Chromium(III) complexes for photochemical nitric oxide generation from coordinated nitrite: Synthesis and photochemistry of macrocyclic complexes with pendant chromophores, trans-[Cr(L)(ONO)2]BF4

Article abstract of DOI:10.1021/ic048311o

Several new dinitritochromium(III) complexes of the type trans-[Cr(L)(ONO)₂]BF₄, where L is a derivative of the macrocyclic ligand cyclam having pendant aromatic chromophores attached (L = 5,7-dimethyl-6-(substituted)1,4,8,11-tetraazacyclotetradecane), have been prepared and characterized. Photoexcitation of aqueous solutions containing these complexes at wavelengths corresponding to the pendant chromophore absorption bands led to the generation of NO as detected by an electrochemical sensor. Photophysical data show that the expected fluorescence of the pendant chromophores is largely quenched when the macrocyclic ligand is coordinated to these Cr(III) centers, and this is interpreted in terms of fast energy transfer processes from the ligand-centered ππ* states to the Cr(III)-centered ligand field states leading to subsequent cleavage of the Cr(III)-coordinated nitrito ligand. Thus, the chromophores tethered to the coordinated cyclam serve as light-gathering antennae for the intramolecular sensitization of the NO-generating photoreactions at the metal center.

Full text of DOI:10.1021/ic048311o

Inorg. Chem. 2005, 44, 4157−4165
Chromium(III) Complexes for Photochemical Nitric Oxide Generation
from Coordinated Nitrite: Synthesis and Photochemistry of Macrocyclic
Complexes with Pendant Chromophores, trans-[Cr(L)(ONO)2]BF4
Frank DeRosa,1 Xianhui Bu, and Peter C. Ford*
Department of Chemistry and Biochemistry, UniVersity of California at Santa Barbara,
Santa Barbara, California 93106-9510
Received November 30, 2004
Several new dinitritochromium(III) complexes of the type trans-[Cr(L)(ONO)2]BF4, where L is a derivative of the
macrocyclic ligand cyclam having pendant aromatic chromophores attached (L 5,7-dimethyl-6-(substituted)-
)
1,4,8,11-tetraazacyclotetradecane), have been prepared and characterized. Photoexcitation of aqueous solutions
containing these complexes at wavelengths corresponding to the pendant chromophore absorption bands led to
the generation of NO as detected by an electrochemical sensor. Photophysical data show that the expected
fluorescence of the pendant chromophores is largely quenched when the macrocyclic ligand is coordinated to
these Cr(III) centers, and this is interpreted in terms of fast energy transfer processes from the ligand-centered
ππ* states to the Cr(III)-centered ligand field states leading to subsequent cleavage of the Cr(III)-coordinated
nitrito ligand. Thus, the chromophores tethered to the coordinated cyclam serve as light-gathering antennae for the
intramolecular sensitization of the NO-generating photoreactions at the metal center.
Introduction
tumors.3-9 For example, this laboratory has reported that
aqueous solutions of the complex trans-[Cr(cyclam)-
(ONO)2]+ (I, cyclam ) 1,4,8,11-tetraazacyclotetradecane)
release NO upon photolysis via the unusual O-N cleavage
of the coordinated nitrito ligand with a quantum yield of
ΦNO ) 0.27 ( 0.03.10 However, the low absorption cross
section for I reduces the potential applicability of this
compound as a photochemical NO precursor in living
It is now well-established that nitric oxide (also known
as nitrogen monoxide) plays key roles in human cardiovas-
cular and nervous systems and in immune response toward
pathogens.2 These properties have aroused considerable
interest in compounds that can be used to deliver NO to
biological targets upon demand. Ongoing studies in this
laboratory and others have been concerned with the prepara-
tion new metal-based compounds having possible applica-
tions as photochemically activated drugs to release NO for
possible use as a sensitizer in the radiation therapy of
(3) Modica-Napolitano, J. S.; Joyal, J. L.; Ara, G.; Oseroff, A. R.; Aprille,
J. R. Cancer Res. 1990, 50, 7876-7881.
(4) (a) Bourassa, J.; DeGraff, W.; Kudo, S.; Wink, D. A.; Mitchell, J. B.;
Ford, P. C. J. Am. Chem. Soc. 1997, 119, 2853-2860. (b) Conrado,
C. L.; Wecksler, S.; Egler, C.; Magde, D.; Ford, P. C. Inorg. Chem.
2004, 43, 5543-5549.
* Author to whom correspondence should be addressed. E-mail:
ford@chem.ucsb.edu.
(1) Taken in part from the Ph.D. dissertation of F.D., University of
California, Santa Barbara, CA, 2003.
(5) Ford, P. C.; Bourassa, J.; Miranda, K.; Lee, B.; Lorkovic, I.; Boggs,
S.; Kudo, S.; Laverman, L Coord. Chem. ReV. 1998, 171, 185-202.
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J. R.; Ford, P. C. J. Am. Chem. Soc. 1998, 120, 11674-11683.
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B. Chem. ReV. 2000, 100, 1973-2011 and references therein.
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(b) Mitchell, J. B.; Wink, D. A.; DeGraff, W.; Gamson, J.; Keefer, L.
K.; Krishna, M. C. Cancer Res. 1993, 53, 5845-5848.
(10) (a) DeLeo, M. A.; Ford, P. C J. Am. Chem. Soc. 1999, 121, 1980-
1981. (b) DeLeo, M. A.; Ford, P. C. Coord. Chem. ReV. 2000, 208,
47-59.
(2) (a) Palmer, R. M. J.; Ferrige, A. G.; Moncada, S. Nature 1987, 327,
524-526. (b) Ignarro, L. J.; Buga, G. M.; Wood, K. S.; Byrns, R. E.;
Chaudhuri, G. Proc. Natl. Acad. Sci. U.S.A. 1987, 84, 9265-9269.
(c) Hibbs, J. B., Jr.; Taintor, R. R.; Vavrin, Z. Science 1987, 235,
473-476. (d) Furchgott, R. F.; Vanhoute, P. M. FASEB J. 1989, 3,
2007-2018. (e) Moncada, S.; Palmer, R. M. J.; Higgs, E. A.
