Quantum chemical study and isothermal titration calorimetry of β-cyclodextrin complexes with mianserin in aqueous solution

Abstract

β-Cyclodextrin (β-CD) is studied as a carrier of the drug mianserin (MIA). β-CD with MIA adducts with 1 : 1 and 2 : 1 stoichiometry are investigated in vacuo and in water using quantum chemical methods: PM6 and B3LYP/6-31G(d,p). An effect of the dispersion correction GD2 and the basis set superposition error on the complexation energies is also evaluated. Additionally, the interaction between MIA hydrochloride and β-CD in aqueous solution at 298.15 K is examined experimentally by isothermal titration calorimetry. Interaction parameters, such as the binding constant, enthalpy, entropy and Gibbs free energy, are presented. Analysis of the obtained data led to the following conclusions: the interaction of MIA with β-CD is rather strong; there is no significant energetic difference between the 1 : 1 complexes of β-CD with S-MIA and R-MIA enantiomers; the 2 : 1 (β-CD : MIA) adduct is energetically more favorable than 1 : 1; the complex formation of MIA + β-CD is enthalpy and entropy driven.

Biological and microbiological performance of new polymer-based chitosan and synthesized amino-cyclodextrin finished polypropylene abdominal wall prosthesis biomaterial

“…ITC analysis is one of the most important and commonly employed technique for the characterization of the complex inclusion formation of CDs and their derivatives with various drugs. [24][25][26] ITC analysis provides the measurement of the different thermodynamic parameters (enthalpy ÁH, free enthalpy ÁG, entropy ÁS, the equilibrium constant K) and the molar ratio (n) involved in the inclusion complex process. Isothermal titration experiments were performed in a MicroCal Omega titration calorimeter at a fixed temperature of 25 C. The analysis of different experimental titration curves was achieved via the MCS Origin-ITC 5.0 program.…”

The Interaction of Heptakis (2,6-di-O-Methyl)-β-cyclodextrin with Mianserin Hydrochloride and Its Influence on the Drug Toxicity

“…This made it clear that the entropy increment occurring during inclusion due to desolvation (the release of water molecules that were originally installed in the cavity of the cyclodextrin and the desolvation of peripheral hydroxyl or substituted hydroxyl groups as well as the guest molecules [24]) is quite meaningful (Table 1). * Reference [14]. ** This work.…”

“…After the removal of one of the peripheral β-CD molecules and re-optimization of the binding free energy for the MIA+2βCD aggregate (Table 2; Figure 6), the obtained energy values have been raised by about 0.4 kcal•mol −1 for the MIA included inside of the two β-CDs oriented "head-to head" to each other, and by 0.9 kcal•mol −1 for the "head-to-tail" orientation of the β-CDs (Table 2). From our previous quantum chemical calculation research [14], it appears that the "head-to-head" orientation of two β-CDs-with or without the MIA molecule inside-is energetically beneficial, mostly because of the hydrogen bonds formation between hydroxyl groups on the secondary carbon atoms in β-cyclodextrins. This hydrogen bonds formation has a major impact on the computed complexation energies [14].…”

“…From our previous quantum chemical calculation research [14], it appears that the "head-to-head" orientation of two β-CDs-with or without the MIA molecule inside-is energetically beneficial, mostly because of the hydrogen bonds formation between hydroxyl groups on the secondary carbon atoms in β-cyclodextrins. This hydrogen bonds formation has a major impact on the computed complexation energies [14]. It is possible that this is the reason why the free energies of binding (for both enantiomers of MIA; Table 2) changed a little bit more rapidly after the removal (from the original MIA+3βCD aggregate) of one β-CD molecule for "head-to-tail" β-CD orientation than for "head-to-head" during the molecular docking examinations.…”

“…Cyclodextrins (Figure 1b) are mostly used in order to improve the solubility of drugs in water [11,12]. They are supramolecules with a hydrophobic interior, which may include hydrophobic parts of the drug molecule and hydrophilic shells, consisting of primary and secondary hydroxyl groups that can interact with water molecules [13,14]. In pharmacological tests of the mianserin antidepressant effect [15], higher potency is found for the optical enantiomer (S)-(+)-mianserin.…”