Synthesis, crystal structure and properties of dinuclear iron(III) complexes containing terminally coordinated phenolate/H2O/OH− groups as models for purple acid phosphatases: efficient hydrolytic DNA cleavage

Horn, Adolfo; Vencato, Ivo; Bortoluzzi, Adaı́lton J.; Hörner, Rosmari; Nome, René A.; Spoganicz, Bruno; Drago, Valderes; Terenzi, Hernán; Oliveira, Maurício César Bof de; Werner, Rüdiger; Haase, Wolfgang; Neves, Ademir

doi:10.1016/j.ica.2004.09.021

Cited by 54 publications

(38 citation statements)

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“…In both cases loss of the bridging acetates would be anticipated under the conditions of catalysis [9, 10, 12-14, 23, 25] (Fig. 8) [17][18][19]21]. Some support for the assignment of the catalytically active entity being a dimer arises from the investigation of the dependence of the complex concentration on [15] the hydrolysis reaction.…”

Section: Discussionmentioning

confidence: 99%

“…1.6e-8 [17]. pK a3 of approximately 8.4 is assigned to the deprotonation of a water molecule bound to the second Fe(III) [20].…”

Section: Discussionmentioning

confidence: 99%

“…Although it is believed that PAPs are only active in the heterovalent state [16], phosphatase activity has been reported for a number of diferric model complexes [17][18][19][20][21][22][23] [8,9,[17][18][19][20][21][22][23][24][25], particularly those for which more than two deprotonation equilibria are considered as part of the profile [9,13,14].…”

Section: Fig 2) Is Able To Selectively Generate Heterobinuclear [Fe(mentioning

confidence: 99%

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Phosphate ester cleavage promoted by a tetrameric iron(III) complex

et al. 2010

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The purple acid phosphatases (PAPs) are the only binuclear metallohydrolases where the necessity for a heterovalent active site [Fe(III)-M(II) (M is Fe, Zn or Mn)] for catalysis has been established. The paradigm for the construction of PAP biomimetics, both structural and functional, is that the ligands possess characteristics which mimic those of the donor sites of the metalloenzyme and permit discrimination between trivalent and divalent metal ions. The donor atom set of the ligand 2-((2-hydroxy-5-methyl-3-((pyridin-2-ylmethylamino)methyl)benzyl) (2-hydroxybenzyl)amino)acetic acid (H 3 HPBA) mimics that of the active site of PAP although the iron(III) complex of this ligand has been characterized as the tetramer [Fe 4 (HPBA) 2 (l-CH 3 COO) 2 (l-O)(l-OH)(OH 2 ) 2 ]ClO 4 Á5H 2 O. The phosphoesterase-like activity of the complex in 1:1 acetonitrile/water has now been investigated using the substrate 2,4-bis(dinitrophenyl)phosphate. The pH dependence of the catalytic rate revealed a non-symmetric bellshaped profile, with a finite but non-zero rate at high pH. Unlike the traditional approach usually employed to analyse these bell-shaped profiles, the approach used here involved incorporating additional species which contribute to the overall activity. Employing this approach, we show that the complex has a k cat of 1.6 (±0.2) 9 10 -3 s -1 , three kinetically relevant pK a values of 5.3, 6.2 and 8.4, with K M of 7.4 ± 0.6 mM. The kinetic parameters are similar to those reported for heterovalent PAP biomimetics. Additionally, it is observed that, unlike the enzyme, the oxidation state is not the determining factor for catalytic activity.

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Section: Discussionmentioning

confidence: 99%

“…1.6e-8 [17]. pK a3 of approximately 8.4 is assigned to the deprotonation of a water molecule bound to the second Fe(III) [20].…”

Section: Discussionmentioning

confidence: 99%

Section: Fig 2) Is Able To Selectively Generate Heterobinuclear [Fe(mentioning

confidence: 99%

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Phosphate ester cleavage promoted by a tetrameric iron(III) complex

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“…Cleavage assays were also performed in argon atmosphere in order to verify the cleavage ability in absence of atmospheric oxygen according to the methodology described. 29 …”

