Near-infrared light activated release of nitric oxide from designed photoactive manganese nitrosyls: Strategy, design, and potential as NO donors

Article abstract of DOI:10.1021/ja710265j

Two new manganese complexes derived from the pentadentate ligand N,N-bis(2-pyridylmethyl)-amine-N-ethyl-2-quinoline-2-carboxamide, PaPy ₂QH, where H is dissociable proton), namely, [Mn(PaPy ₂Q)-(NO)]ClO₄ (2) and [Mn(PaPy₂Q)(OH)]ClO ₄ (3), have been synthesized and structurally characterized. The Mn(III) complex [Mn(PaPy₂Q)(OH)]ClO₄ (3), though insensitive to dioxygen, reacts with nitric oxide (NO) to afford the nitrosyl complex [Mn(PaPy₂Q)(NO)]ClO₄ (2) via reductive nitrosylation. This diamagnetic {Mn-NO}⁶ nitrosyl exhibits ν_NO at 1725 cm^-1 and is highly soluble in water, with λ_max at 500 and 670 nm. Exposure of solutions of 2 to near-infrared (NIR) light (810 nm, 4 mW) results in bleaching of the maroon solution and detection of free NO by an NO-sensitive electrode. The quantum yield of 2 (Φ = 0.694 ± 0.010, λ_irr = 550 nm, H₂O) is much enhanced over the first generation {Mn-NO}⁶ nitrosyl derived from analogous polypyridine ligand, namely, [Mn(PaPy ₃)(NO)]ClO₄ (1, Φ= 0.385 ± 0.010, λ_irr = 550 nm, H₂O), reported by this group in a previous account. Although quite active in the visible range (500-600 nm), 1 exhibits very little photoactivity under NIR light. Both 1 and 2 have been incorporated into sol-gel (SG) matrices to obtain nitrosyl-polymer composites 1·SG and 2·SG. The NO-donating capacities of the polyurethane-coated hybrid materials 1·HM and 2·HM have been determined. 2·HM has been used to transfer NO to reduced myoglobin with 780 nm light. The various strategies for synthesizing photosensitive metal nitrosyls have been discussed to establish the merits of the present approach. The results of the present study confirm that proper ligand design is a very effective way to isolate photoactive manganese nitrosyls that could be used to deliver NO to biological targets under the control of NIR light.

Full text of DOI:10.1021/ja710265j

Published on Web 03/12/2008
Near-Infrared Light Activated Release of Nitric Oxide from
Designed Photoactive Manganese Nitrosyls: Strategy,
Design, and Potential as NO Donors
Aura A. Eroy-Reveles, Yvonne Leung, Christine M. Beavers,
Marilyn M. Olmstead, and Pradip K. Mascharak*
Department of Chemistry and Biochemistry, UniVersity of California, Santa Cruz, California
95064, and the Department of Chemistry, UniVersity of California, DaVis, California, California
95616
Received November 12, 2007; E-mail: pradip@chemistry.ucsc.edu
Abstract: Two new manganese complexes derived from the pentadentate ligand N,N-bis(2-pyridylmethyl)-
amine-N-ethyl-2-quinoline-2-carboxamide, PaPy2QH, where H is dissociable proton), namely, [Mn(PaPy2Q)-
(NO)]ClO4 (2) and [Mn(PaPy2Q)(OH)]ClO4 (3), have been synthesized and structurally characterized. The
Mn(III) complex [Mn(PaPy2Q)(OH)]ClO4 (3), though insensitive to dioxygen, reacts with nitric oxide (NO) to
afford the nitrosyl complex [Mn(PaPy2Q)(NO)]ClO4 (2) via reductive nitrosylation. This diamagnetic {Mn-
NO}6 nitrosyl exhibits νNO at 1725 cm-1 and is highly soluble in water, with λmax at 500 and 670 nm. Exposure
of solutions of 2 to near-infrared (NIR) light (810 nm, 4 mW) results in bleaching of the maroon solution
and detection of free NO by an NO-sensitive electrode. The quantum yield of 2 (Φ ) 0.694 ( 0.010, λirr
)
550 nm, H2O) is much enhanced over the first generation {Mn-NO}6 nitrosyl derived from analogous
polypyridine ligand, namely, [Mn(PaPy3)(NO)]ClO4 (1, Φ ) 0.385 ( 0.010, λirr ) 550 nm, H2O), reported
by this group in a previous account. Although quite active in the visible range (500-600 nm), 1 exhibits
very little photoactivity under NIR light. Both 1 and 2 have been incorporated into sol-gel (SG) matrices
to obtain nitrosyl-polymer composites 1‚SG and 2‚SG. The NO-donating capacities of the polyurethane-
coated hybrid materials 1‚HM and 2‚HM have been determined. 2‚HM has been used to transfer NO to
reduced myoglobin with 780 nm light. The various strategies for synthesizing photosensitive metal nitrosyls
have been discussed to establish the merits of the present approach. The results of the present study
confirm that proper ligand design is a very effective way to isolate photoactive manganese nitrosyls that
could be used to deliver NO to biological targets under the control of NIR light.
Introduction
mission, inhibition of platelet aggregation, cell-mediated immune
response, antimicrobial activity, and cell death.2 The biological
In recent years, nitric oxide (NO) has been recognized as a
key mediator in a diverse array of physiological and pathological
responses.1 This odd-electron diatomic gaseous molecule,
produced endogenously by nitric oxide synthase (NOS), acts
as a signaling molecule to regulate blood pressure, neurotrans-
activity of NO depends heavily on the dose and duration of
exposure, as well as on the cellular sensitivity to NO. For
example, relatively low concentrations (2 to 300 nM) of NO
produced by the constitutive isoforms of NOS (nNOS and
eNOS) are required for its neurological and vascular function.3
Much larger concentrations (low mM) of NO, such as those
produced by activated macrophages via the inducible isoform
of NOS (iNOS), however, lead to cytotoxicity.4,5 Furthermore,
inhibition of respiratory complexes, DNA damage and modi-
fication, gene mutation, and cell apoptosis can all be induced
by high doses of NO, resulting in tumor regression and inhibition
of metastasis.6
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9
10.1021/ja710265j CCC: $40.75 © 2008 American Chemical Society
J. AM. CHEM. SOC. 2008, 130, 4447-4458
4447

A R T I C L E S
Eroy-Reveles et al.
delivering NO (NO donors) on demand.7 To date, a variety of
NO donors, both organic and metal-based, have been synthe-
sized. These exogenous NO sources release NO via enzymatic
pathways as well as by stimuli such as change in pH, heat, and
light.8 Among the organic NO donors, selected diazeniumdi-
olates (NONOates) and S-nitrosothiols (such as S-nitrosoglu-
tathione (GSNO) and S-nitroso-N-acetylpenicillamine SNAP)
have been shown to induce apoptosis in a variety of cell
types.9,10 NO donors that release NO photochemically have
generated much interest because they allow localized release
of NO and could be used for photodynamic therapy (PDT) of
cancer cells.11,12 It has been demonstrated that cells subjected
to PDT produce NO.13 Because NO reacts with various reactive
oxygen species generated by PDT, it has been suggested that
NO contributes to the effective outcome of PDT treatment.14
In recent years, interest in metal NO complexes (nitrosyls) has
been renewed following the successful use of sodium nitro-
prusside (Na2[Fe(CN)5NO], SNP) as a NO donor drug to control
blood pressure during hypertensive episodes.15 Interestingly,
nitrosyls like SNP and Roussin’s salts (iron-sulfur clusters that
store multiple equivalents of NO) release NO upon illumination
with light (300-500 nm).16,17 However, low quantum yields
(Φ) and problems associated with ancillary ligands (such as
cyanide in case of SNP) limit the use of such nitrosyls in PDT.18
We have recently focused our attention on designed metal
nitrosyls that rapidly release NO upon illumination with low-
intensity light of low frequency.19-29 In such attempts, we have
employed nonporphyrin polydentate ligands30 to avoid problems
associated with rapid NO recombination reactions (commonly
observed with metal nitrosyls derived from porphyrin ligands)31,32
and toxicity arising from ancillary ligands.17 Careful consider-
ation of several metric, spectroscopic, and redox parameters (as
discussed in our previous papers) led us to the designed ligand
PaPy3H (N,N-bis(2-pyridylmethyl)amine-N-ethyl-2-pyridine-2-
carboxamide). This pentadentate ligand allowed us to synthesize
the first non-heme diamagnetic {Fe-NO}6 nitrosyl33 [Fe-
(PaPy3)(NO)](ClO4)2 that rapidly releases NO upon illumination
with 5-10 mW of Visible light (500-600 nm) in solvents like
acetonitrile (Φ ) 0.18).19,20 Our results strongly suggest that
the presence of the deprotonated carboxamido nitrogen (a strong
σ-donating negatively charged donor) trans to the bound NO
in this nitrosyl is crucial for its photolability.21 Although [Fe-
(PaPy3)(NO)](ClO4)2 exhibits excellent NO photolability, its
stability in biological media is inadequate.22,23 To circumvent
this problem, we next synthesized the corresponding ruthenium
nitrosyl, namely, [Ru(PaPy3)(NO)](BF4)2.24 This nitrosyl is
soluble in water and very stable in aqueous solution (pH range
5-9), a prerequisite for biological use. Indeed, we have
employed this nitrosyl to deliver NO to biological targets such
as reduced myoglobin and cytochrome c oxidase.24,34 This
success, however, came with a compromise. [Ru(PaPy3)(NO)]-
(BF4)2 releases NO only when exposed to low-intensity UV light
(5-10 mW, 300-450 nm); no appreciable NO photolability is
observed with visible light. Although the intensity of UV light
required for NO photolability is very low for [Ru(PaPy3)(NO)]-
(BF4)2 compared to other UV-sensitive ruthenium nitrosyls,35,36
the need for an efficient NO donor that operates under visible
light remained open. The quest came to a decent stop when we
synthesized the manganese nitrosyl, [Mn(PaPy3)(NO)]ClO4
(1).28 This {Mn-NO}6 nitrosyl is stable in aqueous buffer and
rapidly releases NO when exposed to Visible light (500-650
nm), affording the Mn(II) aqua species [Mn(PaPy3)(H2O)]ClO4.
