Selective detection of mitochondrial Cu in living cells by a near-infrared iridium(III) complex.

The widespread use of copper (Cu) has raised concerns about environmental pollution and adverse effects on human health, highlighting the need to develop copper detection methods. Developing near-infrared (NIR) luminescent probes for imaging subcellular Cu is still a challenge. In this work, we have developed a luminescence probe based on a NIR iridium(III) complex, which rapidly detects Cu by combining salicylaldehyde and amine groups through a simple Schiff base reaction on the N^N ligand.

Visible-Light-Driven Method for the Selective Synthesis of Amides and N-Acylureas from Carboxylic Acids and Thioureas.

In this work, we developed a visible-light-driven method for the selective synthesis of amides and N-acylureas from carboxylic acids and thioureas. This protocol was featured as avoidance of additional oxidants and transition metal catalysts, simple manipulations, low cost, broad substrate scope, and good functional group tolerance. As only oxygen serves as the oxidation reagent, this method provides a promising synthesis candidate for the formation of N-aryl amides and N-acylureas, including late-stage functionalization of complex pharmaceutical molecules and biologically active molecules.

Activation of Toll-like receptor 3 inhibits HIV infection of human iPSC-derived microglia.

As a key immune cell in the brain, microglia are essential for protecting the central nervous system (CNS) from viral infections, including HIV. Microglia possess functional Toll-like receptor 3 (TLR3), a key viral sensor for activating interferon (IFN) signaling pathway-mediated antiviral immunity. We, therefore, studied the effect of poly (I:C), a synthetic ligand of TLR3, on the activation of the intracellular innate immunity against HIV in human iPSC-derived microglia (iMg).

KCO-promoted synthesis of amides from 1-aryl-2,2,2-trifluoroethanones and amines under mild conditions.

A base-promoted amidation of 1-aryl-2,2,2-trifluoroethanones with amines Haller-Bauer reaction has been developed. In this reaction, the direct transformation of 1-aryl-2,2,2-trifluoroethanones into amides C(O)-C bond cleavage occurs without the use of any stoichiometric chemical oxidants or transition-metal catalysts. A series of primary and secondary amines are shown to be compatible with this transformation, and several pharmaceutical molecules were synthesized.

Umpolung Asymmetric 1,5-Conjugate Addition via Palladium Hydride Catalysis.

Electronically matched nucleophilic 1,6-conjugate addition has been well studied and widely applied in synthetic areas. In contrast, nucleophilic 1,5-conjugate addition represents an electronically forbidden process and is considered unfeasible. Here, we describe modular protocols for 1,5-conjugate addition reactions via palladium hydride catalysis.

Cytosolic DNA sensor activation inhibits HIV infection of macrophages.

Cytosolic recognition of microbial DNA in macrophages results in the activation of the interferon (IFN)-dependent antiviral innate immunity. Here, we examined whether activating DNA sensors in peripheral blood monocyte-derived macrophages (MDMs) can inhibit human immunodeficiency virus (HIV). We observed that the stimulation of MDMs with poly(dA:dT) or poly(dG:dC) (synthetic ligands for the DNA sensors) inhibited HIV infection and replication.

Selective halocyclization and iodosulfonylation of -benzothiazol-2-yl alkynamides under mild conditions.

The selective halocyclization and iodosulfonylation of -benzothiazol-2-yl alkynamides under mild conditions is described. An effective synthetic strategy to pyrimidobenzothiazoles a 6- halocyclization of -benzothiazol-2-yl alkynamides was developed at room temperature with a broad substrate scope. Furthermore, several multisubstituted α,β-enones were synthesized using the same starting materials.

Comparison of BNT162b2-, mRNA-1273- and Ad26.COV2.S-Elicited IgG and Neutralizing Titers against SARS-CoV-2 and Its Variants.

Because the vaccine-elicited antibody and neutralizing activity against spike protein of SARS-CoV-2 are associated with protection from COVID-19, it is important to determine the levels of specific IgG and neutralization titers against SARS-CoV-2 elicited by the vaccines. While three widely used vaccine brands (Pfizer-BNT162b2, Moderna-mRNA-1273 and Johnson-Ad26.COV2.

Methamphetamine facilitates HIV infection of primary human monocytes through inhibiting cellular viral restriction factors.

