Determinación de constantes de acidez de compuestos piperidínicos, morfolínicos y tiomorfolínicos con propiedades antihipertensivas y evaluación de su capacidad antioxidante
In this work, physico-chemical characterization studies of piperidinic, morpholinic and thiomorpholinic derivatives of phenol compounds with antihypertensive and antiarrhythmic properties (LQMs) were undertaken. In the first place a systematic study (experimental and theoretical) of the pKa vaues of...
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| Formato: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2014 |
| País: | México |
| Recursos: | Universidad Autónoma Metropolitana |
| Repositorio: | Repositorio Institucional de la UAM Iztapalapa |
| Idioma: | español |
| OAI Identifier: | oai:bindani.izt.uam.mx:kp78gg45f |
| Acesso em linha: | https://doi.org/10.24275/uami.kp78gg45f |
| Access Level: | acceso abierto |
| Palavra-chave: | info:eu-repo/classification/LEM/Hypertension -- Research info:eu-repo/classification/LEM/Hipertensión -- Investigación info:eu-repo/classification/LEM/Química física y teórica info:eu-repo/classification/LEM/Chemistry, Physical and theoretical info:eu-repo/classification/cti/2 |
| Resumo: | In this work, physico-chemical characterization studies of piperidinic, morpholinic and thiomorpholinic derivatives of phenol compounds with antihypertensive and antiarrhythmic properties (LQMs) were undertaken. In the first place a systematic study (experimental and theoretical) of the pKa vaues of four piperidinic LQMs was carried out in order to describe the behavior of the substituents in the para- position to phenol group on the acidity and deprotonation order of the molecules. In the second place, the acidity constants and antioxidant properties of piperidinic, morpholinic and thiomorpholinic derivatives LQMs, bis and tris phenolic, were determined to investigate other possible applications of these kind of compounds. Stability tests of all LQM’s compounds were performed in order to find the time interval of work, besides the optimum working concentrations were obtained in order to have good absorbency readings. The acidity constants for the four piperidinic compounds LQM344, LQM345, LQM346 and LQM351 were determined by UV-Vis spectrophotometry (acid-base titration) at pseudo-physiological conditions (37°C and 0.15 M ionic strength). The acidity constants of the four compounds were determined by the Capillary Zone Electrophoresis (CZE) technique, in order to compare the values determined with those obtained by UV-Vis spectroscopy. In general, a good agreement between both techniques was found. The theoretical study of the four piperidinic compounds was also carried out by DFT to discuss the relative acidity of the protons the molecules. A methodology to calculate the pKa values was established, that can be extended to other LQM compounds; and the calculated values have a correlation with the experimental values. The deprotonation mechanisms were obtained by the theoretical study of the four compounds. The presence of the nitro group in the para- position to the phenol site significantly increases the acidity of the phenolic proton, which is due to the electron acceptor character of the substituent. Moreover, the entire set of pKa values decreases when this substituent, suggesting that also influences the acidity of the protons on the N atoms of the piperidine group, despite of the presence of a methylene group between piperidines and the phenolic ring. The neutral species LQM344 and LQM35 are zwitterionic and, while in the case of LQM346 and LQM351 are neutral molecular species. In addition, the different character can play a significant role in the efficiency of the molecules studied to cross the lipid membrane. Furthermore, the pKa values of other two piperidinic compounds (LQM335 y LQM336): morpholinic compounds (LQM310 y LQM323), tihiomorpholinnic compounds (LQM322 y LQM329); using UV-visible spectrophotometry and CZE techniques. The pKa values were obtained with the aid of SQUAD program for both UV-Vis Spectrophotometry and CZE, the experimental conditions for the first technique are as follows: T= 37 °C and 0.15 M ionic strength (I), for the second T=37 °C and 0.05 M (I) providing a good correlation between values obtained from pKa with both techniques. Finally, the antioxidant capacity of the piperidinic, morpholinic and thiomopholinic compounds was evaluated, using the 1,1-difenil-2-picril-hidrazilo (DPPH) as free radical. From all the LQMs, the LQM322 compound (the thiomorpholinic derivative of pyrogallol) show the best antioxidant capacity in relation with the 6-hidroxi-2,5,7,8-tetrametilcomo-2- carboxylic acid (troxol), the antioxidant of reference. |
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