Photochemistry and Photobiology, 2014, 90: 257–274
Invited Review Singlet Oxygen Generation by Cyclometalated Complexes and Applications† David Ashen-Garry and Matthias Selke* Department of Chemistry and Biochemistry, California State University Los Angeles, Los Angeles, CA Received 20 August 2013, accepted 28 October 2013, DOI: 10.1111/php.12211
ABSTRACT
involved in apoptosis (8), and the chemistry of catalytic antibodies (9,10). Given these very diverse contexts and applications, it is not surprising that a number of different methods for thermal and photochemical singlet oxygen generation have been developed, and, despite the apparent abundance of thermal and photochemical sources of singlet oxygen, this has remained an active area of research. For thermal singlet oxygen generation, the most important group of precursors are arguably aromatic endoperoxides, several hundred of which have been prepared and found to release 1O2 upon heating (11). Among the aromatic endoperoxides, anthracene derivatives have been most thoroughly investigated. Unfortunately, not all these endoperoxides release 1O2 in high yield. In a classic study, Turro et al. showed that the activation barrier for release of dioxygen from 9,10-anthracene endoperoxides via a retro-[4 + 2] cycloaddition is ca. 38 kcal mol1 (12,13). As the excitation energy of singlet oxygen is 22.5 kcal mol1, dioxygen could be released either in the singlet or triplet state. Turro et al. demonstrated that 9,10-endoperoxides may undergo stepwise release of dioxygen, leading to a biradical intermediate which undergoes intersystem crossing (ISC) to a triplet biradical which then loses 3O2 rather than 1O2. On the other hand, the retro[4 + 2] cycloaddition in 1,4-endoperoxides is a concerted process leading only to singlet oxygen and the parent anthracene derivative. In general, attaching various substituents to 1,4-anthracene derivatives allows for control over solubility, stability and thus the temperature and yield of singlet oxygen release during the cycloreversion of the corresponding anthracene endoperoxides, making these compounds the most common thermal source of singlet oxygen in the laboratory (11). In addition to these thermal sources, singlet oxygen can be produced photochemically by various dyes, including porphyrins and related compounds by photosensitization. Just as aromatic endoperoxides can be fine-tuned to affect the parameters of thermal singlet oxygen release, porphyrins and porphyrin derivatives as well as phthalocyanines can be fine-tuned to control the solubility, excitation wavelength and singlet oxygen quantum yield. Several reviews have been published on singlet oxygen generation by these compounds (14–16). One drawback of these sensitizers is that synthetic modification to attach them to other materials or biomolecules is usually not trivial; aggregation of porphyrin-type sensitizers in solution is also a common problem. As an alternative, during the past decade, a number of borondipyrromethene (BODIPY)-based photosensitizers for production
While cyclometalated complexes have been extensively studied for optoelectronic applications, these compounds also represent a relatively new class of photosensitizers for the production of singlet oxygen. Thus far, singlet oxygen generation from cyclometalated Ir and Pt complexes has been studied in detail. In this review, photophysical data for singlet oxygen generation from these complexes are presented, and the mechanism of 1O2 generation is discussed, including evidence for singlet oxygen generation via an electron-transfer mechanism for some of cyclometalated Ir complexes. The period from the first report of singlet oxygen generation by a cyclometalated Ir complex in 2002 through August 2013 is covered in this review. This new class of singlet oxygen photosensitizers may prove to be rather versatile due to the ease of substitution of ancillary ligands without loss of activity. Several cyclometalated complexes have been tethered to zeolites, polystyrene, or quantum dots. Applications for photooxygenation of organic molecules, including “traditional” singlet oxygen reactions (ene reaction, [4 + 2] and [2 + 2] cycloadditions) as well as oxidative coupling of amines are presented. Potential biomedical applications are also reviewed.
