-interchanged congeners with a bidirectional emission shift are structurally similar, which provides an avenue for understanding in-depth the mechanochromic mechanism.

A sensitive colorimetric and fluorescent sensor based on imidazolium-functionalized squaraines for the detection of GTP and alkaline phosphatase in aqueous solution.

Imidazolium-functionalized squaraine ImSQ8 is synthesized as a sensitive colorimetric and fluorescent chemosensor for GTP in aqueous solution. The detection limit of GTP reaches 5.4 ppb. Its applications in the live-cell imaging and enzyme activity assay have also been demonstrated.

Transition-metal-catalyzed C-H bond functionalizations: feasible access to a diversity-oriented ß-carboline library.

Diversification of the ß-carboline skeleton has been demonstrated to assemble a ß-carboline library starting from the tetrahydro-ß-carboline framework. This strategy affords feasible access to heteroaryl-, aryl-, alkenyl-, or alkynyl-substituted ß-carbolines at the C1, C3, or C8 position through three categorically different types of transition-metal-catalyzed CC bond-forming reactions, in the presence of multiple potentially reactive positions. These site-selective functionalizations include; 1) the Cu-catalyzed C1/C3-selective decarboxylative C sp 3C sp 2 and C sp 3Csp coupling of hexahydro-ß-carboline-3-carboxylic acid with a CH bond of a heteroarene or terminal alkyne; 2) the chelation-assisted Pd-catalyzed C1/C8-selective CH arylation of hexahydro-ß-carboline with aryl boron reagents; and 3) the chelation-assisted Pd-catalyzed C1/C3-selective oxidative CH/CH cross-coupling of ß-carboline-N-oxide with arenes, heteroarenes, or alkenes. The saturated structural feature of the hexahydro-ß-carboline framework can increase reactivity and control site selectivity. The robustness of these approaches has been demonstrated through the synthesis of hyrtioerectine analogues and perlolyrine. We believe that these strategies could provide inspiration for late-stage diversifications of bioactive core scaffolds.

Palladium-catalyzed tandem N-H/C-H arylation: regioselective synthesis of N-heterocycle-fused phenanthridines as versatile blue-emitting luminophores.

A general and highly regioselective synthetic protocol for structurally diverse N-heteroaryl-fused phenanthridines has been developed. Varieties of fluorescence molecules comprising imidazole-fused, benzoimidazole-fused, indole-fused and pyrrole-fused phenanthridines were obtained by this modular approach, some of which exhibit excellent blue-emitting performance, high quantum yields, long fluorescence lifetimes, interesting electrochemical properties, and thermal stabilities.

Proteome analysis identifies the role of heat stress in production of progeny HCV in Huh7 cells harboring intact HCV.

OBJECTIVE: The intact hepatitis C virus (HCV) cell culture system has provided a powerful tool for studying the interaction between HCV and host cell. We applied proteomic techniques to globally analyze the protein expression profiles of Huh7 in the absence and presence of HCV, with the aim to elucidate the host cell components response to HCV. METHODS: Proteomic and molecular biology techniques were used for this aim. RESULTS: The expression of many proteins, including regucalcin, centriolin and several keratins, was up-regulated, after HCV transfection. Among the down-regulated expression proteins, the heat-shock protein family was of prime significance. Subsequently, we studied the role of heat stress in the interaction between HCV and host cell, based on proteomics analysis. We found heat stress did not affect the production of HCV in this in vitro cell culture system. CONCLUSIONS: Moreover, this study also provided the global information of proteomic alteration of Huh7 cells in the presence of intact HCV and further improved the understanding of the mechanism of interaction between HCV and host cell. We also draw a conclusion that heat stress had no affect on the production of HCV.

[Differential expression of genes related to transcription in cultured hepatoma cells with intact genome of hepatitis C virus].

OBJECTIVE: To investigate the effects of hepatitis C virus (HCV) on transcription regulation genes of host cells by gene chip assays in cultured cells with intact HCV genome. METHODS: Huh-7 hepatoma cells were cultured and infected with in vitro constructed HCV. The total RNAs, proteins and cell culture supernatants of HCV infected cells and control cells were isolated. Proteins and cell culture supernatants were used to detect the HCV replication and protein expression in cell culture system. The HCV protein expression was detected with Western blotting. Released HCV from infected cells was analyzed by real-time fluorescence quantitative PCR. Total RNA was qualified using 10 g/L agarose gel electrophoresis. cRNA was synthesized, fluorescence labeled and purified, then hybridized with Agilent oligo microarray (20173 probes). Differential expression of genes related to transcription in cell culture system was analyzed. RESULT: HCV was positive in cell culture supernatants and HCV protein expression was also positive according to Western blotting results. Eleven up-regulated and 11 down-regulated genes related to transcription were found after Agilent gene chip screening. CONCLUSION: Intact hepatitis C virus cell culture system provides an useful tool for study on the affects of HCV infection on transcription regulation genes in host cells.