From the Department of Biochemistry, Duke University
Medical Center, Durham, North Carolina 27710 and the
¶ Departamento de Química, ICEx, Universidade Federal de
Minas Gerais, Belo Horizonte, Minas Gerais, 31270-901, Brazil
Received for publication, November 6, 2002, and in revised form, December 2, 2002
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ABSTRACT |
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The Mn(III)
meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin
(MnIIITE-2-PyP5+) 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. Its comparison with the non-alkylated,
singly charged analogue Mn(III) beta-octabromo
meso-tetrakis(2-pyridyl)porphyrin
(MnIIIBr8T-2-PyP+) enabled us to
evaluate the electrostatic contribution to the catalysis of O The thermodynamic (1, 2-8) and electrostatic effects (9-16) in
the catalysis of O
INTRODUCTION
TOP
ABSTRACT
INTRODUCTION
EXPERIMENTAL PROCEDURES
RESULTS
DISCUSSION
REFERENCES
160 mV versus NHE) and for the reduction of O
1 s
1) for both
half-reactions of the catalytic cycles (Reactions 1 and 2)
(18-20). For Escherichia coli Fe-SOD,
the E1/2 is +223 mV versus NHE at pH
7.4, and for Mn-SOD from the Bacillus stearothermophilus and
E. coli the E1/2 were +260 and +310 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 Fe3+ than Mn3+ 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, MnIIITE-2-PyP5+ (AEOL-10113) has been shown (23-27) to possess high SOD-like activity in vitro with log kcat = 7.76. The compound has further proven effective in protection of SOD-deficient E. coli (26) and in stroke (28, 29), spinal cord injury (30, 31), diabetes (32, 33), sickle cell disease (34), and radiation/cancer (35-38) rodent models of oxidative stress injuries. Much like SOD (1, 9, 21, 22) its high catalytic potency has been ascribed both to the favorable redox properties of the metal center and to the effect of the positively charged ortho-N-ethylpyridyl nitrogens that provide electrostatic facilitation for the approach of the negatively charged superoxide (23).
The MnIIITE-2-PyP5+ (Scheme
I) exists as a mixture of rotational
isomers (39). Expectations that the four positive charges in isomer will guide the superoxide anion toward the metal
center in a cooperative fashion making it the most powerful SOD mimics among the isomers, proved to be groundless; all four isomers were found
to be of equal catalytic potency.
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Recently, the synthesis and characterization of the -brominated
non-N-alkylated analogue of
MnIIIT-2-PyP+ 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 (41-47). The effect of eight
-pyrrolic bromines was expected to be similar in magnitude to the
effect of the four quaternized pyridyl nitrogens on the redox
properties of the starting unsubstituted MnIIIT-2-PyP+ porphyrin molecule.
Herein, we show that the redox properties of the brominated
non-N-alkylated and the N-alkylated Mn(III)
ortho-pyridylporphyrins are indeed nearly identical,
allowing us to evaluate the electrostatic contribution in the catalysis
of O
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EXPERIMENTAL PROCEDURES |
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Materials
General-- Xanthine and ferricytochrome c were from Sigma, and NaCl, KOH, KH2PO4, methanol, and EDTA were from Mallinckrodt. Xanthine oxidase was prepared by R. Wiley and was supplied by K. V. Rajagopalan (48). Catalase was from Roche Molecular Biochemicals, ultrapure argon was from National Welders Supply Co., and Tris buffer (ultrapure) was from ICN Biomedicals, Inc.
Mn(III) Porphyrins--
The H2T-2-PyP+
and MnIIITM-3(4)-PyP5+ were obtained from
MidCentury Chemicals (Chicago, IL).
MnIIITE(M)-2-PyP5+ (26, 27) and
MnIIIBr8T-2-PyP+ (40) were prepared
as previously described. The molar absorptivities of the Soret bands of
MnTM-2-PyP5+ (log 453.4 = 5.11),
MnTM-3-PyP5+ (log
459.8 = 5.14),
MnTM-4-PyP5+ (log
462.2 = 5.11), and
MnTE-2-PyP5+ (log
454 = 5.14) (26, 27) all
in water and of MnIIIBr8T-2-PyP+
(log
482 = 4.66) in acetonitrile were used for
quantitation. Due to the low water solubility, a 2 mM stock
solution of MnIIIBr8T-2-PyP+ in
methanol was used throughout this study.
