Aggregation and Solvation of Steroid Molecules in Different Solvents

• Published in: Crystal growth & design Vol. 2; no. 2; pp. 121 - 126
• Main Authors: Päivärinta, Juha T, Poso, Antti T, Hotokka, Matti, Muttonen, Esa
• Format: Journal Article
• Language: English
• Published: Washington,DC American Chemical Society 01.03.2002
• Subjects: Aliphatic, non-condensed and condensed benzenic, and alicyclic compounds; Biological and medical sciences; Condensed matter: structure, mechanical and thermal properties; Exact sciences and technology; Hormones. Endocrine system; Medical sciences; Organic compounds; Pharmacology. Drug treatments; Physics; Structure of solids and liquids; crystallography; Structure of specific crystalline solids; Pentacyclic compound; Water; Budesonide; Hartree-Fock calculations; PM3 calculations; Unsaturated cyclic compound; Molecular structure; Molecular dynamics method; Computerized simulation; Alcohols; Energy; Molecular aggregation; Ab initio calculations; Beclometasone dipropionate; Organic compounds; Solvent effects; Corticosteroids; Organic solvents; Antiinflammatory agent; Thermodynamic stability; Tetracyclic compound; Solvation; Heterocyclic oxygen compounds; Ketoester; Enone; Steroids; Conformation
• ISSN: 1528-7483; 1528-7505
• DOI: 10.1021/cg010032d

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.