Inhaled mRNA Nanoformulation with Biogenic Ribosomal Protein Reverses Established Pulmonary Fibrosis in a Bleomycin-Induced Murine Model.

Idiopathic pulmonary fibrosis (IPF), a lethal respiratory disease with few treatment options, occurs due to repetitive microinjuries to alveolar epithelial cells (AECs) and progresses with an overwhelming deposition of extracellular matrix (ECM), ultimately resulting in fibrotic scars and destroyed the alveolar architecture. Here, an inhaled ribosomal protein-based mRNA nanoformulation is reported for clearing the intrapulmonary ECM and re-epithelializing the disrupted alveolar epithelium, thereby reversing established fibrotic foci in IPF. The nanoformulation is sequentially assembled by a ribosomal protein-condensed mRNA core, a bifunctional peptide-modified corona and keratinocyte growth factor (KGF) with a PEGylated shielding shell.

Direct Observation of Aggregation-Induced Emission Mechanism.

The mechanism of aggregation-induced emission, which overcomes the common aggregation-caused quenching problem in organic optoelectronics, is revealed by monitoring the real time structural evolution and dynamics of electronic excited state with frequency and polarization resolved ultrafast UV/IR spectroscopy and theoretical calculations. The formation of Woodward-Hoffmann cyclic intermediates upon ultraviolet excitation is observed in dilute solutions of tetraphenylethylene and its derivatives but not in their respective solid. The ultrafast cyclization provides an efficient nonradiative relaxation pathway through crossing a conical intersection.

Synthesis of Lactams via Ir-Catalyzed C-H Amidation Involving Ir-Nitrene Intermediates.

-membered lactams were synthesized via either an amidation of sp C-H bonds or an electrophilic substitution of arenes via Ir-nitrene intermediates. With the employment of a readily available iridium catalyst in dichloromethane or hexafluoro-2-propanol, a wide range of lactams were synthesized in good to excellent yields with high selectivity.

Transition metal mediated carbonylative benzannulations.

In carbonylative benzannulations, feedstock carbon monoxide is converted to a benzene ring, which is one of the most fundamentally important and common rings in natural products and pharmaceutical compounds. Carbon monoxide, however, is rather inert in the absence of transition metals. Historically, carbonylative benzannulations have been mediated by stoichiometric chromium and iron in the form of Fischer carbenes.

Total synthesis of diptoindonesin G and its analogues as selective modulators of estrogen receptors.

We have developed a versatile synthetic strategy for the synthesis of the natural product diptoindonesin G and its analogues as selective modulators of estrogen receptors. The strategy involves a regioselective dehydrative cyclization of arylacetals, a regioselective bromination of benzofurans, a sequential cross-coupling of bromo-benzofurans with aryl boronic acids, and a BBr-mediated tandem cyclization and demethylation. Preliminary biological studies uncovered the critical and dispensable phenolic hydroxyl groups in the natural product and also revealed unexpected selectivity for isoforms of estrogen receptor.

Rhodium(I)-Catalyzed Benzannulation of Heteroaryl Propargylic Esters: Synthesis of Indoles and Related Heterocycles.

A de novo synthesis of a benzene ring allows for the preparation of a diverse range of heterocycles including indoles, benzofurans, benzothiophenes, carbazoles, and dibenzofurans from simple heteroaryl propargylic esters using a unified carbonylative benzannulation strategy. Multiple substituents can be easily introduced to the C4-C7 positions of indoles and related heterocycles.

A highly regio- and stereoselective synthesis of α-fluorinated imides via fluorination of chiral enamides.

A highly π-facial selective and regioselective fluorination of chiral enamides is described. The reaction involves an enantioselective fluorination exclusively at the electron-rich enamide olefin with N-F reagents such as Selectfluor and N-fluoro-benzenesulfonimide [NFSI] accompanied by trapping of the β-fluoro-iminium cationic intermediate with water. The resulting N,O-hemiacetal could be oxidized using Dess-Martin periodinane, leading to an asymmetric sequence for syntheses of chiral α-fluoro-imides and optically enriched α-fluoro-ketones.

Protecting-group-free total synthesis of aplykurodinone-1.

A concise, stereoselective, and protecting-group-free total synthesis of aplykurodinone-1 from Hajos-Parrish ketone was described. The synthetic approach features a sequence of aerobic allylic oxidation and elimination of alcohol 9. The key intermediate for this synthesis was formed by a stereoselective intramolecular radical cyclization.

Conversion of fructose into 5-hydroxymethylfurfural (HMF) and its derivatives promoted by inorganic salt in alcohol.

The conversion of D-fructose to 5-hydroxymethylfurfural (HMF) on a 1 mmol scale was achieved in good yield (68%) using NH(4)Cl as catalyst in isopropanol at 120°C. About 3% of 5-i-propoxymethylfurfural was formed. The reaction in ethanol at 100°C on a 10g scale gave a total yield of HMF and 5-ethoxymethylfurfural of 42%.

Tetra-μ-acetato-κO:O'-bis-{[2-(2-fur-yl)-1-(2-furylmeth-yl)-1H-benzimidazole-κN]copper(II)}.

The title complex, [Cu(2)(CH(3)COO)(4)(C(16)H(12)N(2)O(2))(2)], forms a dimer of the paddle-wheel type located on a crystallographic inversion centre. The two Cu(II) atoms [Cu⋯Cu = 2.7254 (11) Å] are bridged by four acetate anions.