Methods
Electrochemistry-- Measurements were performed on a CH Instruments Model 600 voltammetric analyzer. A three-electrode system was utilized with a glassy carbon (3 mm) or gold (2 mm) button working electrode (Bioanalytical Systems), a Ag/AgCl reference, and a platinum wire as auxiliary electrode. Due to the low water solubility of the MnIIIBr8T-2-PyP+, electrochemical studies of both compounds were performed in 9/1 (v/v) methanol/aqueous solutions as previously reported (49). The 9/1 (v/v) methanol/aqueous solutions contained 0.05 M Tris, pH 7.8, 0.1 M NaCl, and 0.3 mM metalloporphyrin. Tris buffer was used instead of phosphate buffer, because the latter precipitates in methanol. The potentials were standardized against potassium ferrocyanide/ferricyanide (51) and MnIIITE-2-PyP5+. The redox potential of the MnIII/MnIV redox couple, which was previously found to be proton-dependent (52) was determined at pH 12.3. The scan rates were 0.01-10 V/s. The E1/2 values for MnII/MnIII and MnIII/MnIV redox couples obtained in 9/1 (v/v) methanol/aqueous solutions were extrapolated to aqueous medium values as previously described (49).
Catalysis of O}2, and
MnIICl2 (49), and it was therefore utilized in
this study. The xanthine/xanthine oxidase reaction was the source of
O
1 s
1 obtained under the same
experimental conditions (pH 7.8, 21 °C, 0.05 M
phosphate buffer, 0.1 mM EDTA) (50) was used to
calculate kcat. The O
1 s
1 and for
MnIIITM-3-PyP5+ and
MnIIITM-4-PyP5+ 4.9 and 4.6 M
1 s
1, respectively. In this
work we found that the
MnIIIBr8T-2-PyP+ proved to be at
least two orders of magnitude more stable.
Kinetic Salt Effect--
The dependence of the catalytic rate
constant for the O
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RESULTS |
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Electrochemistry
The MnII/MnIII Redox
Couple--
Reversible cyclic voltammograms of the
MnII/MnIII redox were obtained for both
compounds, MnIIITE-2-PyP5+ and
MnIIIBr8T-2-PyP+, at scan rates of
0.1 V/s (Fig. 1). Thus it was possible to
determine the half-wave potentials, E1/2, given in
Table I. The two compounds have
almost identical MnII/MnIII metal-centered
E1/2 values at pH 7.8, as predicted from the number
and the nature of the electron-withdrawing substituents on the
meso positions of the porphyrin ring (41-47). Moreover,
their voltammetric behavior in terms of electrochemical reversibility
(peak-to-peak potential separation, Epp (Fig.
2A), and current response to a
change in scan rate (Fig. 2C)) as well as the chemical
reversibility (ratio between the reduction and oxidation peak currents
(Fig. 2B)) is strikingly similar, which leaves us to believe
that the difference in the reactivity toward superoxide is indeed due
to the difference in the overall positive charge (electrostatic
attraction of superoxide anion) and not due to a difference in the
rates of electron transfer (electronic and structural differences).
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The MnIII/MnIV Redox Couple-- Redox properties of the Mn sites were further explored by studying the MnIII/MnIV redox couple. Because the hydroxo-MnIII and oxo-MnIV species are involved (52), this redox process is accessible only in basic solution and is proton-dependent. At pH 12.3, reversible cyclic voltammograms were obtained in the case of both compounds, MnIIITE-2-PyP5+ and MnIIIBr8T-2-PyP+, with essentially equal MnIII/MnIV redox couple potentials of +381 mV and +372 mV versus NHE, respectively (Fig. 1B and Table I). The MnIII/MnIV and MnII/MnIII redox processes are independent as demonstrated on Fig. 1B (dashed traces), whereas reversible voltammetric waves were obtained even when the cycling was done only in a narrow potential range around the E1/2 of the corresponding redox couple.
