Aggregation and Solvation of Steroid Molecules in Different Solvents

Abstract

Ab initio quantum chemical studies at the Hartree−Fock (HF) level with the 6-31G** basis set and molecular dynamics calculations were performed on two pharmaceutical compounds, namely, the budesonide and beclomethasone dipropionate molecules. The possible water binding positions in the budesonide molecule were analyzed using the PM3 Hamiltonian, which gives fairly good geometries for budesonide−water complexes but underestimates dramatically the stabilization energies of the complexes as compared to Hartree−Fock calculations. The most stable complex according to our Hartree−Fock calculations is one where water is bound to the keto group. Its stabilization energy is −30.2 kJ/mol. In the molecular dynamics simulations, clear differences in aggregation of steroid molecules were observed in different solvents. The conformations of steroid molecules from molecular dynamics simulations differ from structures predicted from quantum chemical calculations showing the importance of evaluation of structure in different solvents.