Background: Methamphetamine (METH), a potent addictive psychostimulant, is highly prevalent in HIV-infected individuals. Clinically, METH use is implicated in alteration of immune system and increase of HIV spread/replication. Therefore, it is of importance to examine whether METH has direct effect on HIV infection of monocytes, the major target and reservoir cells for the virus.

TLR7 Activation of Macrophages by Imiquimod Inhibits HIV Infection through Modulation of Viral Entry Cellular Factors.

The Toll-like receptor (TLR) 7 is a viral sensor for detecting single-stranded ribonucleic acid (ssRNA), the activation of which can induce intracellular innate immunity against viral infections. Imiquimod, a synthetic ligand for TLR7, has been successfully used for the topical treatment of genital/perianal warts in immunocompetent individuals. We studied the effect of imiquimod on the human immunodeficiency virus (HIV) infection of primary human macrophages and demonstrated that the treatment of cells with imiquimod effectively inhibited infection with multiple strains (Bal, YU2, and Jago) of HIV.

Structure-guided discovery of a luminescent theranostic toolkit for living cancer cells and the imaging behavior effect.

Dual-functional theranostics are powerful tools that can allow for the in-field understanding of cancer pathology, yet their use is held back by the paucity of suitable theranostics for living systems. Moreover, typical screening conditions for probe molecules do not necessarily generate candidates that can function effectively in the natural environment, limiting their follow-up use in living systems. We introduce herein a general strategy for the development of an iridium(iii) theranostic by grafting a well-known inhibitor as a "binding unit" onto an iridium(iii) complex precursor as a "signaling unit".

CD4 T cell depletion does not affect the level of viremia in chronically SHIV-infected Chinese cynomolgus monkeys.

Chronically SHIV-infected cynomolgus monkeys were used to determine the effects of the antibody-mediated acute CD4 T cell depletion on viral load as well as on the immunological factors associated with disease progression. Compared with the control animals, CD4 T cell-depleted animals with SHIV infection showed (i) little alteration in plasma viral load over the period of 22 weeks after the depletion; (ii) increased CD4 T cell proliferation and turnover of macrophages at the early phase of the depletion, but subsequent decline to the basal levels; and (iii) little impact on the expression of the inflammatory cytokines and CC chemokines associated with disease progression. These findings indicate that the antibody-mediated acute CD4 T cell depletion had minimal impact on plasma viral load and disease progression in chronically SHIV-infected cynomolgus monkeys.

Iron-catalyzed stereoselective haloamidation of amide-tethered alkynes.

In this work, by using N-methoxybenzamides as efficient acyl nitrene precursors, an iron-catalyzed formal cis-haloamidation of alkyne is reported. Without assistance of additives, the reaction worked well in the presence of 50 mol% FeCl3 or FeBr3, leading to a series of chloro/bromo-containing isoindolin-5-ones with high efficiency and wide reaction scope. In the reaction, the iron-facilitated haloamidation proceeds through a halo anion-participating concerted [3+2] cyclization to release the final products.

Radical bromination-induced cyclization- cyclization sequence of -hydroxylethyl--arylpropiolamides.

A facile procedure is reported for the synthesis of various 2-bromo-1-phenyl-5,6-dihydro-3H,7aH-benzo[b]pyrrolo[2,1-c][1,4]oxazin-3-ones via a radical bromination-induced ipso cyclization-ortho cyclization sequence of N-arylpropiolamides in the presence of TBAB and oxone. The radical cyclization sequence involves a radical bromo α-addition into the alkyne, ipso-cyclization, and ortho-trapping of the spirocyclic intermediate.

Iron-catalyzed intramolecular acyl nitrene/alkyne metalation for the synthesis of pyrrolo[2,1-a]isoindol-5-ones.

In this work, by using N-methoxybenzamides as efficient acyl nitrene precursors, an iron-catalyzed acyl nitrene/alkyne metalation is reported for the synthesis of pyrrolo[2,1-a]isoindol-5-ones. In the reaction, a 5-exo-dig acyl nitrene/alkyne metalation is specifically observed; a counter anion-aided acyl nitrene/alkyne metalation accounts for the formation of pyrrolo[2,1-a]isoindol-5-ones. Moreover, pyrrolo[2,1-a]isoindol-5-ones possess good fluorescence properties exhibiting a long Stokes shift (>100 nm), and have been employed as small molecular probes for the detection of Hg, hydrazine, and cysteine.

