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

Eurobic9, 2-6 September, 2008, Wrocław, Poland
P30. Coordination Chemistry of a New Cyclam-based Dinucleating Ligand:
Relevance to Purple Acid Phosphatase Model Systems
P. Comba, M. Zajaczkowski
Institute of Inorganic Chemistry, University of Heidelberg, INF 270, 69120 Heidelberg, Germany
Purple acid phosphatases (PAP) are heterodinuclear enzymes that catalyze the hydrolysis of phosphomonoesters.
Their biological functions are divers and still are not fully understood.[1] Nevertheless, in mammalians there was
found a correlation between high PAP levels and osteoporosis.[2] Therefore, the thorough understanding of the
PAP mechanism is crucial.
The active site of the enzyme contains, independently of the source, seven invariant amino acid residues (see
Scheme 1). However, the metal composition is variable. Mammalian PAP has a Fe(III)/Fe(II) core, whereas
plants and funghi have rather Zn(II) or Mn(II) as divalent metal ion (M2 in Scheme 1).[3]
Scheme 1: Active site of purple acid phosphatases
Our aim is to find a suitable model system to mimick the active site of PAP. We have developed a new ligand
based on cyclam (see Scheme 2), with two distinct coordination sites that may form a (hydr)oxo-bridged
dinuclear complex.
Scheme 2: Cyclam-based ligand for PAP mimicks
The advantages to known model systems are that the cyclam unit can mimick the second coordination sphere of
the enzyme, which stabilizes the substrate coordination, and that the bridging oxygen is not part of the ligand and
therefore may act as nucleophile in the hydrolysis mechanism.
The experimental results on the coordination chemistry of the new ligand are supported by computational
studies.
References:
[1] N. Mitic, S.J. Smith, A. Neves, L.W. Guddat, L.R. Gahan, G.Schenk, Chem. Rev, 106, 3338 (2006).
[2] D.W. Moss, F.D. Raymond, D.B. Wile, Crit. Rev. Clin. Lab. Sci., 32, 431 (1995).
[3] T. Klabunde, N. Strater, B. Krebs, J. Mol. Biol., 259, 737 (1996); L.W. Guddat, A. McAlpine, D. Hume, S.
Hamilton, J. De Jersey, J.L. Martin, Structure Fold Des., 7, 757 (1999).
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