Organometallic Allene [(μ-C)(Fe(CO)4)2]: Bridging Carbon Showing Transformation from Classical Electron-Sharing Bonding to Double σ-Donor and Double π-Acceptor Ligation

Allenes (R₂C=C=CR₂) have been traditionally perceived to feature localized orthogonal π-bonds between the carbon centres. We have carried out quantum-mechanical studies of the organometallic allenes envisioned by the isolobal replacement of the terminal CH₂ groups by the d⁸ Fe(CO)₄ fragment. Our studies have identified two organometallic allenes viz. D_2d symmetric [(μ-C)(Fe(CO)₄)₂] ( 2 ) and D₃ symmetric [(μ-C)(Fe(CO)₄)₂] ( 3 ) with trigonal bipyramidal coordination at the Fe atoms. Compound 2 features the bridging carbon atom in an equatorial position with respect to the ligands on the TM centre, while 3 features the central carbon atom in an axial position. The bis-pseudoallylic anionic delocalisation proposed in the C2-C1-C3 spine of organic allene is retained in the organometallic allene 2 , and is transformed to a typical three-centre bis-allylic anionic delocalisation in the organometallic allene 3 . The topological analysis of electron density also indicates a bis-allylic anionic type delocalisation in the organometallic allenes. The quantitative bonding analysis using the EDA-NOCV method suggests a transition from classical electron-sharing bonding between the central carbon atom and the terminal groups in 1 to donor-acceptor bonding in 3 . Meanwhile, both electron-sharing and donor-acceptor bonding models are found to be probable heuristic bonding representations in the organometallic allene 2 .     

Development of an Organic Dye-Conjugated β-Diketonate-Europium Complex Luminescence Probe for Discrimination and Detection of Intracellular Biothiols

Small molecular biothiols, cysteine (Cys), homocysteine (Hcy) and glutathione (GSH), play important roles in organisms, and their concentration levels are indicative of some human diseases. Herein we report an organic dye-conjugated β-diketonate-Eu³⁺ complex, [Eu(NBD-keto)₃(DPBT)] (NBD-keto: 7-nitro-2,1,3-benzoxadiazole (NBD)-conjugated to 1,1,1,2,2-pentafluoro-5-phenyl-3,5-pentanedionate through a “O” ether bond; DPBT: 2-(N,N-diethylanilin-4-yl)-4,6-bis(3,5-dimethylpyrazol-1-yl)-1,3,5-triazine), which acts as a unique luminescent probe for detecting and discriminating biothiols. [Eu(NBD-keto)₃(DPBT)] itself is not luminescent due to intramolecular interactions between NBD and β-diketonate-Eu³⁺ moieties. Upon reaction with biothiols, the β-diketonate-Eu³⁺ complex [Eu(keto)₃(DPBT)] is generated, which emits long-lived red emission at 610 nm. Meanwhile, three biothiol-substituted NBD derivatives that exhibit different luminescence behaviors, green emissive (short-lived) NBD-NR (R=Cys or Hcy) at 540 nm and non-luminescent NBD-SR (R=GSH), are also generated. These luminescence response behaviors allow time-gated and steady-state luminescence modes to be combined for detecting total biothiols and discriminating GSH and Cys/Hcy. Using this probe, the quantitative detection and discrimination of GSH and Cys/Hcy in lysis solutions of HeLa cells were realized, which revealed the potential of the probe for biomedical applications.     

Molecular Hybridization Strategy on the Design,Synthesis, and Structural Characterization of Ferrocene-N-acyl Hydrazones as Immunomodulatory Agents

