New Ru(ii) photocages operative with near-IR light: New platform for drug delivery in the PDT window

Article abstract of DOI:10.1039/c8sc02094a

A series of Ru(ii) complexes bearing the tridentate 2,6-di(quinolin-2-yl)pyridine (dqpy) ligand were designed to undergo photoinduced ligand dissociation with red/near-IR light. The complexes [Ru(dqpy)(L)(CH₃CN)]²⁺, where L = 2,2′-bipyridine (bpy, 1), 4,4′dimethyl-2,2′-bipyridine (Me₂bpy, 2), and 1,10-phenanthroline (phen, 3). Complexes 1-3 exhibit red-shifted lowest energy metal-to-ligand charge transfer (MLCT) absorption maxima at ～600 nm, as compared to the corresponding tpy (2,2′;6′,2′′-terpyridine) complexes with MLCT bands at ～565 nm which appear as shoulders to the MLCT bands at ～455 nm. This shift is attributed to the lower energy LUMO afforded by the dqpy ligand when compared to tpy, as evidenced by the shift of the first reduction wave to ～0.3 V more positive potentials in the former. In addition, the lowest MLCT maximum of [Ru(dqpy)(acac)(CH₃CN)]⁺ (4; acac^- = acetylacetonate) is observed at 770 nm, attributed to the additional increase in energy of the HOMO afforded by the presence of the π-donating acac^- ligand and supported by calculations. Complexes 1-3 undergo ligand substitution upon irradiation with red light, λ_irr ≥ 610 nm, and the ligand substitution photochemistry of 4 is accessible with near-IR light, λ_irr ≥ 715 nm and λ_irr = 735 nm. Complexes 1-4 exhibit similar quantum yields of ligand exchange, Φ_L, with 450 and 600 nm irradiation, however, that of 4 is 2-3 times greater than those measured for 1-3. This enhancement is explained by the difference in ligand contributions to the HOMO. Density functional theory calculations predict partial dqpy ππ? character in the MLCT states of 1-3 and a mixed Ru/acac^- → dqpy metal/ligand-to-ligand charge transfer (ML-LCT) state in 4. The photoreactivity of 1-4 with tissue-penetrating red and near-IR light, together with their exceptional dark stability (>48 h), makes the new Ru(ii)-dqpy platform ideal for the development of new complexes for photoinduced drug release and for other applications that require broad absorption from the ultraviolet and visible ranges into the near-IR, such as solar energy conversion.

Full text of DOI:10.1039/c8sc02094a

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New Ru(II) photocages operative with near-IR light:
new platform for drug delivery in the PDT window†
Cite this: DOI: 10.1039/c8sc02094a
All publication charges for this article Malik H. Al-Afyouni, Thomas N. Rohrabaugh, Jr, Kathlyn F. Al-Afyouni
have been paid for by the Royal Society
of Chemistry
and Claudia Turro
*
A series of Ru(II) complexes bearing the tridentate 2,6-di(quinolin-2-yl)pyridine (dqpy) ligand were
designed to undergo photoinduced ligand dissociation with red/near-IR light. The complexes
2
+
0
0
0
[
Ru(dqpy)(L)(CH
3
CN)] , where L ¼ 2,2 -bipyridine (bpy, 1), 4,4 dimethyl-2,2 -bipyridine (Me
2
bpy, 2), and
1
,10-phenanthroline (phen, 3). Complexes 1–3 exhibit red-shifted lowest energy metal-to-ligand charge
0
0
00
transfer (MLCT) absorption maxima at ꢀ600 nm, as compared to the corresponding tpy (2,2 ;6 ,2 -
terpyridine) complexes with MLCT bands at ꢀ565 nm which appear as shoulders to the MLCT bands at
ꢀ
455 nm. This shift is attributed to the lower energy LUMO afforded by the dqpy ligand when compared
to tpy, as evidenced by the shift of the first reduction wave to ꢀ0.3 V more positive potentials in the
+
ꢁ
former. In addition, the lowest MLCT maximum of [Ru(dqpy)(acac)(CH
3
CN)] (4; acac
¼
acetylacetonate) is observed at 770 nm, attributed to the additional increase in energy of the HOMO
ꢁ
afforded by the presence of the p-donating acac ligand and supported by calculations. Complexes 1–3
undergo ligand substitution upon irradiation with red light, lirr $ 610 nm, and the ligand substitution
photochemistry of 4 is accessible with near-IR light, lirr $ 715 nm and lirr ¼ 735 nm. Complexes 1–4
L
exhibit similar quantum yields of ligand exchange, F , with 450 and 600 nm irradiation, however, that of
4
is 2–3 times greater than those measured for 1–3. This enhancement is explained by the difference in
ligand contributions to the HOMO. Density functional theory calculations predict partial dqpy pp*
ꢁ
character in the MLCT states of 1–3 and a mixed Ru/acac / dqpy metal/ligand-to-ligand charge
Received 10th May 2018
Accepted 4th July 2018
transfer (ML-LCT) state in 4. The photoreactivity of 1–4 with tissue-penetrating red and near-IR light,
together with their exceptional dark stability (>48 h), makes the new Ru(II)-dqpy platform ideal for the
development of new complexes for photoinduced drug release and for other applications that require
broad absorption from the ultraviolet and visible ranges into the near-IR, such as solar energy conversion.
DOI: 10.1039/c8sc02094a
rsc.li/chemical-science
requirement for oxygen represents a drawback, since hypoxia at
Introduction
12,13
the tumor site limits the action of the drug.
In both PCT and
Conventional chemotherapeutic cancer treatments typically PDT, the approach imparts lowered systemic toxicity and inva-
5–11
exhibit high systemic toxicity and poor selectivity for cancer siveness while increasing selectivity.
cells, resulting in undesirable side effects and off-site activity in
Recent work has demonstrated the versatility and efficacy of
healthy tissue. The drawbacks to conventional cancer treat- ruthenium-based PCT agents as potential anticancer
1
–5
5,8–11,14
ment have motivated the development of new approaches, drugs.
However, most of these systems utilize visible light
including the use of light to attain spatiotemporal control of in the 400–550 nm range, thus limiting tissue penetration since
1
5,16
metallodrug activation and release of active species at the tumor it is outside the PDT window (600–900 nm).
site.
(
A handful of
The use of light for drug release, photochemotherapy ruthenium-based systems capable of releasing a monodentate
PCT), utilizes an agent that is nontoxic in the dark, such that ligand using tissue-penetrating red light in the PDT window
cell death is only initiated through the absorption of light. An have been recently reported, but do not absorb beyond
5
–11
17–20
important distinction between PCT and traditional photody- ꢀ650 nm.
In these systems, the metal-to-ligand charge
namic therapy, PDT, is that the latter relies on the presence of transfer (MLCT) transitions of these complexes are stabilized
oxygen to function, whereas the former does not. The through the extension of conjugation and/or the addition of
steric bulk to ancillary ligands to distort the pseudo-octahedral
17–20
environment around the metal.
