Reversible photolabilization of NO from chromium(III)-coordinated nitrite. A new strategy for nitric oxide delivery [14]

Full text of DOI:10.1021/ja983875a

1980
J. Am. Chem. Soc. 1999, 121, 1980-1981
matrix photochemistry9 and laser flash photolysis studies10
demonstrated this to be a minor pathway, the principal photore-
Reversible Photolabilization of NO from
Chromium(III)-Coordinated Nitrite. A New Strategy
for Nitric Oxide Delivery
III
action for Mn (TPP)(ONO) being reversible Mn-O cleavage to
II
11
2
give Mn (TPP) and NO . Subsequently, Hoshino demonstrated
IV
III
irreversible formation of Cr (TPP)(O) plus NO when Cr (TPP)-
Malcolm De Leo and Peter C. Ford*
(
ONO) is irradiated in benzene, the greater efficiency of N-O
Department of Chemistry, UniVersity of California
cleavage in this case likely due to the more oxophilic character
Santa Barbara, California 93106
of Cr(III). In this context, we have turned attention to the Cr(III)
+
complex trans-Cr(cyclam)(ONO)
2
(I) (cyclam ) 1,4,8,11 tet-
ReceiVed NoVember 9, 1998
raazacyclotetradecane), which is indeed thermally stable in aerated
aqueous solution. We report here that I undergoes a high quantum
yield photoreaction that leads to NO formation (eq 1). Further-
more, unlike the precedents cited, this reaction is rapidly reversible
in anaerobic media.
Biological roles of nitric oxide have attracted considerable
1
scrutiny over the past decade and drawn renewed attention to
the chemistry of NO.2 Potential medical applications have
stimulated interest in designing methodologies for NO delivery
3
to biological targets. Among possible methods, photochemical
trans-[Cr(cyclam)(ONO) ](BF ) was prepared by the stoichio-
2
4
labilization of NO from an otherwise unreactive compound is
attractive, given the opportunity to target specific tissues within
an organism.4 In this context, we have studied the photoreaction
properties of several metal nitrosyl complexes including nitrosyl-
iron sulfur clusters and metalloporphyrins.5 A problem with
certain systems is their thermal instability in the aerobic aqueous
environments encountered under biological conditions. Accord-
ingly, we are exploring other strategies and describe here NO
generation from an air-stable, water-soluble complex via the
photolytic cleavage of coordinated nitrite
2
metric reaction of trans-[Cr(cyclam)Cl ]Cl with AgONO, recrys-
tallized, and characterized by high-resolution FAB mass spec-
-6
12
trometry and X-ray crystallography. Its optical spectrum displays
-1
-1
-1
bands at λmax 336 nm (ꢀ ) 267 M cm ) and 476 nm (40 M
,6
-1
cm ), and these can be assigned as an n-π* intraligand band of
coordinated nitrite (336 nm) and a Cr(III)-centered ligand field
band in analogy to earlier assignments made by Harowfield and
13
+
2 2
Fee for trans-[Cr(en) (ONO) ] (en ) ethylenediamine).
When I was subjected to continuous photolysis (λirr ) 436 nm)
in deaerated pH 7 aqueous solution (or under an Ar or NO
atmosphere), a gradual shift of the absorption spectrum to that
trans-Cr (cyclam)(ONO)2+ νn
98
III
+
14
III
2
of the trans-Cr (cyclam)(H O)(ONO) cation (II) was observed.
IV
+
The quantum yield for this (seemingly) simple photoaquation is
trans-Cr (cyclam)(O)(ONO) + NO (1)
small (Φaq ) 0.0092 ( 0.0008), as has been noted for other trans-
+
Aqueous solutions of nitrite salts are known to undergo
photodecomposition to give NO plus hydroxyl radicals when
Cr(cyclam)X
2
cations (e.g., X ) Cl) when subjected to ligand
field excitation.15 Aqueous solutions of I at pH 7 did not undergo
7
irradiated with UV light. Extrusion of NO from coordinated
measurable thermal reactions.