Immunomodulatory agents are widely used for the treatment of immune-mediated diseases, but the range of side effects of the available drugs makes necessary the search for new immunomodulatory drugs. Here, we investigated the immunomodulatory activity of new ferrocenyl-N-acyl hydrazones derivatives (SintMed(141–156). The evaluated N-acyl hydrazones did not show cytotoxicity at the tested concentrations, presenting CC₅₀ values greater than 50 µM. In addition, all ferrocenyl-N-acyl hydrazones modulated nitrite production in immortalized macrophages, showing inhibition values between 14.4% and 74.2%. By presenting a better activity profile, the ferrocenyl-N-acyl hydrazones SintMed149 and SintMed150 also had their cytotoxicity and anti-inflammatory effect evaluated in cultures of peritoneal macrophages. The molecules were not cytotoxic at any of the concentrations tested in peritoneal macrophages and were able to significantly reduce (p < 0.05) the production of nitrite, TNF-α, and IL-1β. Interestingly, both molecules significantly reduced the production of IL-2 and IFN-γ in cultured splenocytes activated with concanavalin A. Moreover, SintMed150 did not show signs of acute toxicity in animals treated with 50 or 100 mg/kg. Finally, we observed that ferrocenyl-N-acyl hydrazone SintMed150 at 100 mg/kg reduced the migration of neutrophils (44.6%) in an acute peritonitis model and increased animal survival by 20% in an LPS-induced endotoxic shock model. These findings suggest that such compounds have therapeutic potential to be used to treat diseases of inflammatory origin.     

Copper‐Catalyzed Intermolecular Asymmetric Propargylic Dearomatization of Indoles

The first copper‐catalyzed intermolecular dearomatization of indoles by an asymmetric propargylic substitution reaction was developed. This method provides a highly efficient synthesis of versatile furoindoline and pyrroloindoline derivatives containing a quaternary carbon stereogenic center and a terminal alkyne moiety with up to 86 % yield and 98 % ee.     

Directed meta‐Selective Bromination of Arenes with Ruthenium Catalysts

A Ru‐catalyzed direct C? H activation/meta‐bromination of arenes bearing pyridyl, pyrimidyl, and pyrazolyl directing groups has been developed. A series of bromo aryl pyridines and pyrimidines have been synthesized, and further coupling reactions have also been demonstrated for a number of representative functionalized arenes. Preliminary mechanistic studies have revealed that this reaction may proceed through radical‐mediated bromination when NBS is utilized as the bromine source. This type of transformation has opened up a new direction for the radical non‐ipso functionalization of metal with regard to future C? H activation development that would allow the remote functionalization of aromatic systems.     

De Novo Design and Synthesis of a γ‐Turn Peptidomimetic Scaffold and Its Application as JNK3 Allosteric Ligand

As a way to develop a neuroprotective agent for the JNK3‐JIP1‐binding site, peptidomimetics of JIP‐1 as JNK3 allosteric regulators have been examined. The study consisted of in silico scaffold hopping, molecular docking, solution and solid‐phase peptide syntheses, and K_d measurements using surface plasmon resonance. As a peptidomimetic of JIP1, heptamer mimetic 16 (K_d=2.72 μm ) displayed a higher affinity than decamer JIP1 (K_d=23.6 μm ). The high affinity of 16 implies that the characteristic γ‐turn mimetic structure, “”Φ‐X‐Φ“ hydrophobic motif in 16 , increased its affinity toward the JIP‐site of JNK3.     

Mechanism of the Aerobic Homocoupling of Phenylboronic Acid on Au20−: A DFT Study

The mechanism of the gold nanocluster‐catalyzed aerobic homocoupling of arylboronic acids has been elucidated by means of DFT calculations with Au₂₀^? as a model cluster for the Au:[poly(N‐vinylpyrrolidin‐2‐one)] catalyst. We found that oxygen affects the adsorption of phenylboronic acid and, by lowering the energy barrier, a water molecule enhances dissociation of the C?B bond, which is probably the rate‐determining step. The key role of oxygen is in activating the surface of the gold cluster by generating Lewis acidic sites for adsorption and activation of the phenylboronic acid, leading to the formation of biphenyl through a superoxo‐like species. Moreover, the oxygen adsorbed on the Au nanocluster can act as an oxidant for phenylboronic acid, giving phenol as a byproduct. As shown by NBO analysis, the basic aqueous reaction medium facilitates the reductive elimination process by weakening the Au?C bond, thereby enhancing the formation of biphenyl. The coupling of phenyl and reductive elimination of biphenyl occur at the top or facet site with low‐energy‐barrier through spillover of phenyl group on Au NC. The present findings are useful for the interpretation or design of other coupling reactions with Au NC.     