Because a deprotonation of the axially ligated water on Mn(III) porphyrins occurs at pH 12.3, the MnII/MnIII redox potential shifts negatively (52). Therefore, we ascribe the 145-mV difference in the shift between the two redox couples (Fig. 1B and Table I) to a difference in the pKa,ax values of their axially ligated water. We have previously found that E1/2 reflects the electron density of the porphyrin ring and the metal center in such a way that there is a linear relationship between the pKa of the pyrrolic nitrogen protons of the porphyrin ligand and the metal-centered E1/2 for a series of differently substituted manganese porphyrins (26). We have further found that the axial ligation also is influenced by the electron density of the metal center; in the case of ortho, meta, and para MnTM-2-PyP5+ more positive E1/2 correlates with lower pKa,ax (52). However, in the case of a series of Mn(III) ortho N-alkylpyridylporphyrins (alkyl = methyl through octyl) we saw that hydrophobic effects may reverse the trend (54). With more hydrophobic members of the series, despite a more positive E1/2, the creation of charge is hindered resulting in higher pKa values of the pyrrolic nitrogens of the parent ligands (54). In the present work at pH 12.3, the hydrophobic MnIIIBr8T-2-PyP+ with presumably higher pKa,ax (thus resisting deprotonation), exhibits a lower shift of the MnII/MnIII couple than highly hydrophilic MnIIITE-2-PyP5+. In the case of the MnIII/MnIV couple, which is also proton-dependent (52), there was practically no difference in E1/2 between the two compounds, which is in line with findings reported by us (24, 49-52) and others (55-61) that MnIII/MnIV redox potential is fairly insensitive to the porphyrin structure.
Catalysis of O 1 versus concentration obtained from the spectrophotometric cytochrome c assay measurements, as described elsewhere
(49). The kcat values determined in 0.05 M phosphate buffer, pH 7.8, are given in Table I. The
MnIIIBr8T-2-PyP+ is >100-fold less
efficient a catalyst than MnIIITE-2-PyP5+.
Kinetic Salt Effect-- The effect of the ionic strength (µ) on the catalytic rate constant was assessed using Equation 1, which is based on the Debye-Huckel relation (62) for the effect of the ionic strength of the solution on the activity coefficient of an ion,
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(Eq. 1) |
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(Eq. 2) |
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DISCUSSION |
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Log kcat versus E1/2--
To design a
potent, low molecular weight SOD mimic we aimed at approaching
the E1/2 of the enzyme and affording electrostatic
facilitation. We established a relationship between the log
kcat and the E1/2 for the
MnII/MnIII redox couple for a series of Mn(III)
porphyrins. An increase in E1/2 of 120 mV caused a
10-fold increase in kcat (26), which is in
agreement with the Marcus equation for an outer-sphere electron
transfer (63, 64). At potentials that are negative with respect to the
midway potential, a Mn+3 oxidation state is stabilized, and the
reduction of metalloporphyrin becomes rate-limiting. The preliminary
data indicate that, similar to the SODs, when E1/2
approaches the midway potential for O4-fold slower than its oxidation. Thus in a preliminary pulse
radiolysis study the rate constant for the reduction of MnIIITE-2-PyP5+ by O
1
s
1, whereas it was 8.2 × 107
M
1 s
1 for its
oxidation.2 As the
potential increases further, the Mn+2 oxidation state becomes
stabilized and the oxidation of metalloporphyrin becomes rate-limiting
(22, 37, 66). Mn(II) porphyrins can efficiently catalyze dismutation of
O
Based on the log kcat versus
E1/2 relationship, the compound
MnIIITE-2-PyP5+ was chosen as the most
promising one for in vivo testing. It dismutes O1s
1 at E1/2
of +228 mV versus NHE, and it affords electrostatic
facilitation in the catalysis while retaining metal/ligand stability.