Pharmacol. ReV. 1991, 43, 109-142. (f) Feldman, P. L.; Griffith, O.
W.; Stuehr, D. J. Chem. Eng. News 1993, 71, 10, 26-38. (g) Wink,
D. A.; Hanbauer, I.; Grisham, M. B.; Laval, F.; Nims, R. W.; Laval,
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Mitchell, J. B. Curr. Top. Cell. Regul. 1996, 34, 159-187. (h) Feelisch,
M., Stamler, J. S., Eds. Methods in Nitric Oxide Research; John Wiley
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10.1021/ic048311o CCC: $30.25
Published on Web 03/31/2005
© 2005 American Chemical Society
Inorganic Chemistry, Vol. 44, No. 12, 2005 4157

DeRosa et al.
Chart 1. Representations of the Dinitritochromium(III) Complex Ions
I-V
recorded using an updated BioRad model FTS 60 SPC 3200 FTIR
spectrometer. Elemental analyses were carried out by the UCSB
Marine Science Institute using a Control Equipment Corp. 440
elemental analyzer.
2. Synthesis of Chromium(III) Dinitrito Complexes. The
dinitrito complexes were prepared by the reactions of the dichloro
analogues with silver nitrite according to the procedure reported
by DeLeo et al.12 The previously reported12 trans-[Cr(cyclam)-
(ONO)2]BF4 (I) was prepared in this manner from trans-
[Cr(cyclam)Cl2]Cl with 87.2% yield. ESI-MS (m/z): 344 (M+).
UV-vis (H2O) [λmax in nm (ꢀ in M-1 cm-1)]: 336 (271), 476 (33.6).
IR (KBr; cm-1): 1493 (νas, ONO), 987 (νs, ONO), 827 (δwag, ONO).
trans-[Cr(mbc)(ONO)2]BF4 (II). This was prepared by a
procedure adapted from that used to prepare I.12 A solution of trans-
[Cr(mbc)Cl2]Cl (0.200 g, 4.19 × 10-4 mol) in H2O (15 mL) was
heated to reflux, and then a hot aqueous solution of AgNO2
(0.194 g, 1.26 mmol) was added under subdued light. A white
precipitate (AgCl) formed immediately, and the mixture was
refluxed for 45 min during which the solution color turned orange.
Upon completion, the mixture was filtered through a medium glass
frit and the volatiles were removed from the filtrate under reduced
pressure. The orange-brown residue was redissolved in a minimum
amount of H2O (∼3 mL) and passed through a 0.22 µm filter
resulting in a deep orange filtrate. The solution was treated with a
saturated solution of NaBF4 (10 drops), and the resulting orange
precipitate was allowed to settle. Several small scoops of NaNO2
were added, and the solution was sonicated (to ensure dissolution)
to salt out the remaining product. The solution was cooled overnight
in a refrigerator and then was filtered to give a light orange powder.
Yield: 0.210 g (90.9%). ESI-MS (m/z): 462 (M+). UV-vis (H2O)
[λmax in nm (ꢀ in M-1 cm-1)]: 328 (271), 472 (31.0). IR (KBr;
cm-1): 1496 (νas, ONO), 982 (νs, ONO), 818 (δwag, ONO). An
X-ray crystal structure was obtained.
trans-[Cr(mac)(ONO)2]BF4 (III). A procedure analogous to one
used for the preparation of II was employed. Starting with a
0.100 g sample of trans-[Cr(mac)Cl2]Cl (1.73 × 10-4 mol), a yield
of 0.033 g (29.2%) was obtained after recrystallization via ether
diffusion into a methanol solution of the product to give dark orange
crystals. ESI-MS (m/z) 562 (M+). UV-vis (H2O) [λmax in nm (ꢀ in
M-1 cm-1)]: 336 (3.94 × 103), 352 (6.55 × 103), 370 (9.29 ×
103), 392 (8.47 × 103), 476 (56.0). IR (KBr; cm-1): 1506
(νas, ONO), 979 (νs, ONO), 818 (δwag, ONO). Anal. Calcd for
CrC27H38N6O4BF4: C, 49.93; H, 5.89; N, 12.94. Found: C, 50.25;
H, 5.58; N, 12.32. An X-ray crystal structure was obtained.
trans-[Cr(hbc)(ONO)2]BF4 (IV). A procedure analogous to that
used for preparation of II was employed. Starting with a 0.200 g
portion of trans-[Cr(hbc)Cl2]Cl (3.95 × 10-4 mol), a yield of
0.134 g (58.5%) was obtained after recrystallization by ether
diffusion into an acetone solution of the product. ESI-MS (m/z):
492 (M+). UV-vis (H2O) [λmax in nm (ꢀ in M-1 cm-1)]: 334 (243),
476 (32.4). IR (KBr; cm-1): 1482 (νas, ONO), 989 (νs, ONO), 823
(δwag, ONO), 3450 (-OH). Anal. Calcd for CrC20H36N6O5BF4‚
(CH3)2C(O): C, 43.33; H, 6.64; N, 13.18. Found: C, 43.42; H,
6.37; N, 13.13. An X-ray crystal structure was obtained.
systems. As a consequence, the present research was initiated
to prepare compounds having similar features but carrying
chromophores that might act as antennas to absorb light more
efficiently and as internal sensitizers of the desired photo-
chemistry. Reported here are the syntheses, characterizations,
and photochemical properties of several new dinitrito
complexes that include aromatic chromophores tethered to
modified cyclam-like ligand as illustrated in Chart 1. These
compounds provide proof of concept demonstration that
pendant chromophores can serve as antennae to gather light
and to sensitize excited-state reactions localized at the
Cr(III) center leading to the photochemical release of nitric
oxide.
