Oxygen atom transfer from nitrite mediated by Fe(III) porphyrins in aqueous solution

Article abstract of DOI:10.1021/ja804520y

Aqueous solutions of the iron(III) porphyrin complex Fe^III(TPPS) (1, TPPS = tetra(4-sulfonatophenyl)-porphyrinato) and nitrite ion react with various substrates S to generate the ferrous nitrosyl complex Fe^II(TPPS)(NO) (2) plus oxidized substrate. When S is a water-soluble sulfonated phosphine, the product is the resulting monoxide. When air is introduced to the product solutions, 2 is rapidly reoxidized to 1; however, even in the absence of air, there is a slow regeneration of the ferric species with concomitant production of nitrous oxide. Thus, in an anaerobic aqueous environment, Fe^III(TPPS) catalyzes oxygen atom transfer from nitrite ion to substrates with the eventual formation of N₂O. Copyright

Full text of DOI:10.1021/ja804520y

Published on Web 09/27/2008
Oxygen Atom Transfer from Nitrite Mediated by Fe(III) Porphyrins in Aqueous
Solution
Chosu Khin, Julie Heinecke, and Peter C. Ford*
Department of Chemistry and Biochemistry, UniVersity of California, Santa Barbara, California 93106-9510
Received June 13, 2008; E-mail: ford@chem.ucsb.edu
1,2
Nitrite ion is present throughout the mammalian organism and
serves as an intravascular and tissue storage form of nitric oxide
3
-
equivalents. In the absence of dioxygen, NO
2
is converted to
4
NO via reaction with hemoglobin and by blood-free heart and liver
tissues. Thus, nitrite may help regulate vasodilation during hypoxia
and modulate ischemia-reperfusion tissue injury. Another nitrite
5
6
reaction of potential biological relevance is oxygen atom transfer
(
OAT) to substrates (S) as depicted in eq 1 and observed in organic
7
,8
solvents. Here we describe OAT reactions from nitrite in near-
neutral aqueous solutions catalyzed by the water-soluble heme
model Fe (TPPS)(H
III
3-
+
2
O)
2
(1) (Na salt, TPPS ) tetra(sul-
fonatophenyl)porphyrinato anion)).
Figure 1. Spectral changes indicating regeneration of 1 under Ar (296 K).
Red line: initial pH 5.8 solution of Fe (TPPS)(H O) (10 µM) and NaNO2
2 2
III
3-
III
-
2
II
Fe (Por)(NO ) + S f Fe (Por)(NO) + SO
(1)
(
(
10 mM). Green dashed line: formation of 2 after adding tppts (1.0 mM).
Band at ∼350 nm is due to the aq NO2 ; λmax 354 nm, ꢀ ) 23 M cm .)
III
-
- -1 -1
Substrates oxidized by the Fe (TPPS)/NO
2
mixture in buffered
+
Solid blue line: re-formation of 1 overnight.
solutions include the Na salt of tris(3-sulfonatophenyl)phosphine
II
(
tppts) and dimethyl sulfide (DMS). The ferrous nitrosyl Fe -
1
, once the substrate is consumed. If, however, the system in the
(TPPS)(NO) (2) is formed rapidly in accord with eq 1, and product
resting state is interrupted by adding a small amount of air, ferric
complexes, principally 1, are immediately reformed (Figure S-1 in
Supporting Information). Adding more substrate after deaeration
analyses demonstrate these substrates to give the corresponding
monoxides tpptsO and DMSO. Addition of air regenerates 1 and
suggests the possibility of a catalytic autoxidation cycle mediated
by the nitrogen oxides and the heme iron. More surprising, however,
is the slow spontaneous regeneration of 1 observed once the
substrate is depleted. Careful analysis of the tppts oxidation
demonstrates that this is accompanied by nitrous oxide formation
according to eq 2.
regenerated 2.
31
The phosphine oxide product was characterized by in situ
P
NMR spectroscopy and showed complete conversion in the presence
-
2 2
of excess NO . An analogous solution of NaNO and tppts not
containing 1 showed no significant increase in phosphine oxide even
after a week. Mass spectral product studies for S ) DMS
demonstrated complete conversion of DMS to DMSO, but no
reaction with nitrite was seen in the absence of 1. For tppts, the
resting state of the catalyst was 2 when excess S was present, but
Fe(TPPS)
-
+
2
S + 2NO + 2H
8 2SO + N O + H O
(2)
2
2
2
1
was restored once S was consumed.
Temporal absorbance changes representing formation of 2 in the
Figure 1 displays the spectrum of 1 (10 µM) in deaerated, pH
.8 aqueous phosphate buffer (10 mM) solution also containing 10
5
first stage of reaction with tppts did not follow the exponential decay
kinetics expected for a reaction first order in [1] (Figure S-3 in
Supporting Information). Accordingly, the dynamics of the first
stage were examined by using the initial rates method. Table S-1
(Supporting Information) lists initial rate data at varied concentra-
tions of 1, NO
approximately first order in all three components as would be
expected if the rate-limiting step were oxidation of tppts by
Fe (TPPS)(H
2
mM NaNO . The characteristic Soret and Q-band absorptions (λmax
3
94 and 528 nm) are little different than those seen under analogous
conditions in the absence of added nitrite (Figure S-1, Supporting
Information). This is attributed to the small equilibrium constant
-
1
9
for association of 1 with nitrite (eq 3, K ) ∼3 M ).
-
2
, and tppts. These data suggest the reaction to be
K
-
2
III
4-
1
+ NO y
\
z Fe (TPPS)(H O)(NO ) + H O
(3)
2
2
2
III
-
2 2
O)(NO ).
Such solutions were stable in the dark indefinitely. However,
adding tppts (1.0 mM) generated over a few minutes shifts of the
Soret band to 413 nm and the Q-band to 543 nm, consistent with
When the headspace gas in a cell containing 1, NaNO , and tppts
in pH 5.8 solution (5 mL) was examined by FTIR spectroscopy,
2
the spectrum displayed the characteristic P and R branches for the
1
0
-1
complete transformation of 1 to 2. These spectral changes
persisted for several hours then slowly decayed back to the spectrum
of 1 (Figures 1 and S-2 in Supporting Information). When more
substrate was added, the ferrous nitrosyl 2 was again generated.
The system was recycled three times, and spectral changes indicated
that re-formation of 1 was at least 95% complete after each. This
behavior suggests a catalysis cycle, where the resting state of the
metalloporphyrin is 2, but the thermodynamically favored form is
N
2
O stretching vibration at 2211 and 2235 cm
(Supporting
1
1
Information Figure S-4). With the initial parameters, [1] ) 6.1
-
µM, [NO
2
] ) 9.8 mM, and tppts ) 2.33 mM in pH 5.8 buffer
O was generated (average
solution (5.1 mL), 6.4 ( 0.6 µmol of N
2
of two trials) as calculated from the molar absorbances (redeter-
mined in the same IR cell). A control reaction with tppts and nitrite
(but not 1) showed traces of N O, but these were at experimental
2
detection limits.
1
3830 9 J. AM. CHEM. SOC. 2008, 130, 13830–13831
10.1021/ja804520y CCC: $40.75  2008 American Chemical Society