Deviation from the Plot Log kcat versus E1/2-- Although dismutation appears to be an outer-sphere electron transfer, electrostatic, steric, and solvation effects, which are not accounted for by the Marcus equation, do play a role. When one or more of these effects predominate over E1/2, deviation from Marcus plot occurs. The highest degree of deviation was observed with the series of Mn(III) ortho N-alkylpyridyl porphyrins and with the singly charged MnIIIBr8T-2-PyP+. In the case of the former porphyrins, an interplay of steric and solvation effects results in a "V" shape dependence of log kcat upon E1/2 (54). Thus, as the alkyl chains lengthen from methyl to n-octyl accompanied by an increase in hydrophobicity, the E1/2 steadily increases. Yet, from methyl to n-butyl the kcat decreases, whereas it increases from n-butyl to n-octyl. In the case of singly charged MnIIIBr8T-2-PyP+, as discussed below, the deviation from the Marcus plot originates from the lack of electrostatic facilitation.
Electrostatics versus Redox Potential in the Catalysis of
O-pyrrolic positions of MnIIIT-2-PyP+, they cause a
positive shift in E1/2 of the
MnII/MnIII redox couple of 499 mV (Table I and
Fig. 1). Our finding is in agreement with available literature on the
effect of
-bromination on the E1/2 of
metalloporphyrins (41-47). An almost identical increase in
E1/2 (508 mV) was achieved by placing four
quaternized ortho-pyridyls in the meso positions
of the MnIIIT-2-PyP+. Thus the
E1/2 of MnIIITE-2-PyP5+ and
MnIIIBr8T-2-PyP+ are +228 mV and
+219 mV versus NHE, respectively (Table I and Fig. 1). Even
though the E1/2 values for the
MnII/MnIII redox couple responsible for
O
As an additional support for the importance of the electrostatics in
the O
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ACKNOWLEDGEMENTS |
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We are thankful for the financial support provided by Christopher Reeve Paralysis Foundation and by Aeolus/Incara Pharmaceuticals, Research Triangle Park, NC. J. S. R. and Y. M. I. gratefully acknowledge the financial support from The Brazilian Research Council (CNPq) and Fundação de Amparo à Pesquisa do Estado de Minas Gerais (Brazil).
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FOOTNOTES |
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* 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. The 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. Tel.: 919-684-2101; Fax: 919-684-8885; E-mail: ivan@chem.duke.edu.
Supported by The Brazilian Research Council and
Fundação de Amparo à Pesquisa do Estado de Minas
Gerais (Brazil).
Published, JBC Papers in Press, December 9, 2002, DOI 10.1074/jbc.M211346200
2 J. Grodkowski, I. Batinic-Haberle, P. Neta, and I. Fridovich, unpublished data.
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ABBREVIATIONS |
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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;
MnIIIT-2-PyP+, Mn(III)
5,10,15,20-tetrakis(2-pyridyl)porphyrin;
MnIIITE-2-PyP5+ (Mn-2E5+)
(AEOL-10113), manganese(III)
5,10,15,20-tetrakis(N-ethylpyridinium-2-yl)porphyrin;
MnIIITM-2(3, 4)-PyP5+
(Mn-2(3,4)M5+), 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;
MnIIIBr8T-2-PyP+
(Mn-Br8+), Mn(III)
2,3,7,8,12,13,17,18-octabromo-5,10,15,20-tetrakis(2-pyridyl)porphyrin;
MnIIBr8TM-4-PyP4+, Mn(II)
2,3,7,8,12,13,17,18-octabromo-5,10,15,20-tetrakis(N-methylpyridinium-4-yl)porphyrin;
MnIICl5TE-2-PyP4+, Mn(II)
-pentachloro-5,10,15,20-tetrakis(N-ethylpyridinium-2-yl)porphyrin;
{MnIIIBV2
}2, Mn(III)
biliverdin IX;
{MnIIIBVDME}2, Mn(III)
biliverdin IX dimethyl ester.
