ISBN: 978-83-60043-10-3 - eurobic9

Eurobic9, 2-6 September, 2008, Wrocław, Poland
H. Sigel
P181. Metal Ion-Binding Properties of Two Isomeric
Uracilmethylphosphonates
Department of Chemistry, Inorganic Chemistry, University of Basel, Spitalstrasse 51, CH-4056, BASEL,
Switzerland
e-mail: helmut.sigel@unibas.ch
The uracilmethylphosphonates, 5Umpa 2– = uracil(5)-CH2-PO3 2– and 6Umpa 2– = uracil(6)-CH2-PO3 2– , show
interesting pharmacological properties [1] and they fit thus into a series of artificial acyclic nucleotide analogues,
a wellknown member in use in hepatitis B therapy is Adefovir = PMEA 2– = adenine(9)-CH2CH2-O-CH2-PO3 2–
[2]. Since the action of such phosphonates involves metal ions [2], we studied the M 2+ -binding properties of
5/6Umpa 2– in aq. solution [3]. In both cases mainly the phosphonate group determines the stability of the
M(Umpa) complexes (M 2+ = Mg 2+ , Ca 2+ , Cu 2+ , Zn 2+ , Cd 2+ ). However, for M(5Umpa) with Cu 2+ , Zn 2+ or Cd 2+ an
increased stability is observed, which, based on steric considerations, must be attributed to a 7-membered chelate
formed by the phosphonate-coordinated M 2+ with the oxygen of (C4)O. The formation degree of the M(5Umpa)
chelates varies with the metal ion involved; e.g., for Mg 2+ , Cu 2+ and Zn 2+ it is ca. 0, 46 and 26%, respectively. Of
course, the (C4)O interaction facilitates deprotonation of (N3)H giving thus also rise to a larger formation degree
of the chelates (up to 90%) in the M(5Umpa – H) – species. For uracil the (N3) – /(N1) – ratio is about 80/20 [4],
showing that (N1)H is only a bit less acidic than (N3)H. Indeed, the M(6Umpa) complexes undergo (N1)H
deprotonation at physiological pH forming 6-membered M(6Umpa – H) – chelates with high formation
degrees [3].
Acknowledgements:Supported by the Department of Chemistry, University of Basel, Switzerland.
References:
[1] J. Ochocki, J. Graczyk, Pharmazie 53 (1998) 884–885.
[2] H. Sigel, Chem. Soc. Rev. 33 (2004) 191–200.
[3] E. Freisinger, R. Griesser, B. Lippert, C.F. Moreno-Luque, J. Niclós-Gutiérrez, J. Ochocki, B.P. Operschall,
H. Sigel, submitted.
[4] C.F. Moreno-Luque, E. Freisinger, B. Costisella, R. Griesser, J. Ochocki, B. Lippert, H. Sigel, J. Chem. Soc.,
Perkin Trans 2 (2001) 2005–2011.
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