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Electronic Structure and Spectro-Structural Correlations of FeIIIZnII Biomimetics for Purple Acid Phosphatases: Relevance to DNA Cleavage and Cytotoxic Activity

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. (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
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;
Subjects: Science & 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
URI:

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