The latter approach has
been most successful in complexes where the monodentate
Department of Chemistry and Biochemistry, The Ohio State University, Columbus,
Ohio 43210, USA. E-mail: turro.1@osu.edu
†
Electronic supplementary information (ESI) available. CCDC 1841086–1841088. ligand is a functionalized pyridine, however, ligand photodis-
For ESI and crystallographic data in CIF or other electronic format see DOI:
sociation with lirr $ 700 nm has not been achieved to date. A
1
0.1039/c8sc02094a
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ꢂ
red-shi in the absorption of these cages through the control of The mixture was heated to 95 C in an oil bath and stirred
the electronic properties of the complex without the addition of vigorously for 3 hours; the reaction was then allowed to cool to
steric bulk at the metal center is desirable to circumvent room temperature followed by the addition of 2,6-diacetylpyr-
thermal instability in water, an important factor in the design of idine (0.270 g, 1.65 mmol) and KOH pellets (0.725 g, 12.9
PCT agents.
mmol). The reaction was then returned to the oil bath and
ꢂ
Herein we report the synthesis of a series of Ru(II) complexes stirred at 95 C overnight. Aer cooling to room temperature,
2 2
supported by the 2,6-di(quinolin-2-yl)pyridine (dqpy) tridentate the reaction was diluted with 200 mL of CH Cl and the
2
+
0
ligand, [Ru(dqpy)(L)(NCCH
3
)] , where L represents 2,2 -bipyr- suspension was ltered through a pad of celite, followed by
0
0
idine (bpy, 1), 4,4 -dimethyl-2,2 -bipyridine (Me
2
bpy, 2), 1,10- removal of the solvent by rotary evaporation. Methanol (100 mL)
+
phenanthroline (phen, 3), as well as [Ru(dqpy)(acac)(NCCH )]
was added to the residue resulting in a white precipitate. The
3
ꢁ
(
4) featuring the anionic acac (acetylacetonate) ligand. These precipitate was collected by vacuum ltration and washed with
model complexes are designed to probe the ability of the methanol (3 ꢃ 15 mL), resulting in 0.425 g (1.27 mmol, 77%) of
1
[
Ru(dqpy)(L)] fragment to serve as a vehicle for the delivery of white solid product. H NMR (400 MHz) in acetone-d
6
, d ppm
2
nitrile-containing cysteine protease inhibitors with red and near- (splitting, integration, J-coupling): 8.97 (d, 2H, J ¼ 8.8 Hz), 8.85
17,18
2
2
IR light.
We envisioned that the expansion of the p-system of (d, 2H, J ¼ 8.0 Hz), 8.56 (d, 2H, J ¼ 8.8 Hz), 8.21 (m, 3H), 8.06
0
0
00
2
+
+
the common tpy (2,2 :6 ,2 -terpyridine) tridentate ligand would (d, 2H, J ¼ 8.0 Hz), 7.84 (m, 2H), 7.66 (m, 2H). ESI MS: [M + H ]
result in a red-shi to the MLCT absorption maximum without experimental m/z ¼ 334.14 calculated m/z ¼ 334.13.
increasing the steric bulk around the monodentate ligand, since
the quinolinyl groups are positioned in a planar fashion and are [Ru(dqpy)(bpy)Cl][PF ] (1–Cl)
6
perpendicular to the axis containing the Ru–NCCH3 bond.
Additionally, we sought to demonstrate the facile incorporation
of a number of bidentate ancillary ligands with a range of
absorption energies. The present work includes the rst example
In a Schlenk tube, [Ru(p-cymene)(bpy)Cl]Cl (100 mg, 0.21 mmol)
was combined with dqpy (84 mg, 0.25 mmol), excess LiCl (ꢀ100
mg), and DMF (3 mL). The mixture was allowed to reux for 3 h
during which time the color changed from yellow to dark
of photoinduced ligand release from a Ru(II) complex with lirr
$
purple; addition of the reaction mixture to 100 mL of
a concentrated aqueous NH PF solution resulted in the
715 nm and highlights the versatility of the [Ru(dqpy)(L)] frag-
4
6
ment as a caging group for the delivery of nitrile-containing drugs
and inhibitors with irradiation in the PDT window.
precipitation of a purple solid that was isolated on fritted glass,
washed with 3 ꢃ 20 mL water and 3 ꢃ 20 mL diethyl ether. The
solid was dissolved in acetone (100 mL), and ltered through
celite. The acetone solution was concentrated to 10 mL and
puried on an alumina column with acetone as eluent. The
purple solution was concentrated to ꢀ5 mL under vacuum and
Experimental
Materials
All materials were used as received without further purication precipitated with 100 mL diethyl ether. The purple solid was
unless otherwise noted. Diethyl ether, acetone, acetonitrile, and isolated by vacuum ltration (113 mg, 70% yield). H NMR (400
1
methanol were procured from Fisher Scientic, and dichloro- MHz) in acetone-d , d ppm (multiplicity, integration, J-
6
2
2
methane was obtained from Macron Fine Chemicals. N,N-Dime- coupling): 10.82 (d, 1H, J ¼ 5.6 Hz), 9.08 (d, 2H, J ¼ 8.0 Hz),
2
2
2
thylformamide was purchased from Sigma-Aldrich and was dried 8.98 (d, 1H, J ¼ 7.6 Hz), 8.79 (d, 2H, J ¼ 8.4 Hz), 8.66 (t, 1H, J ¼
2
under nitrogen by passing through a column of activated 8.4 Hz), 8.60 (d, 2H, J ¼ 8.4 Hz), 8.47 (m, 2H), 8.41 (m, 1H), 8.01
2
2
alumina. Reineke salt, ammonium hexauorophosphate, lithium (d, 2H, J ¼ 8.0 Hz), 7.61 (m, 3H), 7.31 (m, 2H), 7.24 (d, 2H, J ¼
chloride, sodium chloride, sodium acetate trihydrate, ascorbic 8.8 Hz), 7.09 (m, 2H).
acid, 1,3-diphenylisobenzofuran (DPBF), acetylacetonate, 1,10-
0
phenanthroline, 4,4 -dimethylbipyridyl, acetonitrile-d3 and [Ru(dqpy)(Me bpy)Cl][PF ] (2–Cl)
2
6
0
acetone-d were purchased from Sigma-Aldrich, and 2,2 -bipyr-
6
[
Ru(dqpy)(Me bpy)Cl][PF ] was prepared following the same
2 6
idine was obtained from Alfa Aesar. Sulfuric acid and sodium
bicarbonate were received from Fisher Scientic, and potassium
ferrioxalate was purchased from Strem Chemicals. Neutral
alumina was purchased from Fisher Scientic. The starting
material [Ru(p-cymene)Cl
ne)(bpy)Cl]Cl, [Ru(p-cymene)(4,4 -Me bpy)Cl]Cl, [Ru(p-cymene)-
procedure for 1–Cl using dqpy (82 mg, 0.24 mmol) and
substituting [Ru(p-cymene)(bpy)Cl]Cl for [Ru(p-cymene)(Me
bpy)Cl]Cl (101 mg, 0.20 mmol), resulting 110 mg (67% yield) of
2
-
1
isolated product. H NMR (400 MHz) in acetone-d
6
, d ppm
2
1
2 2
] ,
and the complexes [Ru(p-cyme-
2
(
multiplicity, integration, J-coupling): 10.63 (d, 1H, J ¼ 6.0 Hz),
0
2
2
2
9
8
8
7
.05 (d, 2H, J ¼ 8.0 Hz), 8.85 (s, 1H), 8.77 (d, 2H, J ¼ 8.8 Hz),
(
phen)Cl]Cl, and Ru(p-cymene)(acac)Cl were synthesized accord-
ing to published procedures.
