Mechanism of superoxide dismutase-like activity of Fe(II) and Fe(III) complexes of tetrakis-N,N,N',N'(2-pyridylmethyl)ethylenediamine

Tomohisa Hirano, Masaaki Hirobe, Kazuo Kobayashi, Akira Odani, Osamu Yamauchi, Masanori Osawa, Yoshinori Satow, Tetsuo Nagano

Research output: Contribution to journalArticle

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Abstract

The superoxide dismutase (SOD) activity of iron(II) tetrakis- N,N,N',N'(2-pyridylmethyl)ethylenediamine complex (Fe-TPEN) was reexamined using a pulse radiolysis method. In our previous study (J. Biol. Chem., 264, 9243-9249 (1989)), we reported that this complex has a potent SOD activity in a cyt. c (cytochrome c)-based system (IC50 = 0.8 μM) and protects E. coli cells against paraquat toxicity. The present pulse radiolysis experiment revealed that Fe(II)TPEN reacts stoichiometrically with superoxide to form Fe(III)TPEN with a second-order rate constant of 3.9 x 106 M-1 s-1 at pH 7.1, but superoxide did not reduce Fe(III)TPEN to Fe(II)TPEN. The reaction of Fe(III)TPEN and superoxide was biphasic. In the fast reaction, an adduct (Fe(III)TPEN-superoxide complex) was formed at the second-order rate constant of 8.5 x 105 M-1 s-1 at pH 7.4. In the slow one, the adduct reacted with another molecule of the adduct, regenerating Fe(III)TPEN. In the cyt. c method with catalase, this Fe(III)TPEN-superoxide complex showed cyt. c oxidation activity, which had led to overestimation of its SOD activity. Based on the titration data, the main species of complex in aqueous media at neutral pH was indicated to be Fe(III)TPEN(OH-). A spectral change after the reduction with hydrated electron indicates that the OH- ion coordinates directly to Fe(III) by displacing one of the pyridine rings. The X-ray analysis of [Fe(II)TPEN]SO4 supported this structure. From the above results we propose a novel reaction mechanism of FeTPEN and superoxide which resembles a proton catalyzed dismuting process, involving Fe(III)TPEN- superoxide complex.

Original languageEnglish
Pages (from-to)223-230
Number of pages8
JournalChemical and Pharmaceutical Bulletin
Volume48
Issue number2
Publication statusPublished - 2000 Feb
Externally publishedYes

Fingerprint

Superoxide Dismutase
Superoxides
Pulse Radiolysis
Radiolysis
Rate constants
Paraquat
N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine
tetrakis-N,N,N',N'-(2-pyridylmethyl)ethylenediamineiron(III)
X ray analysis
Cytochromes c
Titration
Catalase
Escherichia coli
Inhibitory Concentration 50
Toxicity
Protons
X-Rays
Electrons
Ions
Oxidation

Keywords

  • Free radical
  • PH-titration
  • Pulse radiolysis
  • Superoxide dismutase mimics
  • Tetrakis-N,N,N',N'(2- pyridylmethyl)ethylenediamine
  • X-ray analysis

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Chemistry(all)
  • Pharmacology

Cite this

Mechanism of superoxide dismutase-like activity of Fe(II) and Fe(III) complexes of tetrakis-N,N,N',N'(2-pyridylmethyl)ethylenediamine. / Hirano, Tomohisa; Hirobe, Masaaki; Kobayashi, Kazuo; Odani, Akira; Yamauchi, Osamu; Osawa, Masanori; Satow, Yoshinori; Nagano, Tetsuo.

In: Chemical and Pharmaceutical Bulletin, Vol. 48, No. 2, 02.2000, p. 223-230.

Research output: Contribution to journalArticle

Hirano, T, Hirobe, M, Kobayashi, K, Odani, A, Yamauchi, O, Osawa, M, Satow, Y & Nagano, T 2000, 'Mechanism of superoxide dismutase-like activity of Fe(II) and Fe(III) complexes of tetrakis-N,N,N',N'(2-pyridylmethyl)ethylenediamine', Chemical and Pharmaceutical Bulletin, vol. 48, no. 2, pp. 223-230.
Hirano, Tomohisa ; Hirobe, Masaaki ; Kobayashi, Kazuo ; Odani, Akira ; Yamauchi, Osamu ; Osawa, Masanori ; Satow, Yoshinori ; Nagano, Tetsuo. / Mechanism of superoxide dismutase-like activity of Fe(II) and Fe(III) complexes of tetrakis-N,N,N',N'(2-pyridylmethyl)ethylenediamine. In: Chemical and Pharmaceutical Bulletin. 2000 ; Vol. 48, No. 2. pp. 223-230.
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abstract = "The superoxide dismutase (SOD) activity of iron(II) tetrakis- N,N,N',N'(2-pyridylmethyl)ethylenediamine complex (Fe-TPEN) was reexamined using a pulse radiolysis method. In our previous study (J. Biol. Chem., 264, 9243-9249 (1989)), we reported that this complex has a potent SOD activity in a cyt. c (cytochrome c)-based system (IC50 = 0.8 μM) and protects E. coli cells against paraquat toxicity. The present pulse radiolysis experiment revealed that Fe(II)TPEN reacts stoichiometrically with superoxide to form Fe(III)TPEN with a second-order rate constant of 3.9 x 106 M-1 s-1 at pH 7.1, but superoxide did not reduce Fe(III)TPEN to Fe(II)TPEN. The reaction of Fe(III)TPEN and superoxide was biphasic. In the fast reaction, an adduct (Fe(III)TPEN-superoxide complex) was formed at the second-order rate constant of 8.5 x 105 M-1 s-1 at pH 7.4. In the slow one, the adduct reacted with another molecule of the adduct, regenerating Fe(III)TPEN. In the cyt. c method with catalase, this Fe(III)TPEN-superoxide complex showed cyt. c oxidation activity, which had led to overestimation of its SOD activity. Based on the titration data, the main species of complex in aqueous media at neutral pH was indicated to be Fe(III)TPEN(OH-). A spectral change after the reduction with hydrated electron indicates that the OH- ion coordinates directly to Fe(III) by displacing one of the pyridine rings. The X-ray analysis of [Fe(II)TPEN]SO4 supported this structure. From the above results we propose a novel reaction mechanism of FeTPEN and superoxide which resembles a proton catalyzed dismuting process, involving Fe(III)TPEN- superoxide complex.",
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T1 - Mechanism of superoxide dismutase-like activity of Fe(II) and Fe(III) complexes of tetrakis-N,N,N',N'(2-pyridylmethyl)ethylenediamine