We have been able to employ 1 as a photosensitive NO donor
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9
4448 J. AM. CHEM. SOC. VOL. 130, NO. 13, 2008

Photoactive Manganese Nitrosyls as NO Donors
A R T I C L E S
Scheme 1. Synthesis of [Mn(PaPy2Q)(NO)]ClO4 (2)
to transfer NO to enzymes such as papain,37 cytochrome c
oxidase,34 and soluble guanylate cyclase.38 In addition, 1 elicits
light-dependent increases of cGMP in smooth muscle cells and
vasorelaxation of rat aortic smooth muscle tissue.38 Finally, the
remarkable stability of 1 allows easy incorporation of 1 into a
sol-gel matrix, resulting in a convenient, biocompatible NO
releasing material that can deliver NO to selective tissues under
the strict control of light.39
To utilize such material in PDT of skin cancer, one has to
make the NO donor sensitive to near-infrared (NIR) light
because light penetration through mammalian tissue is mostly
limited to the 700-1100 nm region.40,41 It is therefore desirable
that the wavelength(s) of the light required for the activation
of the photochemotherapeutics falls in this optical window. To
make 1 more sensitive to lights of longer wavelengths, we
sought further alteration of the ligand frame rather than a change
of the metal center. Previously, we have shown that more
extended conjugation in a similar ligand frame affords metal
nitrosyls that exhibit significant red-shifts in their photobands.25
Following that line of thought, we have now synthesized a new
ligand, N,N-bis(2-pyridylmethyl)amine-N-ethyl-2-quinoline-2-
carboxamide (PaPy2QH, where H is dissociable proton), in
which the pyridyl-carboxamide group of PaPy3H is replaced
by a quinolyl-carboxamide moiety.
purification. Acetonitrile (MeCN), ethanol (EtOH), methanol (MeOH),
and diethyl ether (Et2O) were obtained from Fischer Chemical Co. and
distilled from CaH2, Mg(OEt)2, Mg(OMe)2, and sodium/benzophenone,
respectively, prior to use. Triethylamine (Et3N), ethylene diamine, and
pyridine were purchased from Aldrich Chemical Co. and distilled from
sodium prior to use. Nitric oxide gas was purchased from Spectra Gases
and purified from higher oxides by passage through a long KOH column
before use in reactions. Tecoflex SG-80A polyurethane was a gift from
Noveon, Inc. Elemental analyses were performed by Desert Analytics,
Inc.
Synthesis Safety Note. Transition metal perchlorates should be
handled with great caution and be prepared in small quantities as metal
perchlorates are hazardous and may explode upon heating.
Synthesis of the Compounds. The Mn(III) starting material [Mn-
(DMF)6](ClO4)3,42 PaPy3H,30 and [Mn(PaPy3)(NO)]ClO4 were syn-
28
thesized by following the published procedures. All reactions were
carried out in an inert N2 atmosphere.
Ethylquinaldate. A mixture of 2.0 g (11.57 mmol) of quinaldic acid,
40 mL of EtOH, and 1.5 mL of sulfuric acid was heated to reflux for
24 h. The EtOH was then removed and the remaining solution was
neutralized with 20 mL of saturated sodium bicarbonate solution. The
product was extracted with 50 mL of CH2Cl2 and washed successively
with deionized H2O (3 × 60 mL). Next, the CH2Cl2 solution was dried
over anhydrous MgSO4 and filtered. The product was obtained as a
yellow oil following removal of the solvent in vacuo (1.83 g, 85%
1
yield). H NMR (298 K, CDCl3, 500 MHz, δ, ppm from TMS): 1.50
(t, 3H); 4.57 (q, 2H); 7.65 (m, 1H); 7.79 (m, 1H); 7.88 (d, 1H); 8.20
(m, 1H); 8.31 (m, 2H). ESI-MS m/z 202.09 [M + H]+.
N-(2-Aminoethyl)-2-quinolinecarboxamide. A mixture of 1.83 g
(9.09 mmol) of ethylquinaldate, 2.73 g (45.47 mmol) of ethylenedi-
amine, and 1.4 mL of pyridine was heated at 100 °C for 4 h. Next, the
solvent was removed at reduced pressure and the remaining oil was
acidified to pH 5 with concentrated HCl. The solution was washed
with CH2Cl2 (2 × 100 mL). The aqueous layer was made basic with
30 mL of pH 10 NaOH solution and was extracted with CH2Cl2 (4 ×
75 mL). The organic layer was then dried over anhydrous MgSO4 and
filtered. Removal of the solvent afforded the product as a yellow oil
(1.47 g, 75% yield). 1H NMR (298 K, CDCl3, 500 MHz, δ, ppm from
TMS): 1.38 (s, 2H); 3.02 (t, 2H); 3.62 (q, 2H); 7.62 (m, 1H); 7.77 (m,
1H); 7.88 (m, 1H); 8.12 (d, 1H); 8.32 (s, 2H); 8.54 (s, 1H). ESI-MS
m/z 216.09 [M + H]+.
In this paper, we report the synthesis, structure, and spec-
troscopic properties of the {Mn-NO}6 nitrosyl [Mn(PaPy2Q)-
(NO)]ClO4 (2; Scheme 1), derived from this modified penta-
dentate ligand. In addition, the photochemical properties of 1
and 2 have been compared to show that 2 is truly sensitive to
NIR light. To the best of our knowledge, 2 is the first metal
nitrosyl that releases NO upon exposure to NIR light of low
intensity (<5 mW). We also report that 2 has been encapsulated
in a sol-gel matrix and the nitrosyl-polymer hybrid 2‚HM
transfers NO to reduced myoglobin under NIR light (780 nm)
quite readily.
N,N-Bis(2-pyridylmethyl)amine-N-ethyl-2-quinolinecarboxam-
ide (PaPy2QH). A mixture of 1.47 g (6.83 mmol) of N-(2-aminoethyl)-
2-quinolinecarboxamide, 2.24 g (13.66 mmol) of 2-(chloromethyl)-
pyridine hydrochloride dissolved in 3.6 mL of deionized H2O, and 2.8
mL of 10 M NaOH solution was stirred at 70 °C for 4 h. Then 45 mL
of saturated NaOH solution was added to the mixture followed by
extraction with CH2Cl2 until the CH2Cl2 layer was slightly yellow in
color (4 × 75 mL). The brown solution was washed successively with
an aqueous HCl solution (pH 5, 7 × 130 mL), saturated brine solution
(3 × 100 mL), and 10 M NaOH solution (3 × 100 mL). Next, the
CH2Cl2 solution was dried over anhydrous MgSO4 and filtered. Removal
of the solvent afforded the ligand as a dark brown oil (2.16 g, 80%
Experimental Section
Quinaldic acid, 2-(chloromethyl)-pyridine hydrochloride, Mn(II)
perchlorate hexahydrate, and horse heart myoglobin (Mb) were
purchased from Aldrich Chemical Co. and used without further
(37) Afshar, R. K.; Patra, A. K.; Mascharak, P. K. J. Inorg. Biochem. 2005, 99,
1458-1464.
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J.; Fukuto, J. M.; Mascharak, P. K. J. Med. Chem. 2006, 49, 7325-7330.
(39) Eroy-Reveles, A. A.; Leung, Y.; Mascharak, P. K. J. Am. Chem. Soc. 2006,
128, 7166-7167.
1
yield). H NMR (298 K, CDCl3, 500 MHz, δ, ppm from TMS): 2.91
(t, 2H); 3.68 (q, 2H); 3.97 (s, 4H); 7.10 (m, 2H); 7.52 (m, 2H); 7.68
(m, 3H); 7.83 (m, 1H); 7.94 (m, 1H); 8.18 (d, 1H); 8.33 (q, 2H); 8.53
(40) (a) Hawrysz, D. J.; Sevick-Muraca, E. M. Neoplasia 2000, 2, 388-417.
(b) Anderson, R. R.; Parrish, J. A. J. InVest. Dermatol. 1981, 77, 13-19.
(41) Weissleder, R.; Ntziachristos, V. Nat. Med. 2003, 9, 123 - 128.
(42) Pravakaran, C. P.; Patel, C. C. J. Inorg. Nucl. Chem. 1968, 30, 867.
9
J. AM. CHEM. SOC. VOL. 130, NO. 13, 2008 4449

A R T I C L E S
Eroy-Reveles et al.
Table 1. Summary of Crystal Data, Intensity Collection, and
Structural Refinement Parameters for [Mn(PaPy2Q)(NO)]ClO4 (2)
and [Mn(PaPy2Q)(OH)]ClO4‚CH3CN (3‚CH3CN)
(m, 2H); 8.97 (s, 1H). Selected IR frequency (NaCl plate) νCO ) 1660
cm-1. ESI-MS m/z 398.21 [M + H]+.
[Mn(PaPy2Q)(OH)]ClO4‚CH3CN (3‚CH3CN). A batch of 0.112 g
(1.1 mmol) of Et3N was added dropwise to a solution of 0.200 g (0.5
mmol) of PaPy2QH dissolved in 15 mL of MeOH and the reaction
mixture was stirred for 2 h. Next, a slurry of 0.398 g (0.50 mmol) of
[Mn(DMF)6](ClO4)3 in 5 mL of MeOH was slowly added dropwise
and the reaction mixture turned wine red. Finally, a batch of 20 µL
(1.1 mmol) of H2O was added and the solution was stored at -20 °C.