INTRODUCTION Some sources of singlet oxygen—A brief overview Singlet oxygen (1Δg), the lowest excited state of the dioxygen molecule, can be produced thermally or photochemically (1–5). The former method involves loss of dioxygen in its singlet state from various precursors such as phosphite ozonites or various peroxides while the latter method involves either photochemically induced loss of 1O2 from a peroxide or, much more commonly, excitation of a photosensitizer followed by energy transfer to ground-state (triplet) dioxygen. Singlet oxygen is widely used for oxyfunctionalizations of organic molecules. It is also involved in a variety of biological and biomedical processes: It is the major cytotoxic species in photodynamic therapy (PDT) (6) and some photoactive antiviral drugs (7). It may also be *Corresponding author email: [email protected] (Matthias Selke) †This paper is part of the Special Issue honoring the Memory of Nicholas J. Turro. © 2013 The American Society of Photobiology
257
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David Ashen-Garry and Matthias Selke
of singlet oxygen have been developed. This new class of sensitizers has recently been reviewed (17,18). Yet another major class of singlet oxygen photosensitizers is various metal complexes. Numerous diimine transition metal complexes derived from Ru(II), Os(II) and Pt(II) as well as Ir(III) are singlet oxygen sensitizers (19–26). Perhaps the most promising group of metal-based singlet oxygen sensitizers is cyclometalated complexes of late transition metals. Just like porphyrins and phthalocyanines, the photophysical parameters of these compounds can be systematically manipulated by changes in the electronic properties of the complex (27). In addition, unlike other sensitizers, cyclometalated complexes often possess ancillary ligands that can easily be replaced, thereby allowing facile attachment of the sensitizer to other molecules, including nanomaterials or biomolecules such as DNA bases or proteins. This review will focus on singlet oxygen generation by cyclometalated complexes, and various applications of this relatively new class of sensitizers. All cyclometalated complexes which have thus far been evaluated as singlet oxygen sensitizers are either octahedral d6 Ir(III) complexes or square planar d8 Pt(II) complexes. Photophysical properties of cyclometalated complexes During the past two decades, cyclometalated complexes have been primarily studied for applications in optoelectronic materials, especially organic light-emitting devices (28–31). The emissive properties of the excited states of all these complexes include high luminescence efficiencies and long excited-state lifetimes. Cyclometalating ligands are strong-field ligands as the metal–carbon bond of the cyclometalating ligand enhances splitting of the d orbitals of the metal. Upon excitation of a cyclometalated complex, this large splitting of the metal d orbitals leads to preferential formation of metal-to-ligand charge-transfer (MLCT) states instead of metal-centered excited states. The large extended p system of the cyclometalating ligand may also undergo excitation of an electron to a p* orbital thereby generating a purely ligand-based excited state. The high Z metal center promotes rapid ISC to a triplet p-p* ligand-based excited state. Consistent with this analyses, a computational study by Hay has shown that the LUMO and LUMO + 1 are indeed p* orbitals located on the ligands (32). As the ligand-based MLCT and p-p* states are close in energy, there appears to be significant overlap between these two excited states, leading to a mixed MLCT-3[p-p*] state. In general, this mixed triplet excited state is the long-lived (usually in the microsecond range) emissive state of these complexes (33–36), although interligand energy transfer from the 3MLCT state to an ancillary ligand (which thereby becomes the emitting center) may occur in some cases (37). Ancillary ligands can be used to fine-tune the emission wavelength. For example, Yersin et al. have studied the photophysical properties of two biscyclometalated Ir complexes bearing identical cyclometalating ligands (2-(4′,6′-difluorophenyl)pyridine) (38). These complexes differ only in that one complex has an acetonylacetonato ancillary ligand, whereas the second complex has an N,O-bound picolinato ligand. The nitrogen atom possesses higher ligand field strength than the oxygen atom, thereby lowering the energy of the three occupied d orbitals of the t2g level (HOMO). This increases the d-p* energy gap, thereby causing a blueshift in the emission, as the energy of the MLCT transition is raised (39). The effect of electron-withdrawing substituents on the cyclometalating ligand is somewhat harder to