8
nitrite was first suggested by Suslick et al. as a photoreaction of
The spectral changes were entirely different when I was
photolyzed in aerated aqueous solutions at different λirr ranging
from 365 to 546 nm (Figure 1). A new species III was observed,
and extended photolysis gave a nearly limiting spectrum with a
III
Mn (TPP)(ONO) in benzene (TPP ) tetraphenylporphyrin). Later
(1) (a) Ignarro, L. J.; Buga, G. M.; Wood, K. S.; Byrns, R. E.; Chaudhuri,
-1
-1 16
λ
max ) 364 nm and ꢀmax ∼2600 M cm . On the basis of the
G. Proc. Natl. Acad. Sci. U.S.A. 1987, 84, 9265-9269. (b) Palmer, R. M. J.;
Ferrige, A. G.; Moncada, S. Nature 1987, 327, 524-526. (c) Hibbs, J. B.,
Jr.; Taintor, R. R.; Vavrin, Z. Science 1987, 235, 473-476. (d) Moncada, S.;
Palmer, R. M. J.; Higgs, E. A. Pharmacol. ReV. 1991, 43, 109-142.
spectral changes, the quantum yield for the transformation of I
to III (ΦIII) was determined to be 0.27 ( 0.03 at 436 nm, 30-
fold larger than that for the photoaquation seen in deaerated
(
2) (a) Ford, P. C.; Wink, D. A.; Stanbury, D. M. FEBS Lett. 1993, 326,
solutions. The identity of III has not been firmly established.
1
-3. (b) Bohle, D. S.; Hung, C.-H. J. Am. Chem. Soc. 1995, 117, 9584-
-
9
585. (c) Radi, R. Chem. Res. Toxicol. 1996, 9, 828-835. (d) Kadish, K. M.;
However, when III was isolated as a solid BPh
salt, the 298 K
4
Adamian, V. A.; Caemelbecke, E. V.; Tan, Z.; Tagliatesta, P.; Bianco, P.;
17
EPR spectrum proved to be that expected for a Cr(V) complex.
Furthermore, electrospray injection mass spectra of evolving
photolysis solutions indicated the presence of a species consistent
Boschi, T.; Yi, G.-B.; Khan, M. A.; Richter-Addo, G. B. Inorg. Chem. 1996,
3
5, 1343-1348. (e) Hoshino, M.; Maeda, M.; Konishi, R.; Seki, H.; Ford, P.
C. J. Am. Chem. Soc. 1996, 118, 5702-5707. (f) Dierks, E. A.; Hu, S.; Vogel,
K.; Yu, A. E.; Spiro, T. G.; Burstyn, J. N.; J. Am. Chem. Soc. 1997, 119,
V
2+
+
with the formulation [Cr (cyclam)(O)(ONO) (-H )] (m/z )
7
316-7323. (g) Zavarine, I. S.; Kini, A. D.; Morimoto, B. H.; Kubiak, C. P.
J. Phys. Chem. 1998, 102, 7287-7292.
3) (a) Feelisch, M.; Stamler, J. S. In Methods in Nitric Oxide Research;
Feelisch, M., Stamler, J. S., Eds.; John Wiley and Sons: Chichester, England,
996; Chapter 7, pp. 71-113. (b) Wink, D. A.; Vodovotz, Y.; Laval, J.; Laval,
F.; Dewhirst, M. W.; Mitchell, J. B. Carcinogenesis 1998, 19, 711-721.
4) (a) Matthews, E. K.; Seaton, E. D.; Forsyth, M. J.; Humphrey, P. P.
Br. J. Pharmacol. 1994, 113, 87-94. (b) Makings L. R.; Tsien, R. Y. J. Biol.
Chem. 1994, 269, 6282-6285. (c) Murphy, K. P. S. J.; Williams, J. H.;
Bettache, N.; Bliss, T. V. P. Neuropharmacology 1994, 33, 1375-1985. (d)
Miranda, K. M.; Ford, P. C. Presented at the 207th National ACS Meeting,
San Diego, CA, March, 1994, INORG 313. (d) Namiki, S.; Arai, T.; Fujimori,
K. J. Am. Chem. Soc. 1997, 119, 3840-3841.
(
(9) Suslick, K. S.; Bautista, J. F.; Watson, R. A. J. Am. Chem. Soc. 1991,
113, 6111-6114.
1
(10) Hoshino, M.; Nagashima, Y.; Seki. H.; DeLeo, M.; Ford, P. C. Inorg.
Chem. 1998, 37, 2464-2469.
(
(11) Yamaji, M.; Hama, Y.; Miyazake, M.; Hoshino, M. Inorg. Chem. 1992,
31, 932-934.
(12) DeLeo, M.; Bu, X.; Ford, P. C., manuscript in preparation.
(13) (a) Harrowfield, J. N. M.; Fee, W. W.; Garner, C. S. Inorg Chem.
1967, 6, 87-93. (b) Harrowfield, J. N. M.; Fee, W. W. Inorg Chem. 1971,
10, 290-297.