Experimental Section
1. Materials and Instrumentation. Silver nitrite, cyclam,
dicyclohexylcarbodiimide (DCC), 1-hydroxybenzatriazole, 4-(dim-
ethylamino)pyridine, and 1-pyrenecarboxylic acid were purchased
from Aldrich and used without further purification. Dimethyl-
formamide was dried over 3 Å mol sieves before use. We have
reported elsewhere the preparations of the ligands mbc
(5,7-dimethyl-6-benzylcyclam), mac (5,7-dimethyl-6-anthracylcy-
clam), and hbc (5,7-dimethyl-6-(p-hydroxymethylbenzyl)-1,4,
8,11-cyclam) plus their respective dichlorochromium(III)
complexes trans-[Cr(mbc)Cl2]Cl, trans-[Cr(mac)Cl2]Cl, and trans-
[Cr(hbc)Cl2]Cl.11
Electronic spectra were recorded using a Hewlett-Packard model
HP8452A diode array spectrophotometer or a Shimadzu model
2401PC spectrophotometer. Low-resolution mass spectra were
obtained using a VG Fisons Platform II single quadrupole mass
spectrometer with an electrospray ionization source run with a
Fisons Masslinks data system. Infrared spectra (KBr pellets) were
trans-[Cr(5,7-dimethyl-6-(1′-methyl-4′-(1′′-carboxymethyl-
pyrene)benzyl)-1,4,8,11-tetraazacyclotetradecane)(ONO)2]-
BF4, trans-[Cr(pbc)(ONO)2]BF4 (V). A portion of trans-[Cr(hbc)-
(ONO)2]BF4 (0.020 g, 3.45 × 10-5 mol) was dissolved in dry
dimethylformamide (10 mL), and to this solution were added
1-pyrenecarboxylic acid (8.5 mg, 3.45 × 10-5 mol), (dimethyl-
(12) DeLeo, M. A.; Bu, X.; Bentow, J.; Ford, P. C. Inorg. Chim. Acta
2000, 300, 944-950.
(11) DeRosa, F.; Bu, X.; Pohaku, K.; Ford, P. C. Submitted for publication.
4158 Inorganic Chemistry, Vol. 44, No. 12, 2005

Cr(III) Complexes for Nitric Oxide Generation
amino)pyridine (DMAP) (8.4 mg, 6.90 × 10-5 mol), and hydroxy-
benzatriazole (HOBt) (5.1 mg, 3.80 × 10-5 mol) at 0 °C in subdued
light. The coupling agent dicyclohexylcarbodiimide (DCC) (7.1 mg,
3.45 × 10-5 mol) was added, and the solution was stirred for 1 h
at 0 °C. The solution was then warmed to room temperature and
stirred for 3 days. The reaction progress monitored by +ESI-TOF
mass spectrometry showed an inexplicable nonlinear growth in the
peak (m/z 720), the parent ion trans-[Cr(pbc)(ONO)2]+. There was
only modest growth of this peak even at 48 h, but after 72 h, it
was dominant in the mass spectrum and the starting material was
gone. Upon completion, the solvent was removed under reduced
pressure and the resulting dark yellow residue was rinsed with water
followed by CHCl3. Yield: 0.016 g (57.6%). ESI-MS (m/z):
720 (M+). UV-vis (DMF) [λmax in nm (ꢀ in M-1 cm-1)]: 284
(2.20 × 104), 338 (1.60 × 104), 352 (2.23 × 104), 364 (1.55 ×
104), 386 (7.55 × 103), 476 (41.0). IR (KBr; cm-1): 1493
(νas, ONO), 985 (νs, ONO), 820 (δwag, ONO). Anal. Calcd for
CrC37H44N6O6BF4‚2CHCl3: C, 44.76; H, 4.43; N, 8.03. Found: C,
44.46; H, 4.63; N, 8.37.
Scheme 1. Synthesis of the Pyrene-Tethered Compound V
3. Crystal Growth and Structure Determination. Crystal
structures for compounds II-IV have been determined. Crystals
of II and III were grown via slow vapor diffusion of ether into a
concentrated methanol solution to yield deep orange rectangular
crystals. Orange rectangular crystals of IV were grown in a similar
manner but using acetone in place of methanol.
Suitable crystals were mounted on thin glass fibers with epoxy
resin. Low-temperature (150 K) single-crystal studies were carried
out on a Bruker Smart 1000 diffractometer equipped with normal-
focus 2.4 kW sealed-tube X-ray source (Mo KR radiation) operating
at 50 kV and 40 mA with a two-dimensional CCD detector. The
crystals were solved by direct methods followed by difference
Fourier methods. Hydrogen atoms attached to carbon atoms were
calculated at ideal positions and refined as riding atoms of the parent
carbon atoms. The calculations were performed using SHELXTL
running on Silicon Graphics Indy 5000. Final full-matrix refine-
ments were against F2.
4. Photochemical Procedures. Emission and excitation spectra
were recorded utilizing a SPEX Fluorolog 2 spectro-fluorometer
equipped with a Hamamatsu R928-A water-cooled PMT configured
for photon counting and interfaced with a computer running Spex
DM3000f software. Emission spectra were corrected for PMT
response as well as for lamp intensity variation by the ratio method
with a Rhodamine-6G reference. A cutoff filter was placed in front
of the emission monochromator to block scattered excitation light.
Low-temperature (77 K) emission and excitation data were obtained
in a front-face configuration using 4:1 EtOH-MeOH (v/v) glasses.
Room-temperature (296 K) emission and excitation data were
collected with a right-angle configuration in aqueous media
(I-III) or 1:1 acetonitrile-H2O (v/v) solvent system (V). The more
concentrated solutions were 2 mM while diluted samples of III
and V were 50 and 30 µM, respectively. Emission spectra of the
free ligands mac and 1-pyrenecroxylic acid were recorded in 50
and 30 µM aqueous solutions, respectively.
Continuous-wave (CW) photolysis experiments were performed
in unbuffered aqueous solutions at ambient temperatures with the
exception of trans-[Cr(pbc)(ONO)2]BF4 (V) that was studied using
a 1:1 acetonitrile-H2O solvent system. Photolysis was performed
using a Hg lamp with irradiation wavelengths (λirr) corresponding
to the Hg high-intensity lines at 365 and 436 nm light isolated using
interference filters. Ferrioxalate actinometry was used to evaluate
light intensities.
calibrated using a standard sodium nitrite solution. Care had to be
taken not to irradiate the tip of the sensor to avoid a false response.
