Crystal and Molecular Structure and DFT Calculations of the Steroidal Oxime 6E-Hydroximino-androst-4-ene-3,17-dione (C19H25NO3) a Molecule with Antiproliferative Activity

Rex A. Palmer, David R. Lisgarten, Jeremy K. Cockcroft, John N. Lisgarten, Rosemary Talbert, Trevor Dines, Ranju Bansal, Pratap Chandra Acharya, Amruta Suryan

Research output: Contribution to journalArticle

118 Downloads (Pure)

Abstract

The single crystal X-ray structure of the novel steroid derivative, 6E-hydroximino-androst-4-ene-3,17-dione (C19H25NO3) (code name RB-499), possessing antiproliferative activity against various cell lines is presented. The analysis produced the following results: chemical formula C19H25NO3; Mr = 315.40; crystals are orthorhombic space group P212121 with Z = 4 molecules per unit cell with a = 6.2609(2), b = 12.5711(4), c = 20.0517(4) Å,Vc = 1578.18(7) Å3, crystal density Dc = 1.327 g/cm³. Structure determination was performed by direct methods, Fourier and full-matrix least-squares refinement. Hydrogens were located in the electron density and refined in position with isotropic thermal parameters. The final R-index was 0.0324 for 3140 reflections with I > 2σ and 308 parameters. The Absolute Structure Parameter − 0.07(5) confirms the correct allocation of the absolute configuration. The presence of the double bond C=O at position 3 in Ring A has caused a distortion from the usual chair conformation and created an unusual distorted sofa conformation folded across an approximate m-plane through C(1)–C(4). Ring B is a distorted chair, its conformation being influenced by the presence of the C(6)=N(6)–O(6)H group in position 6. Ring C is a symmetrical chair. Ring D exhibits both a distorted mirror symmetry conformation [influenced by the C(17)=O(17) group] and a distorted twofold conformation. DFT calculations indicated some degree of flexibility in rings A, C and D with ring A showing the greatest variation in torsion angles. The crystal packing is governed by H-bonds involving O(3), O(6) and O(17). DFT calculations of bond distances and angles, optimized at the B3LYP/6–31++G(d,p) level, were in good agreement with the X-ray structure.

Original languageEnglish
Number of pages9
JournalJournal of Chemical Crystallography
Early online date9 Nov 2018
DOIs
Publication statusE-pub ahead of print - 9 Nov 2018

Keywords

  • Antiproliferates
  • Crystal structure
  • Cytotoxic steroids
  • DFT calculations
  • Steroidal oximes
  • X-ray crystallography

Fingerprint Dive into the research topics of 'Crystal and Molecular Structure and DFT Calculations of the Steroidal Oxime 6E-Hydroximino-androst-4-ene-3,17-dione (C<sub>19</sub>H<sub>25</sub>NO<sub>3</sub>) a Molecule with Antiproliferative Activity'. Together they form a unique fingerprint.

  • Cite this