Quantitative structure‐mobility relationship analysis of imidazoline receptor ligands in CDs‐mediated CE

Slavica Filipic, Katarina Nikolic, Irena Vovk, Mitja Krizman, Danica Agbaba

The performed quantitative structure-mobility relationship (QSMR) study has investigated relative migration times of 11 guanidine/imidazoline derivatives, imidazoline receptor ligands, in CE system containing one of CDs, α-, β-, or γ-CD, using linear and nonlinear modeling methods. The analyzed ligands and their inclusion complexes with CDs were fully examined and optimized at semiempirical parametrized model 3 level. The density functional theory, such as B3LYP/6-31G+(d,p)/3-21G(d)/STO-3G(d,p)/STO-3G(d), and ab initio theory, such as HF/3-21G(d)/STO-3G(d), were applied for molecular descriptors computation of the optimized ligands and their complexes. Predictive performances of the developed QSMR models were tested by use of the cross-validation and external test set prediction. Obtained results for Q(2) values (0.869, 0.911, and 0.966 for CE system containing α-, β-, and γ-CD, respectively) and root mean squared error of prediction (0.239, 0.242, and 0.288 for α-, β-, and γ-CD, respectively) were proved high predictive power of the proposed models. Finally, multitarget QSMR model, using the ligands descriptors (X) and the relative migration time in presence of α-CD (Y1), β-CD (Y2), and γ-CD (Y3), has been created. The multitarget QSMR model can be used as initial screening predictive tool for CE migration behavior of other related guanidine/imidazoline derivatives in presence of α-, β-, and γ-CD.