2
2
.57 (d, 2H, J ¼ 8.8 Hz), 8.42 (t, 1H, J ¼ 8.2 Hz), 8.34 (s, 1H),
21b
2
2
.25 (d, 1H, J ¼ 6.4 Hz), 8.00 (d, 2H, J ¼ 8.0 Hz), 7.61 (m, 2H),
2
2
.38 (d, 1H, J ¼ 5.6 Hz), 7.32 (m, 4H), 6.90 (d, 1H, J ¼ 5.6 Hz),
2
,6-Di(quinolin-2-yl)pyridine (dqpy)
3.00 (s, 3H), 2.27 (s, 3H).
The dqpy ligand was synthesized following modications of
2
2,23
[Ru(dqpy)(phen)Cl][PF
6
] (3–Cl)
] was prepared following the same
0.607 g, 4.02 mmol), followed by 8 mL of 0.1 M HCl (0.8 mmol). procedure for 1–Cl using dqpy (82 mg, 0.24 mmol) and
procedures previously reported.
Ethanol (20 mL) was added
to Fe powder (2.259 g, 40.5 mmol) and 2-nitrobenzaldehyde [Ru(dqpy)(phen)Cl][PF
(
6
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substituting [Ru(p-cymene)(bpy)Cl]Cl for [Ru(p-cymene)(phen) acetone-d
6
, d ppm (multiplicity, integration, J-coupling): 11.00
2
2
2
2
Cl]Cl (100 mg, 0.20 mmol), resulting in 92 mg (56% yield) of (dd, 1H, J ¼ 5.2 Hz, J ¼ 1.2 Hz), 9.34 (dd, 1H, J ¼ 8.4 Hz, J ¼
1
2
2
isolated product. H NMR (400 MHz) in acetone-d , d ppm 1.2 Hz), 9.26 (d, 2H, J ¼ 8.0 Hz), 8.90 (d, 2H, J ¼ 8.8 Hz), 8.83
6
2
2
2
2
(
multiplicity, integration, J-coupling): 11.10 (dd, 1H, J ¼ 5.6 Hz, (dd, 1H, J ¼ 8.2 Hz, J ¼ 5.4 Hz), 8.75 (m, 3H), 8.49 (d, 1H, J ¼
2
2
2
2
2
2
2
J ¼ 1.4 Hz), 9.25 (dd, 1H, J ¼ 8.4 Hz, J ¼ 1.2 Hz), 9.13 (d, 2H, J 8.8 Hz), 8.45 (dd, 1H, J ¼ 8.4 Hz, J ¼ 1.2 Hz), 8.20 (d, 1H, J ¼
2
2
2
2
2
¼
¼
8.4 Hz), 8.81 (m, 3H), 8.51 (m, 4H), 8.28 (dd, 1H, J ¼ 8.2 Hz, J 8.8 Hz), 8.10 (dd, 1H, J ¼ 5.2 Hz, J ¼ 1.2 Hz), 8.00 (dd, 2H, J ¼
2 2 2 2 2
1.4 Hz), 8.15 (d, 1H, J ¼ 9.2 Hz), 7.97 (dd, 1H, J ¼ 5.6 Hz, J ¼ 8.2 Hz, J ¼ 1.4 Hz), 7.57 (m, 3H), 7.23 (m, 2H), 7.15 (d, 2H, J ¼
2
2
2+
1
.2 Hz), 7.91 (dd, 2H, J ¼ 8.0 Hz, J ¼ 1.6 Hz), 7.46 (m, 3H), 7.20 8.8 Hz), 2.36 (s, 3H). ESI + MS: [M] experimental m/z ¼ 328.05
2 4
(
dq, 2H, J ¼ 8.8 Hz, J ¼ 0.8 Hz), 7.09 (m, 2H).
calcd m/z ¼ 328.07. Elem. anal. calcd for C37
26 12 6 2
H F N P -
Ru$(CH CH ) O: C: 48.29; H: 3.56; N: 8.24. Found: C: 48.01; H:
3
2 2
[
Ru(dqpy)(bpy)(CH CN)][PF ] (1)
3.56; N: 7.87.
3
6 2
The precursor 1–Cl (50 mg, 0.065 mmol) was dissolved in 20 mL
: 1 (v/v) CH CN/H O in a 50 mL round-bottom ask. The
[
Ru(dqpy)(acac)(CH CN)][PF ] (4)
3
3
6
3
2
solution was allowed to reux for 24 h, resulting in a color
In a Schlenk tube Ru(p-cymene)(acac)Cl (100 mg, 0.24 mmol)
was combined with dqpy (96 mg, 0.29 mmol), excess LiCl (ꢀ100
mg), and DMF (3 mL). The mixture was allowed to reux for 3 h
during which the color changed from yellow to dark green. The
solution was precipitated in 100 mL of a concentrated brine
solution. The resulting green solid was isolated on fritted glass,
change from purple to dark orange. The CH CN/H O reaction
3
2
mixture was then added to 100 mL of concentrated aqueous
NH PF to form an orange precipitate; the solid was isolated on
4
6
fritted glass by vacuum ltration and washed with 3 ꢃ 20 mL
water and 3 ꢃ 20 mL diethyl ether. The solid was then dissolved
in acetone (100 mL) and ltered through celite. The orange
2 2
dissolved in CH Cl (200 mL), and ltered through celite. The

ltrate was concentrated to ꢀ5 mL under reduced pressure, and
green solution was concentrated to ꢀ5 mL under vacuum and
precipitated with 100 mL diethyl ether. The green solid 4–Cl
isolated by vacuum ltration was used without further puri-
cation. In a 50 mL round-bottom ask, 4–Cl was dissolved in
precipitated with 100 mL diethyl ether. The orange solid was
isolated by vacuum ltration (52 mg, 87% yield). H NMR (400
1
6
MHz) in acetone-d , d ppm (multiplicity, integration, J-
2
2
coupling): 10.57 (d, 1H, J ¼ 5.6 Hz), 9.22 (d, 2H, J ¼ 8.4 Hz),
3
0 mL 3 : 1 (v/v) CH CN/H O. The solution was allowed to reux
3 2
2
2
9
8
7
7
.03 (d, 1H, J ¼ 8.0 Hz), 8.90 (d, 2H, J ¼ 8.8 Hz), 8.76 (m, 4H),
for 24 h, during which time the color of the solution changed
from green to dark purple. The CH CN/H O solution was then
added to 100 mL of concentrated aqueous NH PF to form
2
2
.56 (d, 1H, J ¼ 8.0 Hz), 8.46 (m, 1H), 8.11 (d, 2H, J ¼ 8.0 Hz),
3
2
3
2
2
.85 (td, 1H, J ¼ 7.9 Hz, J ¼ 1.3 Hz), 7.78 (d, 1H, J ¼ 5.6 Hz),
4
6
3
.70 (t, 2H, J ¼ 7.6 Hz), 7.43 (m, 2H), 7.21 (m, 3H), 2.29 (s, 3H).