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REFERENCES |
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---|
1. | Vance, C. K., and Miller, A.-F. (2001) Biochemistry 40, 13079-13087[CrossRef][Medline] [Order article via Infotrieve] |
2. | Jackson, T. A., Xie, J., Yikilmaz, E., Miller, A.-F., and Brunold, T. C. (2002) J. Am. Chem. Soc. 124, 10833-10845[CrossRef][Medline] [Order article via Infotrieve] |
3. | Edward, R. A., Whittaker, M. M., Whittaker, J. W., Jameson, G. B., and Baker, E. N. (1998) J. Am. Chem. Soc 120, 9684-9685[CrossRef] |
4. | Choudhury, S. B., Lee, J.-W., Davidson, G., Yim, Y.-I., Bose, K., Sharma, M. L., Kang, S.-O., Cabelli, D. E., and Maroney, M. J. (1999) Biochemistry 38, 3744-3752[CrossRef][Medline] [Order article via Infotrieve] |
5. | Schwartz, A. L., Yikilmaz, E., Vance, C. K., Vathyam, S., Koder, R. L., and Miller, A.-F. (2000) J. Inorg. Biochem. 80, 247-256[CrossRef][Medline] [Order article via Infotrieve] |
6. | Xie, J., Yikilmaz, E., Miller, A.-F., and Brunold, T. C. (2002) J. Am. Chem. Soc. 124, 3769-3774[CrossRef][Medline] [Order article via Infotrieve] |
7. | Yikilmaz, E., Xie, J., Brunold, T. C., and Miller, A.-F. (2002) J. Am. Chem. Soc. 124, 3482-3483[CrossRef][Medline] [Order article via Infotrieve] |
8. | Han, W.-G., Lovell, T., and Noodleman, L. (2002) Inorg. Chem. 41, 205-218[CrossRef][Medline] [Order article via Infotrieve] |
9. | Getzoff, E. D., Cabelli, D. E., Fisher, C. L., Parge, H. E., Viezzoli, M. S., Banci, L., and Hallewell, R. A. (1992) Nature 358, 347-351[CrossRef][Medline] [Order article via Infotrieve] |
10. | Koppenol, W. H. (1981) in Oxygen Oxy-Radicals Chem. Biol. (Rodgers, A. , and Powers, E. L., eds) , pp. 671-674, Academic Press, New York |
11. | Cudd, A., and Fridovich, I. (1982) FEBS Lett. 144, 181-182[CrossRef][Medline] [Order article via Infotrieve] |
12. |
Cudd, A.,
and Fridovich, I.
(1982)
J. Biol. Chem.
257,
11443-11447 |
13. | Getzoff, E. D., Tainer, J. A., Weiner, P. K., Kollman, P. A., Richardson, J. S., and Richardson, D. C. (1983) Nature 306, 287-290[Medline] [Order article via Infotrieve] |
14. | Desideri, A., Falconi, M., Parisi, V., Morante, S., and Rotilio, G. (1988) Free Radic. Biol. Med. 5, 313-317[CrossRef][Medline] [Order article via Infotrieve] |
15. | Sines, J. J., Allison, S. A., and McCammon, J. A. (1990) Biochemistry 29, 9403-9412[Medline] [Order article via Infotrieve] |
16. |
Zhou, H.-X.,
Wong, K.-Y.,
and Vijayakumar, M.
(1997)
Proc. Natl. Acad. Sci. U. S. A.
94,
12372-12377 |
17. | Wood, P. M. (1988) Biochem. J. 253, 287-289[Medline] [Order article via Infotrieve] |
18. | Vance, C. K., and Miller, A.-F. (1998) J. Am. Chem. Soc. 120, 461-467[CrossRef] |
19. | Ellerby, L. M., Cabelli, D. E., Graden, J. A., and Valentine, J. S. (1996) J. Am. Chem. Soc. 118, 6556-6561[CrossRef] |
20. | Klug-Roth, D., Fridovich, I., and Rabani, J. (1973) J. Am. Chem. Soc. 95, 2786-2790[Medline] [Order article via Infotrieve] |
21. | Lawrence, G. D., and Sawyer, D. T. (1979) Biochemistry 18, 3045-3050[Medline] [Order article via Infotrieve] |
22. | Barrette, W. C., Jr., Sawyer, D. T., Free, J. A., and Asada, K. (1983) Biochemistry 22, 624-627[Medline] [Order article via Infotrieve] |
23. | Batinic-Haberle, I. (2002) Methods Enzymol. 349, 223-233[Medline] [Order article via Infotrieve] |
24. | Spasojevic, I., and Batinic-Haberle, I. (2001) Inorg. Chim. Acta 317, 230-242[CrossRef] |
25. |
Batinic-Haberle, I.,
Benov, L.,
Spasojevic, I.,
and Fridovich, I.
