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

Eurobic9, 2-6 September, 2008, Wrocław, Poland
SL6. Bisphosphonates: Coordination Abilities of Potent Chelators for
Metal Ions
E. Gumienna-Kontecka a , J. Gałęzowska b and H. Kozłowski a
a Faculty of Chemistry, University of Wrocław, F. Joliot-Curie 14, 50-383 Wroclaw, Poland.
b Department of Inorganic Chemistry, Faculty of Pharmacy, Wrocław Medical University, Szewska 38,
50-139 Wrocław, Poland.
e-mail: kontecka@wchuwr.pl
The recent approaches to Alzheimer’s and Parkinson’s diseases reflect the current concepts of copper(II) and
iron(III) involvement in the etiology of these very common neurological disorders. From the other side
inexorable increase is observed for cancer diseases causing among others metastases to bones. To find
therapeutic measures which will slow down the onset of these diseases, the design of novel treatment strategies
is currently at the focus of attention.
One of the most promising approaches to search novel ligand systems for development of highly efficient
chelators lie in rational combination of known donor functions with specific characteristics in one ligand
molecule. The principal aims of our work is design of novel ligands of different donor and chelating capacity,
consisting of, among others, bisphosphonate moiety.
Bisphosphonates are highly hydrophilic and low toxic ligands which may accommodate a large number of ionic
radii due to their mobility and flexibility. Earlier studies have shown that bisphosphonates are efficient chelating
agents for Fe(III) [1], as well as Cu(II) [2] but their oral bioavailability is poor. It has inspired us to modify
phosphonic ligand with hydrophobic, well studied chelating agent – hydroxypyridinone (Ligand 1) [3].
The radionuclide complexes of 153 Sm, 166 Ho and 177 Lu with poliaminopolyphosphonates are considered as
possible therapeutic pharmaceuticals in bone pain palliation [4]. The potential properties of the use of Gd(III)
complexes with poliaminopolyphosphonic ligands as MRI imaging agents have been also studied [5].
Considering both, the binding properties and the results of biological trials we have decided to study the
influence of the COOH/PO3H2 substitution in CDTP on the binding properties of this ligand towards Ln(III)
ions (Ligand 2) [6].
O
N
OH
C
O
NH
Ligand 1
CH 2
CH 2
CH
PO 3H 2
PO 3H 2
_____________________________________________________________________
58
N
N
Ligand 2
Acknowledgement: E.G.-K. thanks the Polish Ministry of Science and Higher Education for reintegration grant
(113/6.PR UE/2007/7).
References
[1]. E. Gumienna-Kontecka, R. Salvagni, R. Lipinski, M. Lecouvey, F. Cesare Marincola, G. Crisponi, V.M.
Nurchi, Y. Leroux, H. Kozłowski, Inorg. Chim. Acta, 339, 111-118 (2002).
[2]. E. Gumienna-Kontecka, J. Jezierska, M. Lecouvey, Y. Leroux, H. Kozłowski, J. Inorg. Biochem., 89, 13-17
(2002).
[3]. G. Crisponi, V.M. Nurchi, T. Pivetta, J. Gałęzowska, E. Gumienna-Kontecka, T. Bailly, R. Burgada H.
Kozłowski, J. Inorg. Biochem., 102, 1486-1494 (2008).
[4]. J.R. Zeevart, N.V. Jarvis, W.K.A. Louw, G.E. Jackson, J. Inorg. Biochem., 83, 57-65 (2001).
[5 ] The Chemistry of Contrast Agents in Medical Magnetic Resonance Imaging, ed. A.E. Merbach and E. Tóth
Wiley, Chichester (2001).
[6] J. Gałęzowska, R. Janicki, A. Mondry, R. Burgada, T. Bailly, M. Lecouvey, H. Kozłowski, Dalton Trans,
4384-4394 (2006).
PO 3H 2
PO 3H 2
PO 3H 2
PO 3H 2