Visible light induced reversible extrusion of nitric oxide from a Ruthenium(II) nitrosyl complex: A facile delivery of nitric oxide

Article abstract of DOI:10.1021/ja053758x

The new ruthenium compound [Ru(NO)(py^siS₄)]Br (3) (py^siS₄ = 2,6-bis(3-triphenylsilyl-2-sulfanylphenylthiomethyl)pyridine), containing sterically bulky SiPh3 groups ortho to the thiolate donors, has been synthesized. In solution, 3 releases NO efficiently on exposure to visible light (λ ≥ 455 nm) at room temperature to afford [Ru(Br)(py^siS₄)] (4). Treatment of 4 with NO yielded exclusively 3 without any metal-bound side reaction. Copyright

Full text of DOI:10.1021/ja053758x

Published on Web 09/14/2005
Visible Light Induced Reversible Extrusion of Nitric Oxide from a
Ruthenium(II) Nitrosyl Complex: A Facile Delivery of Nitric Oxide
Raju Prakash,*,‡ Alexander U. Czaja, Frank W. Heinemann, and Dieter Sellmann†
Institut fu¨r Anorganische Chemie, UniVersita¨t Erlangen-Nu¨rnberg, Egerlandstrasse 1, D-91058 Erlangen, Germany
Received June 8, 2005; E-mail: raju.prakash@chemie.uni-erlangen.de
Scheme 1
After the discovery of the role of nitric oxide (NO) in various
physiological processes, such as regulation of blood pressure,
neurotransmission, inhibition of tumor growth, and immune re-
sponse,1 the chemistry of metal nitrosyl complexes has become the
focus of much attention.2 The application of new NO drugs to
medicine3 has reinvigorated the NO research, particularly in
developing new storage-release systems or methodologies for
(1872 cm-1 in MeOH), indicative of the linearity of the Ru-N-O
delivering NO to desired targets.4 The photochemical labilization
of NO from metallonitrosyls is one of the convenient methods for
NO delivery.5 In recent years, ruthenium is the metal of choice for
nitrosyl complexes6 because a number of ruthenium compounds
with anticancer activity appear to penetrate tumors and are unusually
effective in suppressing the immune response.7 Moreover, the
thermal stability of the Ru-NO bond enhances the probability that
the complex will survive under physiological conditions.6a,b Even
though many rutheniumnitrosyls are known to release NO upon
energy-intensive UV light irradiation,2d,6 reports on visible light
NO labilization of rutheniumnitrosyls are rare.8 In addition, the
RuIII-solvent complexes that result after irradiation inevitably
undergo undesired side reactions in solution. One continuing
challenge is, therefore, to find a Ru-NO complex that could release
NO reversibly under very mild conditions without any metal-bound
side reactions for biological applications.
We have reported previously that [RuII(NO)(pybuS4)]Br (1)
(pybuS4 ) 2,6-bis(3,5-di-tert-butyl-2-sulfanylphenylthiomethyl)pyri-
dine) releases NO upon exposure to UV light to form [RuIII(Br)-
(pybuS4)] (1a).9 Now, we found that 1 releases NO even on irradi-
ation with visible light (Supporting Information, Figure 1S). How-
ever, the reverse reaction was slow, and traces of other NO species
were also formed (Figure 2S). Moreover, 1a readily loses the Br-
ligand to form [RuIII(pybuS4)]2Br2 (1b) via Ru-S(thiolate) bridges
in solution (Figure 3S), which exhibits no affinity toward NO.
Herein, we report a new ruthenium compound [RuII(NO)(pysiS4)]-
Br (3) (pysiS4 ) 2,6-bis(3-triphenylsilyl-2-sulfanylphenylthiometh-
yl)pyridine), containing sterically bulky SiPh3 groups in ortho
position with regard to the thiolate donors, that exhibits a remarkable
reactivity of reversible NO release upon visible light irradiation.
The ligand siS2-H2 (3-triphenylsilyl-1,2-benzenedithiol) was
synthesized by ortho lithiation of benzenedithiol,10 followed by
treatment with SiPh3Cl and subsequent hydrolysis. The compound
Bu4N[RuII(NO)(siS2)2] (2) was prepared according to Scheme 1 in
70% yield. The structure of 2 (Figure 1a) reveals a five-coordinated
Ru center with a square-pyramidal geometry. The NO group is at
the apical position, and the thiolate donors are in the basal plane.
