Cobalt(II)-Catalyzed Aerobic Oxidation of Terminal-Capped Alkynyl α-Cyano Alkanone Systems. An Oxygen-Mediated Radical Chain Reaction.

A new N-hydroxyphthalimide (NHPI)/Co(II)-catalyzed protocol, mechanistically involving a sequence of α-hydrogen abstraction, 5-exo-dig cyclization, oxygen capture, hydrogen transfer, and 1,4-dehydration, has been developed to facilitate aerobic oxidation of aryl-, silyl-, and alkyl-capped alkynyl α-cyano alkanone systems to the corresponding highly functionalized products in an effective manner, thus turning this novel chain reaction, originally occurring spontaneously in low yields, into a practical methodology.

A convenient method for the synthesis of α-carboxylate ester bromolactones via bromolactonization of alkenoic diesters.

We developed a simple and efficient method to construct a variety of α-ester bromolactones in good to excellent yields with high diastereoselectivies. The protocol uses readily prepared malonate ester derivatives as substrates, water as an additive and inexpensive N-bromosuccinimide as the halogen source; no catalyst or toxic additive is required. The resulting substituted bromolactones are the fundamental units of many useful molecules.

An unexpected 2,3-dihydrofuran derivative ring opening initiated by electrophilic bromination: scope and mechanistic study.

An unexpected 2,3-dihydrofuran ring opening process at the C(4)-C(5) bond has been developed. N-Bromosuccinimide and DABCO were used as the electrophilic halogen source and the catalyst, respectively. Mechanistic study indicates that moisture in the solvent might contribute to the reaction. The resulting brominated product could be further oxidized to yield a synthetically valuable 1,2-diketo building block.

Conia-ene annulation of the α-cyano ß-TMS-capped alkynyl cycloalkanone system and its synthetic application.

Under catalysis with ZnI(2), an effective annulation process of ω-silylacetylenic α-cyano ketones, leading to the formation of various bicyclic frameworks characterized with a TMS-containing methylenecyclopentane ring, has been developed.

Stable and Bright Commercial CsPbBr3 Quantum Dot-Resin Layers for Apparent X-ray Imaging Screen.

CsPbBr3 quantum dots (QDs) have recently gained much interest due to their excellent optical and scintillation properties and their potential for X-ray imaging applications. In this study, we blended CsPbBr3 QDs with resin at different QD concentrations to achieve thick films and to protect the CsPbBr3 QDs from environmental moisture. Then, their scintillation properties are investigated and compared to the traditional commercial scintillators, CsI:Tl microcolumns, and Gadox layers. The CsPbBr3 QD-resin sheets show a high light yield of up to 21 500 photons/MeV at room temperature and a relatively small variation in light yield across a wide temperature range. In addition, the CsPbBr3 QD-resin sheets feature a small scintillation afterglow. The CsPbBr3 QD-resin sheets show a negligible trap density for the concentration below 50% weight, indicating that traps might arise from the aggregation of the QDs. The CsPbBr3 QD-resin sheets are also very stable at low irradiation intensities and relatively stable at higher intensities, with higher CsPbBr3 QD concentrations being more stable. Gamma-ray-excited-time-resolved emission measurements at 662 keV showed that the CsPbBr3 QD-resin sheets have an average scintillation decay time between 108 and 176 ns, which are still 10 000 and 6000 times faster than CsI:Tl and Gadox, respectively. Imaging tests show that the CsPbBr3 QD-resin sheets have a mean transfer function of 50% at 2 lp/mm and 20% at 4 lp/mm, comparable to that of commercial Gadox layers. This feature makes CsPbBr3 QD-resin sheets a good candidate for the low-cost, flexible X-ray imaging screens and γ-ray applications.

Thermodynamic Control in the Synthesis of Quantum-Confined Blue-Emitting CsPbBr3 Perovskite Nanostrips.