predict. While such substituents lower the energy of the LUMO (i.e. the p* orbital on the cyclometalating ligand), they also withdraw electron density from the metal-based HOMO (i.e. the t2g manifold), thereby raising its energy level. Usually the latter effect predominates (39). Synthesis of cyclometalated iridium (III) complexes Octahedral Ir(III) complexes can possess one, two, or three cyclometalating ligands. Biscyclometalated complexes of the type Ir(C^N)2L2 (C^N=cyclometalating ligand, L=ancillary ligand) are most common, but mono- and tris-cyclometalated Ir(III) complexes (Ir[C^N]3) can be prepared as well. Monocyclometalated Ir(III) complexes are comparatively rare, and have not yet been investigated as sensitizers for the production of singlet oxygen. Most Ir(III) complexes that have been investigated as singlet oxygen sensitizers are biscyclometalated complexes; in addition to the two cyclometalating ligands, they posses either two singly bound ancillary ligands or one chelating ancillary ligand. The synthesis of such biscyclometalated Ir(III) complexes is rather facile, and is usually accomplished by simply refluxing IrCl3 in the presence of four equivalents of the cyclometalating ligand (33). This leads to a chloro-bridged dimer with two cyclometalating ligands on each Ir atom. The dimer can then be cleaved with an ancillary ligand. A wide range of compounds can be used to cleave the chloride-bridged dimer, ranging from 2,4-pentadione in the presence of base to bipyridine to amino acids which can be N,O-bound. Monoamines can also be used to cleave the dimer, in which case each of the monomers retains one of the two bridging chloride atoms. The latter reaction allows for facile linking of these sensitizers with spacers to biomolecules or nanomaterials (33,39). The synthesis of tris-cyclometalated Ir(III) complex is also rather straightforward, as these compounds can be prepared from biscyclometalated precursors via displacement of an ancillary ligand. For example, for complexes containing 2-phenylpyridine as the cyclometalating ligand, displacement of the acetonylacetate (acac) ligand from the biscyclometalated complex with another cyclometalating ligand and reflux at high temperature (>200°C) leads to the facial (fac) isomer of the triscyclometalated complex. The meridional (mer) isomer can be obtained by simply decreasing the reflux temperature after addition of the 2-phenylpyridine to the biscyclometalated complex to 140°C. Alternatively, refluxing Ir(acac)3 with three equiv. of the cyclometalating ligand represents a direct pathway to the fac isomer of the tris-cyclometalated complex (33,40–42). The various routes to bis- and tris-cyclometalated complexes bearing 2-phenylpyridine ligands are shown in Scheme 1 below. Recently, Swager et al. have developed another simple route to a wide range of cyclometalated Ir(III) complexes using a Cu (I) trazolide intermediate for the transmetalation step (43). This simple procedure allows a one-pot procedure for ligand synthesis and cyclometalation, thereby again allowing facile preparation of a wide range of these complexes with different ancillary ligands and substituents on the cyclometalating ligands. Overall, from a synthetic point of view, cyclometalated complexes are a class of singlet oxygen sensitizers that are quite easy to prepare and fine-tune both for different absorption profiles and for different applications. Literally hundreds of different complexes have been prepared during the past decade, and a review of the detailed synthesis and characterization of each of these complexes would be beyond the scope of this study. We will focus on complexes
Photochemistry and Photobiology, 2014, 90
259
Scheme 1. Synthesis of bis- and triscyclometalated Ir(III) complexes.
for which photosensitized generation of singlet oxygen has been experimentally demonstrated.
SINGLET OXYGEN GENERATION BY CYCLOMETALATED COMPLEXES Iridium (III) complexes as sensitizers—mechanistic aspects In 2002, the groups of Thompson and Selke reported that several Ir(III) biscyclometalated complexes are excellent photosensitizers for the production of singlet oxygen (44). This was followed by a full paper in 2007 which explored the mechanism of singlet oxygen generation by these complexes (45). The structures of the Ir complexes (1–10) are depicted in Scheme 2. They all possess two cyclometalating ligands, and several different ancillary ligands, including N,O-bound glycine (Complex 5). Several different cyclometalating ligands were employed in this study, namely 2-phenylpyridine (ppy); 1-naphtylpyridine (1np); 2-phenylquinoline (pq); 2-(1-naphthyl)benzothiazole (bsn); 2-phenylbenzothiazole (bt); 2-phenylbenzo-oxazole (bo) and (2-pyridyl)benzothiophene) (btp). Table 1 gives an overview of the photophysical data for all cyclometalated Ir(III) complexes that have been investigated for the production of singlet oxygen to date (August 2013). Many of these complexes produce singlet oxygen in high yield, with quantum yields approaching unity in some cases. As discussed earlier, cyclometalated complexes possess a long-lived triplet state of mixed MLCT-p-p* character. This triplet state is rapidly quenched by triplet (ground-state) oxygen. The fraction of triplet quenched by ground-state oxygen (PT,O2) can easily be determined by comparison of the triplet lifetime in degassed samples vs in air [Eq. (1)]
Scheme 2. Biscyclometalated Ir(III) complexes 1–10 that produce singlet oxygen.
