Perhalogenated 2-pyridylporphyrin complexes: synthesis, self-coordinating aggregation properties, and catalytic studies

Rebouças, Júlio S.; Carvalho, Maria Eliza Moreira Dai de; Idemori, Ynara Marina

doi:10.1142/s1088424602000087

Cited by 32 publications

(34 citation statements)

References 49 publications

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“…The metal-centered reduction potential of the Mn porphyrin complex and the ring-centered reduction potential of the free-base porphyrin are similarly affected by the bromination of the pyrrolic positions. An anodic shift of 418 mV for the metal-centered process in Mn II Br 8 TM-3-PyP 4+ (as compared to that of Mn III TM-3-PyP 5+ ) was observed (Table 1) and such shift of 52 mV/Br is comparable to that reported for other β-brominated Mn porphyrins [12,[43][44][45]. Likewise, the introduction of bromine atoms on the β-pyrrole positions of metal-free ligand, H 2 TM-3-PyP 4+ resulted in an anodic shift in the reduction potential by 334 mV (i.e., 42 mV/Br, Table 1).…”

Section: Electrochemistrysupporting

confidence: 81%

“…The same may be true for the brominated metal-free ligand HBr 8 TM-3-PyP 3+ . It is less efficient as an SOD mimic in its own right, due to the lower k cat ; however β-octabrominated metal-free porphyrins are severely distorted and well known for their ability to coordinate metals promptly at room temperature under neutral pH [12,30,44]. HBr 8 TM-3-PyP 3+ can thus readily complex metal from medium in situ, whereby acting in the same way as Mn II Br 8 TM-3-PyP 4+ .…”

Section: Protection Of Aerobic Growth Of Sod-deficient E Colimentioning

confidence: 99%

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SOD-like activity of Mn(II) β-octabromo-meso-tetrakis(N-methylpyridinium-3-yl)porphyrin equals that of the enzyme itself

DeFreitas-Silva

Rebouças

Spasojević

et al. 2008

Archives of Biochemistry and Biophysics

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Mn porphyrins are among the most efficient SOD mimics with potency approaching that of SOD enzymes. The most potent ones, Mn(III) N-alkylpyridylporphyrins bear positive charges in a close proximity to the metal site, affording thermodynamic and kinetic facilitation for the reaction with negatively charged superoxide. The addition of electron-withdrawing bromines onto β-pyrrolic positions dramatically improves thermodynamic facilitation for the O 2 •− dismutation. We have previously characterized the para isomer, Mn II Br 8 TM-4-PyP 4+ [Mn(II) β-octabromo-meso-tetrakis (N-methylpyridinium-4-yl)porphyrin]. Herein we fully characterized its meta analogue, Mn II Br 8 TM-3-PyP 4+ with respect to uv/vis spectroscopy, electron spray mass spectrometry, electrochemistry, O 2 •− dismutation, metal-ligand stability, and the ability to protect SOD-deficient E. coli in comparison with its para analogue. The increased electron-deficiency of the metal center stabilizes Mn in its +2 oxidation state. The metal-centered Mn III /Mn II reduction potential, E ½ = + 468 mV vs NHE, is increased by 416 mV with respect to non-brominated analogue, Mn III TM-3-PyP 5+ and is only 12 mV less positive than for para isomer. Yet, the complex is significantly more stable towards the loss of metal than its para analogue. As expected, based on the structure-activity relationships, a large increase in E ½ results in exceptionally high catalytic rate constant for the O 2 •− dismutation, log k cat ≥ 8.85; 1.5-fold increase with respect to the para isomer. The IC 50 was calculated to be ≤ 3.7 nM. Manipulation of the electron-deficiency of a cationic porphyrin resulted, therefore, in the highest k cat ever reported for a metalloporphyrin, being essentially identical to the k cat of superoxide dismutases (log k cat = 8.84 -9.30). The positive kinetic salt effect points to the unexpected, unique and first time recorded behavior of Mn β-octabrominated porphyrins when compared to other Mn porphyrins studied thus far. When species of opposing charges react, the increase in ionic strength invariably results in the decreased rate constant; with brominated porphyrins the opposite was found to be true. The effect is 3.5 -fold greater with meta than with para isomer, which is discussed with respect to the closer proximity of the quaternary nitrogens of the meta isomer to the metal center than that of the para isomer. The potency of Mn II Br 8 TM-3-PyP 4+ was corroborated by in vivo studies, where 500 nM allows SOD-deficient E. coli to grow ≥ 60% of the growth of wild type; at concentrations ≥5 μM it exhibits toxicity. Our work shows that exceptionally high k cat for the O 2 •− disproportionation can be achieved not only with an N 5 -type *Corresponding authors: Ynara Marina Idemori, Ph. D., Departamento de Química, ICEx, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Pampulha, Belo Horizonte, MG, 31270-901, Brazil., Tel: +55-31-3499-5762, Fax: +55-31-3499-5700, e-mail: ynara@ufmg.br NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH...