Therefore, the sensor tip was masked within a plastic cell holder,
which allowed only a small portion of the quartz cell to be irradiated
below the tip by the collimated light. NO-detection experiments
were performed in a dark room using 1 cm quartz cells. The cell
was filled with 3 mL of deionized water and irradiated using band-
pass filters, and small aliquots (30 µL) of aqueous chromium
dinitrito solutions were added.
Results and Discussion
1. Syntheses. Reaction of the dichloro complexes trans-
[Cr(L)Cl2]Cl (L ) mbc, mac, or hbc) with AgNO2 led to
formation of the respective dinitrito complexes as reported
-
earlier for I.12 These were recrystallized as BF4 salts, and
their structures were determined by single-crystal X-ray
diffraction methods. The alcohol functionality on the benzyl
substituent of trans-[Cr(hbc)(ONO)2]BF4 (IV) provides the
means to tether additional chromophores to the macrocyclic
complex. This was demonstrated using a 1-pyrenecarboxylic
acid that was attached via an ester linkage to form
trans-[Cr(pbc)(ONO)2]BF4 (V) as illustrated by Scheme 1.
2. Spectroscopic Properties. The optical absorption
spectra of II-IV were recorded in aqueous solution. Each
displays a quartet to quartet (Q1 r Qo), ligand field (LF)
transition at approximately 475 nm (Figure 1, Table 1),
4
4
derived from the T2g r A2g transition expected under
octahedral symmetry. Under the roughly D4h symmetry of
4
2
these complexes, this band would split into B2g and E2g
components, but such splitting is not obvious here. The
position of this band is in good agreement with those found
for previously characterized chromium(III) nitrito com-
plexes.12,13 The peak centered at 328 nm (ꢀ ) 271 M-1 cm-1)
for II and at 334 nm (243 M-1 cm-1) for IV has been
assigned as an intraligand n-π* transition localized to the
coordinated nitrite in analogy to assignments by Fee and
Qualitative detection of NO was accomplished using a Harvard
Apparatus ami-NO 700 electrochemical NO sensor. The sensor was
(13) Fee, W. W.; Garner, C. S.; Harrowfield, J. N. B. Inorg. Chem. 1967,
6, 87-93.
Inorganic Chemistry, Vol. 44, No. 12, 2005 4159

DeRosa et al.
Figure 2. Molecular structure and numbering of atoms for the cation of
trans-[Cr(mbc)(ONO)2]BF4 (II). Hydrogen atoms are omitted for clarity.
Thermal ellipsoids are drawn at the 30% level.
bands were too weak to be seen in the absorption spectra of
these compounds recorded in 5 mM solutions. (Supporting
Information Figure S1 displays the absorption spectrum in
this region for the parent cylam complex I).
II-V were characterized by electrospray ionization time-
of-flight (+ESI-TOF) mass spectrometry. In each case, the
parent cation (M+) was seen as well as another, smaller peak
30 m/z units lower corresponding to the loss of one NO.
Similar fragmentation patterns were observed for trans-
[Cr(cyclam)(ONO)2]BF4 (I).12
The FTIR absorbance spectra recorded for II-V in KBr
pellets each displayed three bands characteristic of an
O-bound nitrito ligand.15 For example, trans-[Cr(mbc)-
(ONO)2]BF4 (II) showed bands at 1496 cm-1 (νas, ONO),
982 cm-1 (νs, ONO), and 818 cm-1 (δwag, ONO) in
agreement with previously reported chromium(III) nitrito
complexes (Supporting Information, Table S1).12,13 Each
complex also displayed two relatively weak bands represent-
ing the N-H wagging modes of trans-configured cyclam
ring, for example, at 878 and 892 cm-1 for II, while the cis
isomers would have four bands in this region.16
3. Structures. X-ray crystal structures were determined
for trans-[Cr(mbc)(ONO)2]BF4 (II), trans-[Cr(mac)(ONO)2]-
BF4 (III), and trans-[Cr(hbc)(ONO)2]BF4 (IV). The macro-
cycle resides in the more stable trans-III isoform following
nomenclature designated by Bosnich et al.17 (Figures 2-4).
The two methyl groups, C(21) and C(31), are located in
equatorial positions while the aryl methyl chromophore is
positioned axially on the macrocycle. The higher Rf value
for III (7.26%) can be attributed to the orientation disorder
of the BF4- counteranion that persisted even at low temper-
Figure 1. Top: Optical spectra for trans-Cr(III) dinitrito complexes I-V.
All spectra are taken in aqueous solutions. Bottom: Absorbance spectra of
III (50 µM) and V (30 µM) in aqueous solution.
Table 1. UV/Vis Spectral Data for Chromium(III) Nitrito Complexes
n-π*
λ (nm)
d-d
λ (nm)
complex
(ꢀ, M-1 cm-1
)
(ꢀ, M-1 cm-1
)
ref
trans-[Cr(en)2(ONO)2]+
328 (185)
477 (44)
476 (34)
480 (39)
472 (31)
476 (56)
476 (32)
476 (41)
13
12
12
this work
this work
this work
this work
trans-[Cr(cyclam)(ONO)2]+ (I) 336 (271)
trans-[Cr(tetA)(ONO)2]+
344 (213)
328 (271)
a
trans-[Cr(mbc)(ONO)2]+ (II)
trans-[Cr(mac)(ONO)2]+ (III)
trans-[Cr(hbc)(ONO)2]+ (IV) 334 (243)
trans-[Cr(pbc)(ONO)2]+ (V)
a
a n-π* band is masked by π-π* absorption of the aromatic appendage.
These bands are listed in the Experimental Section.
Harrowfield13 for the complex trans-[Cr(en)2(ONO)2]ClO4.
This band tails out to ∼400 nm and apparently obscures the
higher energy quartet absorptions expected for a D4h Cr(III)
diacido tetraamine complex (found at ∼370 nm for the
dichloro analogues).11 The ligand-localized n-π* band is
obscured in the spectrum of trans-[Cr(mac)(ONO)2]BF4 by
the intense π-π* absorption band of the anthracene moiety.
