Stereochemical Determination of Fistularins Isolated from the Marine Sponge Ecionemia acervus and Their Regulatory Effect on Intestinal Inflammation

By activity-guided fractionation based on inhibition of nitric oxide (NO) and prostaglandin E2 (PGE2), six fistularin compounds (1–6) were isolated from the marine sponge Ecionemia acervus (order Astrophorida). Based on stereochemical structure determination using Mosher’s method, fistularin-3 was assigned as a new stereoisomer. On the basis of the stereochemistry of fistularin-3, the stereochemical homogeneity of all six compounds was established by comparing carbon and proton chemical shifts. For fistularin-1 (1) and -2 (2), quantum calculations were performed to confirm their stereochemistry. In a co-culture system of human epithelial Caco-2 cells and THP-1 macrophages, all six isolated compounds showed potent anti-inflammatory activities. These bioactive fistularins inhibited the production of NO, PGE2, TNF-α, IL-1β, and IL-6 induced by lipopolysaccharide and interferon gamma. Inducible NO synthase and cyclooxygenase-2 expression and MAPK phosphorylation were downregulated in response to the inhibition of NF-κB nuclear translocation. Among the compounds tested, fistularin-1 (1) and 19-deoxyfistularin-3 (4) showed the highest activity. These findings suggest the potential use of the marine sponge E. acervus and its metabolites as pharmaceuticals for the treatment of inflammation-related diseases including inflammatory bowel disease.

Real-time prediction of 1H and 13C chemical shifts with DFT accuracy using a 3D graph neural network

From quantum chemical and experimental NMR data, a 3D graph neural network, CASCADE, has been developed to predict carbon and proton chemical shifts. Stereoisomers and conformers of organic molecules can be correctly distinguished.

Cyclic trimers of phosphinic acids in polar aprotic solvent: symmetry, chirality and H/D isotope effects on NMR chemical shifts

By using NMR in liquefied gases, the stoichiometry of hydrogen-bonded complexes is determined via H/D isotope effects on proton chemical shifts.

MgF3− and AlF4− transition state analogue complexes of yeast phosphoglycerate kinase

The phospho-transfer mechanism of yeast phosphoglycerate kinase (PGK) has been probed through formation of trifluoromagnesate (MgF3−) and tetrafluoroaluminate (AlF4−) transition state analogue complexes and analyzed using 19F, 1H waterLOGSY and 1H chemical shift perturbation NMR spectroscopy. We observed the first 19F NMR spectroscopic evidence for the formation of metal fluoride transition state analogues of yeast PGK and also observed significant changes to proton chemical shifts of PGK in the presence, but not in the absence, of fluoride upon titration of ligands, providing indirect evidence of the formation of a closed ternary transition state. WaterLOGSY NMR spectroscopy experiments using an uncompetitive model were used in an attempt to measure ligand binding affinities within the transition state analogue complexes.

Access to aliphatic protons as reporters in non-deuterated proteins by solid-state NMR

Aliphatic protons as reporters: aliphatic protons are abundant nuclei in biopolymers and rich in spectroscopic, chemical, and biophysical information. Readout of individual proton chemical shifts with a backbone amide resolution via iSOCP enables facilitated access to this information content despite minimal protein amounts without deuteration.

Accurate ab initio calculations of O–H⋯O and O–H⋯−O proton chemical shifts: towards elucidation of the nature of the hydrogen bond and prediction of hydrogen bond distances

Ab initio calculations of O–H⋯O and O–H⋯−O 1H chemical shifts provide accurate electronic description of hydrogen bonding and sensitive measure of hydrogen bond lengths.