The two SiPh3 groups are trans to each other. Reaction of 2 with
2,6-bis(bromomethyl)pyridine (Scheme 1) leads to the formation
of purple microcrystalline 3 in high yield. In the solid state, 3 is
stable toward air and light, and well soluble in MeOH, DMF, and
DMSO. The IR (KBr) spectrum of 3 displays νNO at 1858 cm-1
1
bond.11 The well-resolved H and 13C NMR spectra of 3 indicate
its ground state spin is zero and are typical for a complex having
C2 symmetry. Due to the NO group, the bridging CH2 protons are
more acidic and undergo H+/D+ exchange with CD3OD. The cyclic
voltammogram of 3 exhibits two quasi-reversible one-electron
waves at E1/2 ) 0.46 and -0.38 V in the region between 1.0 and
-0.8 V (Figure 4S). The anodic and cathodic waves are assigned
to the redox couples of [3]0/+1 and [3]0/-1, respectively. This is in
accordance with 1,12 indicating that the 19 valence-electron neutral
species [RuII(NO)(pysiS4)] exists in solution at approximately
0.0 V. 3 crystallizes in the monoclinic space group P21/n (Figure
1b). The local geometry of the RuII site is a pseudooctahedron
composed of two N and four S donors. The two thiolate and two
thioether S atoms comprise in the equatorial plane in mutual trans
position, with the pyridine and nitrosyl N atoms occupying the axial
positions. The Ru-N(O) distance (1.748(4) Å) is slightly longer
than that of the complex 1 (1.721(6) Å).13 The Ru-S distances
compare well with those in other thioether-thiolate complexes.14
The Ru-N-O bond angle of 178.8(4)° suggests that the sp-
hybridized N atom of the NO ligand formally coordinates as RuII-
NO+.2b
Figure 1. ORTEP diagrams of (a) the anion of 2 and (b) the cation of 3
(50% probability ellipsoids; H atoms and solvent molecules omitted).
Selected distances [Å] and angles [°] for 2: Ru1-N1 1.699(5), Ru1-S1
2.338(2), Ru1-S2 2.321(2), N1-O1 1.195(7), N1-Ru1-S1 108.2(2), N1-
Ru1-S2 104.9(2), S1-Ru1-S2 85.43(6), S1-Ru1-S3 148.65(7), S2-
Ru1-S4 151.78(7), Ru1-N1-O1 177.4(6). 3: Ru1-N1 2.099(4), Ru1-
N2 1.748(4), Ru1-S1 2.393(2), Ru1-S2 2.345(2), Ru1-S3 2.363(2), Ru1-
S4 2.371(2), N2-O1 1.144(5), N1-Ru1-N2 178.1(2), N1-Ru1-S1
85.7(2), N2-Ru1-S1 96.2(2), S1-Ru1-S2 87.36(4), S1-Ru1-S4 170.26(5),
S2-Ru1-S3 164.51(4), Ru1-N2-O1 178.8(4).
‡ Present address: Institut fu¨r Organische Chemie, Universita¨t Erlangen-
Nu¨rnberg, Henkestrasse 42, D-91054 Erlangen, Germany.
† Deceased on May 06, 2003.
9
13758
J. AM. CHEM. SOC. 2005, 127, 13758-13759
10.1021/ja053758x CCC: $30.25 © 2005 American Chemical Society

C O M M U N I C A T I O N S
Scheme 2
NO releasing ability varies dramatically. Complex 3 releases NO
much faster than 1 on visible light (λ g 455 nm) irradiation. In the
case of 3, the reaction is completely reversible, without involving
any metal-bound side reaction. The facile lability of the NO group
of 3 can directly be related to the presence of SiPh3 groups in the
vicinity of the thiolate donors. Due to the steric effect of the SiPh3
groups, formation of a thiolate-bridged dimer is hindered, which
indirectly helps to stabilize the Ru-Br bond of 4 in solution.