AU - Hirano, Tomohisa

AU - Hirobe, Masaaki

AU - Kobayashi, Kazuo

AU - Odani, Akira

AU - Yamauchi, Osamu

AU - Osawa, Masanori

AU - Satow, Yoshinori

AU - Nagano, Tetsuo

PY - 2000/2

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N2 - The superoxide dismutase (SOD) activity of iron(II) tetrakis- N,N,N',N'(2-pyridylmethyl)ethylenediamine complex (Fe-TPEN) was reexamined using a pulse radiolysis method. In our previous study (J. Biol. Chem., 264, 9243-9249 (1989)), we reported that this complex has a potent SOD activity in a cyt. c (cytochrome c)-based system (IC50 = 0.8 μM) and protects E. coli cells against paraquat toxicity. The present pulse radiolysis experiment revealed that Fe(II)TPEN reacts stoichiometrically with superoxide to form Fe(III)TPEN with a second-order rate constant of 3.9 x 106 M-1 s-1 at pH 7.1, but superoxide did not reduce Fe(III)TPEN to Fe(II)TPEN. The reaction of Fe(III)TPEN and superoxide was biphasic. In the fast reaction, an adduct (Fe(III)TPEN-superoxide complex) was formed at the second-order rate constant of 8.5 x 105 M-1 s-1 at pH 7.4. In the slow one, the adduct reacted with another molecule of the adduct, regenerating Fe(III)TPEN. In the cyt. c method with catalase, this Fe(III)TPEN-superoxide complex showed cyt. c oxidation activity, which had led to overestimation of its SOD activity. Based on the titration data, the main species of complex in aqueous media at neutral pH was indicated to be Fe(III)TPEN(OH-). A spectral change after the reduction with hydrated electron indicates that the OH- ion coordinates directly to Fe(III) by displacing one of the pyridine rings. The X-ray analysis of [Fe(II)TPEN]SO4 supported this structure. From the above results we propose a novel reaction mechanism of FeTPEN and superoxide which resembles a proton catalyzed dismuting process, involving Fe(III)TPEN- superoxide complex.

AB - The superoxide dismutase (SOD) activity of iron(II) tetrakis- N,N,N',N'(2-pyridylmethyl)ethylenediamine complex (Fe-TPEN) was reexamined using a pulse radiolysis method. In our previous study (J. Biol. Chem., 264, 9243-9249 (1989)), we reported that this complex has a potent SOD activity in a cyt. c (cytochrome c)-based system (IC50 = 0.8 μM) and protects E. coli cells against paraquat toxicity. The present pulse radiolysis experiment revealed that Fe(II)TPEN reacts stoichiometrically with superoxide to form Fe(III)TPEN with a second-order rate constant of 3.9 x 106 M-1 s-1 at pH 7.1, but superoxide did not reduce Fe(III)TPEN to Fe(II)TPEN. The reaction of Fe(III)TPEN and superoxide was biphasic. In the fast reaction, an adduct (Fe(III)TPEN-superoxide complex) was formed at the second-order rate constant of 8.5 x 105 M-1 s-1 at pH 7.4. In the slow one, the adduct reacted with another molecule of the adduct, regenerating Fe(III)TPEN. In the cyt. c method with catalase, this Fe(III)TPEN-superoxide complex showed cyt. c oxidation activity, which had led to overestimation of its SOD activity. Based on the titration data, the main species of complex in aqueous media at neutral pH was indicated to be Fe(III)TPEN(OH-). A spectral change after the reduction with hydrated electron indicates that the OH- ion coordinates directly to Fe(III) by displacing one of the pyridine rings. The X-ray analysis of [Fe(II)TPEN]SO4 supported this structure. From the above results we propose a novel reaction mechanism of FeTPEN and superoxide which resembles a proton catalyzed dismuting process, involving Fe(III)TPEN- superoxide complex.

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KW - Pulse radiolysis

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KW - Tetrakis-N,N,N',N'(2- pyridylmethyl)ethylenediamine

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