[(bsn)2Ir(acac)] 1 [(bsn)2Ir(dpm)] 2 [(pq)2Ir(acac)] 3 [(bt)2Ir(acac)] 4 [(bsn)2Ir(gly)] 5 [(bt)2Ir(py)Cl] 6 [(ppy)2Ir(acac)] 7 [(bo)2Ir(acac)] 8 [(1np)2Ir(acac)] 9 [(btp)2Ir(acac)] 10 [Ir(dpyx) (phbpy)]+ 11 [Ir(ppy)2(bpy)]+ 12 [Ir(ppy)2(bpy)]+ 12 [(ppy)2Ir(bpy)]+ 12 [Ir(dppy)(tpy-CO2Et)]+ 13 [(pip)2Ir(acac)] 14 [fac-Ir(ppy)3] 15 [(ppy)2Ir(phen)]+ 16 [(ppy)2Ir (dmbpy)]+ 17 [Ir(deatpy)3] 18 [Ir(deatpy)3-H3]3+ 19 [Ir(btpy)2(biS)]+ 20
Compound
None detected
1.5
DMSO/H2O/HCl
CH2Cl2
0.78 1.2
27
0.78
0.93
+
†
+
None detected
0.78
0.93
CH2Cl2:MeOH (9:1) CH3CN DMSO/H2O
33
0.5
0.5
46
1.9 1.6 0.88
CH2Cl2:MeOH (9:1) Toluene CH2Cl2:MeOH (9:1) 0.036
0.26
CH2Cl2:MeOH (9:1)
54
53
52 34 53
52 65 52
52
51
52
51
45 33 51
0.6 0.05
0.98
0.5 0.05
1.25
CH3CN
43
6.4
0.049
0.68
45 33 45 33 45
44
44,45 33 44,45 33 44
44 33 44,45
Ref.
54
0.34
CH2Cl2:MeOH (9:1)
6.8
0.079
1.35
1.31
1.63
1.27
1.28
1.06
E1/2 (Sen+/*) (V)*
0.97
0.18
THF
CH3CN
None detected
0.72 0.06
5.66 5.8 0.12
Toluene 2MeTHF CH3CN
0.97
0.81
0.4 0.05
None detected
0.76 0.05
5.2
0.104
0.18 0.03
0.76 0.06
7.1
0.076
None detected
0.92
0.90 0.05
23
1.43 1.6 1.31 1.1 3.45
Toluene 2MeTHF Toluene 2MeTHF Toluene
0.026
None detected
0.95 0.09
1.0 0.2
4.0 0.3
6.3 0.2
C6H6
0.92
5.9 0.6
0.085
0.62 0.05
0.60 0.06
0.59 0.07
O2 quantum yield (ΦD)
2.1 0.5
0.65
7.2 0.3
0.071
1
1 O2 quenching rate (kT, 106 M1 s1)
0.54 0.02
0.73
2.9 0.1
0.165
Emission quenching by 3O2 (kq, 109 M1 s1)
0.5 0.2
1.5 2 1.41 1.8
1.8 1.49
Emission lifetime (aerated) (s, ls)
Fraction of T1 quenched by 3O2 leading to formation of 1O2 (fT,D)
0.86 0.07
C6H6 2MeTHF C6H6 2MeTHF C6H6
C6H6 2MeTHF C6H6
Solvent
Emission lifetime (degassed) (s, ls)
Table 1. Singlet oxygen generation and related photophysical data for Ir-cyclometallated complexes.
260 David Ashen-Garry and Matthias Selke
[(ppy)2Ir(deac)] 36
[(bsn)2Ir(bpy-CONH-Et)]+ 35
[(bsn)2Ir(bpy-CONH-PEG)]+ 34
[(pq)2Ir(bpy-CONH-Et)]+ 33
[(pq)2Ir(bpy-CONH-PEG)]+ 32
[(pba)2Ir(bpy-CONH-Et)]+ 31
[(pba)2Ir(bpy-CONH-PEG)]+ 30
[(pppy)2Ir(bpy-CONH-Et)]+ 29
[(pppy)2Ir(bpy-CONH-PEG)]+ 28
[(ppy)2Ir(bpy-CONH-Et)]+ 27
[Ir(btpy)2(biSe)]+ 21 [Ir(Mebib)(ppy)]+ on SBA-15 22 [Ir(Mebib)(ppy)]+ on MCM48 23 [Ir(Mebib)(ppy)]+on MCM-41 24 [(piq)2Ir(pypzS2)]–CdSe/ZnS 25 [(ppy)2Ir(bpy-CONH-PEG)]+ 26
Compound
Table 1. (continued)
CH2Cl2 CH3CN DMSO CH2Cl2 CH3CN DMSO CH2Cl2 CH3CN DMSO CH2Cl2 CH3CN DMSO CH2Cl2 CH3CN DMSO CH2Cl2 CH3CN DMSO CH2Cl2 CH3CN DMSO CH2Cl2 CH3CN DMSO CH2Cl2 CH3CN DMSO CH2Cl2 CH3CN DMSO CH3CN 2-Propanol 4:1 75.5
4.26 3.72
4.1 3.76
0.67 0.54
2.08(10%) 0.78(90%) 2.16(15%) 0.54(85%)
2.86 3.72
4.26 2.86
0.50 0.33
0.49 0.34
0.40 0.23
0.78
0.80
0.29
0.31
0.54
0.54
0.21
0.24
0.16
0.83 +§
0.69
0.58
0.51
0.79
0.58
0.50
0.38
0.38
0.24
0.87
MeOH
58 58 58 58 58 58 58 58 58 58 58 58 58 58 58 58 58 58 58 58 58 58 58 58 58 58 58 58 58 58 62
57
56
+‡
CH3CN
56
54
56
None detected
Ref.