a purple precipitate. The solid was isolated on fritted glass by
vacuum ltration and washed with 3 ꢃ 20 mL water and 3 ꢃ
20 mL diethyl ether. The solid was then dissolved in acetone
2
+
ESI + MS: [M] experimental m/z ¼ 316.07 calcd m/z ¼ 316.07.
Elem. anal. calcd for C H F N P Ru$2H O$(CH ) CO: C:
3
5
26 12
6
2
2
3 2
44.93; H: 3.57; N: 8.27. Found: C: 45.12; H: 3.19; N: 8.30.
(100 mL) and ltered through celite. The ltrate was concen-
trated to ꢀ5 mL under reduced pressure, and puried on an
alumina column with acetone as eluent. The purple solution
was concentrated to ꢀ5 mL under vacuum and precipitated
with 100 mL diethyl ether. The purple solid was isolated by
0
[
Ru(dqpy)(4,4 -Me
2
bpy)(CH
3
CN)][PF
6
]
2
(2)
0
Ru(dqpy)(4,4 -Me bpy)(CH CN)][PF ] was prepared following
2 3 6 2
the same procedure for 1 starting with 2–Cl (50 mg, 0.063 mmol)
instead of 1–Cl, which resulted in isolation of 55 mg of product
[
1
vacuum ltration (55 mg, 32% yield). H NMR (400 MHz) in
6
acetone-d , d ppm (multiplicity, integration, J-coupling): 9.34 (d,
(
93% yield). Single crystals were grown from diffusion of diethyl
2
2
1
2
3
7
3
5
H, J ¼ 9.2 Hz), 8.84 (d, 2H, J ¼ 8.0 Hz), 8.72 (m, 4H), 8.17 (m,
ether into a concentrated acetonitrile solution. H NMR (400
MHz) in acetone-d , d ppm (multiplicity, integration, J-
3 2 3
H), 8.05 (td, 2H, J ¼ 7.8 Hz, J ¼ 1.6 Hz), 7.88 (td, 2H, J ¼
6
2
2
2
.5 Hz, J ¼ 1.0 Hz), 5.29 (s, 1H), 2.58 (s, 3H), 2.11 (s, 3H), 1.29 (s,
coupling): 10.38 (d, 1H, J ¼ 5.6 Hz), 9.21 (d, 2H, J ¼ 8.0 Hz),
+
2
3
H). ESI + MS: [M] experimental m/z ¼ 575.11 calcd m/z ¼
8
8
7
7
2
3
.90 (m, 3H), 8.79 (d, 2H, J ¼ 8.4 Hz), 8.70 (t, 1H, J ¼ 8.2 Hz),
2
2
23 6 4 2 2
75.10. Elem. anal. calcd for C30H F N PO Ru$H O: C: 48.85;
.42 (s, 1H), 8.32 (d, 1H, J ¼ 5.6 Hz), 8.11 (d, 2H, J ¼ 8.0 Hz),
2
2
H: 3.69; N: 7.60. Found: C: 49.33; H: 4.07; N: 7.85.
.71 (t, 2H, J ¼ 7.4 Hz), 7.55 (d, 1H, J ¼ 5.6 Hz), 7.47 (m, 2H),
2
2
.26 (d, 2H, J ¼ 8.8 Hz), 7.05 (d, 1H, J ¼ 6.0 Hz), 2.99 (s, 3H),
2
+
.31 (s, 3H), 2.27 (s, 3H). ESI + MS: [M] experimental m/z ¼ Instrumentation and methods
30.08 calcd m/z ¼ 330.08. Elem. anal. calcd for C38
Ru$(CH CO: C: 46.67; H: 3.60; N: 8.34. Found: C: 47.75; H:
.84; N: 8.07.
H
30
F
12
N
6
-
1
H NMR spectra were collected with a Bruker 400 MHz DPX
P
3
2
3 2
)
spectrometer. Electrospray ionization mass spectrometry (ESI-
MS) was performed with a Bruker micrOTOF instrument dis-
solved in methanol. Microanalysis samples were weighed with
a PerkinElmer Model AD-6 Autobalance and their compositions
[Ru(dqpy)(phen)(CH CN)][PF ] (3)
3 6 2
3 6 2
[Ru(dqpy)(phen)(CH CN)][PF ] was prepared following the were determined with a PerkinElmer 2400 Series II Analyzer.
same procedure for 1, using 3–Cl (50 mg, 0.063 mmol) instead Steady state absorption spectra were recorded on a Hewlett-
of 1–Cl, which resulted in 51 mg of isolated product (86% yield). Packard 8453 diode array spectrometer. Sample irradiation
Single crystals were grown from diffusion of diethyl ether into was performed using a 150 W Xe arc lamp (USHIO) in a MilliArc
1
a concentrated acetonitrile solution. H NMR (400 MHz) in lamp housing unit with an LPS-220 power supply and an LPS-
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2
7
21 igniter (PTI) or two LUXEON Far Red Rebel LEDs (lmax
35 ꢄ 15 nm). The desired irradiation wavelengths using the Xe SDD basis set on Ru and the TZVP basis set on all other
¼
vibrational frequency calculations were performed with the
28
29
30
arc lamp were controlled by selecting the appropriate long pass atoms with the PBE exchange–correlation functional. The
CVI Melles Griot) or bandpass (Thorlabs) lters. In general, the geometries of all complexes were fully optimized starting from
(
samples were irradiated in water (ꢀ5% acetone) in a 1 x 1 cm X-ray crystal structures, when available. Complex 1 was opti-
quartz cuvette. For photolysis experiments, electronic absorp- mized starting from the optimized structure of 2, replacing the
0
tion spectra were recorded at various time points of irradiation. methyl groups of 4,4 -dimethylbipyridine with hydrogen atoms.
