European Journal of Chemistry 2022, 13(2), 186-195 | doi: https://doi.org/10.5155/eurjchem.13.2.186-195.2275 | Get rights and content

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Molecular dynamics of fibric acids


Chad Miller (1) orcid , Steven Schildcrout (2) orcid , Howard Mettee (3) orcid , Ganesaratnam Balendiran (4,*) orcid

(1) Department of Chemistry, Youngstown State University, Youngstown, OH 44555, U.S.A.
(2) Department of Chemistry, Youngstown State University, Youngstown, OH 44555, U.S.A.
(3) Department of Chemistry, Youngstown State University, Youngstown, OH 44555, U.S.A.
(4) Department of Chemistry, Youngstown State University, Youngstown, OH 44555, U.S.A.
(*) Corresponding Author

Received: 17 Mar 2022 | Revised: 16 Apr 2022 | Accepted: 22 Apr 2022 | Published: 30 Jun 2022 | Issue Date: June 2022

Abstract


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.


Keywords


Computation; Thermochemistry; Molecular Scaffold; Molecular dynamics; Molecular modeling; Conformational analysis

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DOI: 10.5155/eurjchem.13.2.186-195.2275

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Funding information


The National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health, USA.

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How to cite


Miller, C.; Schildcrout, S.; Mettee, H.; Balendiran, G. Eur. J. Chem. 2022, 13(2), 186-195. doi:10.5155/eurjchem.13.2.186-195.2275
Miller, C.; Schildcrout, S.; Mettee, H.; Balendiran, G. Molecular dynamics of fibric acids. Eur. J. Chem. 2022, 13(2), 186-195. doi:10.5155/eurjchem.13.2.186-195.2275
Miller, C., Schildcrout, S., Mettee, H., & Balendiran, G. (2022). Molecular dynamics of fibric acids. European Journal of Chemistry, 13(2), 186-195. doi:10.5155/eurjchem.13.2.186-195.2275
Miller, Chad, Steven Schildcrout, Howard Mettee, & Ganesaratnam Balendiran. "Molecular dynamics of fibric acids." European Journal of Chemistry [Online], 13.2 (2022): 186-195. Web. 19 Aug. 2022
Miller, Chad, Schildcrout, Steven, Mettee, Howard, AND Balendiran, Ganesaratnam. "Molecular dynamics of fibric acids" European Journal of Chemistry [Online], Volume 13 Number 2 (30 June 2022)

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