After 24 h, the burgundy microcrystalline product (3) was collected
on a sintered glass filter, washed with Et2O, and dried under vacuum
(0.200 g, 70% yield). Slow diffusion of Et2O into a solution of 3 in
CH3CN afforded crystals of 3‚CH3CN, which were suitable for
crystallographic analysis. Anal. Calcd for C26H26ClMnN6O6 (3‚CH3-
CN): C, 51.29; H, 4.30; N, 13.80. Found: C, 51.34; H, 4.32; N, 13.75.
Selected IR frequencies (KBr disk, cm-1): 3382 (w), 1630 (vs), 1606
(s), 1566 (m), 1444 (m), 1394 (m), 1142 (m), 1086 (vs), 1023 (m),
765 (s), 636 (s), 624 (s). Electronic absorption spectrum in MeCN,
λmax (nm, ꢀ (M-1 cm-1)): 485 (280), 740 (120); in H2O, 470 (320),
800 (110). µeff (298 K, polycryst) ) 4.92 µB.
2
3‚CH3CN
formula
molecular weight
cryst color, habit
T, K
cryst syst
space group
a, Å
C25H26ClMnN6O7
612.91
red needle
90(2)
C26H26ClMnN6O6
608.92
light green plates
90(2)
monoclinic
P21
8.059(2)
14.320(4)
11.900(4)
90
105.661(10)°
90
1322.3(6)
2
1.529
0.654
triclinic
P-1
7.193(3)
14.147(6)
14.691(6)
63.558(6)
77.297(6)
81.994(6)
1304.4(9)
2
b, Å
c, Å
R, deg
â, deg
γ, deg
V, Å3
Z
d
cald, g cm-3
1.665
0.856
1.040
0.0805
abs coeff, mm-1
GOFa on F2
R1b %
0.986
0.0393
0.0702
wR2c %
0.1514
[Mn(PaPy2Q)(H2O)]ClO4 (4). A batch of 200 mg (0.50 mmol)
PaPy2QH was dissolved in EtOH (15 mL) and degassed thoroughly.
Next, 15 mg (0.60 mmol) of NaH was added and the solution was
stirred for 2 h. Finally, 182 mg (0.50 mmol) of [Mn(H2O)6](ClO4)2
was added as a solid to the yellow solution. Within 5 min of stirring,
[Mn(PaPy2Q)(H2O)]ClO4 precipitated out as a beige precipitate, which
was collected on a sintered glass funnel and dried under vacuum for 4
h (0.150 g, 52% yield). Anal. Calcd for C24H24ClMnN5O6 (4): C, 50.67;
H, 4.25; N, 12.31. Found: C, 50.65; H, 4.31; N, 12.28. Selected IR
bands (KBr disk, cm-1): 3425 (m, br), 1605 (vs), 1565 (m), 1441 (m),
1370 (s), 1330 (m), 1090 (vs), 1015 (m), 770 (m), 624 (s). X-band
EPR spectrum (289 K, polycrystal): strong broad signal with g ≈ 2.
[Mn(PaPy2Q)(NO)]ClO4 (2). Method A. A batch of 3 (0.100 g,
1.6 mmol) was dissolved in 20 mL of a MeCN/MeOH mixture (2:18)
and thoroughly degassed. The Schlenk flask was then wrapped in Al
foil and NO gas was passed over the solution for 10 min. The maroon
solution was stored under NO pressure for 12 h while stirring at room
temperature. Finally, the solution was placed in -20 °C for 24 h, upon
which dark green crystals of [Mn(PaPy2Q)(NO)]ClO4 (2), suitable for
X-ray diffraction, separated out of solution (0.050 g, 53% yield). Anal.
Calcd for C24H22ClMnN6O6 (2): C, 49.63; H, 3.82; N, 14.47. Found:
C, 49.59; H, 3.80; N, 14.51. Selected IR frequencies (KBr disk, cm-1):
3427 (w), 1725 (vs), 1634 (vs), 1608 (m), 1450 (m), 1403 (m), 1096
(vs), 1028 (m), 766 (s), 622 (s). Electronic absorption spectrum in
MeCN, λmax (nm, ꢀ (M-1 cm-1)): 240 (29500), 290 (7700), 495 (2030),
650 (420). Electronic absorption spectrum in H2O, λmax (nm, ꢀ (M-1
cm-1)): 240 (25150), 280 (6120), 310 (5250), 500 (1725), 670 (450).
1H NMR (298 K, CD3CN, 500 MHz, δ, ppm from TMS): 9.37 (d,
1H), 8.55 (s, 1H), 8.10 (dd, 3H), 7.83 (s, 3H), 7.44 (s, 2H), 7.05 (s,
2H), 6.44 (s, 2H), 4.43 (d, 4H), 3.31 (s, 2H), 3.22 (s, 2H) ppm.
a GOF ) [Σ[w(F°2 - Fc )2]/(M - N)]1/2 (M ) number of reflections, N
2
) number of parameters refined). b R1 ) Σ×ef×efF°×ef -×ef Fc×ef×ef/
2
Σ×efF°×ef. c wR2 ) [Σ[w(F°2 - Fc )2]/Σ[w(F°2)2]]1/2
.
to prepare 1‚SG and 2‚SG without the addition of alcohol.43 A batch
of 7.5 mL of tetramethylorthosilicate (TMOS) and 4.0 mL H2O was
stirred for 30 min until the two-phase system formed a homogeneous
solution. At this point, the TMOS solution was partitioned into four
test tubes or cuvettes (2.75 mL in each) and allowed to cool to room
temperature. In the dark, a batch of 2 mg of 1 or 2 was dissolved in a
300 µL mixture of H2O and MeCN (1:1). The highly colored solution
was added to the TMOS solution and allowed to gel in the dark. The
desired transparent gel was formed within 3 h. The test tubes were
then carefully broken and samples of 1‚SG or 2‚SG were collected.
2‚HM. Cylinders of the nitrosyl-TMOS gel polymer 2‚SG were cut
into thin slices, and the disks were coated with a solution of Tecoflex
SG-80A polyurethane (2.0 g) dissolved in 20 mL of THF and dried
for 30 min (in the dark). The coating process was repeated three times
and the final disks of hybrid material were dried for 4 h in the dark.
1‚HM was also prepared following the procedure described for 2‚
HM.
X-ray Data Collection and Structure Solution and Refinement.
Diffraction data for single crystals of 2 and 3 were collected at 90 K
on a Bruker APEX II diffractometer. Mo KR (0.717073 Å) radiation
was used, and the data were corrected for absorption effects. The
structures were solved by direct methods (SHELXS-97). All nonhy-
drogen atoms were refined with anisotropic displacement parameters,
and hydrogen atoms were added geometrically and refined with the
use of a riding model. Machine parameters, crystal data, and data
collection parameters for complexes 2 and 3 are summarized in Table
1, while selected bond distances and angles are listed in Table 2.
Complete crystallographic data for [Mn(PaPy2Q)(NO)]ClO4 (2) and
[Mn(PaPy2Q)(OH)]ClO4‚CH3CN (3‚CH3CN) have been submitted as
Supporting Information.
Method B. A batch of 15 mL of MeCN was thoroughly degassed
by freeze-pump-thaw cycles. To the frozen MeCN, a batch of 0.100
g (1.6 mmol) of 4 was added and the frozen solution was allowed to
warm to room temperature. Next, the Schlenk flask was covered in Al
foil and NO gas was passed over the yellow slurry for 10 min until the
solution turned maroon in color. The solution was stirred for 12 h.
Finally, the solvent was removed by reduced pressure, and the solid
was redissolved in 10 mL of a mixture of MeCN and MeOH (2:18). A
portion of 15 mL of Et2O was added and the mixture was stored at
-20 °C for 48 h. The dark green needles were filtered and washed
with Et2O (0.040 g, 42% yield).
Other Physical Measurements. 1H NMR spectra were recorded at
298 K on a Bruker 500 MHz spectrometer. Purity of the synthesized
organic compounds was checked by liquid chromatography tandem
mass spectrometry (LC/MS) with the aid of a Thermo Finnigan LTQ
set up. Absorption spectra were recorded on a Varian Cary 50
spectrophotometer. Real-time detection of NO in solution under aerobic
conditions was monitored with an inNO Nitric Oxide Measuring System
(Innovative Instruments, Inc.) using an amiNO-2000 electrode.
Photochemical Experiments. Continuous-wave photolysis studies
were performed using a Newport Oriel Apex Illuminator (150 W xenon
1‚SG and 2‚SG. We previously reported the synthesis of 1‚SG from
tetraethylorthosilicate (TEOS), EtOH, H2O (pH 5 with HClO4), and 1.
In the present study, the method of Avnir and Kaufman was followed
(43) Avnir, D.; Kaufman, V. R. J. Non-Cryst. Solids 1987, 192, 180-182.
9
4450 J. AM. CHEM. SOC. VOL. 130, NO. 13, 2008

Photoactive Manganese Nitrosyls as NO Donors
A R T I C L E S
Table 2. Selected Bond Distances (Å) and Bond Angles (deg) for
[Mn(PaPy2Q)(NO)]ClO4 (2) and [Mn(PaPy2Q)(OH)]ClO4‚CH3CN
(3‚CH3CN)
NO Transfer to Reduced Myoglobin (Mb). All manipulations of
Mb were monitored by electronic absorption spectroscopy. Reduced
Mb was prepared from metMb in 20 mM phosphate buffer (pH 7.5)
by addition of dithionite (∼1.2 equiv). Then a pellet of 2‚HM was
placed in the cuvette and the spectrum was taken after 10 min to ensure
that Mb was still reduced. Finally, monochromatic light of 780 nm
(40 mW, continuous wave diode laser, IR laser system, Intelite, Inc.)
was used to illuminate the sample and transfer NO to reduced Mb.
2
3‚CH3CN
Mn-N1
Mn-N2
Mn-N3
Mn-N4
Mn-N5
Mn-N6
2.087(3)
1.956(3)
2.066(3)
2.062(3)
2.033(3)
1.678(3)
2.1945(19)
1.9680(18)
2.2415(19)
2.138(2)
2.171(2)
Results and Discussion
Mn-O2
1.8180(16)
0.79(3)
O2-H2
Syntheses. In our continuing effort toward synthesis of
photolabile metal nitrosyls derived from designed ligands with
carboxamide groups, we have previously discovered that addi-
tion of conjugated ring systems to ligand frames often shifts
the photoband of the resulting nitrosyls to a lower-energy region.
