Inclusion complex thermodynamics: The β-cyclodextrin and sertraline complex example.

Area of Science:

• Computational Chemistry
• Physical Chemistry
• Molecular Modeling

Background:

• β-cyclodextrin (β-CD) is a cyclic oligosaccharide used as a host molecule.
• Sertraline is a selective serotonin reuptake inhibitor (SSRI) antidepressant.
• Understanding the inclusion complex formation between β-CD and Sertraline is important for drug delivery applications.

Purpose of the Study:

• To computationally investigate the thermodynamic properties of the β-cyclodextrin-Sertraline inclusion complex.
• To evaluate the accuracy of different theoretical methods and basis sets for modeling this complex.
• To determine the crucial factors influencing the complex formation thermodynamics.

Main Methods:

• Density Functional Theory (DFT) calculations using the PBE0 functional.
• Employment of various basis sets: 6-31G(d,p), 6-31++G(d,p), and 6-311++G(2df,p).
• Assessment of electron correlation using Møller-Plesset second-order perturbation theory (MP2).
• Application of statistical thermodynamic approaches to calculate entropic contributions.
• Inclusion of hydration waters in the reaction model.

Main Results:

• The PBE0 functional with specified basis sets provided reliable thermodynamic data.
• MP2 calculations were used to refine the evaluation of electron correlation.
• The inclusion of hydration waters significantly improved the agreement with experimental data.
• Thermodynamic calculations showed good coherence with fundamental thermodynamic principles.

Conclusions:

• Computational modeling, particularly DFT, is a valuable tool for studying host-guest complexation.
• Accurate representation of solvation effects, specifically hydration, is critical for reliable thermodynamic predictions.
• The findings support the use of β-cyclodextrin-Sertraline inclusion complexes in pharmaceutical formulations.