The ligand exchange quantum yields (F) were determined by All optimized geometries have positive harmonic frequencies
irradiating the samples in water using the appropriate band- (conrming the calculated structures as electronic energy
pass lter. Electronic absorption spectra were recorded at early minima). Further calculations of molecular orbitals and TD-
31
irradiation times (<10% conversion) during the quantum yield DFT utilized the B3LYP hybrid functional, again with the
determination, and the rate of consumption of the reactant was SDD basis set on Ru and with the TZVP basis set on all other
determined from the slope of the line of a plot of the moles of atoms with the inclusion of solvation effects using the polarized
reactant vs. irradiation time. The photon ux of the lamp was continuum model (PCM) with acetonitrile as the solvent in the
32
determined using potassium ferrioxalate (lirr ¼ 450 nm) or TD calculations. TD-DFT was used to calculate the electronic
24
Reineke salt (lirr ¼ 600 nm) as the chemical actinometer. The transition state energies and intensities of the 75 lowest-energy
quantum yield for ligand dissociation was calculated as the rate states. Orbitals from the Gaussian calculations were plotted
of moles of reactant consumed divided by the photon ux and using the Chemcra program. The analysis of the MO compo-
33
corrected for the mean fraction of light absorbed by the sitions were performed using the AOMix program.
24
sample.
Electrochemical measurements were performed
under a nitrogen atmosphere using a BASi model CV-50W vol-
tammetric analyzer (Bioanalytical Systems Inc.). Cyclic voltam-
magrams were obtained using a three electrode conguration
Results and discussion
Synthesis and characterization
with a glassy carbon (3 mm) working electrode, a Ag/AgCl (3 M The synthetic steps for the preparation of 1–4 are displayed in
6
NaClaq) reference electrode, and a Pt wire auxiliary electrode in Scheme 1 starting from the dinuclear Ru(II) h -arene complex,
21
a glass tube tted with a vycor tip. Ferrocene (Fc) was added at [Ru(p-cymene)Cl ] . The reaction of the p-cymene dimer with
2
2
the end of each cyclic voltammetry experiment as a secondary the desired bidentate ligand, L, in CH CN resulted in mono-
3
+
n+
reference; Fc /Fc redox couple in 1 M TBAPF in acetonitrile E
meric [Ru(p-cymene)(L)Cl] , which was then heated to displace
6
1/2
¼
+0.45 V.
the arene in the presence of the dqpy ligand, affording the
+
corresponding [Ru(dqpy)(L)Cl] (L ¼ bpy, Me bpy, phen)
2
20
complex or [Ru(dqpy)(acac)Cl]. In the nal step, the desired
acetonitrile complex, 1–4, was obtained by heating each chlo-
X-ray crystallography
Single crystal X-ray diffraction data was collected on a Bruker D8
Venture with a Photon II CPAD detector. All structures were
solved using ShelXT and rened using ShelXL in the Olex2
ride precursor in 3 : 1 (v/v) CH
salt metathesis with NH PF
3
CN/H
2
O, followed by aqueous
4
6
.
1
The chemical structures of 1–4 were conrmed by H NMR
25
program. The space groups were determined based on
systematic absences and intensity statistics. An intrinsic
phasing solution method provided most non-hydrogen atoms
from the E-map. Full-matrix least squares/difference Fourier
cycles were performed which located the remaining non-
hydrogen atoms. All non-hydrogen atoms were rened with
anisotropic displacement parameters. All hydrogen atoms were
placed in ideal positions and rened as riding atoms with
relative isotropic displacement parameters. For complexes 2, 3,
and 4, reection contributions from disordered solvent mole-
spectroscopy and positive mode electrospray ionization mass
spectrometry (ESI-MS+). In general, the H NMR spectra of 1–4
1
in acetone-d exhibit aryl resonances in the 7.0–9.0 ppm range
6
20a,34–36
that are typical for polypyridyl compounds.
In 1–3,
a distinctive resonance is observed at ꢀ10.5–11.0 ppm known to
correspond to the aryl proton of the bidentate ligand positioned
directly adjacent to the CN triple bond of the acetonitrile ligand.
The deshielding of this resonance in 1–3 is a result of proximity
to the nitrile group in an orientation perpendicular to the
cylindrical magnetic anisotropy along the nitrile CN bond. In 4,
26
cules were removed using Platon, function: Squeeze. A total of
1
a distinctive H resonance at 5.30 ppm is observed, assigned to
3
˚
5
7 electrons and a 255 A solvent accessible void per cell, 101
ꢁ
the proton bound to the central carbon of the acac ligand. In
3
˚
electrons and a 295 A solvent accessible void per cell, and 555
electrons and a 1822 A solvent accessible void per cell for 2, 3,
and 4, respectively. Both PF6 polyatomic ions in 2 exhibit
1–4 a single methyl proton resonance is observed in the 2.0–
3
˚
2
.3 ppm range corresponding to the coordinated CH CN ligand,
3
ꢁ
20a,34,37
as previously reported for related complexes.
signicant positional disorder, and were modeled by dividing
the disordered atoms into groups (PART instruction), and
allowing the atoms to rene freely.
The solid-state single crystal X-ray diffraction structures of 2–
4
are shown in Fig. 1 and additional information is provided in
3
Table S1.† The bond lengths from the metal to the CH CN
ligand, Ru–N1, and to the central pyridine ring of the dqpy
DFT calculations
˚
ligand, Ru–N3, in 2, 2.044(1) and 1.979(2) A, respectively, are
0
Spin restricted DFT calculations were performed with the similar to those previously reported for [Ru(tpy)(4,4 -Me
2
-
27
2+
36
˚
Gaussian 09 package.
All geometry optimization and bpy)(NCCH
3
)] at 2.037 and 1.968 A, respectively. The Ru–N2
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Scheme 1
˚
and Ru–N4 bonds to the quinolinyl units of the dqpy ligand in 2
The Ru–N1 distance in 3, 2.036(3) A, is in good agreement
34
are signicantly lengthened relative to Ru–N3, and are on with that previously reported in related nitrile complexes, and
˚
˚
2+ 34
average 0.085 A longer than the corresponding Ru–N bonds in the Ru–N3 distance of 1.972(3) A is consistent with that reported
0
2+ 36
[
Ru(tpy)(4,4 -Me bpy)(NCCH )] . This is a result of steric for [Ru(tpy)(phen)(CH CN)] . As expected, the structural
2
3
3
clashes between the quinolinyl protons of the dqpy ligand and features of 3 are similar to those of 2, where the Ru–N2 and Ru–
˚
the adjacent ring system of the bidentate ligand. Nevertheless, N4 bonds in 3 are on average 0.076 A longer than the corre-
2
+
the sum of the angles around Ru formed by the three N atoms of sponding Ru–N bonds in [Ru(tpy)(phen)(CH CN)] and the
3
ꢂ
the dqpy ligand and N5 of the bidentate ligand in 2 is 359.7 , sum of the angles formed by the three N atoms of the dqpy
ꢂ
indicating that despite the introduction of relatively bulky ligand and N5 of the bidentate ligand is nearly planar at 359.9 .
quinolinyl groups, dqpy binds to Ru(II) in a rigorously planar The N1–Ru–N6 and the Ru–N1–C1 angles in 3 are close to linear
ꢂ
ꢂ
fashion analogous to terpyridine. The N1–Ru–N6 and Ru–N1– at 174.6 and 178.5 , respectively.
