No abstract

The rotational spectrum of 2-thiophenecarboxaldehyde was investigated by using supersonic jet Fourier transform microwave spectroscopy. The measurements were extended to the 34S, 33S, 13C, and 18O isotopologs for the cis conformer, as well as to the 34S and 13C isotopologs for the trans conformer, leading to an accurately structural determination of the two observed conformers. The unchanged experimental Pcc values upon isotopic substitution indicate effective planar geometries of the two conformers. The ring structures of thiophene are slightly different between the cis and trans conformers. Two isomers of the monohydrated complex of 2-thiophenecarboxaldehyde, formed between a cis or trans monomer with water stabilized by an O—H⋯O hydrogen bond (HB) and an additional (C=O)CH⋯O(H2O) or (Cring)CH⋯O(H2O) HB, respectively, were observed in jet expansion. The noncovalent interactions attributed to the stabilization of the monomer and the monohydrated complex are revealed by quantum chemical methods. The interaction energy for trans-w-1 is 4 kJ mol−1 larger than that of cis-w-1, attributed to the relative stronger CH⋯O HB. The relative abundance of the two conformers of the 2-thiophenecarboxaldehyde monomer and the two isomers of the complex was estimated in the jet.

Oral delivery of small interfering RNA (siRNA) provides a promising paradigm for treating diseases that require regular injections. However, the multiple gastrointestinal (GI) and systemic barriers often lead to inefficient oral absorption and low bioavailability of siRNA. Technologies that can overcome these barriers are still lacking, which hinders the clinical potential of orally delivered siRNA. Herein, small‐sized, fluorinated nanocapsules (F‐NCs) are developed to mediate efficient oral delivery of tumor necrosis factor α (TNF‐α) siRNA for anti‐inflammation treatment. The NCs possess a disulfide‐cross‐linked shell structure, thus featuring robust stability in the GI tract. Because of their small size (≈30 nm) and fluorocarbon‐assisted repelling of mucin adsorption, the best‐performing F3‐NCs show excellent mucus penetration and intestinal transport capabilities without impairing the intestinal tight junction, conferring the oral bioavailability of 20.4% in relative to intravenous injection. The disulfide cross‐linker can be cleaved inside target cells, causing NCs dissociation and siRNA release to potentiate the TNF‐α silencing efficiency. In murine models of acute and chronic inflammation, orally delivered F3‐NCs provoke efficient TNF‐α silencing and pronounced anti‐inflammatory efficacies. This study therefore provides a transformative strategy for oral siRNA delivery, and will render promising utilities for anti‐inflammation treatment.

The jet-cooled rotational spectrum of 1,2-butanedithiol was observed in the frequency region 2-8 GHz. Two conformers were detected for the molecule, corresponding to trans-and gauchecarbon molecular skeletons, both sharing a gauche arrangement of the two thiol groups. The structural analysis included a ground-state effective structure, isotopic substitution coordinates, B3LYP-D3(BJ) density functional molecular orbital calculations and non-covalent interactions mapping with NCIPlot. The structural data confirm that the two thiol groups synchronize their orientation either parallel or antiparallel to support intramolecular S-H•••S weak hydrogen bonding, reminiscent of the intramolecular hydrogen bond networks observed with adjacent alcohol groups. DFT calculations on 1,2-butanediol and 1,2-ethanedithiol offered structural comparisons with the title compound.

The conformations and molecular structures of diisopropyl disulfide have been studied by high-resolution microwave spectroscopy and quantum chemical calculations. Three conformers, G′GG′, G′GT, and GGG′, have been observed in the jet expansion. The global minimum, G′GG′, adopts a configuration with the G′ orientation of H–C–S–S and S–S–C–H and the G orientation of C–S–S–C showing the C 2 symmetry. The rotational spectra of monosubstituted 13C and 34S isotopologues have also been recorded for G′GG′, leading to an accurate structural determination of this conformer. Two additional 34S isotopologues have also been measured for G′GT. The relative energies of three observed conformers calculated at the MP2/6-311++(d,p) level of theory are within 2 kJ mol–1, while the relative intensity measurements suggested their population ratio to be N G′GG′ /N G′GT /N GGG′ ≈ 5:3:2.