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Synthesis, Properties and Crystal Structure of the 2,4-Dichlorophenyl-cyanoxime: A Powerful Carbonyl Reductase Inhibitor

Journal of Chemical Crystallography volume 43, pages 157–164 (2013)Cite this article

Abstract

The compound 2,4-dichlorophenylcyanoxime (later H(2,4-diCl-PhCO)) has significance in its possible application in cancer chemotherapy treatments since it acts as an inhibitor of the human carbonic reductase. This enzyme decreases the effectiveness of anthracycline drug treatment of some types of cancer. The compound was synthesized in high yield at ambient conditions from 2,4-dichlorophenylacetonitrile, using gaseous methylnitrite. The compound was characterized by means of UV–visible, IR, 1H, 13C NMR spectroscopy and X-ray analysis. The cyanoxime crystallizes in a monoclinic space group P21/c (#14) with unit cell constants: a = 3.7587(9) Å, b = 30.087(7) Å, c = 7.6874(17) Å, β = 96.163(3)°; V = 864.3(3) Å3, Z = 4. The structure was solved, using direct methods, to final R indices [I > 2σ (I)] R1 = 0.0551 (wR2 = 0.1217). The compound adopts a non-planar, trans-anti configuration with the value of the dihedral angle between the cyanoxime and dichlorophenyl planes equal to 50.61°.

Graphical Abstract

The title compound was characterized by means of UV–visible, IR, 1H, 13C NMR spectroscopy and X-ray analysis.

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Acknowledgments

NG is grateful to Mr. Leon Goeden for his pioneering work on the Project and Ms. Alex Corbett for technical help. A financial support from the ACS PRF award # 39079-B3 and the Cottrell Research Corporation award # CC6598 is highly appreciated.

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Authors and Affiliations

  1. Department of Chemistry, Missouri State University, Temple Hall 456 and 431, 901 South National Avenue, Springfield, MO, 65897, USA

    Michael Hilton & Nikolay Gerasimchuk

  2. Absorption Systems, Inc., 440 Creamery Way, S.300, Exton, PA, 19341, USA

    Svitlana Silchenko

  3. Department of Chemistry and Biochemistry, Boise State University, 1910 University Drive, Boise, ID, 83725-1520, USA

    Henry A. Charlier

Authors
  1. Michael Hilton
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  2. Nikolay Gerasimchuk
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  3. Svitlana Silchenko
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  4. Henry A. Charlier
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Corresponding author

Correspondence to Nikolay Gerasimchuk.

Electronic supplementary material

Below is the link to the electronic supplementary material.

10870_2013_401_MOESM1_ESM.doc

Supplementary material 1 (DOC 2425 kb). Video microscope photographs of single crystal used for structure determination and face indexing (SI 1, 2); details of measurements of the partitioning coefficient (SI 3–5); delocalization of negative charge throughout the anion (SI 6); results of UV-visible spectroscopy studies of HL and KL (SI 7); observed linear correlations between energy of transition in spectra and solvents’ parameters (SI 8); NMR 1H and 13C of the title compound (SI 9, 10); unit cell content in the structure of H(2,4-diCl-PhCO) (SI 11).

Supplementary material 2 (DOC 87 kb)

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Hilton, M., Gerasimchuk, N., Silchenko, S. et al. Synthesis, Properties and Crystal Structure of the 2,4-Dichlorophenyl-cyanoxime: A Powerful Carbonyl Reductase Inhibitor. J Chem Crystallogr 43, 157–164 (2013). https://doi.org/10.1007/s10870-013-0401-6

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  • DOI: https://doi.org/10.1007/s10870-013-0401-6

Keywords

  • Arylcyanoximes
  • Uncompetitive carbonyl reductase inhibitor
  • Crystal structure
  • UV–visible
  • IR
  • NMR spectroscopy