Electronic structure and spectro-structural correlations of FeIIIZnII biomimetics for purple acid phosphatases: Relevance to DNA cleavage and cytotoxic activity

Peralta, RA, Bortoluzzi, AJ, de Souza, B, Jovito, R, Xavier, FR, Couto, RAA, Casellato, A, Nome, F, Dick, A, Gahan, LR, Schenk, G, Hanson, GR, de Paula, FCS, Pereira-Maia, EC, Machado, SD, Severino, PC, Pich, C, Bortolotto, T, Terenzi, H, Castellano, EE, Neves, A and Riley, MJ (2010) Electronic structure and spectro-structural correlations of FeIIIZnII biomimetics for purple acid phosphatases: Relevance to DNA cleavage and cytotoxic activity. Inorganic Chemistry, 49 24: 11421-11438.


Author Peralta, RA
Bortoluzzi, AJ
de Souza, B
Jovito, R
Xavier, FR
Couto, RAA
Casellato, A
Nome, F
Dick, A
Gahan, LR
Schenk, G
Hanson, GR
de Paula, FCS
Pereira-Maia, EC
Machado, SD
Severino, PC
Pich, C
Bortolotto, T
Terenzi, H
Castellano, EE
Neves, A
Riley, MJ
Title Electronic structure and spectro-structural correlations of FeIIIZnII biomimetics for purple acid phosphatases: Relevance to DNA cleavage and cytotoxic activity
Formatted title Electronic structure and spectro-structural correlations of FeIIIZnII biomimetics for purple acid phosphatases: Relevance to DNA cleavage and cytotoxic activity
Journal name Inorganic Chemistry   Check publisher's open access policy
ISSN 0020-1669
1520-510X
Publication date 2010-12-20
Sub-type Article (original research)
DOI 10.1021/ic101433t
Volume 49
Issue 24
Start page 11421
End page 11438
Total pages 18
Place of publication Washington, DC, United States
Publisher American Chemical Society
Collection year 2011
Language eng
Formatted 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-[N′-(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-O phenolate direction. To probe the role of the Fe-O phenolate bond, the phenolate moiety was modified to contain electron-donating or -withdrawing groups (-CH3, -H, -Br, -NO 2) 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 -NO2 ←Br ←H ←CH3 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.
© 2010 American Chemical Society.
Keyword Diester hydrolysis
Crystal-structures
Model
Sweet-potato
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Chemistry and Molecular Biosciences
Centre for Advanced Imaging Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 22 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 23 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Access Statistics: 72 Abstract Views  -  Detailed Statistics
Created: Sun, 23 Jan 2011, 00:04:49 EST