In conclusion, the new rutheniumnitrosyl compound 3, containing
sterically bulky SiPh3 groups ortho to the thiolate donors, has been
synthesized. In solution, 3 releases NO on visible light (λ g 455
nm) irradiation to afford the bromo compound 4. The reverse
reaction was also achieved efficiently with no metal-bound side
reaction. The reaction is unique because the Br- ion plays a dual
role as counterion and nucleophile, which prevented the formation
of a labile RuIII-solvent complex. Thus, 3 has the potential to serve
as NO deliverer to various targets. However, efforts are underway
to make a water-soluble derivative of this type to use as a NO
delivering agent to biological targets.
When a red solution of 3 in MeOH is kept in dark, the color or
IR spectrum does not change appreciably even after 10 days.
However, when the solution is subjected to photolysis with visible
light (Scheme 2), the color changes to green, and subsequently,
green microcrystals of [RuIII(Br)(pysiS4)] (4) precipitated from the
solution. The IR spectral changes during the conversion of 3 to 4
are depicted in Figure 2. When the suspension is stirred in dark
under an atmosphere of NO for about 60 min, it goes back to the
red solution and the NO band of 3 reappeared, showing this reaction
to be reversible. It is quite interesting that no thiolate-bridged
dinuclear compound or any other side product is observed.
Complex 4 has been isolated in the solid state with very high
yield (92%) and is soluble in THF, CH2Cl2, and acetone. It exhibits
two quasi-reversible one-electron waves at E1/2 ) -0.58 and
0.41 V. The cathodic and anodic waves are ascribed for the redox
couples of [4]0/-1 and [4]0/+1, respectively. In a multi-sweep experi-
ment, both the waves showed complete reversibility over several
cycles confirming that 4 is stable in solution. Crystals of 4 suitable
for X-ray structure analysis were obtained from a THF/DMF
mixture at 20 °C. The RuIII center is in pseudooctahedral geometry
(Figure 3) with the Br ligand being trans to the pyridine N donor.
4 possesses a crystallographically imposed C2 symmetry with the
C2 axis lying along N1-Ru1-Br1 bonds. All four Ru-S distances
lie in the same range (av. 2.31 Å), which is in contrast to the RuII
complexes, where the Ru-S(thiolate) distances (av. 2.38 Å) are
usually longer than Ru(thioether) distances (av. 2.30 Å).14
When irradiation of 3 (similar to Scheme 2) was carried out with
low-intensity UV light source (xenon lamp 150 W, λ g 320 nm),
the NO band of 3 disappeared completely in 5 min (Figure 5S),
and the resulting bromo derivative 4 was isolated in the solid state
as high as 86% yield.
Acknowledgment. This work was supported by a grant from
the Deutsche Forschungsgemeinschaft. We thank Prof. Horst Kisch
and Prof. Andreas Grohmann for helpful suggestions. This paper
is dedicated to Prof. Rolf W. Saalfrank on his 65th birthday.
Supporting Information Available: IR spectra (Figures S1, S2,
and S5), X-ray structure (Figure S3), cyclic voltammogram (Figure
S4), comparative spectroscopic and structural data (Table 1), CIF files
and experimental details. This material is available free of charge via
the Internet at http://pubs.acs.org.
References
(1) (a) Snyder, S. H. Science 1992, 257, 494. (b) Koshland, D. E. Science
1992, 258, 1861. (c) Feelisch, M.; Stamler, J. S. In Methods in Nitric
Oxide Research; Feelisch, M., Stamler, J. S., Eds.; Wiley: Chichester,
England 1996; p 71. (d) Fukuto, J. M.; Wink, D. A. Met. Ions Biol. Syst.
1999, 36, 547.
(2) (a) Clarke, M. J.; Gaul, J. B. Struct. Bonding 1993, 81, 147. (b) Ford, P.
C.; Bourassa, J.; Miranda, K.; Lee, B.; Lorkovic, I.; Boggs, S.; Kudo, S.;
Laverman, L. Coord. Chem. ReV. 1998, 171, 185 and references therein.
(c) McCleverty, J. A. Chem. ReV. 2004, 104, 403. (d) Carlos, R. M.; Ferro,
A. A.; Silva, H. A. S.; Gomes, M. G.; Borges, S. S. S.; Ford, P. C.; Tfouni,
E.; Franco, D. W. Inorg. Chim. Acta 2004, 357, 1381.