Similar absorption bands are seen for the pyrene-derivatized
complex, trans-[Cr(pbc)(ONO)2]BF4 (V). The quartet to
quartet (Q1 r Qo), LF transition appears at 476 nm
(41.0 M-1 cm-1), but the n-π* intraligand band is masked
by the intense π-π* bands of the pyrene chromophore. For
all of these Cr(III) complexes, relatively sharp doublet
absorptions (D0 r Qo) are predicted to occur at ap-
proximately 650-700 nm;14 however, these spin-forbidden
(14) Porter, G. B. In Concepts of Inorganic Photochemistry; Adamson, A.
W., Fleischauer, P. D., Eds.; John Wiley and Sons: New York, 1975;
Chapter 2. Zinato, E. In Concepts of Inorganic Photochemistry;
Adamson, A. W., Fleischauer, P. D., Eds.; John Wiley and Sons: New
York, 1975; Chapter 4.
(15) (a) Nakamoto, K. Infrared and Raman Spectra of Inorganic and
Coordination Compounds; Wiley: New York, 1986, pp 150 and 224
and references therein. (b) Hitchman, M. A.; Rowbottom, G. L. Coord.
Chem. ReV. 1982, 42, 55.
(16) Poon, C. K.; Pun, K. C. Inorg. Chem. 1980, 19, 568-569.
(17) Bosnich, B.; Poon, C. K.; Tobe, M. L. Inorg. Chem. 1965, 4, 1102-
1108.
4160 Inorganic Chemistry, Vol. 44, No. 12, 2005

Cr(III) Complexes for Nitric Oxide Generation
Table 2. Selected Bond Lengths (Å) for trans-[Cr(mbc)(ONO)2]BF4
(II), trans-[Cr(mac)(ONO)2]BF4 (III), and trans-[Cr(hbc)(ONO)2]BF4
(IV)
II
III
IV
Cr(1)-O(1)
Cr(1)-O(3)
Cr(1)-N(3)
Cr(1)-N(4)
Cr(1)-N(5)
Cr(1)-N(6)
N(1)-O(1)
N(1)-O(2)
N(2)-O(3)
N(2)-O(4)
1.944(2)
1.971(2)
2.064(3)
2.060(2)
2.065(2)
2.067(3)
1.296(5)
1.166(4)
1.284(4)
1.206(4)
1.946(4)
1.968(3)
2.073(4)
2.058(4)
2.065(4)
2.065(5)
1.129(8)
1.232(8)
1.239(6)
1.196(5)
1.968(2)
1.971(2)
2.064(3)
2.062(3)
2.075(3)
2.065(3)
1.290(4)
1.209(4)
1.301(4)
1.196(4)
Figure 3. Molecular structure and numbering of atoms for the cation of
trans-[Cr(mac)(ONO)2]BF4 (III). Hydrogen atoms are omitted for clarity.
Thermal ellipsoids are drawn at the 30% level.
Table 3. Selected Bond Angles (deg) for trans-[Cr(mbc)(ONO)2]BF4
(II), trans-[Cr(mac)(ONO)2]BF4 (III), and trans-[Cr(hbc)(ONO)2]BF4
(IV)
II
III
IV
O(1)-Cr(1)-O(3)
O(1)-Cr(1)-N(3)
O(3)-Cr(1)-N(3)
O(1)-Cr(1)-N(4)
O(3)-Cr(1)-N(4)
O(1)-Cr(1)-N(5)
O(3)-Cr(1)-N(5)
O(1)-Cr(1)-N(6)
O(3)-Cr(1)-N(6)
N(3)-Cr(1)-N(4)
N(3)-Cr(1)-N(5)
N(3)-Cr(1)-N(6)
N(4)-Cr(1)-N(5)
N(4)-Cr(1)-N(6)
N(1)-O(1)-Cr(1)
N(2)-O(3)-Cr(1)
O(1)-N(1)-O(2)
O(3)-N(2)-O(4)
176.80(10)
89.22(10)
93.18(10)
93.12(10)
89.17(10)
87.87(10)
89.81(10)
90.73(11)
86.90(10)
85.80(10)
94.96(10)
179.34(10)
178.76(10)
93.55(10)
121.2(2)
175.8(2)
86.8(2)
89.3(2)
90.9(2)
87.4(2)
87.6(2)
94.2(2)
93.3(2)
90.6(2)
86.0(2)
94.5(2)
179.5(2)
178.4(2)
93.5(2)
135.6(6)
121.7(3)
122.1(8)
118.1(5)
176.97(10)
86.83(10)
90.25(10)
91.20(11)
87.79(10)
88.03(11)
93.00(10)
93.00(10)
89.92(10)
86.08(10)
94.36(10)
179.58(11)
179.09(11)
86.01(11)
122.8(2)
Figure 4. Molecular structure and numbering of atoms for the cation of
trans-[Cr(hbc)(ONO)2]BF4 (IV). Hydrogen atoms are omitted for clarity.
Thermal ellipsoids are drawn at the 30% level.
123.2(2)
116.5(4)
116.8(3)
119.4(2)
114.8(3)
115.4(3)
using λirr ) 365 and 436 nm. The qualitative spectral changes
were independent of λirr. Within the first 20 min a new
absorption band grew in at 364 nm (ꢀ ) ∼900 M-1 cm-1)
(Figure 5). The quantum yield was calculated by monitoring
these absorption changes at λmon ) 370 nm and plotting the
incremental Φi versus time. Extrapolation of this plot to the
y-intercept accounted for inner-filter effects and gave quan-
tum yields of 0.19 ( 0.01 (365 nm) and 0.31 ( 0.03
(436 nm). On the basis of an analogy to the photochemistry
of I,10 the product was assigned as the Cr(V) oxo species
trans-[Cr(mbc)(O)(ONO)]2+, formed after the photochemical
release of NO and the subsequent oxidation of the putative
Cr(IV) primary photoproduct, trans-[Cr(mbc)(O)(ONO)]+.
In deaerated solutions the absorption changes were very
small, consistent with DeLeo’s demonstration that the
primary photoreaction, NO generation from Cr(III)-co-
ordinated nitrite, was rapidly reversible, unless O2 is present
to trap the photochemically generated intermediates
(Scheme 2).10,18
Figure 5. Absorbance increases upon photolysis (λirr ) 365 nm) of an
aqueous solution of trans-[Cr(mbc)(ONO)2]BF4 (II) (1 mM) under aerated
conditions at ambient temperature at 1 min intervals for 20 min.
atures (150 K). Selected bond lengths and bond angles are
summarized in Tables 2 and 3 and show few differences in
key parameters between the four complexes.