Fluorescent and Colorimetric Sensors Based on the Oxidation of -Phenylenediamine.

-Phenylenediamine (OPD) can be readily oxidized by several types of oxidants to generate fluorescent 2,3-diaminophenazine (oxidized OPD, OPDox). The unique fluorescence response process during the oxidation of OPD provides an important model for the design of novel sensors. In recent years, a series of fluorescent and colorimetric sensors have been developed based on the oxidation of OPD.

Palladium-Catalyzed Imidoylation-Triggered [2 + 2 + 1] Cyclization of Internal Alkyne with Isocyanides.

In this work, a palladium-catalyzed [2 + 2 + 1] cyclization of internal alkynes with double isocyanides is described. This facile procedure is efficient for synthesizing various pyrrolo[3,2-]quinolin-2-amines. The reaction worked well with a broad reaction scope.

Copper-catalyzed synthesis of sulfonamides from nitroarenes via the insertion of sulfur dioxide.

Nitroarenes are used as the coupling partners in the preparation of sulfonamides via the insertion of sulfur dioxide. A three-component reaction of arylboronic acids, nitroarenes, and potassium metabisulfite under copper catalysis proceeds smoothly, giving rise to a range of sulfonamides in good to excellent yields with broad substrate scope. Various functional groups including hydroxyl, cyano, amino, and carbonyl are all tolerated.

Synthesis of Trifluoromethyl- and Ester Group-Substituted α-Carbolines via Iron-Catalyzed Tandem Cyclization Reaction.

An efficient approach to prepare trifluoromethyl-α-carbolines and ester group-substituted α-carbolines via the tandem cyclization reaction of 2-(2-aminophenyl)acetonitriles and trifluoromethyl 1,3-diones or β,γ-unsaturated α-ketoesters was reported. The transformation proceeded smoothly in the presence of catalytic environmental-benign iron salts, which are used to prepare the desired products in moderate to good yields.

A copper-catalyzed insertion of sulfur dioxide via radical coupling.

A copper-catalyzed three-component reaction of O-acyl oximes, DABCO·(SO2)2, and 2H-azirines under mild conditions has been achieved. This protocol provides an efficient route for the construction of various tetrasubstituted β-sulfonyl N-unprotected enamines in moderate to good yields with excellent stereoselectivity and regioselectivity. Notably, this method represents a rare example of 2H-azirines as useful synthons for β-functionalized N-unprotected enamines.

Photoinduced synthesis of 2-sulfonylacetonitriles with the insertion of sulfur dioxide under ultraviolet irradiation.

Metal-free insertion of sulfur dioxide with aryl iodides and 3-azido-2-methylbut-3-en-2-ol under ultraviolet irradiation at room temperature is achieved, giving rise to 2-(arylsulfonyl)acetonitriles in moderate to good yields. Alkyl iodide is also workable under these conditions. This transformation proceeds smoothly under mild conditions with a broad substrate scope.

-Hydroxylative -Cyclization of -arylpropiolamide.

A facile protocol for the tunable synthesis of 10-hydroxy-1-azaspiro[4.5]deca-3,6,8-trien-2-ones and benzo[]pyrrolo[2,1-][1,4]oxazin-3-ones is described. A tunable synthesis has been realized by the use of ZnBr/oxone and tetra--butylammonium bromide (TBAB)/oxone.

ZnBr/Oxone-mediated -cyclization of -(3-phenylprop-2-yn-1-yl)aniline.

In this work, a selective synthetic strategy towards 1-azaspiro[4.5]deca-3,6,9-trien-8-ones from -tosyl--(prop-2-yn-1-yl)aniline is developed. The transformation proceeds smoothly in a mixed solvent including acetonitrile and water when ZnBr and Oxone are employed.

A simple iridium(III) dimer as a switch-on luminescent chemosensor for carbon disulfide detection in water samples.

A series of iridium(III) dimers were synthesized and their ability to interact with diethyldithiocarbamate for CS sensing was evaluated. Upon the addition of CS, diethylamine can capture CS to form diethyldithiocarbamate, which could chelate with the iridium(III) dimer to form a diethyldithiocarbamate iridium(III) complex, resulting in a yellow luminescence. Dimer 8 exhibited a maximum 18-fold of luminescence enhancement upon the addition of CS.