Although the spectroscopic, electrochemical, and structural data
of 3 and 1 (Table 1S) did not show any significant deviations, the
(3) (a) Keefer, L. K. Nat. Mater. 2003, 2, 357. (b) Napoli, C.; Ignarro, L. J.
Annu. ReV. Pharmacol. 2003, 43, 97. (c) Sadler, P. J.; Gun, Z. Pure Appl.
Chem. 1998, 70, 863.
(4) (a) Mitchell-Koch, J. T.; Reed, T. M.; Borovik, A. S. Angew. Chem., Int.
Ed. 2004, 43, 2806. (b) Patra, A. K.; Afshar, R.; Olmstead, M. M.;
Mascharak, P. K. Angew. Chem., Int. Ed. 2002, 41, 2512. (c) De Leo,
M.; Ford, P. C. J. Am. Chem. Soc. 1999, 121, 1980.
(5) (a) Ackroyd, R.; Kelty, C.; Brown, N.; Reed, M. Photochem. Photobiol.
2001, 74, 656. (b) Pandey, R. K. J. Phorphyrins Phathalocyanines 2000,
4, 368. (a) Ford, P. C.; Laverman, L. Coord. Chem. ReV. 2005, 249, 391.
(6) (a) Oliveria, F. S.; Togniolo, V.; Pupo, T. T.; Tedesco, A. C.; da Silva,
R. S. Inorg. Chem. Commun. 2004, 7, 160. (b) Fortney, C. F.; Shepherd,
R. E. Inorg. Chem. Commun. 2004, 7, 1065. (c) Patra, A. K.; Mascharak,
P. K. Inorg. Chem. 2003, 42, 7363 and references therein. (d) Bordini, J.;
Hughes, D. L.; Da Motta Neto, J. D.; da Cunha, C. J. Inorg. Chem. 2002,
41, 5410. (e) Works, C. F.; Ford, P. C. J. Am. Chem. Soc. 2000, 122,
7592.
Figure 2. IR spectra of 3 in MeOH, before (a) and after 10 (b), 20 (c),
and 30 min (d) of irradiation (λ g 455 nm) at 20 °C.
(7) Clarke, M. J. Coord. Chem. ReV. 2003, 171, 185 and references therein.
(8) Sauaia, M. G.; de Lima, R. G.; Tedesco, A. C.; da Silva, R. S. J. Am.
Chem. Soc. 2003, 125, 14718.
(9) Sellmann, D.; Prakash, R.; Heinemann, F. W.; Moll, M.; Klimowicz, M.
Angew Chem., Int. Ed. 2004, 43, 1877.
(10) Sellmann, D.; Prakash, R.; Geipel, F.; Heinemann, F. W. Eur. J. Inorg.
Chem. 2002, 2138.
(11) Nakamoto, K. Infrared and Raman Spectra of Inorganic and Coordination
Compounds, 5th ed.; John Wiley & Sons: New York, 1997; Part A, p
261.
(12) Sellmann, D.; Gottschalk-Gaudig, T.; Haeussinger, D.; Heinemann, F. W.
Hess, B. A. Chem.sEur. J. 2001, 7, 2099.
(13) (a) Sellmann, D.; Gottschalk-Gaudig, T.; Haeussinger, D.; Heinemann,
F. W. Z. Naturforsch. B 2000, 55, 723. (b) Sellmann, D.; Prakash, R.;
Heinemann, F. W. Dalton Trans. 2004, 3991.
Figure 3. ORTEP diagram of 4 (50% probability ellipsoids; H atoms and
solvent molecules omitted). Selected distances [Å] and angles [°]: Ru1-
N1 2.055(3), Ru1-Br1 2.5239(4), Ru1-S1 2.3153(6), Ru1-S2 2.3101(6),
N1-Ru1-Br1 180.000(1), N1-Ru1-S1 86.90(2), N1-Ru1-S2 84.66(2),
S1-Ru1-S2 88.14(2), S1-Ru1-S1A 173.79(3), S2-Ru1-S2A 169.33(3).
(14) Sellmann, D.; Sutter, J. Prog. Inorg. Chem. 2003, 581.
JA053758X
9
J. AM. CHEM. SOC. VOL. 127, NO. 40, 2005 13759