Signature of Glycylglutamic Acid Structure

Hoff, Amanda; Rath, Nigam P.; Lisko, John; Zeller, Mat­thias; Balendiran, Ganesaratnam K.

doi:10.13189/ijbb.2021.090102

Cited by 2 publications

(1 citation statement)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Only Beza among these fibric acids has an amide group. The amide N-C bond length is near 1.36 Å, consistent with significant double-bond character [26] and limited torsion. This is supported by the computed NMR results, which show the two phenyl atoms C7 and C9 to be non-equivalent, with the C cis to the amide O more deshielded by δ 4.4 ppm compared to the C cis to the N. The average δ for these two C atoms is in Table 6.…”

Section: -Europeanmentioning

confidence: 75%

Molecular dynamics of fibric acids

et al. 2022

View full text Add to dashboard Cite

1H- and 13C-NMR chemical shifts were measured for four fibric acids (bezafibrate, clofibric acid, fenofibric acid, and gemfibrozil), which are lipid-lowering drugs. Correlation is found with DFT-computed chemical shifts from the conformational analysis. Equilibrium populations of optimized conformers at 298 K are very different when based on computed Gibbs energies rather than on potential energies. This is due to the significant entropic advantages of extended rather than bent conformational shapes. Abundant conformers with intramolecular hydrogen bonding via five-member rings are computed for three fibric acids, but not gemfibrozil, which lacks suitable connectivity of carboxyl and phenoxy groups. Trends in computed atom-positional deviations, molecular volumes, surface areas, and dipole moments among the fibric acids and their constituent conformations indicate that bezafibrate has the greatest hydrophilicity and fenofibric acid has the greatest flexibility. Theoretical and experimental comparison of chemical shifts of standards with sufficient overlap of fragments containing common atoms, groups, and connectivity may provide a reliable minimal set to benchmark and generate leads.

show abstract

Section: -Europeanmentioning

confidence: 75%