The Quantitative Structure-Retention Relationship (QSRR) analysis of some centrally acting antihypertensives and diuretics

publication · 8 years ago
by Katarina M. Nikolic, Slavica Filipic, Danica Agbaba, Mitja Krizman (University of Belgrade)
MarvinSketch
The complete separation of 15 guanidine/imidazoline derivatives, acting as antihypertensive drugs, was achieved by capillary electrophoresis employing 30 mM phosphate background electrolyte (pH 1.5) containing 15 mM P-Cyclodextrin (BCD). Here the Quantitative Structure-Retention Relationship (QSRR) models of the inclusion complexes between the analyzed compounds (ligands) and BCD were performed to investigate the correlations between electrophoresis migration order and the constitutional, geometrical, physico-chemical, and electronical properties of the molecular models. The ChemPro, Marvin 4.0.5 ChemAxon, and CS Gaussian 98 [B3LYP/6 - 3 1 G + (d,p) and HF/3-21G(d) basis sets] programs were applied for molecular parameters computation of the optimized ligands and ligand-BCD complexes. Total charge of the analyzed compounds at experimental pH 1.5., HOMO (BCD-ligand) energy, and Solvent-Accessible Surface (SAS) (BCD - ligand) area account for the electrophoresis retention parameter log(t). The multiple linear regression models with three variables, log(t)=f [Total Charge (ligand), SAS (BCD - ligand), HOMO (BCD - ligand)], were obtained with R-2=0.914 and crossvalidation parameter of prediction q(pre)(2)=0.778. The developed QSRR approach can help in understanding the structural features that contribute to the electrophoresis retention parameter [log(t)] of the investigated antihypertensives. Therefore, the theoretical method presented could be used as a fast, easy, and reliable tool for electrophoretic migration parameters prediction of other related antihypertensives.
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