Study of the Stability, Solubility and Geometry of the Complex of Inclusion β-CD with Nimesulide by Computer Chemistry Methods

During this study, a molecular system was modeled: a nimesulide, β-cyclodextrin, inclusion complex. The use of the Gaussian 16W software package allowed us to optimize geometry and determine the thermochemical characteristics of molecular systems without considering a solvent. And this was also carried out in water media, accounted for by the polarized continuum model (PCM). To confirm the accuracy of the geometry of the β-cyclodextrin molecule, a structural alignment of 46 β-cyclodextrin molecules, accessible by a corresponding search query in the RCSB database, was performed. The RSMD values of carbon and oxygen atom deviations, as well as the total number of atoms aligned, were calculated. This calculation showed a complete conformational coincidence between the β-cyclodextrin structure designed by us and the RCSB database structures. This ensures the correct approach to subsequent calculations involving this structure. Quantum-mechanical modeling of the relationship was carried out in several stages with a gradual complexity of the basic set. The hybrid method of functional density B3LYP and 6-31G(d) was used. At the end of the calculation stage, on the surface of the studied complex, the potential energy of several minimal elements was detected. This means that there are several conformational forms of the molecular system with likely differences. The change in potential energies of the investigated compounds, caused by their application to optimize the in vacuum molecules of the PCM, allowed us to determine the values of the solvatization energies. The greater magnitude of these values in the complex under consideration indicates its better solubility in water compared to nimesulide.