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Section: Electrochemistrysupporting

confidence: 81%

Section: Protection Of Aerobic Growth Of Sod-deficient E Colimentioning

confidence: 99%

SOD-like activity of Mn(II) β-octabromo-meso-tetrakis(N-methylpyridinium-3-yl)porphyrin equals that of the enzyme itself

DeFreitas-Silva

Rebouças

Spasojević

et al. 2008

Archives of Biochemistry and Biophysics

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“…Synthetic manganese porphyrins are remarkably active mimics for cytochromes P450, ligninases, and superoxide dismutases (SOD) [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]. Their catalytic efficiency in these biomimetic systems is usually related to the metal-centered reduction potential [1,3,8,[19][20][21], a property that may be conveniently tuned by the appropriate design of the porphyrin ligand.…”

Section: Introductionmentioning

confidence: 99%

“…Their catalytic efficiency in these biomimetic systems is usually related to the metal-centered reduction potential [1,3,8,[19][20][21], a property that may be conveniently tuned by the appropriate design of the porphyrin ligand. b-Halogenated manganese porphyrins comprise the third generation of porphyrin-based catalysts and are among the most efficient catalytic systems [17].…”

Section: Introductionmentioning

confidence: 99%

Partially and fully β-brominated Mn-porphyrins in P450 biomimetic systems: Effects of the degree of bromination on electrochemical and catalytic properties

Nascimento¹,

Silva²,

Caetano³

et al. 2005

Journal of Inorganic Biochemistry

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“…Recently, the synthesis and characterization of the ␤-brominated non-N-alkylated analogue of Mn III T-2-PyP ϩ has been reported (40). The electron-withdrawing effect of the ␤-pyrrolic bromines on the redox properties of the metal center of the porphyrins (50 -70 mV/bromine) has been previously established (41)(42)(43)(44)(45)(46)(47).…”

mentioning

confidence: 99%

Electrostatic Contribution in the Catalysis of O 2·_Dismutation by Superoxide Dismutase Mimics

Spasojević

Batinić‐Haberle

Rebouças

et al. 2003

Journal of Biological Chemistry

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The Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)-porphyrin (Mn III TE-2-PyP 5؉ ) is a potent superoxide dismutase (SOD) mimic in vitro and was beneficial in rodent models of oxidative stress pathologies. Its high activity has been ascribed to both the favorable redox potential of its metal center and to the electrostatic facilitation assured by the four positive charges encircling the metal center. (ϩ890 mV versus NHE). Thus it allows equal driving force (hence k ox ϭ k red ϭ ϳ2 ϫ 10 9 M Ϫ1 s Ϫ1 ) for both half-reactions of the catalytic cycles (Reactions 1 and 2) (18 -20). For Escherichia coli Fe-SOD,the E1 ⁄2 is ϩ223 mV versus NHE at pH 7.4, and for Mn-SOD from the Bacillus stearothermophilus and E. coli the E1 ⁄2 were ϩ260 and ϩ310 mV versus NHE at pH 7 (1, 21, 22). However, when manganese was replaced by iron in the active site of Mn-SOD the enzymatic activity was lost (18), which has been attributed to the decrease of the redox potential below that required for the oxidation of superoxide ion (3, 18). Such metal ion specificity (2) has been recently explained by the higher affinity of Fe 3ϩ than Mn 3ϩ for hydroxide (6, 8).The crystal structures of different SODs reveal a highly conserved electrostatic "funnel" (13,14,16) that is believed to guide the negatively charged superoxide toward the active site of the enzyme. In the past there have been considerable efforts to evaluate the extent of electrostatic facilitation, but a major difficulty lies in the inability to specifically modify the positively charged residues without affecting the structural integrity of the active site (9).The Mn(III) porphyrin, Mn III TE-2-PyP 5ϩ (AEOL-10113) has been shown (23-27) to possess high SOD-like activity in vitro * This work was supported in part by Grant BA1-0103-1 from the Christopher Reeve Paralysis Foundation and by Aeolus/Incara Pharmaceuticals, Research Triangle Park, NC. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.§ To whom correspondence should be addressed. 1 The abbreviations used are: NHE, normal hydrogen electrode; SOD, superoxide dismutase; meso, refers to the substituents at the 5, 10, 15, and 20 (meso carbon) position of the porphyrin core; ␤, refers to the substituents at ␤-pyrrolic carbons; Mn III T-2-PyP ϩ , Mn(III) 5,10,-15,20-tetrakis(2-pyridyl)porphyrin; Mn III TE-2-PyP 5ϩ (Mn-2E 5ϩ ) (AEOL-10113), manganese(III) 5,10,15,20-tetrakis(N-ethylpyridinium-2-yl)porphyrin; Mn III TM-2(3,4)-PyP 5ϩ (Mn-2(3,4)M 5ϩ ), manganese(III) 5,10,15,20-tetrakis(N-methylpyridinium-2(3,4)-yl)porphyrin, where 2 (AEOL-10112), 3, and 4 refer to ortho, meta, and para isomers, respectively; Mn III Br 8 T-2-PyP ϩ (Mn-Br 8 ϩ ), Mn(III) 2,3,7,8,12,13,17,18-octabromo-5,10,15,20-tetrakis(2-pyridyl)porphyrin; Mn II Br 8 TM-4-PyP 4ϩ , Mn(II) 2,3,7,8,12,13,17,10,15,porphyrin; Mn II Cl 5 TE-2-PyP 4ϩ , Mn(II) ␤-pentachloro-5,10,15,20-tetrakis(N-ethylpyridi...

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Perhalogenated 2-pyridylporphyrin complexes: synthesis, self-coordinating aggregation properties, and catalytic studies

Cited by 32 publications

References 49 publications

SOD-like activity of Mn(II) β-octabromo-meso-tetrakis(N-methylpyridinium-3-yl)porphyrin equals that of the enzyme itself

SOD-like activity of Mn(II) β-octabromo-meso-tetrakis(N-methylpyridinium-3-yl)porphyrin equals that of the enzyme itself

Partially and fully β-brominated Mn-porphyrins in P450 biomimetic systems: Effects of the degree of bromination on electrochemical and catalytic properties

Electrostatic Contribution in the Catalysis of O 2·_Dismutation by Superoxide Dismutase Mimics

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