Size control is critical in the synthesis of quantum-confined semiconductor nanocrystals, otherwise known as quantum dots. The achievement of size-uniformity and narrow spectral line-width in quantum dots conventionally relies on a very precise kinetic control of the reactions, where reaction time plays a significant role in defining the final crystal sizes and distribution. Here, we show that synthesis of quantum-confined perovskite nanostrips could be achieved through a thermodynamically controlled reaction, using a low-temperature and ligand-rich approach. The nanostrip growth proceeds through an initial one-dimensional (1D) nanorod stage, followed by the lateral widening of the rod to form a two-dimensional (2D) nanostrip. The spectral characteristics of the final product remain unchanged after prolonged reaction, indicating no signs of crystal ripening and confirming the thermodynamic nature of this reaction. The CsPbBr3 perovskite nanostrips were highly uniform and emit at a deep-blue wavelength of 462 nm with a remarkably narrow line-width of 13 nm. This corresponds to color coordinates of (0.136, 0.049) on the CIE 1931 color space, which fulfils the stringent Rec. 2020 standard for next-generation color displays. The well-passivated nanostrips also possess negligible defects and provide a near-unity photoluminescence quantum yield at 94%. Crucially, the achievement of blue emission through a pure-halide perovskite circumvents the problems of spectral instability that are frequently experienced in mixed-halide perovskite systems. The convenience and scalability of our thermodynamic approach, coupled with the excellent optical attributes, would likely enable these quantum-confined perovskite systems to be the preferred method toward color control in trichromatic display applications.

Cobalt-catalyzed regioselective synthesis of pyrrolidinone derivatives by reductive coupling of nitriles and acrylamides.

A convenient and highly regioselective method for the synthesis of 5-methylenepyrrolidinone derivatives from various nitriles and acrylamides via a cobalt-catalyzed reductive coupling reaction is described. A possible mechanism that involves the formation of a cobaltaazacyclopentene intermediate from nitrile and acrylamide, protonation, keto-amide cyclization, and dehydration is proposed.

Color Patterning of Luminescent Perovskites via Light-Mediated Halide Exchange with Haloalkanes.

Lead halide perovskite possesses a semiconductor bandgap that is readily tunable by a variation in its halide composition. Here, a photo-activated halide exchange process between perovskite nanocrystals and molecular haloalkanes is reported, which enables the perovskite luminescence to be controllably shifted across the entire visible spectrum. Mechanistic investigations reveal a mutual exchange of halogens between the perovskite crystal surface and a chemisorbed haloalkane, yielding nanocrystals and haloalkanes with mixed halide contents. Exchange kinetics studies involving primary, secondary, and tertiary haloalkanes show that the rate of reaction is governed by the activation barrier in the breakage of the covalent carbon-halogen (CX) bond, which is a function of the CX bond energy and carbon radical stability. Employing this halide exchange approach, a micrometer-scale trichromatic patterning of perovskites is demonstrated using a light-source-integrated inkjet printer and tertiary haloalkanes as color-conversion inks. The haloalkanes volatilize after halide exchange and leave no residues, thereby offering significant processing advantage over conventional salt-based exchange techniques. Beyond the possible applications in new-generation micro-LED and electroluminescent quantum dot displays, this work exemplifies the rich surface and photochemistry of perovskite nanocrystals, and could lead to further opportunities in perovskite-based photocatalysis and photochemical sensing.

Perovskite-Initiated Photopolymerization for Singly Dispersed Luminescent Nanocomposites.

Metal halide perovskites have demonstrated rich photophysics and remarkable potential in photovoltaic and electroluminescent devices. However, the photoactivity of perovskite semiconductors in chemical processes remains relatively unexplored. Here, a general approach toward the synthesis of luminescent perovskite-polymer nanocomposites is reported, whereby perovskite nanocrystals are used as photoinitiators in the polymerization of vinyl monomers. The white-light illumination of a perovskite-monomer mixture triggers a free-radical chain-growth polymerization process, giving rise to high molecular weight polymers of ≈200 kDa. The in situ growth of polymer chains from the perovskite crystal surface allows the formation of individually dispersed nanocrystal cores within an encapsulating polymer matrix, and leads to a significant threefold enhancement in photoluminescence quantum yield. This photoluminescence enhancement is attributed to the spatial separation of the perovskite nanocrystals and hence the deactivation of energy transfer to dark crystals. The resulting perovskite-polymer nanocomposites exhibit excellent stability against moisture and are shown to be useful as functional downconversion phosphor films for luminescent displays and lighting.

Cobalt-catalyzed aryl-sulfur bond formation.

A new cobalt-catalyzed coupling of aryl halides with thiophenols and alkanethiols is reported. A variety of aryl sulfides can be prepared in excellent yields under mild reaction conditions using 1-2 mol % of CoI2(dppe) and Zn. This new cobalt-catalyzed coupling represents an interesting addition to previously known methods to synthesize thioethers. [reaction: see text].

Lewis Basic Sulfide Catalyzed Electrophilic Bromocyclization of Cyclopropylmethyl Amide.

A Lewis basic sulfide catalyzed electrophilic bromocyclization of cyclopropylmethyl amide has been developed. The catalytic protocol is applicable to both 1,1- and 1,2-substituted cyclopropylmethyl amides, giving oxazolines and oxazines in good yields and excellent diastereoselectivity.