ꢂ
ꢂ
C1 angles at 171.1 and 169.7 , respectively, in the solid-state
The structure of 4 is similar to that previously reported for
structure of 2 deviate slightly from 180 due to steric clashes [Ru(tpy)(acac)(dmso)] with Ru–N3, Ru–O1, and Ru–O2
anion and co-crystallized acetonitrile solvent distances determined to be 1.937(2) A, 2.053(2) A, and 2.090(2)
Fig. S1†). The N2–Ru–N4 angle in 2 at 156.5 is consistent with A˚ , respectively. The Ru–N2 and Ru–N4 bond distances of
ꢂ
+
ꢁ
˚
˚
with the PF
6
ꢂ
35
(
0
˚
˚
the corresponding N–Ru–N angle in [Ru(tpy)(4,4 -Me - 2.096(3) A and 2.124(2) A, respectively, are consistent with the
2
2
+
bpy)(NCCH
3
)] , highlighting the distortion from octahedral elongation of the corresponding bonds observed in 2 and 3. The
˚
coordination geometry imposed by both the dqpy and tpy Ru–N1 bond length, 2.016(2) A, is similar to those observed in 2
3
6
ꢂ
ꢂ
ligands. The N5–Ru–N6 angle in 2 at 78.4 is also consistent and 3. The angle in 4 formed by O1–Ru–O2 at 89.9 is large
36
with the corresponding angle in the tpy supported analog.
compared with the corresponding N5–Ru–N6 angles in 2 and 3
6ꢁ
Fig. 1 Thermal ellipsoid plots of (a) 2, (b) 3, and (c) 4 shown at 50% probability. H atoms, PF ions, and co-crystallized solvent molecules omitted
for clarity.
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ꢂ
ꢂ
1
at 78.4 and 79.3 , respectively, as expected for the six-
MLCT shoulders in 1–3 are attributed to transitions from
ꢁ
membered ring formed upon coordination of acac in Ru(dp) to dqpy(p*) orbitals, likely localized on the quinoline
contrast to the ve-membered rings in 2 and 3. Interestingly, moieties based on the similar red-shi of the MLCT absorption
the short Cquinoline–O2 distance observed in 4 suggests that an observed in analogous Ru(II) complexes containing the 2,2 -
intramolecular H-bonding interaction may occur in the absence biquinoline ligand.
1
0
20,42
of an external H-bond donor. Accordingly, as discussed below,
a solvochromatic shi is observed for 4 in protic solvents.
In addition to being signicantly red-shied relative to 1–3,
the MLCT maximum of 4 at 540 nm is accompanied by two
1
bands with signicant absorption of near-IR light at 703 nm (3 ¼
ꢁ
1
ꢁ1
ꢁ1
ꢁ1
1
600 M cm ) and 770 nm (3 ¼ 1500 M cm ), the latter
Electronic absorption and electrochemistry
tailing to 950 nm. It is evident that the dqpy ligand provides
a low-energy ligand-centered p* orbital to shi the absorption
of 1–4 into the therapeutic window. In the case of 4, the
The electronic absorption spectra of 1–4 are shown in Fig. 2 and
relevant information is listed in Table 1. Absorption features in
the ultraviolet (UV) and near-UV regions are assigned as arising
ꢁ
electron-donating acac ligand also raises the energy of the
1
from pp* transitions of dqpy and the bidentate ligands, as is
1
metal-based HOMO, further shiing the MLCT absorption to
3
8,39
typical in Ru(II) polypyridyl complexes.
Complex 1 exhibits
lower energy.
1
an MLCT absorption maximum at 471 nm in acetone,
Cyclic voltammagrams of 1–4 collected in CH
3
CN (0.1 M
which is only slightly red-shied compared to that of
TBAPF ) are shown in Fig. 3. Complexes 1–3 exhibit fully
6
2
+
40
1
[Ru(tpy)(bpy)(NCCH
3
)] at 468 nm. However the MLCT
reversible oxidation events ranging from +1.43 to +1.49 V vs. Ag/
transition of 1 also exhibits two shoulders at ꢀ550 (3 ¼
AgCl assigned to the Ru(III/II) couples, similar to those for the tpy
ꢁ
1
ꢁ1
ꢁ1
ꢁ1
1
800 M cm ) and ꢀ609 nm (3 ¼ 800 M cm ), and the
2+
analogs [Ru(tpy)(L)(CH CN)] (L ¼ bpy, phen, Me bpy), re-
3
2
latter tails to ꢀ690 nm (Fig. 2). Complexes 2 and 3 exhibit
ported to range from +1.32 to +1.36 V vs. Ag/AgCl in the same
1
slightly red-shied MLCT transitions compared to their ter-
34,43,44
solvent (Table 1).
A signicant cathodic shi is observed
34,36
pyridine analogs,
Table 1 and Fig. 2). It was previously shown in an in-depth
electronic structure study that the low-energy shoulders of the
MLCT transitions in [Ru(tpy)(bpy)(L)] complexes arise from
Ru(II)/tpy MLCT transitions. Therefore, the low-energy
and also feature low energy shoulders
for the reversible Ru(III/II) couple of 4 as compared to 1–3,
attributed to the destabilization of lled Ru(dp) orbitals by the
(
ꢁ
strongly p-donating acac ligand and it appears at a similar
1
2+
+
potential to that reported for [Ru(tpy)(acac)(dmso)] , +0.83 V vs.
1
41
35
Ag/AgCl, in the same solvent.
Three reversible reduction waves are observed for 1–3 and
the potentials of the rst two reduction couples are indepen-
dent of the bidentate ligand and appear at ꢀꢁ0.93 V and
ꢀ
ꢁ1.38 V vs. Ag/AgCl (Table 1). As such, these two couples are
assigned to the placement of two successive electrons on the
dqpy ligand. Two irreversible reduction waves are observed for
free dqpy at ꢀꢁ2.04 V and ꢀꢁ2.56 V vs. Ag/AgCl under identical
experimental conditions (Fig. S2†). A third reversible reduction
wave is also present in 1–3 that is associated with the bidentate
ligand. Complex 4 exhibits one reversible reduction couple at
ꢀ
ꢁ1.15 V vs. Ag/AgCl and two irreversible waves at ꢀꢁ1.86 V
and at ꢀꢁ2.19 V vs. Ag/AgCl (Fig. S3†), shied to more negative
potentials relative to 1–3. As expected, the monocationic
complex 4 is more difficult to reduce than the divalent 1–3 ions.