For example, when the two pyridine donors of the 1,2-bis-
(pyridine-2-carboxamide)-4,5-dimethylbenzene (Me2bpbH2) ligand
are replaced with quinoline moieties, the resulting 1,2-bis-
(quinaldine-2-carboxamide)-4,5-dimethylbenzene (Me2bqbH2)
ligand affords NO complexes with red-shifted photobands. The
extent of red shift of the visible bands of the metal nitrosyls
with these two ligands varies with the metal center; in the case
of ruthenium, [Ru(Me2bqb)(NO)Cl] exhibits its absorption band
with λmax at 465 nm, while analogous [Ru(Me2bpb)(NO)Cl]
displays its band with λmax at 400 nm.25 A similar principle has
been adopted in the design of the pentadentate ligand N,N-bis-
(2-pyridylmethyl)amine-N-ethyl-2-quinoline-2-carboxamide(PaPy2-
QH, H is dissociable proton) used in the present study. PaPy2QH
has been synthesized in 80% yield via coupling of N-(2-
aminoethyl)-2-quinolinecarboxamide (formed in reaction be-
tween ethylquinaldate and ethylenediamine) with 2 equiv of
2-(aminomethyl)-pyridine in H2O (pH 10, made basic with
NaOH).
The desired {Mn-NO}6 nitrosyl [Mn(PaPy2Q)(NO)]ClO4 (2)
has been synthesized in two distinctly different ways. In our
previous work with PaPy3H ligand, we discovered that Mn(III)
complexes of the type [Mn(PaPy3)(B)]+ (where B ) a basic
ligand such phenolate or benzoate) undergo reductive nitrosy-
lation45 when reacted with excess NO and afford 1 in high
yield.29 This reactivity appears to be a general one and, indeed,
the Mn(III) complex [Mn(PaPy2Q)(OH)]ClO4 (3) allows ready
entry to the nitrosyl chemistry in the present case. Addition of
[Mn(DMF)6](ClO4)3 to a mixture of PaPy2QH and NEt3 (1:2)
in aqueous MeOH affords crystalline 3 in high yield. In this
complex, the deprotonated PaPy2Q- ligand is coordinated to
the Mn(III) center along with one hydroxide (vide infra).
Coordination of the deprotonated carboxamido nitrogen to the
high-spin Mn(III) center (S ) 2) in 3 is indicated by shift in
the position of νCO to lower energy (1630 cm-1 compared to
1660 cm-1 for the free ligand). When purified NO gas is passed
through a solution of 3 in MeCN, the purple color of the solution
(λmax ) 485 and 740 nm) turns maroon (λmax ) 495 and 650
nm), which upon proper workup affords the diamagnetic {Mn-
NO}6 nitrosyl [Mn(PaPy2Q)(NO)]ClO4 (2).
N6-O2
1.237(18)
1.243(4)
1.310(5)
O1-C10
1.253(2)
1.328(3)
116.3(19)
174.20(7)
N2-C10
Mn-O2-H2
O2-Mn-N2
Mn-N6-O2
N2-Mn-N6
N1-Mn-N2
N1-Mn-N3
N1-Mn-N4
N1-Mn-N5
N2-Mn-N3
N2-Mn-N4
N2-Mn-N5
N3-Mn-N4
N3-Mn-N5
N3-Mn-O2
N3-Mn-N6
N4-Mn-N5
N4-Mn-O2
N4-Mn-N6
N5-Mn-O2
N5-Mn-N6
171.5(8)
174.54(13)
78.88(12)
160.08(12)
95.45(12)
100.54(12)
81.83(12)
91.69(12)
84.99(12)
80.15(12)
82.56(12)
77.60(7)
157.28(7)
106.78(7)
99.48(7)
80.77(7)
83.78(7)
95.31(7)
77.45(7)
75.61(7)
102.60(7)
94.74(13)
162.69(12)
152.82(7)
92.31(7)
91.91(13)
90.36(13)
90.12(7)
lamp) equipped with an Oriel 1/8 m Cornerstone Monochromator. The
intensity of light was checked prior to each experiment with a Coherent
Field Max II-T0 Laser Power Meter. Known concentrations of the
samples were prepared under dim light and protected from extraneous
light. All irradiations were performed under aerated conditions. Standard
actinometry using Reinecke’s salt was employed to calibrate the light
source at various wavelengths.44 The light intensity for the photolysis
experiments ranged from 1.0 × 10-5 to 1.5 × 10-5 Ein L-1 s-1. For
quantum yield measurements, a 2.8 mM solution of 1 or 2 was prepared
and placed in a 10 × 4 mm quartz cuvette. The absorbance along the
10 mm path was greater than 2.0 at the desired wavelength, ensuring
that >99% of the incident light was absorbed. The sample was irradiated
with monochromatic light (<5 mW) for defined time intervals. The
photolysis was monitored by recording the electronic absorption
spectrum along the 4 mm path of the cuvette at an appropriate
wavelength for maximal change in the absorption spectrum. For
example, aqueous solutions of 2 were monitored at 670 nm. Because
the photoproduct does not exhibit any absorption in the visible region,
complete loss of absorption at both 500 and 670 nm was taken as the
endpoint of the photolysis (100% conversion to photoproduct).
Kinetic Studies. The rates of NO release were measured by
recording the electronic absorption spectrum of 1 or 2 in MeCN and
H2O (<2 mM, 1.5 mL) and monitoring the loss of absorbance at an
appropriate wavelength of samples exposed to monochromatic light
(of selected wavelengths, power range 2-5 mW) for defined intervals.
The plots of concentration versus time were first fitted to the three
parameter exponential equation C(t) ) C∞ + (C0 - C∞){exp(-kNOt)},
where C0 and C∞ are the initial and final concentrations, respectively.
The apparent rate constant values of NO loss (kNO) were then calculated
from the ln(C) versus time plot for the various NO donors.
Complex 2 has also be synthesized from the Mn(II) complex
[Mn(PaPy2Q)(H2O)]ClO4 (4), which is isolated as a light tan
precipitate in the reaction of [Mn(H2O)6](ClO4)2 and PaPy2Q-
in EtOH. Complex 4 displays a shift in νCO of the ligand to
1605 cm-1, and room-temperature EPR measurements indicate
(44) (a) Murov, S. L. Handbook of Photochemistry; M. Dekker: New York,
1973. (b) Wegner, E. E.; Adamson, A. W. J. Am. Chem. Soc. 1966, 88,
394-404.
(45) Gwost, D.; Caulton, K. G. Inorg. Chem. 1973, 12, 2095-2099.
9
J. AM. CHEM. SOC. VOL. 130, NO. 13, 2008 4451

A R T I C L E S
Eroy-Reveles et al.
Figure 1. Thermal ellipsoid (probability level 50%) plot of [Mn(PaPy2Q)-
(OH)]+ (cation of 3) showing the atom labeling scheme. All H atoms have
been omitted for the sake of clarity.
Figure 2. Thermal ellipsoid (probability level 50%) plot of [Mn(PaPy2Q)-
(NO)]+ (cation of 2) showing the atom labeling scheme. All H atoms have
been omitted for the sake of clarity.
that the Mn(II) center is high-spin (S ) 5/2). Although we have
not been able to determine the structure of 4, this Mn(II) species
also serves as a starting material for the synthesis of 2. When
a slurry of 4 in MeCN is exposed to purified NO gas, one obtains
a clear maroon solution from which 2 can be isolated in
moderate yield. In this reaction, NO simply replaces the
coordinated H2O molecule in 4 to afford 2. Because 4 is highly
sensitive to oxygen, the more stable Mn(III) complex 3 is the
preferred starting material for the synthesis of 2.
(19) Å long in 3. This same trend was noted during formation
of 1 via reductive nitrosylation of 5 with NO.29 Comparison of
the metric parameters of 2 and 1 reveals that the five Mn-
N(ligand) distances are similar in these two nitrosyls. The only
noticeable differences between 2 and 1 exist in the Mn-N-O
unit.28 Both the Mn-N(O) and N-O distances of 2 (1.678(3)
and 1.237(18) Å) are longer than the corresponding distances
of 1 (1.6601(14) and 1.1918(18) Å). The slight elongation of
the N-O bond is consistent with the shift in νNO observed for
these two nitrosyls (1745 cm-1 for 1 compared to 1725 cm-1
for 2). Overall, the Mn-N(O) and N-O distances of both 1
and 2 fall within the range of other manganese nitrosyls (Mn-
N(O), 1.58-1.69 Å; and N-O, 1.18-1.23 Å).47,48 Interestingly,
the corresponding iron nitrosyls [Fe(PaPy3)NO](ClO4)2 and [Fe-
(PaPy2Q)NO](ClO4)2 do not exhibit such changes in the Fe-
N-O unit upon change in the ligand frame.20,23 Finally, the
almost linear Mn-N6-O2 angle of 2 (171.5(8)°) is very close
to that noted in 1 (171.91(13)°).28
Structures of the Complexes. [Mn(PaPy2Q)(OH)]ClO4‚
CH3CN (3‚CH3CN). As shown in Figure 1, the Mn(III) center
of 3 exists in a pseudo octahedral geometry. The tert-amine
nitrogen, the two pyridine nitrogens, and the quinoline nitrogen
of the PaPy2Q- ligand are coordinated in the equatorial plane,
while the carboxamido nitrogen and the hydroxide occupy the
axial positions. The outermost ring of the quinoline moiety is
positioned above the equatorial plane. The mode of binding of
PaPy2Q- to the Mn(III) center is very similar to that observed
in other Mn(III) complexes of PaPy3-, such as [Mn(PaPy3)-
(OPh)]ClO4 (5).29 Comparison of the metric parameters of 3
with 5 (both containing high-spin S ) 2 Mn(III) centers) reveal
only slight changes despite modification of the ligand frame.
