Chem. Pharm. Bull., 53(7),792-795, July 2005

Regular Articles

Intermolecular Hydrogen Bonding of Steroid Compounds: PFG NMR Diffusion Study, Cold-Spray Ionization (CSI)-MS and X-Ray Analysis

Kazuaki SHIKII,^a,b Hiroko SEKI,^a,c Shigeru SAKAMOTO,^a Yoshihisa SEI,^d Hiroaki UTSUMI,^e and Kentaro YAMAGUCHI^*,c,d

^a Chemical Analysis Center, Chiba University; 1-33 Yayoi-cho, Inage-ku, Chiba, Chiba 263-8522, Japan: ^b Nissan Chemical Industries Ltd.; 722-1 Tsuboi-cho, Funabashi, Chiba 275-0026, Japan: ^c CREST, Japan Science and Technology Agency (JST); 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan: and ^d Faculty of Phrmaceutical Sciences at Kagawa Campus, Tokushima Bunri University; 1314-1 Shido, Sanuki, Kagawa 769-2193, Japan: and ^e NMR Application Lab., JEOL Ltd.; 3-1-2 Musashino, Akishima, Tokyo 196-8558, Japan. * To whom correspondence should be addressed. e-mail: yamaguchi@kph.bunri-u.ac.jp

An extensive analysis of hydrogen bonding of steroid compounds in diluted solution is preformed by pulsed field gradient (PFG) NMR and cold-spray ionization (CSI)-MS, in the solid state by X-ray crystallographic analysis. The formation of hydrogen bond interaction are quantified and discussed. Although X-ray analysis in the crystalline state and CSI-MS measurement in solution suggested that the observed diffusion coefficient D_obs of the steroid compounds may vary in accordance with the number of hydrogen bonds, the actual observed D_obs value determined from the diffusion studies diminished constantly without correlation on the decreasing numbers of hydrogen bonds. Comparison of two different calibration profiles of calculated molecular volume (V_cal) vs. D_obs, which are obtained from compounds possessing no hydrogen bonding and the steroid compounds, formation of a chain structure (cluster) based on intermolecular hydrogen bonding of the steroid compounds is unambiguously confirmed.

Key words NMR diffusion study; standard curve; hydrogen bonding; steroid compound; cold-spray ionization (CSI)-MS; X-ray