(14) The spectral changes closely match those seen in the acid hydrolysis
of I at pH 2 and are analogous to those reported for the acid hydrolysis of
(
5) (a) Hoshino, M.; Ozawa, K.; Seki, H.; Ford, P. C. J. Am. Chem. Soc.
+
12
1
993, 115, 9568-9575. (b) Bourassa, J. L.; DeGraff, W.; Kudo, S.; Wink, D.
trans-[Cr(en) (ONO) ] .
2 2
A.; Mitchell, J. B.; Ford, P. C. J. Am. Chem. Soc. 1997, 119, 2853-2861. (c)
(15) (a) Kutal, C.; Adamson, A. W. Inorg Chem. 1973, 12, 1990-1994.
(b) Kane-Maguire, N. A. P.; Wallace, K. C.; and Speece, D. G. Inorg Chem.
1986, 25, 4650-4654.
Laverman, L. E.; Hoshino, M.; Ford, P. C. J. Am. Chem. Soc. 1997, 119,
1
2663-12664.
(
6) (a) Miranda, K. M.; Bu, X.; Lorkovi c´ , I.; Ford, P. C. Inorg. Chem.
(16) Solutions of III are not photoinert but evolve slowly under continued
photolysis to a new species with a λmax at ∼354 nm (perhaps the result of
further nitrite photoaquation).
1
997, 36, 4838-4848. (b) Ford, P. C.; Bourassa, J.; Miranda, K.; Lee, B.;
Lorkovi c´ , I.; Boggs, S.; Kudo, S.; Laverman, L Coord. Chem. ReV. 1998,
1
71, 185-202. (c) Lorkovi c´ , I.; Miranda, K. M.; Lee, B.; Bernard, S.;
(17) (a) Lay, P. A.; Farrell, R. P. Comments Inorg. Chem. 1992, 3, 134-
Schoonover, J.; Ford, P. C. J. Am. Chem. Soc. 1998, 120, 11674-11683.
175. (b) The EPR spectrum of the solid isolated after long-term photolysis
2
+
(
7) Fischer, M.; Warneck, F. J. Phys. Chem. 1996, 100, 18750-18756.
8) Suslick, K.; Watson, R. Inorg. Chem. 1991, 30, 912-919.
suggests a mixture of two Cr(V) species, one trans-Cr(cyclam)(O)(ONO) ,
+
(
2
the other perhaps trans-Cr(cyclam)(O) .
1
0.1021/ja983875a CCC: $18.00 © 1999 American Chemical Society
Published on Web 02/20/1999

Communications to the Editor
J. Am. Chem. Soc., Vol. 121, No. 9, 1999 1981
Scheme 1
flash experiment in aerated aqueous solution showed some decay
back to the starting complex but gave residual absorbances
consistent with some permanent photoproduct.
Figure 1. Continuous photolysis (λirr ) 436 nm) of trans-Cr(cyclam)-
+
(ONO)
2
in pH 7, aerated aqueous solution over 140 min.
We interpret these observations in terms of two competing
+
primary photoreactions of trans-Cr(cyclam)(ONO)
2
, homolytic
dissociation of NO from a coordinated nitrite to form the Cr(IV)
intermediate IV20 and Cr-ONO photoaquation to II (Scheme 1).
The latter reaction is irreversible, but IV can either back react
with NO to regenerate I or be trapped by oxygen to give a more
stable Cr(V) complex, i.e., III. The latter leads to net release of
NO detectable by the electrochemical experiment. In the absence
of such trapping the only net photoreaction seen is the low
quantum yield formation of II.
In summary, we have demonstrated that photolysis of trans-
+
Cr(cyclam)(ONO)
2
in aqueous solution leads to the formation
IV
of an intermediate complex believed to be trans-Cr (cyclam)-
O)(ONO) with concurrent production of NO. In the presence
+
(
of O , the putative Cr(IV) species is trapped to give a more stable
2
Cr(V) complex. However, in the absence of such oxidative
quenching, the unprecedented back reaction of IV with NO occurs
Figure 2. Plot of kobs vs [NO] for transient decay of IV in 296 K aqueous
solutions.(λmon ) 560, λirr ) 355 nm. Inset shows point by point spectrum
of IV.
6
-1 -1
with the second-order rate constant kNO ) 3.06 × 10 M s .
Under such conditions, the only net reaction is the competing
-
low yield photoaquation of NO
2
. These results clearly demon-
strate the viability of NO-delivery schemes based upon the
photochemical decomposition of coordinated nitrite.