(1998)
J. Biol. Chem.
273,
24521-24528 |
26. | Batinic-Haberle, I., Spasojevic, I., Hambright, P., Benov, L., Crumbliss, A. L., and Fridovich, I. (1999) Inorg. Chem. 38, 4011-4022[CrossRef] |
27. | Kachadourian, R., Batinic-Haberle, I., and Fridovich, I. (1999) Inorg. Chem. 38, 391-396[CrossRef] |
28. |
Mackensen, G. B.,
Patel, M.,
Sheng, H.,
Calvi, C. L.,
Batinic-Haberle, I.,
Day, B. J.,
Liang, L. P.,
Fridovich, I.,
Crapo, J. D.,
Pearlstein, R. D.,
and Warner, D. S.
(2001)
J. Neurosci.
21,
4582-4592 |
29. | Sheng, H., Enghild, J. J., Bowler, R., Patel, M., Batinic-Haberle, I., Calvi, C. L., Day, B. J., Pearlstein, R. D., Crapo, J. D., and Warner, D. S. (2002) Free. Radic. Biol. Med. 33, 947-961[CrossRef][Medline] [Order article via Infotrieve] |
30. | Sheng, H., Batinic-Haberle, I., Spasojevic, I., Fridovich, I., and Warner, D. S. (2002) Free Rad. Biol. Med. 33 (Suppl. 2), S436 |
31. | Sheng, H., Batinic-Haberle, I., Spasojevic, I., Fridovich, I., and Warner, D. S. (2002) Free Radic. Biol. Med. S33 (Suppl. 1), S125 |
32. |
Piganelli, J. D.,
Flores, S. C.,
Cruz, C.,
Koepp, J.,
Batinic-Haberle, I.,
Crapo, J.,
Day, B.,
Kachadourian, R.,
Young, R.,
Bradley, B.,
and Haskins, K.
(2002)
Diabetes
51,
347-355 |
33. |
Bottino, R.,
Balamurugan, A. N.,
Bertera, S.,
Pietropaolo, M.,
Trucco, M.,
and Piganelli, J. D.
(2002)
Diabetes
51,
2561-2567 |
34. |
Aslan, M.,
Ryan, T. M.,
Adler, B.,
Townes, T. M.,
Parks, D. A.,
Thompson, J. A.,
Tousson, A.,
Gladwin, M. T.,
Patel, R. P.,
Tarpey, M. M.,
Batinic-Haberle, I.,
White, C. R.,
and Freeman, B. A.
(2001)
Proc. Natl. Acad. Sci. U. S. A.
98,
15215-15220 |
35. | Batinic-Haberle, I., Spasojevic, I., Fridovich, I., Anscher, M. S., and Vujaskovic, Z. (2001) Int. J. Radiat. Oncol. Biol. Phys. 51 (Suppl. 1), 235-236 |
36. | Vujaskovic, Z., Batinic-Haberle, I., Spasojevic, I., Samulski, T. V., Dewhirst, M. W., and Anscher, M. S. Proc. of the 48th Annual Meeting of Radiation Research Society, San Juan, Puerto Rico 2001, p 161 |
37. | Vujaskovic, Z., Batinic-Haberle, I., Spasojevic, I., Fridovich, I., Anscher, M. S., and Dewhirst, M. W. (2001) Free Radic. Biol. Med. 31, S128 |
38. | Vujaskovic, Z., Batinic-Haberle, I., Rabbani, Z. N., Feng, Q.-F., Kang, S. K., Spasojevic, I., Samulski, T. V., Fridovich, I., Dewhirst, M. W., and Anscher, M. S. (2002) Free Radic. Biol. Med. 32, 857-863[CrossRef] |
39. | Spasojevic, I., Menzeleev, R., White, P. S., and Fridovich, I. (2002) Inorg. Chem. 41, 5874-5881[CrossRef][Medline] [Order article via Infotrieve] |
40. | Reboucas, J. S., de Carvalho, M. E. M. D., and Idemori, Y. M. (2002) J. Porphyrins Phthalocyanines 6, 50-57 |
41. | Batinic-Haberle, I., Liochev, S. I., Spasojevic, I., and Fridovich, I. (1997) Arch. Biochem. Biophys. 343, 225-233[CrossRef][Medline] [Order article via Infotrieve] |