The HOMO–LUMO gaps in 1, 2, and 3 can be estimated at
2.40 eV, 2.38 eV, and 2.41 eV, respectively, from the difference in
the rst oxidation and rst reduction couples of each complex.
A value of 1.93 eV is calculated for 4, attributed to the highly
cathodically shied Ru(III/II) oxidation potential in this complex.
Fig. 2 Electronic absorption spectra of 1 (orange), 2 (red), 3 (green),
and 4 (purple) in acetone.
1
Table 1 MLCT absorption maxima, labs, and extinction coefficients, 3, in acetone, redox potentials, E1/2, and quantum yields, F, for 1–4 in
3
CH CN
3
ꢁ1
ꢁ1
a
Complex
l
abs/nm (3/ꢃ10 M cm
)
E
1/2 /V
F450, F600
1
2
3
4
352 (16), 371 (22), 471 (5.3), 550 (1.8), 609 (0.8)
353 (22), 372 (27), 456 (7.5), 558 (2.1), 608 (1.2)
353 (19), 372 (29), 469 (7.5), 534 (2.3), 600 (1.1)
346 (25), 366 (16), 540 (5.0), 703 (1.6), 770 (1.5)
+1.47, ꢁ0.93, ꢁ1.38, ꢁ1.67
+1.43, ꢁ0.95, ꢁ1.39, ꢁ1.74
+1.49, ꢁ0.92, ꢁ1.37, ꢁ1.65
0.0039(1), 0.0042(3)
0.0032(3), 0.0029(2)
0.0048(4), 0.0050(2)
0.0096(8), 0.010(1)
b
b
+0.78, ꢁ1.15, ꢁ1.67, ꢁ1.86
a
b
vs Ag/AgCl, 0.1 M TBAPF
6
.
Irreversible.
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2
MOs, LUMO+1 and LUMO+2, are of dqpy/p* (96%) and Me bpy/
p* (92%) character, respectively, which supports the assign-
ments of the second and third reduction waves in the CV of 2 as
dqpy- and Me bpy-based, respectively. As expected, the calcu-
2
lated MOs and Mulliken population densities of 1 and 3 show
similar properties to 2. The HOMO in each is of mixed Ru/dyz
and dqpy/p character, the LUMO and LUMO+1 are of predom-
inately dqpy/p* character, and the LUMO+2 has mainly biden-
tate/p* character (Fig. S20 and S21†), also consistent with the
electrochemical assignments for these complexes.
The calculated ground state HOMO of 4 shown in Fig. 4b is
ꢁ
of mixed Ru/dyz (53%) character with considerable acac /p
(27%) character, with only 17% localization on the dqpy ligand.
This result is expected based on the signicant donating ability
ꢁ
Fig. 3 Cyclic voltammagrams of 1–4 in CH
3
CN (0.1 M TBAPF
6
,
of the acac ligand. The LUMO of 4 is calculated to be
ꢁ1
200 mV s ).
predominately dqpy/p* (90%), analogous to 1–3. It is therefore
evident that the p-interaction of Ru/dyz orbitals with the acac
ꢁ
p-orbitals signicantly destabilizes the HOMO in 4, consistent
with the cathodic shi of the oxidation potential observed
electrochemically. The LUMO + 1 in 4 is predominately of dqpy/
p* (96%) character, but in contrast to 1–3, the LUMO + 2 is also
localized on the dqpy ligand (98% dqpy/p*), reecting the
Electronic structure calculations
DFT calculations were performed to gain further insight into
the electronic structures of 1–4. Geometry optimizations using
the PBE functional, the SDD basis set for Ru, and the TZVP basis
set on all other atoms gave structures in excellent agreement
with experimentally determined crystal structures for 2–4
ꢁ
electron-rich character of the acac ligand.
The calculated electronic absorption spectra of 1–4 using TD-
DFT are in good agreement with experimental data. The calcu-
lated HOMO–LUMO energy difference in 2 is 2.17 eV, which is
in good agreement with the 2.38 eV determined electrochemi-
(Tables S2–S4†). The calculated molecular orbitals (MOs) and
Mulliken population densities for 2 suggest that in the ground
state the HOMO is of mixed Ru/dyz (58%) and dqpy/p (30%)
character with minor contributions from Me bpy/p* (7%) and
1
cally. The lowest energy transition is predicted to be a MLCT
2
predominately from the HOMO (Ru/dyz) to the LUMO (dqpy/p*)
with a maximum at 570 nm, corresponding to the experimen-
tally observed lowest-energy shoulder at 608 nm. The slightly
higher-energy shoulder transition at 558 nm is calculated at
CH CN/p* (5%), while the LUMO is of almost entirely (92%)
3
dqpy/p* in character. The rendered contour plot of the LUMO
in Fig. 4a shows signicant delocalization on the quinolinyl
groups of the dqpy ligand. The next two higher unoccupied
Fig. 4 Calculated frontier molecular orbitals for (a) 2 and (b) 4.
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1
5
44 nm to be a mixed MLCT from HOMO-2 (Ru/dxy) and a function of irradiation time with lirr $ 395 nm and lirr $
HOMO-1 (Ru/d ) to the LUMO (dqpy/p*). Four predicted 610 nm (Fig. 5a). During the photolysis of 1, a single set of
xz
1
MLCT transitions comprise the intense features in the 420– isosbestic points at 402, 480, and 540 nm were observed,
4
80 nm range of the absorption spectrum of 2. The most intense indicative of a single transformation without secondary reac-
transition at 456 nm, calculated at 446 nm, is of mostly HOMO tions. Similar results were observed for 2 and 3 with lirr
Ru/dyz) to LUMO+2 (Me bpy/p*) character, while the other 395 nm and lirr $ 610 nm (Fig. S9–S11†). It should also be noted
three transitions are of mixed Ru/d to dqpy/p* character. that no changes to the electronic absorption spectra of 1–4 were
Calculated absorption energies of 1 and 3 parallel those of 2 observed in the absence of light for at least 48 h in H O (5%
See Table S5†). The most intense MLCT transitions in 1–3 are acetone), consistent with the dark stability of the complexes
to the bidentate ligand, whereas those at lower energies are (Fig. S14–S17†).
localized on the dqpy ligand. The photoreactivity of 4 in H O (5% acetone) with near-IR
$
(
2
2
1
(
2
The HOMO–LUMO energy difference in 4 is calculated to be light lirr $ 715 nm is shown in Fig. 5b. The irradiation of
1
.70 eV, consistent with the electrochemical gap 1.93 eV. Using nitrogen-purged samples of 4 results in similar spectral changes
1
TD-DFT, a pure HOMO–LUMO transition is calculated at as those observed for 1–3, with a decrease in the MLCT band at
730 nm, which corresponds to the absorption feature at 770 nm. 533 nm and the appearance of a new peak at 600 nm with an
A mixed HOMO and HOMO-1 (Ru/dxy) to dqpy/p* transition is isosbestic point at 551 nm, conrming the release of CH CN
3
calculated with a maximum at 598 nm, and four additional and the formation of a single product. Whereas the photo-
1
MLCT transitions of predominately Ru/d to LUMO ꢁ LUMO+2 chemistry of 1–3 is independent of oxygen, 4 undergoes
character are calculated within the visible spectrum (Table S5†). a secondary photochemical reaction in water in the presence
No transitions involving the acac ligand are predicted in the of oxygen (Fig. S12†). Given the low Ru(III/II) oxidation
ꢁ
visible/near-IR range.
potential of 4, it is believed that the photochemical product,
+
[
Ru(dqpy)(acac)(OH
cac)(OH), is oxidized by O
Ag/AgCl in water) upon absorption of a photon. Analysis of the
2
)] or its deprotonated form, Ru(dqpy)(a-
0
/ꢁ
2
in solution (E1/2(O
2
) ¼ ꢁ0.82 V vs.
