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

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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

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Oximes
Androstenedione
Dione
Molecular Structure
Discrete Fourier transforms
Molecular structure
Conformations
molecular structure
Crystal structure
X-Rays
crystal structure
Molecules
rings
Least-Squares Analysis
seats
Names
molecules
Hydrogen
Hot Temperature
Steroids

Keywords

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

Cite this

Palmer, Rex A. ; Lisgarten, David R. ; Cockcroft, Jeremy K. ; Lisgarten, John N. ; Talbert, Rosemary ; Dines, Trevor ; Bansal, Ranju ; Acharya, Pratap Chandra ; Suryan, Amruta. / 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. In: Journal of Chemical Crystallography. 2018.
@article{429fb2a0f8bb4b65a5df93d5585f259e,
title = "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",
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) {\AA},Vc = 1578.18(7) {\AA}3, 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.",
keywords = "Antiproliferates, Crystal structure, Cytotoxic steroids, DFT calculations, Steroidal oximes, X-ray crystallography",
author = "Palmer, {Rex A.} and Lisgarten, {David R.} and Cockcroft, {Jeremy K.} and Lisgarten, {John N.} and Rosemary Talbert and Trevor Dines and Ranju Bansal and Acharya, {Pratap Chandra} and Amruta Suryan",
note = "s We acknowledge financial support from the EPSRC for funding the X-ray diffractometers (Grant Reference EP/ K03930X/1).",
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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. / Palmer, Rex A.; Lisgarten, David R.; Cockcroft, Jeremy K.; Lisgarten, John N.; Talbert, Rosemary; Dines, Trevor; Bansal, Ranju; Acharya, Pratap Chandra; Suryan, Amruta.

In: Journal of Chemical Crystallography, 09.11.2018.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 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

AU - Palmer, Rex A.

AU - Lisgarten, David R.

AU - Cockcroft, Jeremy K.

AU - Lisgarten, John N.

AU - Talbert, Rosemary

AU - Dines, Trevor

AU - Bansal, Ranju

AU - Acharya, Pratap Chandra

AU - Suryan, Amruta

N1 - s We acknowledge financial support from the EPSRC for funding the X-ray diffractometers (Grant Reference EP/ K03930X/1).

PY - 2018/11/9

Y1 - 2018/11/9

N2 - 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.

AB - 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.

KW - Antiproliferates

KW - Crystal structure

KW - Cytotoxic steroids

KW - DFT calculations

KW - Steroidal oximes

KW - X-ray crystallography

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DO - 10.1007/s10870-018-0747-x

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JO - Journal of Chemical Crystallography

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SN - 1074-1542

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