++‡
‡
E1/2 (Sen+/*) (V)*
CH3CN
0.17
O2 quantum yield (ΦD)
++†
1
1 O2 quenching rate (kT, 106 M1 s1)
+++
0.38 0.21
Emission lifetime (aerated) (s, ls)
Fraction of T1 quenched by 3O2 leading to formation of 1O2 (fT,D)
CH3CN
CH2Cl2
Solvent
Emission lifetime (degassed) (s, ls)
Emission quenching by 3O2 (kq, 109 M1 s1)
Photochemistry and Photobiology, 2014, 90 261
0.97
0.52
0.15 0.177
0.133
87.2 MeOH
23.7 MeOH
8.7 CH2Cl2/MeOH
22.3
CH3CN 2-Propanol 4:1 MeOH
[(ppy)2Ir(pdeac)] 37 [(ppy)2Ir(bpy-PBI)]+[PF6] 38 [(ppy)2Ir(bpy-aPBI)]+[PF6] 39 [(ppy)2Ir(pBodipy)]+[PF6] 40 [(ppy)2Ir(2Bodipy)]+[PF6] 41
Compound
Solvent
73.6
Emission lifetime (degassed) (s, ls) Table 1. (continued)
*E(Sen+/0*) = E(Sen+/0) E0-0; †not quantified, but [Ir(btpy)2(biSe)]+ had 2.4 times larger 1O2 emission intensity than [Ir(btpy)2(biS)]+; ‡not quantified, but relative singlet oxygen levels were SBA15 > MCM-48 > MCM-41; §not quantified, but efficient photooxidation of 1,5-dihydroxynaphthalene to 5-hydroxy 1,4-naphthalenedione (juglone).
63
63
64
64 0.91
+
§
Emission lifetime (aerated) (s, ls)
Emission quenching by 3O2 (kq, 109 M1 s1)
Fraction of T1 quenched by 3O2 leading to formation of 1O2 (fT,D)
1
O2 quantum yield (ΦD)
1 O2 quenching rate (kT, 106 M1 s1)
E1/2 (Sen+/*) (V)*
62
David Ashen-Garry and Matthias Selke Ref.