For example, the Mn-Nquin distance (2.1945(19) Å) of 3 is
slightly longer than the Mn-Npy distance of 5 (2.1147(13) Å),
while the other Mn-Npy distances of 3 (average value 2.1545-
(2) Å) are slightly shorter than those in 5 (average value 2.2002-
(13) Å). The Mn-O bond distance of 3 (1.8180(6) Å) is typical
for a Mn(III)-OH bond in a cationic complex, such as in the
high-spin Mn(III) complex of the neutral pentadentate ligand
PY5, [Mn(PY5)(OH)](ClO4)2 (Mn-O distance ) 1.807(3) Å).46
Electronic Description. Complex 2 is diamagnetic both in
solid state and in solution. The S ) 0 ground state of this nitrosyl
is also confirmed by its 1H NMR spectrum in CD3CN (prepared
and run in the dark). The IR spectrum of 2 displays one strong
NO stretch at 1725 cm-1, a value similar to the NO stretch of
1 (1745 cm-1).28 The νNO values of both 1 and 2 fall within the
range of other diamagnetic manganese nitrosyls (1700-1775
cm-1).47
The diamagnetism of 2 indicates a strong coupling between
the low-spin Mn(II) center and NO much like that observed in
1.28 The corresponding {Fe-NO}6 nitrosyls [Fe(PaPy3)NO]-
(ClO4)2 and [Fe(PaPy2Q)NO](ClO4)2 are also diamagnetic with
linear NO bond.20,23 Interestingly, while the metal-N(O)
distances are very similar in these four nitrosyls (range:
1.6601-1.6817 Å), significant differences exist when one
compares the N-O bond distance in manganese versus iron
[Mn(PaPy2Q)(NO)]ClO4 (2). In 2, the Mn center is in a
distorted octahedral environment with PaPy2Q- coordinated in
the same fashion as in 3 (Figure 2). However, the Mn-N bond
distances of 2 are uniformly shorter than those of 3 due to the
presence of a low-spin Mn(II) center in 2 instead of the high-
spin Mn(III) center present in 3. For example, the Mn-Nquin
and Mn-Namine distances of 2 are 2.087(3) and 2.066(3) Å,
respectively, while the same bonds are 2.1945(19) and 2.2415-
(47) (a) Franceschi, F.; Hesschenbrouck, J.; Solari, E.; Floriani, C.; Re, N.;
Rizzoli, C.; Chiesi-Villa, A. J. Chem. Soc., Dalton Trans. 2000, 593-604.
(b) Cooper, D. J.; Ravenscroft, M. D.; Stotter, D. A. J. Chem. Res. A 1979,
3359-3384. (c) Coleman, W. M.; Taylor, L. T. J. Am. Chem. Soc. 1978,
100, 1705-1710. (d) Cotton, F. A.; Monchamp, R. R.; Henry, R. J. M.;
Young, R. C. J. Inorg. Nucl. Chem. 1959, 10, 28-38.
(46) Goldsmith, C. R.; Cole, A. P.; Stack, D. P. J. Am. Chem. Soc. 2005, 127,
9904-9912.
(48) Franz, K. J.; Lippard, S. J. J. Am. Chem. Soc. 1998, 120, 9034-9040.
9
4452 J. AM. CHEM. SOC. VOL. 130, NO. 13, 2008

Photoactive Manganese Nitrosyls as NO Donors
A R T I C L E S
Figure 3. Comparison of the electronic absorption spectra of [Mn(PaPy3)-
(NO)]ClO4 (1, green trace) and [Mn(PaPy2Q)(NO)]ClO4 (2, maroon trace)
in H2O.
Figure 4. Chronoamperogram generated with amiNO-2000 electrode upon
photodissociation of NO from 2 in H2O under illumination with 810 nm
light (4.23 mW). The numbers above the peaks indicate the number of
seconds of illumination.
species. The N-O bond distance is ∼ 0.05 Å longer in 1 and
2 (1.1918(18) Å and 1.237(8) Å, respectively) compared to the
same distance in the iron nitrosyls (1.139(3) Å and 1.1435(18)
Å, respectively). This explains the lower νNO values of 1 and 2
(1745, 1725 cm-1) compared to their iron analogues (1920, 1885
cm-1). Based on spectroscopic evidence, we have previously
assigned a low-spin Fe(II)-NO+ formulation for the {Fe-NO}6
iron nitrosyls.20,23 In contrast, the {Fe-NO}7 nitrosyl [Fe-
(PaPy3)NO](ClO4), which has been assigned an Fe(II)-NO•
formulation, exhibits a N-O bond distance of 1.190(2) Å.20
This distance is much closer to the N-O bond distances noted
with the manganese nitrosyls, a fact that provides further support
to the Mn(II)-NO• formulation for 1 and 2.
NO}6 (10 nm red shift)27 nitrosyls in MeCN and other solvents.
The overall color change is however more dramatic in case of
manganese due to greater extent of changes in the absorption
spectrum (particularly the second absorption band in the 400-
500 nm range, Figure 3) compared to the other two isoelectronic
nitrosyls. Also, in the case of manganese, the nitrosyls exhibit
significant absorption in the 600-800 nm range, a fact that
renders these two nitrosyls sensitive to visible and NIR light,
respectively.
NO Photolability of 1 and 2. In the solid state, 2 is stable
for over 6 months when stored in the dark. No significant
decomposition is noted even when the crystals are kept under
room light and in air. Also, when aerobic solutions of 2 in
MeCN are kept in the dark, the electronic absorption spectrum
does not change appreciably, even after two weeks. However,
exposure of a solution of 2 to visible light causes rapid release
of NO (detected by an amiNO-2000 electrode) and bleaching
of the dark maroon color (Figure S5, Supporting Information).
We have previously reported that solutions of 1 releases NO
upon exposure to Visible light.28 Based on results of computa-
tional studies, Richards and co-workers have assigned the
photoactivity of [Fe(PaPy3)(NO)](ClO4)2 to the promotion of
an electron from a metal-based molecular orbital (with signifi-
cant contribution from the ligated carboxamido group) to a Fe-
NO π* antibonding molecular orbital.49 Ford and others have
also assigned the photoactivity of {Ru-NO}6 nitrosyls to dπ-
(Ru) f π*(NO) transitions.50,51 It is now evident that the
sensitivity of {M-NO}6 nitrosyls of this type to light depends
on the specific locations of their corresponding M f π*(NO)
transitions (photobands). Both 1 and 2 display absorptions in
the 500-800 nm range and, hence, exhibit excellent NO
photolability when exposed to light of longer wavelengths.
Careful examination of the wavelength dependence of the
photobleaching reaction of 2 reveals that this new {Mn-NO}6
nitrosyl is sensitive to light from UV to NIR region (300-850
nm). For example, exposure of an aqueous solution of 2 to 810
nm light (4.23 mW) elicits an immediate response of the NO
specific electrode and bleaching of the maroon color. The
chronoamperogram of NO detection from 2 (Figure 4) demon-
strates that 2 is quite sensitive to 810 nm light and exhibits a
linear on-off response to illumination. This confirms that the
release of NO from 2 can be triggered by NIR light. The process
Franz and Lippard have recently reported a {Mn-NO}6
nitrosyl [Mn(NO)(TC-5,5)] derived from the dianionic tetra-
dentate tropocoronand macrocycle TC-5,5.48 Based on the
metric and spectroscopic parameters, they have assigned a
Mn(III)-O- formulation for the {Mn-NO}6 core of this
nitrosyl. Close scrutiny of the properties however distinguishes
the present {Mn-NO}6 nitrosyls 1 and 2 from [Mn(NO)(TC-
5,5)]. For example, [Mn(NO)(TC-5,5)] is not diamagnetic and
its room-temperature magnetic moment (4.3 µB) is consistent
with other high-spin Mn(III) complexes. In addition, [Mn(NO)-
(TC-5,5)] exhibits a considerably lower value of νNO (1662
cm-1), a fact that supports its Mn(III)-NO- description. The
diamagnetic ground states and greater values of νNO (1745 and
1725 cm-1) of 1 and 2 are clearly distinct and hence we formally
assign both 1 and 2 as Mn(II)-NO• (instead of Mn(III)-NO-)
species.28
Electronic Absorption Spectrum. In MeCN, both 1 and 2
exhibit a quasireversible cyclic voltammogram with E1/2 ) 0.9
V vs SCE (Figure S4, Supporting Information).28 It therefore
appears that there is little effect of the additional conjugation
on the redox state of the manganese center. However, in the
same solvent, the two nitrosyls dissolve to afford two distinctly
different colored solutions. The green solution of 1 in MeCN
exhibits its visible absorption bands with λmax at 440 and 635
nm,28 while the maroon solution of 2 in the same solvent
displays bands with λmax at 495 and 650 nm. In H2O, 2 exhibits
absorption bands with λmax at 500 and 670 nm (Figure 3).
Clearly, change in the ligand frame (from PaPy3- to PaPy2Q-)
brings about changes in the absorption parameters of 2 in the
desired direction (to lower energy). In addition, the extinction
coefficient of the low-energy band of 2 is enhanced to a
significant extent, from 220 M-1 cm-1 (for 1)28 to 450 M-1
cm-1. Similar red shift of the absorption band(s) upon change
(49) Greene, S. N.; Richards, N. G. J. Inorg. Chem. 2004, 43, 7030-7041.
(50) Works, C. F.; Jocher, C. J.; Bart, G. D.; Bu, X.; Ford, P. C. Inorg. Chem.
2002, 41, 3728-3739.
(51) Gorelsky, S. I.; Lever, A. B. P. Int. J. Quantum Chem. 2000, 80, 636-
645.
in the ligand from PaPy3 to PaPy2Q- has been observed in
-
the corresponding {Fe-NO}6 (10 nm red shift)23 and {Ru-
9
J. AM. CHEM. SOC. VOL. 130, NO. 13, 2008 4453

A R T I C L E S
Eroy-Reveles et al.
