Peralta, Rosely A. and Bortoluzzi, Adailton J. and de Souza, Bernardo and Jovito, Rafael and Xavier, Fernando R. and Couto, Ricardo A. A. and Casellato, Annelise and Nome, Faruk and Dick, Andrew and Gahan, Lawrence R. and Schenk, Gerhard and Hanson, Graeme R. and de Paula, Flavia C. S. and Pereira-Maia, Elene C. and Machado, Sergio de P. and Severino, Patricia C. and Pich, Claus and Bortolotto, Tiago and Terenzi, Hernan and Castellano, Eduardo E. and Neves, Ademir and Riley, Mark J.
Electronic Structure and Spectro-Structural Correlations of FeIIIZnII Biomimetics
for Purple Acid Phosphatases: Relevance to DNA Cleavage and Cytotoxic Activity.
Inorganic Chemistry, 49.
Purple acid phosphatases (PAPs) are a group of metallohydrolases that contain a dinuclear FeIIIMII center (MII = Fe,
Mn, Zn) in the active site and are able to catalyze the hydrolysis of a variety of phosphoric acid esters. The dinuclear
complex [(H2O)FeIII( μ-OH)ZnII(L-H)](ClO4)2 (2) with the ligand 2-[N-bis(2-pyridylmethyl)aminomethyl]-4-methyl-
6-[N0-(2-pyridylmethyl)(2-hydroxybenzyl) aminomethyl]phenol (H2L-H) has recently been prepared and is found to
closely mimic the coordination environment of the FeIIIZnII active site found in red kidney bean PAP (Neves et al. J. Am.
Chem. Soc. 2007, 129, 7486). The biomimetic shows significant catalytic activity in hydrolytic reactions. By using a
variety of structural, spectroscopic, and computational techniques the electronic structure of the FeIII center of this
biomimetic complex was determined. In the solid state the electronic ground state reflects the rhombically distorted
FeIIIN2O4 octahedron with a dominant tetragonal compression aligned along the μ-OH-Fe-Ophenolate direction.
To probe the role of the Fe-Ophenolate bond, the phenolate moiety was modified to contain electron-donating
or -withdrawing groups (-CH3, -H, -Br, -NO2) in the 5-position. The effects of the substituents on the electronic
properties of the biomimetic complexes were studied with a range of experimental and computational techniques. This
study establishes benchmarks against accurate crystallographic structural information using spectroscopic techniques
that are not restricted to single crystals. Kinetic studies on the hydrolysis reaction revealed that the phosphodiesterase
activity increases in the order-NO2rBrrHrCH3 when 2,4-bis(dinitrophenyl)phosphate (2,4-bdnpp) was used as
substrate, and a linear free energy relationship is found when log(kcat/k0) is plotted against the Hammett parameter σ.
However, nuclease activity measurements in the cleavage of double stranded DNA showed that the complexes
containing the electron-withdrawing-NO2 and electron-donating-CH3 groups are the most active while the cytotoxic
activity of the biomimetics on leukemia and lung tumoral cells is highest for complexes with electron-donating groups.
||The definitive version of this article is available in Inorganic Chemistry, 2010, 49, pp.11421–11438, DOI: 10.1021/ic101433t
||Electronic Structure; Spectro-Structural Correlations; FeIIIZnII Biomimetics; Purple Acid Phosphatases; DNA Cleavage; Cytotoxic Activity;
||Faculty of Science and Engineering > Chemistry
||30 May 2012 16:14
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||American Chemical Society
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