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

Nascimento, Eliane do; Silva, Gilson de F.; Caetano, Fabiana A.; Fernandes, Marcela A.M.; Silva, Dayse C. da; Carvalho, Maria Eliza Moreira Dai de; Pernaut, Jean Michel; Rebouças, Júlio S.; Idemori, Ynara Marina

doi:10.1016/j.jinorgbio.2005.02.019

Cited by 66 publications

(44 citation statements)

References 85 publications

(173 reference statements)

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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%

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%

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

Self Cite

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“…Synthetically prepared metalloporphyrins, highly stable low-molecular weight molecules capable of catalyzing electron-transfer reactions, have been successfully utilized in industrial catalysis, as imaging contrast agents, in photodynamic therapy [10,11] and as biological catalysts -enzyme mimics [12][13][14][15][16][17][18][19][20]. Both the Fe and Mn porphyrins have been studied as mimics of cytochrome P450 in oxidation, epoxidation, and hydroxylation in the presence of oxidants [21][22][23][24][25][26][27][28][29][30][31] and reductants/excess oxygen either in organic or biphasic systems [32][33][34][35][36][37][38]. Mimicing cytochrome P450-catalyzed dehydration [39] and cytochrome P450 reductase activity have been reported also [40].…”

Section: Introductionmentioning

confidence: 99%

New approach to the activation of anti-cancer pro-drugs by metalloporphyrin-based cytochrome P450 mimics in all-aqueous biologically relevant system

Spasojević¹,

Colvin²,

Warshany³

et al. 2006

Journal of Inorganic Biochemistry

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“…The 1-hexene epoxidation with various molar ratios of alkenes to aldehyde and the significance of the catalyst and aldehyde was also examined. There is no reaction in the absence of isobutyraldehyde (entry 6), which also proved that aldehyde could be used as a reducing agent in the presence of molecular oxygen for the reductive activation of oxygen in metalloporphyrin-catalyzed homogenous aerobic epoxidation of olefins [7,9]. When the molar ratio of alkenes to aldehyde reached 1∶5, the yield of 1,2-epoxyhexane could be given as 39.2% (entry 3).…”

Section: Resultsmentioning

confidence: 88%

“…During the past two decades, more processes involved in the catalysis of metalloporphyrins under mild conditions have been developed [4,5]. For example, metalloporphyrins have been widely applied for epoxidation of olefins to give epoxides under mild conditions, since the leading works of Groves and other groups were published [6,7]. A variety of oxygen donors such as iodosylarenes, alkylhydroperoxides, hydrogen peroxide and organic periodates have been applied in the catalytic epoxidation of olefins to the corresponding epoxides in combination with different catalysts.…”

Section: Introductionmentioning

confidence: 99%

Selective epoxidation of linear terminal olefins with metalloporphyrins under mild conditions

Xiu-juan

She

2009

Front. Chem. Eng. China

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The epoxidation of linear terminal olefins with metalloporphyrins in the presence of dioxygen and isobutyraldehyde under ambient temperature and atmospheric pressure was investigated. The results show that all olefins could be smoothly converted to epoxides with high selectivities (70%-90%). For the metalloporphyrins with different catalytic activities within 1-hexene epoxidation in the order of Fe > Mn > Co, T(o-Cl)PPFe(III)Cl was most effective, with a 41.7% yield and 80.2% selectivity of 1,2-epoxyhexane. Various amounts of catalyst were investigated, and it was found that with only 10 ppm catalyst the yield of 1,2-epoxyhexane and turnover number (TON) could reach up to 41.9% and 41859, respectively.

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

Cited by 66 publications

References 85 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

New approach to the activation of anti-cancer pro-drugs by metalloporphyrin-based cytochrome P450 mimics in all-aqueous biologically relevant system

Selective epoxidation of linear terminal olefins with metalloporphyrins under mild conditions

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