Photochemistry
46
The ligand substitution photochemistry of 1–4, depicted in photochemically generated species present in aerated aqueous
Scheme 2, was monitored through the changes in the electronic solutions of 4 by mass spectrometry reveals a peak with m/z ¼
1
+
absorption and H NMR spectra as a function of irradiation 551.13, consistent with [Ru(dqpy)(acac)(OH)] (Fig. S19†).
time in D
O (5% acetone-d
peak at 2.07 ppm associated with the coordinated CH
2
O and CD
) featured a decrease in the intensity of the a photon; when the photolysis of 4 is conducted in N
CN
O and only opened to air aer the sample is removed from
3
CN (lirr $ 395 nm). The photolysis of 1 in However, control experiments show that this reaction requires
-purged
D
2
6
2
H
2
3
ligand, and an increase in intensity of that corresponding to the light, the oxidation side-reaction is not observed (Fig. S13†).
free CH CN at 2.06 ppm. However, the ligand exchange product, Moreover, when 4 is irradiated in water in the presence of the
3
2
+
[
Ru(dqpy)(bpy)(D O)] , generally precipitated in solution at reducing agent ascorbic acid in air, no product oxidation is
concentrations necessary for H NMR characterization. Moni- apparent, consistent with the regeneration of the Ru(II) product
2
1
toring the photolysis of 1 in CD
3
CN was more successful. A by ascorbate (Fig. S13†). In contrast to the reactivity in water, the
decrease in intensity of the H NMR peak at 2.02 ppm associ- photoinduced ligand exchange of 4 in aerated CD CN is not
ated with the coordinated CH
CN ligand was observed with the accompanied by oxidation, as determined by following the
concomitant increase of the resonance at 1.96 ppm known to reaction by H NMR spectroscopy upon irradiation of 4 in
1
3
3
1
2
0,45
correspond to free CH CN (Fig. S4†).
No other spectral CD
3
CN using LEDs with lirr ¼ 735 ꢄ 15 nm, which results in the
CN aer 2 h with no other observable spectral
for solvent CD CN during the photolysis. Similar spectral changes (Fig. S8†). These results indicate that the secondary
3
changes are observed, consistent with the exchange of CH CN release of free CH
3
3
3
changes are observed for the photolyses of 2–4 in CD
Fig. S5–S7†).
The irradiation of 1 results in a decrease in the MLCT band
3
CN pathway likely involves photoinduced electron transfer to O
generate superoxide and is a topic of future work.
2
to
(
1
The quantum yields of CH CN exchange, F450, for 1–4 in
3
at 471 nm and the appearance of a new band at 474 nm as deaerated water with lirr ¼ 450 nm are listed in Table 1, and
Scheme 2
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this difference in the localization of charge in the excited state
may play a role in the ligand dissociation. In the case of 1–3, the
MLCT state should possess signicant dqpy pp* character,
ꢁ
whereas in 4 the excited state is mixed Ru/acac /dqpy metal/
ligand-to-ligand charge transfer (ML-LCT). Removal of electron
ꢁ
density from the acac ligand with one coordination site posi-
tioned trans to the leaving ligand may weaken the Ru–NCCH
3
3
bond and lead to dissociation. Alternatively, the ML-LCT
excited state in 4 may be able to mix with the dissociative
metal-centered state, thus promoting ligand exchange.
Conclusion
The series of dqpy supported Ru(II) complexes presented above
undergo ligand substitution upon absorption of tissue-
penetrating red and near-IR light. These complexes are stable
in the dark, and exhibit similar quantum yields with 450 and
600 nm irradiation. Electrochemical studies conrm that the
lowered LUMO energy resulting from the extended p-system in
the dqpy ligand in 1–3 relative to the terpyridine substituted
analogs is responsible for the red-shied MLCT transition
energies, whereas in 4 the predominant cause of the excep-
tionally low energy MLCT transitions is the relatively destabi-
lized HOMO resulting from the strongly electron-donating
ꢁ
acac ligand. Structural evidence reveals that dqpy imposes
little or no steric hindrance on the monodentate nitrile ligand,
and the inuence of the dqpy ligand is primarily electronic,
allowing for sterics to be easily added or removed through
choice of bidentate ligand. The versatility, photoreactivity, and
exceptional dark stability of dqpy supported Ru(II) complexes
makes them ideal candidates for PCT agents. Studies using
complexes of this type as photocages for anticancer drugs in
biological systems are currently underway.
Fig. 5 Changes in the electronic absorption spectra upon irradiation
of (a) 1 (lirr $ 610) nm and (b) 4 (lirr $ 715 nm) in H
irr ¼ 0–2 h under a N atmosphere.
2
O (5% acetone),
t
2
Conflicts of interest
those recorded using lirr ¼ 600 nm were identical within the There are no conicts of interest.
error of the measurement. The values of F450 measured for 1–3
are generally similar to each other, but the photoaquation
Acknowledgements
quantum yield of 4 is greater by a factor of ꢀ2–3 (Table 1). In
contrast to 4, photoisomerization in the related [Ru(tpy)- The authors thank Pelotonia for nancial support and the Ohio
+
35
(
acac)(dmso)] complex is not observed (F < 0.0001), whereas Supercomputer Center. Elemental analyses were obtained from
2
+
47
that of [Ru(tpy)(bpy)(dmso)] is more efficient (F ¼ 0.024). It the CENTC Elemental Analysis Facility at the University of
is therefore likely that ligand photosubstitution in 4 occurs by Rochester, funded by NSF CHE-0650456. The authors are
a different mechanism than the photoisomerization of the grateful to Dr Judith C. Gallucci and Dr William W. Brennessel
related dmso complexes.
for their guidance in crystallography.
It is important to note that the Ru-based HOMO of 4
ꢁ
possesses a signicant contribution from the acac ligand
(
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lowest energy MLCT band is calculated to arise from a HOMO–
LUMO transition. Therefore, the hole in the lowest energy
MLCT states of 1–3 is expected to have signicant contribution
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