3
13).18 Nitric oxide formation was confirmed by carrying out
similar photolyses of I in aerated solutions in the presence of a
NO-specific electrode sensor.19
Acknowledgment. This work was supported by the National Science
Foundation (CHE 9726889). TRO experiments were carried out on
systems constructed with grants from the DOE University Research
Instrumentation Grant Program (No. DE-FG-05-91ER79039) and the NSF.
We thank James Bourassa and Leroy Laverman (UCSB) for help with
the TRO experiments, Jasper Bendix (U. Copenhagen) for a preprint of
ref 19b and Andreja Bakac (Ames NL) for discussion of the spectra of
oxidized chromium complexes.
The continuous photolysis experiments suggested the possibility
that NO is liberated from I, but the back reaction is efficient unless
O is present to trap some key intermediate. To test this model,
2
flash photolysis experiments (λirr ) 355 nm) were carried out on
aqueous solutions of I (1 mM) using time-resolved optical (TRO)
techniques with variable, single wavelength (PMT) or multiple
wavelength (CCD) detection.6 In deaerated solution, a transient
c
(
5
IV) was observed with difference spectrum maxima at 400 and
60 nm (Figure 2). This decayed back to the spectrum of I via
JA983875A
temporal absorbance changes which could be fit, roughly, to a
second-order rate law. The kinetics behavior was more firmly
established by carrying out TRO experiments with varying [NO],
under which conditions exponential decay of the 560 nm
absorbance was seen. A plot of the resulting kobs values vs [NO]
was linear with an intercept near the origin (Figure 2); thus, kobs
(
20) (a) Assigning IV as the Cr(IV) oxo complex trans-Cr(cyclam)(O)-
(ONO) draws support from spectral comparison with the isoelectronic Mn-
V
(
V) nitrido complexes trans-Mn (cyclam)(N)(X) which display overlapping
20b
spin allowed d-d bands with λmax at ∼580 and 495 nm. Also, Bakac has
generates a
II
2+
demonstrated that Tl(III) oxidation of trans-Cr (cyclam)(H
2
O)
2
spectrum with features analogous to IV and proposed this short-lived species
IV
2+ 20c
to be trans-[Cr (cyclam)(O)(H
Nolte, N.; Wehermuller, T.; Wieghardt, K. J. Am. Chem. Soc. 1998, 120,
260-7270. (c) Bakac, A., personal communication.
21) (a) A reviewer suggested that I should be viewed as a precursor for
photochemical generation of peroxynitrite ion (rather than of NO). The
reasoning was that IV is trapped by O , and a likely product of that reaction
is superoxide ion which is known to react very rapidly with NO to give
2
O)]
.
(b) Meyer, K.; Bendix, J.; Metzer-
6
-1 -1
)
k
NO[NO] with kNO ) (3.06 ( 0.07) × 10 M s . A similar
7
(
(
18) (a) De Leo, M. A.; Pavolich, J.; Ford, P. C., manuscript in preparation.
b) De Leo, M. A. Ph. D. Dissertation, University of California, Santa Barbara,
December, 1998.
19) (a) Kudo, S.; Bourassa, J. L.; Boggs, S. E.; Sato, Y.; Ford, P. C. Anal.
(
2
-
21b
(
OONO . This point indeed was probed using negative ion electrospray mass
18
Biochem. 1997, 247, 193-202. (b) I in aerated aqueous solution was irradiated
with the IR-filtered output from a 75-W Xe lamp, and NO was monitored
with a WPI NO electrode. Strong signals indicating the photogeneration of
NO were observed. Qualitatively, these signals indicated that the efficiency
of NO labilization from I was the same order of magnitude as that seen in
spectroscopic analysis of photolysis products of I in aerated aqueous
solutions. Peaks for nitrate ion (the expected product of peroxynitrite
rearrangement) were comparable in intensity to those for nitrite (the product
2
1c
of NO autoxidation), suggesting that some NO was indeed trapped by
superoxide. However, it should be emphasized that the major primary
photoreaction is the high quantum yield transformation of I to IV, and flash
and continuous photolysis evidence point convincingly to NO as the other
primary photoproduct. (b) Blough, N. V.; Zaffiriou, O. C. Inorg. Chem. 1985,
24, 3502-3504. (c) Wink, D. A.; Darbyshire, J. F.; Nims, R. W.; Saavedra,
J. E.; Ford, P. C. Chem. Res. Toxicol. 1993, 6, 23-27.
5
b
photolyses of the Roussin’s red salt anion and esters (ΦNO ≈ 0.1) under
analogous conditions. The signals from I, however, decayed at rates faster
than those generated by adding standard NO solutions, suggesting that decay
processes other than autoxidation or diffusion from the solution are playing
a role in this case.