Peralta, Rosely A., Bortoluzzi, Adailton J., de Souza, Bernardo, Jovito, Rafael, Xavier, Fernando R., Couto, Ricardo A. A., Casellato, Annelise, Nome, Faruk, Dick, Andrew, Gahan, Lawrence R., Schenk, Gerhard, Hanson, Graeme R., de Paula, Flavia C. S., Pereira-Maia, Elene C., Machado, Sergio de P., Severino, Patricia C., Pich, Claus, Bortolotto, Tiago, Terenzi, Hernan, Castellano, Eduardo E., Neves, Ademir and Riley, Mark J. (2010) Electronic Structure and Spectro-Structural Correlations of FeIIIZnII Biomimetics for Purple Acid Phosphatases: Relevance to DNA Cleavage and Cytotoxic Activity. Inorganic Chemistry, 49. pp. 11421-11438. ISSN 0020-1669
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Abstract
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.
Item Type: | Article |
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Additional Information: | The definitive version of this article is available in Inorganic Chemistry, 2010, 49, pp.11421–11438, DOI: 10.1021/ic101433t |
Keywords: | Electronic Structure; Spectro-Structural Correlations; FeIIIZnII Biomimetics; Purple Acid Phosphatases; DNA Cleavage; Cytotoxic Activity; |
Academic Unit: | Faculty of Science and Engineering > Chemistry |
Item ID: | 3715 |
Depositing User: | Gary Schenk |
Date Deposited: | 30 May 2012 16:14 |
Journal or Publication Title: | Inorganic Chemistry |
Publisher: | American Chemical Society |
Refereed: | Yes |
Related URLs: | |
URI: | https://mu.eprints-hosting.org/id/eprint/3715 |
Use Licence: | This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here |
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