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Journal of Chemical Crystallography

, Volume 25, Issue 7, pp 393–400 | Cite as

Crystal and molecular structures of three modifications of the androgen dehydroepiandrosterone (DHEA)

  • Mino R. Caira
  • J. Keith Guillory
  • Luh-Chian Chang
Article

Abstract

The crystal and molecular structures of three forms of the androgen DHEA (dehydroepiandrosterone) have been determined by single crystal X-ray diffraction. They are: Form I, a polymorph crystallizing in space group P21 withZ=4; Form S1, a hydrate with composition DHEA. (1/4)H2O, space group C2,Z=8; and Form S4, a methanol half-solvate, DHEA. (1/2)CH3OH, space group C2221,Z=8. The A, B, and C steroid ring conformations adopted in the five crystallographically independent DHEA molecules are invariably: chair, 8β, 9α-half-chair, and chair, respectively, while the D ring conformation ranges from a 14α-envelope to a 13β, 14α-half-chair. In Forms I and S1, intermolecular hydrogen bonding is of the head-to-tail type with water molecules participating as donors in Form S1. In Form S4, DHEA molecules pack in head-to-head fashion, their hydroxyl groups being linked by hydrogen bonding to the solvent hydroxyl group. The hydroxyl H atoms of both DHEA and the included methanol are disordered, giving rise to an unusual linearly-propagating ‘flip-flop’ hydrogen bonding scheme.

Key Words

DHEA drug polymorphism 

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References

  1. 1.
    Schwartz, A.G.; Pashko, L.L.J. Cell. Biol. 1993,17G, 73.Google Scholar
  2. 2.
    Wild, R.A.; Buchanan, J.R.; Myer, C.; Demers, L.M.Proc. Soc. Exp. Biol. Med. 1987,186, 355.Google Scholar
  3. 3.
    Lucas, J.A.; Ahmed, S.A.; Casey, M.L.; MacDonald, P.C.J. Clin. Invest. 1985,75, 2091.Google Scholar
  4. 4.
    Haleblian, J.K.J. Pharm. Sci. 1975,64, 1269.Google Scholar
  5. 5.
    Chang, L.; Caira, M.R.; Guillory, J.K.J. Pharm. Sci. 1995, Submitted.Google Scholar
  6. 6.
    Li, J.; Vrielink, A.; Brick, P.; Blow, D.M.Biochemistry.1993,32, 11507.Google Scholar
  7. 7.
    Cox, P.J.; MacManus, S.M.; Gibb, B.C.; Nowell, I.W.; Howie, R.A.Acta. Crystallogr. 1990,C46, 334.Google Scholar
  8. 8.
    Sheldrick, G.M. SHELXS86. InCrystallographic Computing 3, Sheldrick, G.M.; Kruger, C.; Goddard, R., Eds.; Oxford University Press 1985; p 175.Google Scholar
  9. 9.
    Sheldrick, G.M.SHELX. A system of computer programs for X-ray structure determination; University of Cambridge: England, 1976.Google Scholar
  10. 10.
    International Tables for X-Ray Crystallography, Vol IV. Kynoch Press: Birmingham; (Present distributor: Reidel D., Dordrecht), 1974.Google Scholar
  11. 11.
    Nardelli, M.Acta Crystallogr. 1983,C39, 1141.Google Scholar
  12. 12.
    Duax, W.L.; Norton, D.A.Atlas of Steroid Structure, Vol. 1; Plenum: New York, 1975.Google Scholar
  13. 13.
    Thomas, S.A.J. Crystallogr. Spectr. Res. 1982,12, 171.Google Scholar
  14. 14.
    Saenger, W.; Betzel, Ch.; Hingerty, B.; Brown, G.M.Nature 1982,296, 581.Google Scholar
  15. 15.
    Lessinger, L.; Low, B.W.J. Crystallogr. Spectr. Res. 1993,23, 85.Google Scholar

Copyright information

© Plenum Publishing Corporation 1995

Authors and Affiliations

  • Mino R. Caira
    • 1
  • J. Keith Guillory
    • 2
  • Luh-Chian Chang
    • 2
  1. 1.Department of ChemistryUniversity of Cape TownRondeboschSouth Africa
  2. 2.College of PharmacyThe University of IowaIowa City

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