Luminescent Di‐ and Trinuclear Boron Complexes Based on Aromatic Iminopyrrolyl Spacer Ligands: Synthesis,Characterization, and Application in OLEDs

New bis‐ and tris(iminopyrrole)‐functionalized linear (1,2‐(HNC₄H₃‐C(H)?N)₂‐C₆H₄ ( 2 ), 1,3‐(HNC₄H₃‐C(H)?N)₂‐C₆H₄ ( 3 ), 1,4‐(HNC₄H₃‐C(H)?N)₂‐C₆H₄ ( 4 ), 4,4′‐(HNC₄H₃‐C(H)?N)₂‐(C₆H₄‐C₆H₄) ( 5 ), 1,5‐(HNC₄H₃C‐(H)?N)₂‐C₁₀H₆ ( 6 ), 2,6‐(HNC₄H₃C‐(H)?N)₂‐C₁₀H₆ ( 7 ), 2,6‐(HNC₄H₃C‐(H)?N)₂‐C₁₄H₈ ( 8 )) and star‐shaped (1,3,5‐(HNC₄H₃‐C(H)?N‐1,4‐C₆H₄)₃‐C₆H₃ ( 9 )) π‐conjugated molecules were synthesized by the condensation reactions of 2‐formylpyrrole ( 1 ) with several aromatic di‐ and triamines. The corresponding linear diboron chelate complexes (Ph₂B[1,3‐bis(iminopyrrolyl)‐phenyl]BPh₂ ( 10 ), Ph₂B[1,4‐bis(iminopyrrolyl)‐phenyl]BPh₂ ( 11 ), Ph₂B[4,4′‐bis(iminopyrrolyl)‐biphenyl]BPh₂ ( 12 ), Ph₂B[1,5‐bis(iminopyrrolyl)‐naphthyl]BPh₂ ( 13 ), Ph₂B[2,6‐bis(iminopyrrolyl)‐naphthyl]BPh₂ ( 14 ), Ph₂B[2,6‐bis(iminopyrrolyl)‐anthracenyl]BPh₂ ( 15 )) and the star‐shaped triboron complex ([4′,4′′,4′′′‐tris(iminopyrrolyl)‐1,3,5‐triphenylbenzene](BPh₂)₃ ( 16 )) were obtained in moderate to good yields, by the treatment of 3 – 9 with B(C₆H₅)₃. The ligand precursors are non‐emissive, whereas most of their boron complexes are highly fluorescent; their emission color depends on the π‐conjugation length. The photophysical properties of the luminescent polyboron compounds were measured, showing good solution fluorescence quantum yields ranging from 0.15 to 0.69. DFT and time‐dependent DFT calculations confirmed that molecules 10 and 16 are blue emitters, because only one of the iminopyrrolyl groups becomes planar in the singlet excited state, whereas the second (and third) keeps the same geometry. Compound 13 , in which planarity is not achieved in any of the groups, is poorly emissive. In the other examples ( 11 , 12 , 14 , and 15 ), the LUMO is stabilized, narrowing the gap between the highest occupied molecular orbital and the lowest unoccupied molecular orbital (HOMO–LUMO), and the two iminopyrrolyl groups become planar, extending the size of the π‐system, to afford green to yellow emissions. Organic light‐emitting diodes (OLEDs) were fabricated by using the new polyboron complexes and their luminance was found to be in the order of 2400 cd m^?2, for single layer devices, increasing to 4400 cd m^?2 when a hole‐transporting layer is used.     

Sensitive and Multiplexed On‐chip microRNA Profiling in Oil‐Isolated Hydrogel Chambers

Although microRNAs (miRNAs) have been shown to be excellent indicators of disease state, current profiling platforms are insufficient for clinical translation. Here, we demonstrate a versatile hydrogel‐based microfluidic approach and novel amplification scheme for entirely on‐chip, sensitive, and highly specific miRNA detection without the risk of sequence bias. A simulation‐driven approach is used to engineer the hydrogel geometry and the gel‐reaction environment is chemically optimized for robust detection performance. The assay provides 22.6 fM sensitivity over a three log range, demonstrates multiplexing across at least four targets, and requires just 10.3 ng of total RNA input in a 2 hour and 15 minutes assay.