Section: Dna Cleavage Studiesmentioning

confidence: 99%

In vitro evaluation of triazenes: DNA cleavage, antibacterial activity and cytotoxicity against acute myeloid leukemia cells

Domingues

Hörner

Reetz

et al. 2010

J. Braz. Chem. Soc.

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triazeno (3) foram avaliadas quanto à capacidade de clivagem do DNA plasmidial pUC18 e pBSKII, atividade antibacteriana e citotoxicidade in vitro frente a células de leucemia mielóide aguda e leucócitos normais utilizando o bioensaio da redução do sal brometo de 3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetrazólio (MTT). Os triazenos analisados demonstraram capacidade de clivagem dos dois tipos de DNA plasmidial: triazeno 1 em pH 8,0 e 50 °C; triazeno 2 em pH 6,5 a 37 e 50 °C; triazeno 3 em pH 6,5 e 37 °C. Os compostos apresentaram atividade citotóxica frente a células leucêmicas. O composto 1 mostrou alta atividade frente a B. cereus (CIM = 32 mg mL -1 ). A associação molecular através de ligações de hidrogênio no estado sólido do composto 3 com base na análise estrutural por difratometria de raios X em monocristal, bem como os resultados das análises espectroscópicas nas regiões do IV e UV-Vis dos compostos 1, 2 e 3 são discutidos no presente trabalho.The asymmetric diazoamines 1-(2-chlorophenyl)-3-(4-carboxyphenyl)triazene (1), 1-(2-fluorophenyl)-3-(4-carboxyphenyl)triazene (2) and 1-(2-fluorophenyl)-3-(4-amidophenyl) triazene (3) were evaluated for their ability to cleave pUC18 and pBSKII plasmid DNA, antibacterial activity and in vitro cytotoxicity against acute myeloid leukemia cells and normal leukocytes using the bioassay of reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The triazenes showed ability to cleave the two types of plasmid DNA: triazene 1 at pH 8.0 and 50 °C; triazene 2 at pH 6.5 and 37 and 50 °C; triazene 3 at pH 6.5 and 37 °C. The compounds presented cytotoxic activity against myeloid leukemia cells. Compound 1 showed high activity against B. cereus (MIC = 32 mg mL -1 ). The observation of intermolecular hydrogen bonding in the solid state of compound 3, based on the structural analysis by X-ray crystallography, as well as the results of IR and UV-Vis spectroscopic analyses of compounds 1, 2 and 3 are discussed in the present work.Keywords: triazenes, DNA cleavage, antibacterial activity, cytotoxicity IntroductionTriazenes or diazoamines constitute a class of compounds containing three consecutive nitrogen atoms in an acyclic arrangement. 1 Diazoamino compounds can be obtained by diverse synthetic ways, the classical method including the coupling reaction of a diazonium salt, [R-N≡N] + X -, with an amine (R'-NH 2 ) in acidic medium. This is followed by formation of the respective diazoamino compound R-N=N-N(H)-R' (R = R' for Domingues et al. 2227 Vol. 21, No. 12, 2010 symmetric triazenes; R ≠ R' for asymmetric compounds) by stepwise neutralization of the reaction system. They have diverse applications as DNA alkylating agents in tumor therapy, protecting groups in natural product synthesis and combinatorial chemistry, as well as precursors incorporated into polymer and oligomer synthesis. [2][3][4][5][6][7][8] Hydrolysis of DNA or RNA catalyzed by relevant enzymes is an important subject in biotechnology, medicine and drug development. 9,10 Synthetic nuclease...

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“…18 The elucidation of the molecular structure through X-ray diffraction of a number of different PAP enzymes has shown unequivocally that only one tyrosine residue is present in their active site, this being bound to the nonreducible iron ion. [12][13][14] As part of our continuing investigation into dinuclear iron complexes as models for the active site of PAPs, 2 21,22 Although the same ligand was used in the synthesis of complexes 1 and 2 (Table 1), the compounds exhibited distinct structural and physicochemical properties. In 1 the ligand H 2 BPClNOL showed a facial coordination mode and three bridging groups were formed (two alkoxo and one acetate), while in 2 the ligand showed a meridional coordination mode with only two alkoxo bridges.…”

Section: Introductionmentioning

confidence: 99%