Structural probes for sweetnessmicrowave spectroscopic studies of edulcorants

Resumen

The determination of the three-dimensional (3D) molecular geometry of biomolecules is of great interest because it helps us to obtain plausible answers about the implications of compounds in their biological environment. In this thesis, we pursue the structural characterization of molecules perceived as sweet: perillartine, dulcin and allose. Additionally, caffeic acid, which is a compound used in the pharmaceutical industry is also studied. All the investigations were carried out using rotational spectroscopy. More precisely, two spectrometers known as Laser Ablation Chirped Pulse Fourier Transform Microwave (LA-CP-FTMW) were used in the 2 to 8 and 6 to 14 GHz frequency ranges. The results were complemented with computational methods using molecular mechanics and quantum-mechanical calculations to facilitate the analysis. The results obtained for the sweet compounds were used in order to verify the molecular theory of sweetness postulated by Shallenberger-Acree-Kier. This theory could not be verified so far due to the lack of intrinsic structural information of the molecules. The results obtained in this work allows to satisfactorily analyze the "glucophore" arrangement of the three characterized molecules. Four conformers were identified in perillartine under the isolated conditions of a supersonic expansion. All the conformers show a E configuration of the C=N group with respect to the double bond of the ring. Additionally, the characterized geometries meet the requirements of the sweetness theory, and it was possible to conjecture that perillartine has a double chance of interacting with the receptors located in the taste buds. In the study of dulcin, two conformers were detected, both structures being stabilized by an intramolecular N-H···¿ interaction between -NH2 and the phenyl ring. Furthermore, a third isomer was predicted but could not be detected due to conformational interconversion phenomenon. All the species analyzed are in agreement with the theory proposed by Shallenberger, Acree and Kier. Regarding allose, three species were detected which exhibit a counterclockwise arrangement of the intramolecular hydrogen bond network. Additionally, the results were complemented with calculations using non-covalent interactions (NCIplot), to ascertain the glucophore disposition. All the conformers observed fulfill the requirement of the sweetness theory. The similarity of the glucophore points in allose and glucose could explain their similar sweetness. Finally, the structural investigation of caffeic acid materialized the subtlety in the characterization provided by rotational spectroscopy, since it was possible to decipher the complete conformational landscape of this compound. This molecule has eight species, which differ slightly from each other. Additionally, this structural study provides us with valuable information that would help us to elucidate the mechanisms underlying the biological activity of this compound.