Table 3. Quantum Yields (Φ) for Photoreactions of [Mn(PaPy3)
(NO)]ClO4 (1) and [Mn(PaPy2Q)(NO)]ClO4 (2)
Table 4. Apparent Rates of NO Release (s-1) from [Mn(PaPy3)
(NO)]ClO4 (1) and [Mn(PaPy2Q)(NO)]ClO4 (2) in H2O.
Concentrations of 1 and 2 ) 1.8 mM.
complex
solvent
λ
irr (nm)
Φ (mol/einst)
1
complex
λirr (nm)
power (mW)
kNO
×
10-3 (s-
)
1
1
2
2
1
1
2
2
H2O
H2O
H2O
H2O
MeCN
MeCN
MeCN
MeCN
500
550
500
550
500
550
500
550
0.400 ( 0.010
0.385 ( 0.010
0.742 ( 0.010
0.694 ( 0.010
0.326 ( 0.010
0.309 ( 0.010
0.623 ( 0.010
0.579 ( 0.010
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
380
450
500
540
635
810
425
500
575
670
810
810
810
850
900
3.90
4.23
3.40
4.16
3.78
4.23
3.75
3.40
4.50
3.78
4.23
2.02
1.03
2.18
2.11
2.9 ( 0.1
2.9 ( 0.1
0.9 ( 0.1
0.7 ( 0.1
1.3 ( 0.1
0.9 ( 0.1
4.1 ( 0.1
5.3 ( 0.2
2.3 ( 0.1
3.8 ( 0.1
3.1 ( 0.1
1.4 ( 0.1
0.9 ( 0.1
1.0 ( 0.1
0.4 ( 0.1
of NO photorelease from 2 upon exposure to light is clean (much
like 1). The absorption spectra of photolyzed solutions of 2 (in
H2O or MeCN) display isosbestic points (at 850 nm in H2O, at
340 and 790 nm in MeCN), indicating clean conversion of 2
into the colorless solvato Mn(II) species [Mn(PaPy2Q)(Solv)]+
(reaction 1), which exhibits a strong and broad EPR signal at g
) 2. It must be mentioned that this process results in complete
(100%) release of NO, as indicated by total loss of the two
Table 5. Apparent Rates of NO Release (s-1) from [Mn(PaPy3)
(NO)]ClO4 (1) and [Mn(PaPy2Q)(NO)]ClO4 (2) in MeCNa
1
complex
λirr (nm)
power (mW)
kNO
×
10-3 (s-
)
1
1
1
1
2
2
2
450
540
635
800
500
670
810
4.23
4.16
3.78
2.83
3.40
3.78
4.23
1.5 ( 0.1
0.6 ( 0.1
0.9 ( 0.1
0.4 ( 0.1
4.5 ( 0.1
2.9 ( 0.1
1.5 ( 0.1
photobands of 2. Passage of NO through the Mn(II) solvato
species in MeCN under anaerobic conditions results in slow
regeneration of the {Mn-NO}6 nitrosyl 2, a process that can
be monitored by the growth of νNO at 1725 cm-1. In aqueous
solution, [Mn(PaPy2Q)(H2O)]+ eventually decomposes into
[Mn(H2O)6]2+ (detected by EPR spectroscopy) and free ligand
(confirmed by its NMR spectrum following extraction into
CDCl3) over a period of 5 days, regardless of the presence or
absence of oxygen.
Quantum Yield Measurements. Quantum yield values (Φ)
for the generation of NO from 1 and 2 are listed in Table 3.
These values were determined from changes in the electronic
absorption spectra upon exposure to light of two different
wavelengths (500 and 550 nm) and in different solvents (H2O
and MeCN). The Φ values for 2 are significantly greater than
the values of 1 in both solvents. This indicates that incorporation
of a quinolyl-carboxamide moiety in place of the pyridyl-
carboxamide group is not only effective in moving the photo-
sensitivity to light of longer wavelengths, but also in improving
Φ values of the resulting {Mn-NO}6 nitrosyl. The iron and
ruthenium nitrosyls of these two ligands also see a significant
increase in photoactivity (vide infra, Table 6).
It must be mentioned here that the availability (and properties)
of chemical actinometers52 restricted our Φ value measurements
to 500 and 550 nm. Inspection of Figure 3 reveals that 1 has
much less absorption than 2 at these wavelengths. However,
because the Φ values were measured with solutions of absor-
bance value of 2, the Φ values in Table 3 truly represent the
efficiency of NO photorelease of these two nitrosyls. Thus, 2
is not only sensitive to NIR light (Figure 4) but also is a superior
NO donor in the visible range. Unfortunately, we could not
measure Φ values at wavelengths in the NIR region due to lack
of appropriate actinometer.52 However, we have measured the
apparent rate of NO photorelease from these two nitrosyls at
longer wavelengths and compared their efficiencies (vide infra).
a Concentrations of 1 and 2 ) 1.8 mM.
Kinetic Measurements. To establish (and compare) the NIR
sensitivity of 1 and 2, we have determined the apparent rates
of NO loss (kNO) under lights of selected frequencies in the 500-
900 nm range. The light-induced NO loss from 1 and 2 has
been monitored by recording the electronic spectrum of the
samples after irradiation (at a certain wavelength) for a known
period of time. The light-induced NO loss from 2 in all cases
follows a pseudo-first order behavior in solvents such as H2O
and MeCN. The apparent rate of photodissociation of NO from
2 under illumination with 810 nm light is shown in Figure 5.
As illustrated in the inset of Figure 5, the rate of NO release is
proportional to the power of the monochromatic light (810 nm).
The kNO values for 1 and 2 are listed in Tables 4 and 5,
respectively. As shown in Figure 6, the variation of the kNO
value with the wavelength of light indicates that the rate of NO
release follows the absorbance profile of 2. For example, the
largest kNO values are found at the λmax values of 2 (500 and
670 nm). In addition, the response of 2 to light beyond 800 nm
is noteworthy. These results demonstrate that 2 is a much
superior NO donor compared to 1 in the entire range of 380-
900 nm. Also, both 1 and 2 release NO faster in H2O than in
MeCN, presumably due to the preference of Mn(II) for O- over
N-donor ligands.
Comparison with Other Photoactive NO Donors. To date,
a number of metal nitrosyls that release NO upon illumination
have been reported. In most cases, NO is released only when
irradiated with UV light (300-400 nm). This is particularly true
with the {Ru-NO}6 nitrosyls.35,36 Because NO delivery to
malignant sites in PDT requires susceptibility of the NO donor
to visible or NIR light, various strategies have been developed
to sensitize metal nitrosyls to light in the 600-900 nm region.
For example, da Silva and co-workers have reported a dinuclear
ruthenium complex, [Ru(NH3)5(pz)Ru(bpy)2(NO)](PF6)5, in
(52) K3[Fe(C2O4)3] operates optimally in the 250-450 nm range (see Hatchard,
C. G.; Parker, C. A. Proc. R. Soc. London 1956, A235, 518-536).
Reinecke’s salt K[Cr(NH3)2(NCS)4] is suitable for the 400-600 nm range.44
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4454 J. AM. CHEM. SOC. VOL. 130, NO. 13, 2008

Photoactive Manganese Nitrosyls as NO Donors
A R T I C L E S
Table 6. Quantum Yields (Φ) of NO Donors That Operate in the Visible Range
1
complex
solvent
λirr (nm)
Φ
(mol Ein-
)
ref.
Manganese Nitrosyls
[Mn(PaPy3)(NO)]ClO4 (1)
[Mn(PaPy2Q)(NO)]ClO4 (2)
H2O
H2O
550
550
0.385
0.742
this work
this work
Iron Nitrosyls
[Fe(PaPy3)(NO)](ClO4)2
[Fe(PaPy2Q)(NO)](ClO4)2
RBS
MeCN
MeCN
H2O
500
500
546
546
546
546
436
436
436
0.185
0.258
0.001
0.13
19, 23
23
16
RRS
H2O
16
RSE ([Fe(µ-SCH2Ph)2(NO)4])
PPIX-RSE
RSE ([Fe(µ-SCH2Ph)2(NO)4])
fluor-RSE
sodium nitroprusside (SNP)
CHCl3
CHCl3
CHCl3
MeCN/H2O
H2O
1.9 × 10-4
2.5 × 10-4
3.2 × 10-4
0.0036
55c
55b
55c
56b
58
0.18
Ruthenium Nitrosyls
[Ru(PaPy3)(NO)](BF4)2
[Ru(PaPy2Q)(NO)](BF4)2
[Ru(PaPy3)(NO)](BF4)2
[Ru(PaPy2Q)(NO)](BF4)2
[Ru(Me2bpb)(NO)(Resf)]
[Ru(Me2bqb)(NO)(Resf)]
[Ru(NH3)5(pz)Ru(bpy)2(NO)](PF6)5
H2O
H2O
355
355
410
410
500
500
532
0.12
0.20
0.050
0.17
0.05
21, 27
27
27
27
57
MeCN
MeCN
DMF
DMF
H2O
0.102
0.025
57
53
Organic NO Donors
S-nitrosoglutathione (GSNO)
S-nitroso-N-acetylpenicillamine (SNAP)
S-nitroso-N-acetylcysteine (SNAC)
H2O
H2O
H2O
545
550
550
0.056
0.039
0.128
59
60
60
Figure 6. Electronic absorption spectrum of 2 in H2O (solid line), kNO vs
λirr used during photolysis of 2 in H2O (dashed line).
