Structural Chemistry

, Volume 16, Issue 5, pp 541–549 | Cite as

X-ray Crystal and Ab Initio Structures of 3′,5′-di-O-Acetyl-N(4)-Hydroxy-2′-Deoxycytidine and Its 5-Fluoro Analogue: Models of the N(4)-OH-dCMP and N(4)-OH-FdCMP Molecules Interacting with Thymidylate Synthase

  • Adam Jarmuła
  • Wojciech R. Rypniewski
  • Krzysztof Felczak
  • Wojciech Rode


The crystal and molecular structures of the 3′,5′-di-O-acetyl-N(4)-hydroxy-2′-deoxycytidine molecule and its 5-fluoro congener have been determined by X-ray single crystal diffraction. The 3′,5′-di-O-acetyl-N(4)-hydroxy-5-fluoro-2′-deoxycytidine molecule crystallizes in the space group C2 with the following unit cell parameters: a = 21.72 Å, b = 8.72 Å, c = 8.61 Å, and β = 90.42. 3′,5′-di-O-acetyl-N(4)-hydroxy-2′-deoxycytidine also belongs to the monoclinic space group C2 and the unit cell parameters are: a = 39.54 Å, b = 8.72 Å, c = 22.89 Å, and β = 95.26. The non-fluorine analogue demonstrates a rare example of crystal structure with five symmetry-independent molecules in the unit cell. All the molecules in both crystal structures have the sugar residue anti oriented with respect to the base, as well as have the N(4)-OH residue in cis conformation relatively to the N(3)-nitrogen atom. In addition to the molecular geometries from X-ray experiment, the optimized molecular geometries have been obtained with the use of theoretical ab initio calculations at the RHF/6-31G(d) level. The corresponding geometric parameters in the molecules of 3′,5′-di-O-acetyl-N(4)-hydroxy-2′-deoxycytidine and its 5-fluoro congener have been compared. The differences including the C(5)=C(6) bond shortening and C(4)—C(5)—C(6) angle widening in the fluorine analogue are discussed in this paper in relation to the molecular mechanism of enzyme, thymidylate synthase, inhibition by N(4)-hydroxy-2′-deoxycytidine monophosphate and its 5-fluoro congener.


Crystal structure ab initio structure nucleoside analogues of N(4)-OH-dCMP and N(4)-OH-FdCMP thymidylate synthase 


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Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Adam Jarmuła
    • 1
  • Wojciech R. Rypniewski
    • 2
  • Krzysztof Felczak
    • 3
  • Wojciech Rode
    • 1
  1. 1.Nencki Institute of Experimental BiologyPolish Academy of SciencesWarszawaPoland
  2. 2.Institute of Bioorganic ChemistryPolish Academy of SciencesPoznańPoland
  3. 3.Institute of Biochemistry and BiophysicsPolish Academy of SciencesWarszawaPoland

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