Continued photolysis (λirr ) 365 nm) of these solutions
over much longer time periods (48 h) gave evidence of a
secondary photolysis process. Slower spectral changes
including a hypsochromic shift to λmax ) 356 nm occurred.
These slower changes are particularly evident when differ-
ence spectra were calculated (Supporting Information Figure
S2 top) but did not correspond to the spectrum of a known
species. Reinvestigation of the photochemistry of the previ-
4. Continuous Photolysis Studies. trans-[Cr(mbc)-
(ONO)2]BF4. The photochemistry of the benzyl derivative
II is nearly identical with that reported for the unsubstituted
complex I.10,18 Aqueous solutions (1 mM) of II were
photolyzed under aerated conditions at ambient temperature
(18) DeLeo, M. A. Ph.D. Dissertation, University of California, Santa
Barbara, CA, 1998.
Inorganic Chemistry, Vol. 44, No. 12, 2005 4161

DeRosa et al.
Scheme 2. Photoreactions of Compound I As Outlined by DeLeo10
ously studied10 trans-[Cr(cyclam)(ONO)2]BF4 (I) in aqueous
solutions demonstrated a very similar secondary process
(Supporting Information Figure S2 bottom). Quantum yield
approximations based upon absorbance changes suggested
that the Φ for the second process was about 1 order of
magnitude less than that of the first process.
Figure 6. Photolysis of an aqueous solution of trans-[Cr(mac)(ONO)2]-
BF4 (III) (50 µM) under aerated conditions at ambient temperature over a
period 20 h. λirr ) 365 nm.
trans-[Cr(mac)(ONO)2]BF4. The strong π-π* absorption
of the anthracene derivative III overlapped other key
absorption bands but was only modestly affected by the
photochemistry at the Cr(III) center. Photolysis of III
(50 µM) in an aerated solution with 365 nm light led to small
absorption increases in the region where the anthracene
π-π* bands dominate (Figure 6). The largest differences
occurred at 278 nm, and the quantum yield based on
absorbance changes at this λmon was calculated to be 0.17,
although a clear assignment of the photochemical processes
taking place could not be assessed from these data (see
below). When III was photolyzed in deaerated aqueous
solution (λirr ) 365 nm), changes in the optical spectrum
were much smaller (Φ < 3.0 × 10-3 based on ∆Abs at
278 nm). The latter observation parallels the photochemistry
of I and II, which show only small changes in deaerated
solutions owing the reversibility of the NO photolabilization
(Scheme 2).
trans-[Cr(pbc)(ONO)2]BF4. Like III, continuous photo-
lysis of the pyrene-derivatized complex V was carried out
at very low concentrations owing to the very strong π-π*
absorption bands of the pyrene chromophore that dominated
the spectrum. An aerated solution of V (30 µM) in aceto-
nitrile-H2O (1:1 v/v) at ambient temperature was photolyzed
(λirr ) 365 nm) under conditions similar to those described
for I-III. The changes in the optical spectrum were small
owing to the insensitivity of the pyrene group’s spectrum
(λmax ) 352 nm, ꢀ ) 22 000 M-1 cm-1) to changes at the
Cr(III) center. However, a ∆ꢀ value of ∼800 M-1 cm-1 at
314 nm was determined by examining the spectrum after
exhaustive photolysis, and from this a quantum yield of
∼0.18 was calculated from spectral changes in the initial
stages of the photolysis.
Electrochemical NO Detection. Since the spectral changes
seen for continuous photolysis experiments were inconclusive
with regard to the photochemical processes for III and V, a
NO-specific electrochemical sensor was utilized to monitor
the potential photolabilization of NO. For II and III, aqueous
stock solutions (100 µM) were prepared at ambient temper-
ature for these experiments. A cuvette with 3.0 mL of
distilled, deionized H2O was placed in front of the photolysis
lamp, and the NO-specific electrode was inserted into the
cuvette in a manner such that no light was shining on the
Figure 7. Electrochemical detection of NO upon photolysis of aqueous
solutions of II, III, and V irradiating with 360-440 nm light (band-pass
filter).
tip. The solution was irradiated with light from a high-
pressure Hg arc lamp using a 360-440 nm band-pass filter
for wavelength selection. To this solution, a 30 µL aliquot
of the Cr(III) stock solution was injected with constant
stirring to give a 990 nM concentration of the Cr(III) complex
in the photolysis cell. The NO sensor immediately recorded
a marked increase in current indicating the formation of free
NO in the solution, as expected from the first step of Scheme
2. In contrast, NO was not detected for solutions of the
chromium(III) dinitrito complexes in the absence of light.
These experiments clearly demonstrated that the an-
thracene derivative trans-[Cr(mac)(ONO)2]BF4 produced
about eight times as much NO (124 nM) as did the benzyl
derivative II (16 nM) after 20 s photolysis under identical
conditions (Figure 7). This difference can be attributed to
the much larger absorption cross section at λirr for III at the
same concentration. For example, at 365 nm the absorbance
of 990 nM III is 5.9 × 10-3 while that of 990 nM II is
∼2 × 10-4, and III would absorb about 30 times as much
light as II at that wavelength. (However, at the longer
wavelengths of the 360-440 nm band-pass filter, the
4162 Inorganic Chemistry, Vol. 44, No. 12, 2005

Cr(III) Complexes for Nitric Oxide Generation
absorbance differences between II and III, or for that matter
between II and V, are smaller than at 365 nm; see
Figure 1.)
photoproduct peaks in this example suggests a sequential
process beginning with NO photodissociation in the first step
followed by a secondary photoreaction or thermal reaction
leading to loss of a second NO. However, such a scenario
would requires spacing of these peaks by 30, not 29, m/z
units, unless during the MS analysis process the new Cr(III)
oxo species generated are reduced to give mono- and
dihydroxyl complexes rather than the oxo or dioxo analogues.
