Journal of the American Chemical Society
COMMUNICATION
solution of 2 to room temperature, signifying that intermediate 2
is a crucial species in phenol nitration and oxidation. At room tem-
perature, 2 is too unstable to be monitored by regular UV-vis spec-
troscopy, although a glimpse of purple color can be seen momenta-
NIH (P.M.-L., GM74785; J.S. P20 RR-016464), the NSF (J.S.
CH-0844623), and a Vertex pharmaceutical scholarship (T.H.).
E.K. thanks Mr. Andrew Dineen at the Charles Stark Draper
Laboratory for the initial DFT calculations. Work performed at
the NSLS was supported by the DOE (98CH1086)
rily. Despite the short lifetime of 2 at room temperature, when O is
2
added to a mixture of 1 and DBP (1 equiv) at room temperature
nitration chemistry still occurs, yielding NO -DBP, while only a small
’ REFERENCES
2
amount (2%) of the oxidative coupling product is generated. This
(
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indicates that 1/O induces nitration much more efficiently than
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6, 8088–8095.
2
23
18
oxidation at room temperature. When O is used, approximately
0% of the O atom incorporates into the substrate. GC-MS analysis
of NO -DBP displays a distribution of O N-DBP,
and O N-DBP in a ratio of 30(2)%, 48(1)%, and 22(2)%.
2
18
5
1
8
18/16
O N-DBP,
2
2
2
1
6
12
2
Although the mechanistic investigation of phenol nitration by 2 is
beyond the scope of this report, the O atom isotope distribution in
1
7
NO -BDP warrants future mechanistic studies and likely involves
2
24
the cleavage of peroxynitrite and participation of the other NO.
The nitration of biological phenols, such as seen in protein
tyrosine nitration (PTN), is an important posttranslational modi-
fication associated with various pathological conditions including
2
5
inflammatory, neurodegenerative, and cardiovascular diseases.
25d
Although elusive, the current view of PTN suggests that different
types of cellular nitrating agents could be responsible for its specificity
at various sites. Two major ways to generate PTN are known. One
6
5
1
25
-
is through peroxynitrite (ONOO ) that is formed from nitric oxide
(
6) Tonzetich, Z. J.; Do, L. H.; Lippard, S. J. J. Am. Chem. Soc. 2009,
-
(
NO) and superoxide (O ). The other involves reactions of
131, 7964–7965.
2
-
heme peroxidases with hydrogen peroxide and nitrite (NO ).
(7) (a) Commoner, B.; Ternberg, J. L. Proc. Natl. Acad. Sci. U.S.A.
1961, 47, 1374–1384. (b) Vithayathil, A. J.; Ternberg, J. L.; Commoner,
B. Nature 1965, 207, 1246–1249. (c) Mallard, J. R.; Kent, M. Nature
964, 204, 1192. (d) Vanin, A. F.; Nalbandian, R. M. Biofizika 1965, 10,
67–168.
2
10
The reactivity of the {Fe(NO) } DNIC we report herein suggests
2
that cellular DNICs could provide a new route to generate PTN; the
DNIC derived peroxynitrite moiety in 2 may directly nitrate the
phenol or biological tyrosine (via homolytic cleavage to •O(H)
þ •NO ) or act as a •NO generator (where 2 equiv may lead to
1
1
(
(
8) Enemark, J. H.; Feltham, R. D. Coord. Chem. Rev. 1974, 13, 339–406.
9) (a) Woolum, J. C.; Tiezzi, E.; Commoner, B. Biochim. Biophys.
2
2
21,25
ArOH nitration).
examples of the oxidation chemistry of metal-nitrosyls, though
observation of metal-peroxynitrite is rare.