Stem cell mobilizers targeting chemokine receptor CXCR4: renoprotective application in acute kidney injury.

We have discovered a novel series of quinazoline-based CXCR4 antagonists. Of these, compound 19 mobilized CXCR4(+) cell types, including hematopoietic stem cells and endothelial progenitor cells, more efficiently than the marketed 1 (AMD3100) with subcutaneous administration at the same dose (6 mg/kg) in mice. This series of compounds thus provides a set of valuable tools to study diseases mediated by the CXCR4/SDF-1 axis, including myocardial infarction, ischemic stroke, and cancer metastasis. More importantly, treatment with compound 19 significantly lowered levels of blood urea nitrogen and serum creatinine in rats with renal ischemia-reperfusion injury, providing evidence for its therapeutic potential in preventing ischemic acute kidney injury. CXCR4 antagonists such as 19 might also be useful to increase circulating levels of adult stem cells, thereby exerting beneficial effects on damaged and/or inflamed tissues in diseases that currently are not treated by standard approaches.

Function-oriented development of CXCR4 antagonists as selective human immunodeficiency virus (HIV)-1 entry inhibitors.

Motivated by the pivotal role of CXCR4 as an HIV entry co-receptor, we herein report a de novo hit-to-lead effort on the identification of subnanomolar purine-based CXCR4 antagonists against HIV-1 infection. Compound 24, with an EC50 of 0.5 nM against HIV-1 entry into host cells and an IC50 of 16.4 nM for inhibition of radioligand stromal-derived factor-1α (SDF-1α) binding to CXCR4, was also found to be highly selective against closely related chemokine receptors. We rationalized that compound 24 complementarily interacted with the critical CXCR4 residues that are essential for binding to HIV-1 gp120 V3 loop and subsequent viral entry. Compound 24 showed a 130-fold increase in anti-HIV activity compared to that of the marketed CXCR4 antagonist, AMD3100 (Plerixafor), whereas both compounds exhibited similar potency in mobilization of CXCR4(+)/CD34(+) stem cells at a high dose. Our study offers insight into the design of anti-HIV therapeutics devoid of major interference with SDF-1α function.

Discovery of 1-(2,4-dichlorophenyl)-N-(piperidin-1-yl)-4-((pyrrolidine-1-sulfonamido)methyl)-5-(5-((4-(trifluoromethyl)phenyl)ethynyl)thiophene-2-yl)-1H-pyrazole-3-carboxamide as a novel peripherally restricted cannabinoid-1 receptor antagonist with significant weight-loss efficacy in diet-induced obese mice.

After extensive synthetic efforts, we found that many structurally diverse bioisosteres could be generated via derivatizing the C-4 alkyl chain on the pyrazole ring of compound 3 (B/P = 1/33) with different electronegative groups. Especially when a sulfonamide or sulfamide moiety was added, resulting compounds exhibited not only potent CB1R activity but also a desired tPSA value over 90 Å(2), a threshold considered to possess a low probability to cross BBB, leading to the identification of compound 4 (B/P = 1/64) as a peripherally restricted CB1R antagonist. Apart from its significant weight-loss efficacy in DIO mice, compound 4 also displays 163 clean off-target profiles and is currently under development for treating obesity and the related metabolic syndrome.

Tandem cyclization of α-cyano α-alkynyl aryl ketones induced by tert-butyl hydroperoxide and tetrabutylammonium iodide.

The radical cascade protocol of the α-cyano α-TMS/aryl-capped alkynyl aryl ketones promoted by tert-butyl hydroperoxide under catalysis with tetrabutylammonium iodide in refluxing benzene has been developed, leading to the construction of a variety of highly functionalized [6,6,5] tricyclic frameworks in an efficient manner.

Autoxidative annulation cascade of the α-cyano ß-TMS-capped alkynyl cycloalkanone system.

The autoxidative annulation cascade promoted by an α-cyano ß-TMS-capped alkynyl cycloalkanone system under catalysis with pyridine in one oxygen atmosphere has proven to be highly viable. On the basis of this newly developed protocol, a variety of highly functionalized bicyclic frameworks can be effectively constructed.

Direct synthesis of arylketones by nickel-catalyzed addition of arylboronic acids to nitriles.

A convenient and efficient method for the synthesis of various arylketones by nickel-catalyzed addition of arylboronic acids to nitriles is described. A catalytic cycle involving Ni(II) species as the catalytic intermediates is proposed to account for the present catalytic reaction.