This might be expected for high-valent chromium-oxo
complexes.19
The pattern seen in the photoproduct mass spectral analysis
of III was also seen for analogous experiments with trans-
[Cr(cyclam)(ONO)2]BF4 (I) and trans-[Cr(mbc)(ONO)2]BF4
(II) done under the same conditions. In general, when the
solutions resulting from the photolysis of [Cr(L)(ONO)2]+
(L ) cyclam, mbc, mac) were subjected to mass spectral
analysis, the products consistently demonstrate decreased
mass from the parent peak (M+) of m/z 29 or 58. Since nitric
oxide sensor experiments (described above) confirm the
direct photochemical release of NO, we conclude that the
mass changes of m/z 29 of the peaks observed upon
photolysis of the chromium(III) dinitrito compounds must
represent the photochemical loss of NO and with the addition
of 1 H- equiv during the MS experiment.20
If one combines the results of the continuous-wave
photolysis experiments along with the +ESI-TOF MS
experiments and the electrochemical NO detection, it is
hypothesized that the growth in absorption seen at 328 nm
(species A) after prolonged photolysis of both trans-
[Cr(cyclam)(ONO)2]BF4 (I) and trans-[Cr(mbc)(ONO)2]BF4
(II) is due to the photochemical formation of the Cr(VI)
dioxo species trans-[Cr(L)(O)2]2+ (where L ) cyclam or
mbc), perhaps via photochemical NO dissociation (eq 1) from
the Cr(V) product trans-[Cr(L)(O)(ONO)]2+ formed accord-
ing to processes summarized by Scheme 2.
Analogous experiments were performed on the pyrene-
derivatized analogue V. In this case the stock solution was
an acetonitrile-H2O (1:1 v/v) solution of V (100 µM) at
ambient temperature, and the total concentration after 30 µL
aliquot addition was again 990 nM. Photolysis for 20 s using
the band-pass filter resulted in NO release (194 nM) (Figure
7) ∼60% greater than found for III and more than 12 times
that found for II. Again, the difference can be attributed to
the larger absorption cross section of the pyrene chromophore
(0.014 at 365 nm). As noted above, the use of the band-pass
filter for excitation makes an accurate calculation of the
relative intensity of light absorbed by each of these dilute
solutions very difficult. Thus, the correlation between the
relative NO signals and the different absorptivities (estimated
at 365 nm, but relative differences would be smaller if
integrated over the entire excitation range) suggests that the
quantum yields for NO loss from these species are compa-
rable. This is consistent with the quantum yield values
determined above from changes in the optical spectra.
Therefore, the principal differences between these systems
in very dilute solutions are the greater absorptivities of III
and V owing to the presence of the light-absorbing antenna
tethered to the cyclam ring.
These experiments suggest that photoexcitation of the
pendant pyrene and anthracene chromophores is followed
by energy transfer to the respective dinitritochromium(III)
centers. The efficient NO labilization from the latter dem-
onstrates that the aromatic chromophores can act as antennas
for the photosensitization of these systems. Electron transfer
from the excited aromatic pendant group to the Cr(III) center
would be an alternative mechanism for quenching the
fluorescence from these chromophore; however, reduction
of the metal center to Cr(II) would lead to nitrite labilization
rather than NO release. Since the photochemistry of III and
V parallels that resulting from the direct excitation of the
metal-centered ligand field transitions of I,10 we conclude
that an energy transfer, rather than excited-state electron-
transfer, mechanism is the dominant source of the photo-
chemistry reported here.
Mass Spectral Studies of Photolysis Products. +ESI-
TOF mass spectroscopy was used to probe the transforma-
tions of the Cr(III) species that accompanied NO photo-
generation. For example, 365 nm photolysis of an aqueous
solution of III (100 µM) was monitored at 10 min intervals
over the course of 2 h by taking small aliquots (30 µL) that
were then diluted with 100 µL of H2O and injected into the
ESI-TOF instrument. Before photolysis, a large peak at m/z
562 consistent with the parent cation, trans-[Cr(mac)-
(ONO)2]+ (M+), was present. Over the course of the first 1
h, this peak disappears while new ones at m/z 533 (M+ -
29) and 504 (M+ - 58) appeared. Over the course of a
second 1 h, the peak at m/z 533 diminished while that at
m/z 504 intensified. No further changes in the mass spectra
were observed after the first 2 h for photolysis up to 21 h
(Supporting Information Figure S3). The spacing of the
hν
trans-CrV(L)(O)(ONO)2+ 98 trans-CrVI(L)(O)22+ + NO
(1)
5. Photoluminescence Studies. The luminescence spectra
of I-IV were recorded in 77 K (4:1 EtOH-MeOH) glasses
at solution concentrations of 2 mM in each case. No
phosphorescence from the Cr(III)-centered doublet ligand
field state was observed for any of the complexes regardless
of the excitation wavelength (355, 370, or 470 nm). This
contrasts with the easily observed doublet emission spectra
(λem ∼ 704 nm) for the analogous dichloro complexes trans-
[Cr(L)Cl2]Cl under similar conditions. For example, excita-
tion of trans-[Cr(cyclam)Cl2]Cl or trans-[Cr(mbc)Cl2]Cl in
low-temperature glasses at 470 nm leads to phosphor-
esecence,11,21 but no such emission is seen for quartet LF
(470 nm) or n-π* intraligand (355 nm) excitation of I or II
under analogous conditions. Thus, the latter complexes must
(19) Farrell, R. P.; Lay, P. A. Commun. Inorg. Chem. 1992, 13, 133-175.
(20) It should be noted that ESR experiments reported only in ref 18 clearly
indicated that the photolysis of trans-[Cr(cyclam)(ONO)2]+ (I) in
aerated aqueous solution leads to the formation of a chromium(V)
product trans-[Cr(cyclam)(O)(ONO)]+.
(21) Forster, L. S.; Mønsted, O. J. Phys. Chem. 1986, 90, 5131-5134.
Inorganic Chemistry, Vol. 44, No. 12, 2005 4163

DeRosa et al.