42. | D'Souza, F., Zandler, M. E., Tagliatesta, P., Ou, Z., Shao, J., Van Caemelbecke, E., and Kadish, K. M. (1998) Inorg. Chem. 37, 4567-4572[CrossRef][Medline] [Order article via Infotrieve] |
43. | Hariprasad, G., Dahal, S., and Maiya, B. G. (1996) J. Chem. Soc. Dalton Trans. 3429-3436 |
44. | Giraudeau, A., Callot, H. J., Jordan, J., Ezhar, I., and Gross, M. (1979) J. Am. Chem. Soc. 101, 3857-3862 |
45. | D'Souza, F., Villard, A., Van Caemelbecke, E., Franzen, M, Boschi, T., Tagliatesta, P., and Kadish, K. M. (1993) Inorg. Chem. 32, 4042-4048 |
46. | Bhyrappa, P., and Krishnan, V. (1991) Inorg. Chem. 30, 239-245 |
47. | Reddy, D., Ravikanth, M., and Chandrashekar, T. K. (1993) J. Chem. Soc. Dalton Trans. 3575-3580 |
48. | Waud, W. R., Brady, F. O., Wiley, R. D., and Rajagopalan, K. V. (1975) Arch. Biochem. Biophys. 169, 695-701[Medline] [Order article via Infotrieve] |
49. | Spasojevic, I., Batinic-Haberle, I., Stevens, R. D., Hambright, P., Thorpe, A. N., Grodkowski, J., Neta, P., and Fridovich, I. (2001) Inorg. Chem. 40, 726-739[CrossRef][Medline] [Order article via Infotrieve] |
50. | Butler, J., Koppenol, W. H., and Margoliash, E. (1982) J. Biol. Chem. 257, 10747-10750[Abstract] |
51. | Kolthoff, I. M., and Tomsicek, W. J. (1935) J. Phys. Chem. 39, 945-954 |
52. | Ferrer-Sueta, G., Batinic-Haberle, I., Spasojevic, I., Fridovich, I., and Radi, R. (1999) Chem. Res. Toxicol. 12, 442-449[CrossRef][Medline] [Order article via Infotrieve] |
53. |
McCord, J. M.,
and Fridovich, I.
(1969)
J. Biol. Chem.
244,
6049-6055 |
54. | Batinic-Haberle, I., Spasojevic, I., Stevens, R. D., Hambright, P., and Fridovich, I. (2002) J. Chem. Soc. Dalton Trans. 2689-2696 |
55. | Chen, S.-M., Sun, P.-J., and Su, Y. O. (1990) J. Electroanal. Chem. Interfacial Electrochem. 294, 151-164 |
56. | Rodgers, K. R., Reed, R. A., Su, Y. O., and Spiro, T. G. (1992) Inorg. Chem. 31, 2688-2700 |
57. | Boucher, L. J. (1972) Coord. Chem. Rev. 7, 289-329[CrossRef] |
58. | Jin, N., and Groves, J. T. (1999) J. Am. Chem. Soc. 121, 2923-2924[CrossRef] |
59. | Carnieri, N., Harriman, A., and Porter, G. (1982) J. Chem. Soc. Dalton Trans. 931-938 |
60. | Liu, M.-H., and Su, Y. O. (1997) J. Electroanal. Chem. Interfacial Electrochem. 426, 197-203 |
61. | Harriman, A., and Porter, G. (1979) J. Chem. Soc. Faraday Trans. 2 75, 1543-1552 |
62. | Espenson, J. H. (1981) Chemical Kinetics and Reaction Mechanisms , p. 172, McGraw-Hill Book Company, New York |
63. | Bennett, L. E. (1973) Prog. Inorg. Chem. 18, 1-176 |
64. | Jordan, R. B. (1998) Reaction Mechanisms of Inorganic and Organometallic Systems , 2nd ed. , pp. 188-220, Oxford University Press, New York |
65. |
Faraggi, M.
(1984)
in
O![]() |
66. | Kachadourian, R., Batinic-Haberle, I., and Fridovich, I. (1998) Free Radic. Biol. Med. 25 (Suppl. 1), S17 |