Figure 5. Plot of changes in ln([2]) vs time (s) in H2O (as monitored by
noting the absorbance at 670 nm of an aqueous solution of 2 upon
illumination with 810 nm light (4.23 mW)). Inset: Plot of kNO values with
the power of the 810 nm light source.
sensitize the metal nitrosyls. For example, the Roussin’s red
salt [Fe(µ-SCH2Ph)2(NO)4] (RSE) has been sensitized to visible
light via attachment of protoporphyrin IX (PPIX) and fluores-
cein.55,56 However, insufficient energy transfer from the light-
harvesting chromophores to the iron centers due to multiple
methylene groups in the linkers results in minor improvement
in NO releasing capacity of PPIX-RSE and Fluor-RSE conju-
gates (Table 6). We have recently attached the bright red dye
Resorufin (Resf) directly to the M-NO moiety of [Ru(Me2-
bqb)(NO)Cl] to improve its sensitivity to visible light.57 The
which a pyrazine (pz) bridge links [Ru(NH3)5]2+ and [Ru(bpy)2-
(NO)]3+ units.53 While [Ru(bpy)2(pz)(NO)]3+ is not sensitive
to visible light, the dinuclear species exhibits a strong metal-
to-ligand charge transfer (MLCT) absorption band of dπRu(II)
f π*(pz) origin in the visible region at 530 nm. As a result,
this dinuclear nitrosyl releases of NO in pH 4.5 acetate buffer
when exposed to 532 nm laser light (Table 6). In another attempt
to sensitize a ruthenium nitrosyl to visible light, Sellman and
co-workers have utilized a highly negatively charged ligand
frame to shift the dπ(Ru) f π*(NO) transition to lower energy.54
The nitrosyl reported by this group, namely, [Ru(NO)(pySiS4)]-
Br, releases NO under illumination with visible light (g455
nm).54 Ford and co-workers have utilized a different strategy,
namely, attachment of strongly colored chromophores, to
(55) (a) Wecksler, S. R.; Mikhailovsky, A.; Ford, P. C. J. Am. Chem. Soc. 2004,
126, 13566-13567. (b) Conrado, C. L.; Wecksler, S.; Egler, E.; Magde,
D.; Ford, P. C. Inorg. Chem. 2004, 43, 5543-5549. (c) Conrado, C. L.;
Bourassa, J. L.; Egler, E.; Wecksler, S.; Ford, P. C. Inorg. Chem. 2003,
42, 2288-2293.
(56) (a) Wecksler, S. R.; Mikhailovsky, A.; Korystov, D.; Ford, P. C. J. Am.
Chem. Soc. 2006, 128, 3831-3837. (b) Wecksler, S. R.; Hutchinson, J.;
Ford, P. C. Inorg. Chem. 2006, 45, 1192-1200.
(57) Rose, M. J.; Olmstead, M. M.; Mascharak, P. K. J. Am. Chem. Soc. 2007,
129, 5342-5343.
(53) Sauaia, M. G.; de Lima, R. G.; Tedesco, A. C.; da Silva, R. S. J. Am.
Chem. Soc. 2003, 125, 14718-14719.
(54) Prakash, R.; Czaja, A. U.; Heinemann, F. W.; Sellman, D. J. Am. Chem.
Soc. 2005, 127, 13758-13759.
(58) (a) Singh, R. J.; Hogg, N.; Neese, F.; Joseph, J.; Kalyanaraman, B.
Photochem. Photobiol. 1995, 61, 325-330. (b) Wolfe, S. K.; Swinehart,
J. H. Inorg. Chem. 1975, 14, 1049-1053.
9
J. AM. CHEM. SOC. VOL. 130, NO. 13, 2008 4455

A R T I C L E S
Eroy-Reveles et al.
dye-conjugate [Ru(Me2bqb)(NO)(Resf)] exhibits a very strong
absorption band at 500 nm and rapidly releases NO when
exposed to visible light (Table 6). In the present work, we have
adopted yet another strategy to improve the NO releasing
capacity of our metal nitrosyls, namely, alteration of the ligand
frame. By adding extended conjugation in the ligand frame, we
have been able to move the photoband more into the NIR region.
As a result, 2 is more sensitive to NIR light compared to 1,
although both are very efficient NO donor in the visible range.
In Table 6, we have listed the quantum yield values of selected
organic NO donors along with reported metal nitrosyls that
release NO when exposed to visible light. A close look at Table
6 reveals that the NO donating capacity of 1 and 2 far exceeds
that of the other nitrosyls.
In recent years, Ford and co-workers have utilized the
technique of two-photon excitation (TPE) to promote NO
photorelease from PPIX-RSE and Fluor-RSE via exposure to
femtosecond laser pulses of NIR light (λirr ) 810 nm, 210-
450 mW).55,56 This strategy is somewhat restricted by the large
dependency of the technique on the photochemistry of the NO-
containing species in the visible range. Also, the TPE technique
requires ultrafast pulses of laser light to cause the simultaneous
two-photon absorption required for NO photorelease. Illumina-
tion with lower-intensity light (<200 mW) does not release NO
(as detected by an NO electrode) from PPIX-RSE and Fluor-
RSE. Quite in contrast, 2 releases NO upon single photon
excitation and hence can be triggered by simple exposure to
NIR light (<5 mW).
Figure 7. Selective irradiation of a circular slice of 2‚SG with a black
plastic maple leaf on top. The nonirradiated area is maroon, while the
photolyzed area is colorless. Light source: 25 W tungsten bulb.
Table 7. Apparent Rates of NO Release (s-1) from 1‚SG and
2‚SGa
1
complex
λirr (nm)
power (mW)
kNO
×
10-3 (s-
)
1‚SG
1‚SG
2‚SG
2‚SG
450
810
500
810
4.23
4.23
3.40
4.23
4.5 ( 0.5
1.5 ( 0.1
12.6 ( 0.5
5.6 ( 0.1
a Concentration of 1 or 2 in nitrosyl sol-gel hybrid ) 1.8 mM.
Immobilization of 1 and 2 in Porous Material. To deliver
NO at selected targets under the total control of NIR light, we
have immobilized 2 in a silica-based porous material via sol-
gel chemistry. When a mixture of an aqueous solution of 2 and
tetramethylorthosilicate (TMOS) is allowed to gel for 3 h in
the dark, an optically transparent maroon sol-gel, 2‚SG, is
obtained. The electronic absorption spectrum of 2‚SG is identical
to that of 2 in H2O, a fact that confirms that the manganese
nitrosyl survives the gelation process. Also, the sol-gel
entrapment/occlusion process does not change the ability of 2
to release NO. When 2‚SG is exposed to light, the color of the
maroon gel bleaches to faint pink (indicating formation of the
photoproduct [Mn(PaPy2Q)(H2O)]ClO4) and a steady release
of NO is detected. As shown in Figure 7, 2‚SG exhibits excellent
spatial differentiation when selectively irradiated with light. The
sharp contrast between illuminated (faint pink) and nonillumi-
nated (maroon) areas demonstrates that careful delivery of light
will result in precise spatial release of NO by 2‚SG.
The light-induced NO loss from 2‚SG can be monitored by
recording the electronic spectrum of the optically transparent
samples. Photolysis of NO from 2‚SG follows a pseudo-first
order behavior, similar to 2 in solution. This behavior mirrors
that reported of 1‚SG under illumination.39 Comparison of the
apparent rate of NO loss (kNO) between these two materials
(Table 7) indicates the kNO values of 2‚SG are much larger than
1‚SG, again reflecting the behavior of the free nitrosyls in
solution.61 These values demonstrate that 2‚SG is a superior
NO donating material than 1‚SG. In addition, the NIR sensitivity
is retained in 2‚SG (Table 7).
The rapid photorelease of NO from 1‚SG and 2‚SG raised
the question regarding the ease with which the NO-depleted
material could be regenerated. It is encouraging to note that
1‚SG can be regenerated by simply exposing the NO-depleted
material to NO under anaerobic conditions. The regeneration
process can be followed visually, because the yellow photolyzed
material turns deep green when placed under NO. The comple-
tion of the process, checked by monitoring the growth of the
635 nm band, usually takes 24 h. The ability to regenerate a
NO donating material upon exposure to NO gas has been noted
in materials incorporating diazeniumdiolates and ruthenium
nitrosyls by other groups.9,62,63 Unfortunately, such regeneration
has not been possible for 2‚SG due to the inherent instability
of [Mn(PaPy2Q)(Solv)]ClO4, the photoproduct of 2, in aqueous
environments such as in the water-containing sol-gel material.
This fact is also responsible for the reduced shelf life of 2‚SG
compared to 1‚SG. For instance, 1‚SG can be stored in the dark
for many weeks (as indicated by its electronic spectrum), while
the color of 2‚SG starts to fade after 2 days.64
Because the nitrosyl compounds are not covalently attached
to the silicate framework of the sol-gel material in 1‚SG and
(61) The apparent rates of NO release from 1‚SG and 2‚SG (Table 7) are much
faster than 1 and 2 in water (Table 4) due to immobilization of the nitrosyls
in the polymeric matrix. The light beam from the monochromator only
illuminates a small section of the cuvette containing 1‚SG or 2‚SG and no
stirring of the medium is possible. As a result, the light-exposed area is
not replenished by a fresh supply of the nitrosyl complex. The apparent
rate law calculation therefore affords a higher value of kNO in case of the
nitrosyl sol-gel hybrids.
(62) Mitchell-Koch, J. T.; Reed, T. M.; Borovik, A. S. Angew. Chem., Int. Ed.
2004, 43, 2806-2809.
(63) Ferreira, K. Q.; Schneider, J. F.; Nascente, P. A. P.; Rodrigues-Filho, U.
P.; Tfouni, E. J. Colloid Interface Sci. 2006, 300, 543-552.
(64) This behavior parallels the behavior of the nitrosyls in aqueous solution.
While aqueous solutions of 1 can be kept intact for weeks at room
temperature, solutions of 2 are stable for several hours and decomposes
significantly (∼40%) within 24 h.
(59) Sexton, D. J.; Muruganandam, A.; McKenney, D. J.; Mutus, B. Photochem.
Photobiol. 1994, 59, 463-467.