(λmon ) 420 nm) also showed bands (332, 347, 366, and
385 nm) very similar to the π-π* absorption spectra (336,
354, 372, and 392 nm, measured in aqueous solution) with
an intensity about 3 orders of magnitude larger than that of
III. Thus, coordination to the dinitritochromium(III) center
quenches this emission more than 99.9%, presumably via
energy transfer to the states responsible for the photochemical
cleavage of the nitrite O-N bond and NO formation. A
similar situation was observed with the dichloro analogues
trans-[Cr(mac)Cl2]Cl, namely, weak emission from the
anthracene chromophore about 0.1% as intense as that seen
for the free ligand under similar conditions.11 However, as
noted above, for the trans-dichloro complex, phosphorescence
from the Cr(III) doublet ligand field state was evident, while
this was apparently too weak to see for any of the trans-
dinitrito analogues.
Figure 8. Emission spectra of a dilute aqueous solutions of trans-[Cr-
(mac)(ONO)2]BF4 (III) (50 µM) and its respective free ligand, mac
(50 µM). λirr ) 360 nm.
The emission spectrum of the free chromophore 1-pyrene-
carboxylic acid was recorded for comparison to that of V.
The former displayed a strong emission with a λmax at
394 nm and a shoulder at 408 nm (λirr ) 340 nm), the
qualitative aspects of the spectrum being very similar to that
observed for V. As with the mac ligand, fluorescence from
the metal-free 1-pyrenecarboxylic acid chromophore was
much stronger than from V, although the ratio (∼15-fold)
was considerably smaller (Supporting Information Figure
S5). The excitation spectrum (λmon ) 420 nm) of the former
showed a intense, broad peak at 345 nm with a shoulder at
379 nm, shifted slightly from the π-π* absorption bands
(350 and 384 nm) (Supporting Information Figure S6). This
comparison suggests that ππ* excited states formed by direct
excitation of the pyrene chromophore in V are deactivated
(>90%) by energy transfer to the metal-centered excited
states; however, the process may be considerably less
efficient than seen with the anthracene derivative III. At this
stage, we speculate that the lower efficiency of the intra-
molecular energy-transfer process in V can be attributed to
the significantly greater distance between the aromatic
chromophore and the Cr(III) dinitrito center in V than in
III. From the standpoint of the goals of this paper, it is clear
that even in the former case, the overwhelming fraction of
the excitation localized on the antenna attached to the
macrocyclic cyclam ligand transfers energy to the metal
center, thereby sensitizing the photochemical reactions at that
site.
In summary, it has been clearly demonstrated that nitric
oxide can be photochemically released from these novel
chromium(III) dinitrito complexes with high quantum yields.
More importantly, it has been shown that such photochemical
release can occur via energy transfer from a pendant
chromophore to the chromium(III) metal center as demon-
strated with the anthracene and pyrene derivatives trans-
[Cr(mac)(ONO)2]+ and trans-[Cr(pbc)(ONO)2]+ resulting in
marked increase in the rate of photochemical NO release
owing to their greater absorbance at the irradiation wave-
lengths. These complexes provide proof-of-concept demon-
strations that such strategies might be applied to the design
of photochemically activated NO donors for biomedical
applications.
undergo efficient excited state deactivation by nonradiative
pathways not accessible to the dichloro complexes. Given
that chromium(III) dinitrito complexes display fairly large
quantum yields for NO release from the coordinated ONO-,10
this reaction pathway may be playing a significant role in
excited-state deactivation. Since the first step in Scheme 2
is rapidly reversible,10a re-formation of the CrIII-ONO entity
by the back-reaction of CrIVdO with NO trapped in the
matrix would be fast in low-temperature glasses and net
photoreaction might not be detected under these conditions.
The photophysical behavior of the anthracenyl and pyrenyl
derivatives trans-[Cr(mac)(ONO)2]BF4 (III) and trans-
[Cr(pbc)(ONO)2]BF4 (V) are somewhat different. Both
display weak luminescence even from dilute ambient-
temperature solutions (50 µM in water and 30 µM in
(1:1 v:v) acetonitrile-H2O, respectively). The weak emission
from III (λirr ) 360 nm) was characteristic anthracene-type
fluorescence with maxima at 397, 414, 440, and 464 nm
(Figure 8). The excitation spectrum of this solution (λmon
)
420 nm) displayed peaks at 334, 349, 368, and 386 nm nearly
matching the π-π* absorption bands of the tethered an-
thracene (336, 354, 372, and 392 nm, respectively) (Sup-
porting Information Figure S4). A much more intense broad
emission centered at 395 nm with a shoulder at 408 nm was
observed from the ambient solutions of the pyrene derivative
V (λirr ) 340 nm). The excitation spectrum displayed an
intense, broad band centered at approximately 346 nm with
a shoulder at 380 nm similar to the π-π* absorption bands
of the appended pyrene (352 and 386 nm). Monitoring a
solution of V for several days showed no changes in the
spectroscopic properties; thus, the ester linkage connecting
the pyrene carboxylate to the rest of the complex appears to
be extremely stable.
The emission and excitation spectra for the free mac ligand
(mac ) 5,7-dimethyl-6-(9′-methylanthracyl)-1,4,8,11-tetra-
azacyclotetradecane) (50 mM in aqueous solution) are
presented in Figures 8 and S4, respectively. Emission from
the free ligand (λirr ) 360 nm) is extremely strong, with
bands nearly the same as III (394, 414, 438, and 464 nm)
but >1000-fold more intense. The excitation spectrum
4164 Inorganic Chemistry, Vol. 44, No. 12, 2005

Cr(III) Complexes for Nitric Oxide Generation
Supporting Information Available: Listings of complete
structure refinement details, bond lengths and angles, aniso-
tropic displacement parameters for non-hydrogen atoms, and
hydrogen coordinates and isotropic displacement parameters.
This material is available free of charge via the Internet at
http://pubs.acs.org.
Acknowledgment. These studies were supported by the
U.S. National Science Foundation (Grants CHE 0095144 and
CHE-0352650). The mass spectrometry instrumentation
(ESI/TOF) was purchased with the support of an ARO award
No. DAAD19-00-1-0026. We thank Malcolm DeLeo (Clorox
Corp.) and Ryan Absalonson (UCSB) for intellectual and
technical input. We also thank Dr. Ziad Taha for his
generosity in providing a nitric oxide electrochemical sensor
to advance this research.
IC048311O
Inorganic Chemistry, Vol. 44, No. 12, 2005 4165