The results also agree with several literature
Acta 1968, 160, 311–320. (b) D’Autreaux, B.; Horner, O.; Oddou, J. L.;
Jeandey, C.; Gambarelli, S.; Berthomieu, C.; Latour, J. M.; Michaud-
Soret, I. J. Am. Chem. Soc. 2004, 126, 6005–6016. (c) Cesareo, E.; Parker,
L. J.; Pedersen, J. Z.; Nuccetelli, M.; Mazzetti, A. P.; Pastore, A.; Federici,
G.; Caccuri, A. M.; Ricci, G.; Adams, J. J.; Parker, M. W.; Lo Bello, M. J.
Biol. Chem. 2005, 280, 42172–42180.
(10) (a) Boese, M.; Mordvintcev, P. I.; Vanin, A. F.; Busse, R.;
M €u lsch, A. J. Biol. Chem. 1995, 270, 29244–29249. (b) Ueno, T.; Suzuki,
Y.; Fujii, S.; Vanin, A. F.; Yoshimura, T. Biochem. Pharmacol. 2002, 63,
85–93. (c) Chen, Y.-J.; Ku, W.-C.; Feng, L.-T.; Tsai, M.-L.; Hsieh, C.-
H.; Hsu, W.-H.; Liaw, W.-F.; Hung, C.-H.; Chen, Y.-J. J. Am. Chem. Soc.
008, 130, 10929–10938.
(11) The presence of nitrite (NO2 ), Fe, and TMEDA in the
2
6
26d,26e
It is conceivable that
small molecule metal species such as DNICs act as mobile nitrating
agents in cells.
In summary, we have described the unprecedented O reac-
2
10
tivity of an {Fe(NO) } iron-dinitrosyl complex [Fe(TMEDA)-
2
(
NO) ] (1). In the presence of O , 1 becomes a potent nitrating
2 2
agent via formation of a putative iron-peroxynitrite species. The
4
O reactivity of 1 demonstrated here suggests that the physio-
2
logical functions of DNICs are not limited to NO storage and
transfer and deserve further study.
2
-
1
2
precipitate has been qualitatively confirmed. Further speculation
’
ASSOCIATED CONTENT
concerning the nature of decomposition product(s) is not warranted.
(
12) See Supporting Information.
1
5
S
Supporting Information. Experimental details concern-
(13) Synthesis of the intermediate using NO shows a clear IR shift
b
to lower energy supporting the νNO assignments and formation of
ing spectroscopy, reaction product characterization and quanti-
fication, isotope labeling, electrochemistry, and nitrite detection.
This material is available free of charge via the Internet at http://
pubs.acs.org.
1
2
putative [Fe(TMEDA)(NO)(ONOO)] (2) (vide infra).
9
/10
(
14) The reversible {Fe(NO)
cyclic voltammetry, with E1/2 = -0.527 V (vs ferrocene/ferrocenium).
Chemical oxidation of 1 by I has been shown to yield a five-coordinate
compound [Fe(TMEDA)(NO)
2
}
redox behavior of 1 is observed in
2
1
5
2
I]. Attempts to isolate a four-
þ
’
AUTHOR INFORMATION
coordinate counterpart, [Fe(TMEDA)(NO) ] , were not successful
2
probably due to its strong preference to be five-coordinate, as was
Corresponding Author
15
previously discussed.
-1
(15) νNO = 1773 and 1719 cm in diethyl ether. Chen, C.-H.; Ho,
Y.-C.; Lee, G.-H. J. Organomet. Chem. 2009, 694, 3395–3400.
16) Even more evidence to disfavor a superoxide adduct formation
(
’
ACKNOWLEDGMENT
-1
includes the lack of an isotope sensitive νO-O in the region of ∼1100 cm
This work was supported by Brown University (E.K.), the
(Figure 1b) and the inconsistent EXAFS data for such a model. See
,
Camille and Henry Dreyfus New Faculty Award Program (E.K.),
Supporting Information for alternative EXAFS fitting results.
1
186
dx.doi.org/10.1021/ja108313u |J. Am. Chem. Soc. 2011, 133, 1184–1187