(60) Singh, R. J.; Hogg, N.; Joseph, J.; Kalyanaraman, B. FEBS Lett. 1995,
360, 47-51.
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4456 J. AM. CHEM. SOC. VOL. 130, NO. 13, 2008

Photoactive Manganese Nitrosyls as NO Donors
A R T I C L E S
when the cuvette was exposed to 780 nm light (40 mW NIR
laser), NO was smoothly transferred from 2‚HM to Mb (λmax
) 420 nm) in a light-dependent manner, as illustrated in Figure
8. The success in NO delivery to Mb by 2‚HM opens up the
possibility of using this material to promote NO-induced
apoptosis in skin cancer cell lines. Such experiments are
currently in progress in this laboratory.
Comparison with Other Light-Activated NO Donating
Materials. Prolonged exposure to NO at elevated concentrations
can result in severe side effects to the vascular system, thus
limiting the therapeutic potential of systemic NO donors. To
localize the release of NO, various materials have been
developed that incorporate NO donors to restrict the release of
NO to target cells in their immediate vicinity. Currently
most reports of materials that release NO when exposed to
visible light utilize S-nitrosothiols,68 which are known to
decompose and release NO when exposed to light.69 Etchenique
and co-workers have shown photorelease of NO from mono-
layers of nitrosated dithiothreitol attached to gold surfaces
with a tungsten lamp (30 W).70 Meyerhoff and co-workers have
developed a trilayer silicone rubber film utilizing SNAP-
derivatized fumed silica to prevent leaching of the NO donor
and reaction byproducts, and this material exhibits light-
dependent release of NO upon exposure to visible light
(40-100 W tungsten lamps).71 The low extinction coeffi-
cients and quantum yields (Table 6) of S-nitrosothiols in the
visible range are often counteracted by means of a high
power laser source or by increasing the irradiation time. In recent
years, metal nitrosyls have also been used as immobilized
NO donors because the NO delivery from nitrosyl complexes
can be tuned photochemically via a variety of strategies
mentioned earlier. Borovik and co-workers have developed a
polymerizable styrene-modified salen ligand for covalent at-
tachment of metal complexes to a porous organic material.72a
The Co(II) adduct of this material displayed a higher
affinity for NO over other gases (such as O2 and CO), but
removal of NO proved to be difficult.72b However, when the
ruthenium nitrosyl was incorporated in the material, NO
was rapidly released upon exposure to UV light.62 Tfouni and
co-workers have also entrapped various ruthenium nitrosyls in
a silica matrix by sol-gel chemistry that release NO when
illuminated with UV light.63,73 In a recent report, da Silva and
co-workers have utilized intense visible light (three 250 W
tungsten bulbs) to release NO from a Ru-terpy complex
immobilized in a sol-gel material to show the vasodilatory
effects of NO on rat aortic rings.74 The majority of metal
nitrosyls incorporated into polymeric materials are {Ru-NO}6
Figure 8. Transfer of NO from 2‚HM to reduced Mb (λmax ) 435 nm),
resulting in the Mb-NO adduct (λmax ) 420 nm) in pH 7.5 phosphate buffer
with 780 nm light (40 mW continuous wave diode laser, spectra collected
at 20 s intervals of illumination). Inset: NO chronoamperogram showing
NO photorelease from 2‚HM in H2O upon illumination with 810 nm light.
The numbers above peaks indicate the number of seconds of illumination.
2‚SG, one needs to worry about leakage of the nitrosyls and
their photoproducts in solution. In general, when TMOS is used
in the sol-gel formulation instead of tetraethylorthosilicate
(TEOS), the gelation time is much shorter (a few hours instead
of a few days) and the sol-gel polymer is more cross-linked
(and, hence, less porous). This results in less leakage of the
nitrosyls into the surrounding solutions (<5% for the TMOS
gel compared to 10% for the TEOS gel over 24 h, as measured
by their absorption spectra). Previously, we have circumvented
this problem of leaching by coating 1‚SG (prepared via TEOS
gelation) with polyurethane to completely seal 1 inside the
hybrid material 1‚HM (HM ) hybrid material, sol-gel +
polyurethane).39 Polyurethanes are widely used in medical
devices due to their excellent biocompatibility65 and have been
shown to improve the stability of materials by preventing the
leakage of toxic compounds.66 In the present work, we have
formulated both 1‚SG and 2‚SG with TMOS and then dip-
coated the materials in THF solutions of dissolved polyurethane
to effectively lock the nitrosyls inside the material. That NO
permeates the polyurethane coat of both 1‚HM and 2‚HM is
readily confirmed by the immediate response of the NO-specific
electrode when these materials are exposed to visible light. The
chronoamperogram of NO photoreleased from 2‚HM upon
exposure to 810 nm light, shown in the inset of Figure 8, also
demonstrates that 2‚HM exhibits a linear on-off response to
NIR irradiation.
NO Transfer to Biological Target with NIR Light. The
utility of 2‚HM has been evaluated through delivery of NO to
a biological target, myoglobin (Mb), with NIR light. Because
Mb readily reacts with NO, it has been suggested that Mb plays
a role in NO homeostasis in the vasculature and in red muscle
cells.67 When a pellet of 2‚HM was placed inside a cuvette
containing a sample of reduced Mb (λmax ) 435 nm) in the
dark, there was no change in optical spectrum of Mb. However,
(67) (a) Moller, J. K. S.; Skibsted, L. H. Chem. ReV. 2002, 102, 1167-1178.
(b) Andriambeloson, E.; Wittig, P. K. Redox Rep. 2002, 7, 131-136. (c)
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(b) Lelah, M. D.; Cooper, S. L. Polyurethanes in Medicine; CRC Press:
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(66) (a) Nablo, B. J.; Schoenfisch, M. H. Biomaterials 2005, 26, 4405-4415.
(b) Zhang, H.; Annich, G. M.; Miskulin, J.; Stankiewicz, K.; Osterholzer,
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A R T I C L E S
Eroy-Reveles et al.
nitrosyls due to their inherent thermal stability. The two
nitrosyl-polymer hybrids, 1‚HM and 2‚HM, however, utilize
{Mn-NO}6 nitrosyls that exhibit excellent stability and
NO donating capacities in biological systems. These materials
are notable for their capacity to photorelease NO under
lights of low-intensity (usually in mWs). In addition, 2‚HM is
sensitive to NIR light. The results of the present work
thus demonstrate the utility of the ligand-modification strategy
to isolate new and improved photosensitive nitrosyls
(and materials) that could act as efficient NO donors in the
visible or NIR range. The total amount of NO released
from 1‚HM and 2‚HM can be easily adjusted by (i) changing
the concentration of the nitrosyls in the polymer matrix,
(ii) varying the thickness of the polymer disk, and/or (iii)
modulating the intensity of the light used in photolysis.
yield (Φ) of 2 (0.742 ( 0.010, λirr ) 500 nm, solvent: H2O) is
the largest of all Φ values of photosensitive metal nitrosyls
reported so far. Even more noteworthy is the fact that 2 is
sensitive to low-intensity, continuous NIR light (800-900 nm).
No TPE was required to elicit its NIR sensitivity.
(c) To date, research on light-activated NO donors has been
almost exclusively focused on iron and ruthenium nitrosyls in
addition to S-nitrosothiols. Our results now establish that
properly designed manganese nitrosyls can also deliver NO
under light and their photoactivity can be modulated by
alterations in the ligand frame.
(d) Both 1 and 2 have been immobilized in sol-gel matrices
to afford 1‚SG and 2‚SG. These materials have been coated
with polyurethane to generate biocompatible hybrid materials
1‚HM and 2‚HM. Both these nitrosyl-polymer hybrids deliver
NO to Mb upon exposure to visible light. In addition, NO
transfer to Mb has been achieved by 2‚HM under NIR light
(780 nm). Such controlled release of NO to biological targets
could be exploited in PDT of skin cancer.
Summary and Conclusions
The following are the summary and conclusions of this study.
(a) The second generation {Mn-NO}6 nitrosyl [Mn(PaPy2Q)-
(NO)]ClO4 (2) has been synthesized and characterized by
X-ray crystallography. The metric parameters of 2 have been
compared with those of the first generation {Mn-NO}6 nitrosyl
[Mn(PaPy3)(NO)]ClO4 (1), reported by us previously. In addi-
tion, the synthesis and structure of a starting material for
2, namely, [Mn(PaPy2Q)(OH)]ClO4 (3), have also been com-
pleted.
(b) The electronic absorption and photochemical properties
of 2 and 1 have been investigated thoroughly to determine the
effects of the ligand frames on the photorelease of NO from
these two photoactive nitrosyls. Incorporation of more conjuga-
tion into the PaPy3H ligand frame (of 1) via replacement of a
pyridine moiety with a quinoline (in 2) red shifts the absorption
maxima of 2 and increases the extinction coefficient of the lower
energy band. Modification of the ligand frame has doubled the
NO releasing capacity of 2 (in comparison to 1) under visible
light (500-650 nm) of low-intensity (5-50 mW). The quantum
Acknowledgment. Financial support from the NSF Grant
CHE-0553405 is gratefully acknowledged. A.A.E.-R. and Y.L,
were supported by NIH IMSD Grant No. GM58903.
Supporting Information Available: LC-MS of ethylquinal-
date, N-(2-aminoethyl)-2-quinolinecarboxamide, and N,N-bis-
(2-pyridylmethyl)amine-N-ethyl-2-quinolinecarboxamide (PaPy2-
QH) (Figures S1-S3), cyclic voltammogram of 2 in MeCN
(Figure S4), electronic absorption (800-300 nm) spectra
showing photodissociation of NO from 2 in MeCN under
aerobic conditions (Figure S5), X-ray crystallographic data (in
CIF format), and tables for the structure determination of [Mn-
(PaPy2Q)(NO)]ClO4 (2) and [Mn(PaPy2Q)(OH)]ClO4‚CH3CN
(3‚CH3CN). This material is available free of charge via the
Internet at http://pubs.acs.org.
JA710265J
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