Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/170197
Title: Interplay between Ionization and Tautomerism in Bioactive β-Enamino Ester-Containing Cyclic Compounds: Study of Annulated 1,2,3,6-Tetrahydroazocine Derivatives
Author: Viayna Gaza, Antonio
Antermite, Salvatore G.
de Candia, Modesto
Altomare, Cosimo D.
Luque Garriga, F. Xavier
Keywords: Compostos heterocíclics
Mecanismes de reacció (Química)
Bioquímica
Heterocyclic compounds
Reaction mechanisms (Chemistry)
Biochemistry
Issue Date: 16-Dec-2019
Publisher: American Chemical Society
Abstract: Depending on the chemical scaffold, the bioactive species could reflect the interplay between ionization and tautomerism, often complicated by the possibility to populate different conformational states in the case of flexible ligands. In this context, theoretical methods can be valuable to discern the role of these factors, as shown here for β-enamino esters of 1,2,3,6 tetrahydroazocino fused ring systems, some of which had proven to be suitable scaffolds for designing novel acetylcholinesterase inhibitors. The compounds investigated herein form two clusters with distinctive experimental pKa values (i.e., α,β-diesters and β-esters ranging within 6.1-7.3 and 8.2-9.0 pKa intervals, respectively), which implies a drastic difference in the most populated species at physiological conditions. While chemoinformatic tools did not provide a consistent description of the actual pKa values, the theoretical analysis performed for the protonated and neutral species of these compounds revealed a marked change in the tautomeric preference of the tetrahydroazocine moiety upon (de)protonation. Excellent agreement between calculated and experimental pKa values was found when the tautomeric preference of protonated and neutral species was considered. Overall, this study highlights the potential use of high-level computational methods to disclose the mutual influence between ionization, tautomerism and conformational preferences in multifunctional (bio)organic compounds.
Note: Versió postprint del document publicat a: https://doi.org/10.1021/acs.jpcb.9b08904
It is part of: Journal of Physical Chemistry B, 2019, vol. 124, p. 28-37
URI: http://hdl.handle.net/2445/170197
Related resource: https://doi.org/10.1021/acs.jpcb.9b08904
ISSN: 1520-6106
Appears in Collections:Articles publicats en revistes (Nutrició, Ciències de l'Alimentació i Gastronomia)

Files in This Item:
File Description SizeFormat 
694644.pdf6.26 MBAdobe PDFView/Open


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.