A theoretical study on ionization of sartans in aqueous media and on interactions with surfactant micelles
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The ionization order of sartans in aqueous media and possible way of interactions between their equilibrium forms and surfactant micelles have been theoretically investigated. The examined sartans are ampholytes (irbesartan and losartan) and a diacid (valsartan) with the close values of ionization constants. In order to get a better insight in the overlapped protolytic equilibria of sartans and to predict an affinity of the equilibrium forms interacting with micelles as biomembrane mimetic systems, the theoretical study was performed. Energy calculation of the optimized structures of the equilibrium forms was performed at the B3LYP/6-31G (d,p) level of the Density Functional Theory (DFT). The results of the theoretical study helped to assign the experimentally determined pK(a) values to the corresponding ionizable centers and confirmed that in all examined compounds, the higher pK(a) values can be attributed to ionization of tetrazole. The molecular descriptor values showed that sartan...s interact predominantly with the micelle surfaces. The equilibrium forms of ampholytes demonstrate higher affinity to the micelles, as compared to the forms of the diprotic acid. Additionally, it was shown that the uncharged molecular forms of ampholytes are more lipophylic then their zwitterionic forms.
Keywords:AT(1) receptor antagonists / pK(a) / Ampholytes / DFT study / Molecular descriptors / B3LYP method
Source:Journal of Molecular Graphics & Modelling, 2018, 82, 67-73
- Elsevier Science Inc, New York