Sildenafil/cyclodextrin complexation: Stability constants, thermodynamics, and guest–host interactions probed by 1H NMR and molecular modeling studies

摘要: Abstract Guest–host interactions of sildenafil (Sild) with cyclodextrins (CyDs) have been investigated using several techniques including phase solubility diagrams (PSD), differential scanning calorimetry (DSC), X-ray powder diffractometry (XRPD), proton nuclear magnetic resonance (1H NMR) and molecular mechanical modeling (MM+). Estimates the complex formation constant (K11) show that tendency Sild to CyDs follows order: β-CyD > HP-β-CyD > γ-CyD, α-CyD, where K11 values at pH 8.7 30 °C were 150, 68 46, 43 M−1, respectively. Ionization reduces its β-CyD, protonated (at 3.6) anionic 12.1) species 17 42 M−1, respectively, compared 150 M−1 for neutral 8.7). The hydrophobic character was found provide 39% driving force stability, while other factors specific contribute −7.9 kJ/mol. Complex β-CyD (ΔG° = −22.9 kJ/mol) is largely driven by enthalpy (ΔH° = −19.8 kJ/mol) slight entropy (ΔS° = 10.3 J/mol K) changes. 1H NMR MM+ studies indicate two isomeric 1:1 complexes: one involving complete inclusion phenyl-moiety into cavity pertaining partial pyrimidinone moiety. dominant complexation evidently van der Waals very little electrostatic contribution. DSC, XRPD proved in solution solid state.