C O M M U N I C A T I O N S
III
3-
Scheme 1. Proposed Catalytic Cycle
Fe (TPPS)(H
O)
2
in aqueous media. This reaction is ac-
2
II
companied by formation of the ferrous nitrosyl Fe (TPPS)(NO).
Over time, the latter species spontaneously returns to 1 with
formation of N
2
O, the overall reaction being that described by eq
III
-
2
catalyzed by Fe(TPPS). The aqueous Fe (TPPS)/NO
2
system
also rapidly oxidizes the biological thiols cysteine and glutathione
to give 2. The other products were the respective disulfides, but it
is yet unknown whether these are formed via OAT-generated
intermediate sulfenic acids, which react with excess thiols to give
17
disulfides. Notably, N
2
O was not a product with these substrates,
and while this might signify a different mechanism for catalyst
18
recycling, such thiols are also known to trap HNO. Clearly, these
studies further illustrate that the redox chemistry of nitrite with
hemes is very rich and may have significant biological consequences.
Ongoing studies are focused on elucidating the mechanisms of
Scheme 2
2
the oxygen atom transfers and of pathway(s) responsible for N O
release closing the catalytic cycle. We are also working to develop
a quantitative model for the fast regeneration of ferric species when
small quantities of air have been added to the system.
Acknowledgment. These studies were supported by the U.S.
National Science Foundation. C.K. thanks the UCSB Graduate
Division for the Rosati Fellowship in Science & Engineering.
Supporting Information Available: Table S-1: Initial rates for tppts
reaction with 1 and nitrite in pH 5.8 solution. Figures S-1: Spectral
change when air is added to reaction solution. Figures S-2 and S-3:
Temporal spectral changes. Figure S-4: FTIR spectrum of reaction
headspace. This material is available free of charge via the Internet at
http://pubs.acs.org.
The nitrous oxide thus formed is 200 times the equivalents of 1
-8
-5
(
3.2 × 10 ) and half the tppts initially present (1.2 × 10 ). In
other words, N O formation is clearly catalytic in Fe(TPPS) and
2
corresponds to the stoichiometry indicated by eq 2.
Scheme 1 postulates a pathway to the spontaneous regeneration
III
of 1. This involves HNO formation from 2 to give Fe (TPPS), a
1
2
reaction that has been speculated for heme proteins. The ferrous
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(
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(
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[
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(
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(
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(
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(
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JA804520Y
J. AM. CHEM. SOC. 9 VOL. 130, NO. 42, 2008 13831