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

Eurobic9, 2-6 September, 2008, Wrocław, Poland
P123. Aminomethane-1, 1-diphosphonic Acids with N-2-pyridyl, N-2thiazolyl,
and N-2-benzothiazolyl Side Chains. Structure − Properties −
Complex-forming Abilities Relationships
E. Matczak-Jon a , T. Kowalik-Jankowska b , P. Kafarski a , J. Jezierska b
a
Department of Chemistry, Wrocław University of Technology, Wybrzeże Wyspiańskiego 27, 50-370 Wrocław,
Poland
e-mail: ewa.matczak-jon@pwr.wroc.pl
b
Faculty of Chemistry, University of Wrocław, Joliot-Curie 14, 50-383 Wrocław, Poland.
Bisphosphonates are now the most widely used drugs for diseases associated with increased bone resorption or
turnover such as osteoporosis, Paget’s disease or cancer induced osteolysis. The reason for that is their
exceptional affinity for bone mineral, most of which is in the form of hydroxyapatite [Ca10(PO4)4(OH)2] with
some impurities, including magnesium. In addition, bisphosphonates act at cellular level inhibiting the
magnesium-dependent enzyme of the mevalonate pathway, the farnesyl pyrophosphate (FPP) synthase. It is thus
apparent that complexation of calcium and magnesium is of vital importance for their biological activity.
Compounds 1 ÷ 6 (scheme 1), recognized as potent inhibitors of the FPPS, represent a class of nitrogen
containing bisphosphonates with a nitrogen atom directly attached to the α-carbon. Continuing our systematic
studies on the relations between the structure and properties of this special class of acids [1, 2] herein we report
solution speciation, stability constants and possible coordination modes of the Ca(II), Mg(II), Zn(II) and Cu(II)
complexes with 1 ÷ 6.
Scheme 1
The complexation features of studied ligands are discussed in the context of intramolecular dynamics and ligands
predispositions for the formation of hydrogen-bonded aggregates. The main complex species proven to exist in
solution are compared with those found in the gas phase. The role of N−H…O versus O−H…O hydrogen bonds
on the formation of multinuclear metal−bisphosphonate complexes is demonstrated as well.
Acknowledgement: The financial support from the Polish Ministry of Higher Education and Science (project
R05 034 03) is thankfully acknowledged.
References:
[1] E. Matczak-Jon, V. Videnova-Adrabińska, Coord. Chem. Rev., 249, 2458 (2005).
[2] E. Matczak-Jon, B. Kurzak, P. Kafarski, A. Woźna, J. Inorg. Biochem., 100, 1155 (2006)
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