262
PT;O2 ¼ 1 ðsair =sN2 Þ
ð1Þ
where sair and sN2 are the triplet lifetimes in air and under nitrogen respectively. PT,O2 can also be expressed as the fraction of the rate of triplet quenching (kq) by triplet oxygen relative to the intrinsic rate of decay of the triplet state under anaerobic conditions (i.e. sN21) [Eq. (2)]. PT;O2 ¼ kq ½3 O2 =ðsN2 1 þ kq ½3 O2 Þ
ð2Þ
In the absence of any chemical reaction, the rate of decay of the triplet state is the sum of the rate constants for nonradiative decay and phosphorescence, and hence Eq. (2) can be rewritten as PT;O2 ¼ kq ½3 O2 =ðkq ½3 O2 þ knr þ kp Þ
ð3Þ
where knr and kp are the rate constant for nonradiative decay and phosphorescence respectively. The overall quantum yield of singlet oxygen production (ΦD) is given by Eq. (3). UD ¼ UT PT;O2 fT;D
ð4Þ
where ΦT is the quantum yield of triplet formation and fT,D is the fraction of triplet quenched by ground-state oxygen leading to formation of singlet oxygen. In cyclometalated complexes, the value of ΦT is usually unity, as the heavy metal atom of these complexes facilitates intersystem crossing to the triplet mixed MLCT-p-p* state. On the other hand, the values of the fraction of triplet quenched by ground-state oxygen leading to formation of singlet oxygen fT,D may vary considerably. Triplet oxygen may quench the triplet excited MLCT-p-p* state of the cyclometalated Ir complex by three different mechanisms, namely energy transfer which directly leads to formation of singlet oxygen 1O2 [Eq. (5)], or electron transfer leading to formation of superoxide anion [O2•, Eq. (6)], or simple physical deactivation [Eq. (7)]. ½Ir(C^ N)2 L2 þ3 O2 ! 1 O2 þ ½Ir(C^ N)2 L2
ð5Þ
þ ^ ½Ir(C^ N)2 L2 þ3 O2 ! O 2 þ ½Ir(C N)2 L2
ð6Þ
½Ir(C^ N)2 L2 þ3 O2 ! 3 O2 þ ½Ir(C^ N)2 L2
ð7Þ
A classic scheme for singlet oxygen generation by energy transfer [Eq. (5)] developed originally by Gijzeman et al. (46,47) correlates the values of the rate constant for quenching of triplet excited states by triplet oxygen [kq, Eq. (2)] with values of fT,D, i.e. the fraction of triplet quenched by ground-state oxygen leading to formation of singlet oxygen. A triplet excited sensitizer and triplet oxygen reversibly form an encounter complex of (T13Σ) spin configuration. There are four unpaired electrons, and hence nine different spin configurations for this encounter complex, but only the singlet (1[T13Σ]) state of the encounter complex can dissociate to form singlet oxygen and ground-state sensitizer. Quenching rates of 1/9 of the diffusioncontrolled rate limit (kdiff) thus imply exclusive quenching of the triplet excited sensitizer by energy transfer and a value of unity for fT,D. Larger values for kq should lead to fT,D values of less than unity, as quenching from other states besides the singlet (1[T13Σ]) state of the encounter complex must occur.
Photochemistry and Photobiology, 2014, 90
occurs at least partly by an electron-transfer/back electron-transfer mechanism, it follows that the singlet oxygen quantum yield should decrease as an unfavorable excited-state reduction potential diminishes formation of such electron-transfer or charge-transfer intermediates. Several other groups have determined singlet oxygen quantum yields for cyclometalated iridium complexes. In 2008, Williams et al. reported singlet oxygen generation by two interesting Ir(III) complexes possessing two terdentate ligands of the type Ir (N^C^N)(N^N^C, 11) and Ir(C^N^C)(N^N^N, 13), as well as the biscyclometalated complex 12 which has an ancillary bipyridine ligand (Scheme 3) (51). Time-resolved measurements of singlet oxygen luminescence (excitation wavelength at 355 nm) gave singlet oxygen quantum yields of 0.4–0.6. The reason for the somewhat lower quantum yields (compared with complexes 1–10) is not known. Murata et al. subsequently studied singlet oxygen generation by a number of neutral and cationic cyclometalated complexes (12 and 14–17, Scheme 3) (52). This includes cationic complexes 12, 16 and 17 as well as the tris-cyclometalated complex fac(Ir(ppy)3) (15). Singlet oxygen quantum yields were measured by a chemical method, namely trapping of 1O2 by 1,5dihydroxynaphthalene. They also determined values for quenching of the triplet state of these complexes by triplet oxygen, and obtained values near the diffusion-controlled rate limit. However, only the cationic complexes—except complex 17—gave very high singlet oxygen yields, whereas those for the neutral complexes were lower. The reduced quantum yield of 17 was attributed to a steric blocking effect of the methyl groups on the bipyridine moiety. For the neutral complexes, the authors suggested that although electron transfer from the excited complex to triplet oxygen (Eq. (6)) is extremely rapid, the back electron transfer required to produce singlet oxygen by the electron-transfer mechanism is unfavorable (52). Aoki et al. prepared tris-cyclometalated Ir complexes bearing amino-substituted 2-phenyl pyridine ligands (18–19, Scheme 4) (53). They reported that the neutral complex 18 does not produce any singlet oxygen while the triprotonated complex 19 does, although the quantum yield is not known at this time. Singlet oxygen production was monitored by a chemical trap, i.e. 1,3-
Empirically, quenching rates near 1/9 kdiff and very high singlet oxygen quantum yields have been observed for many different sensitizers, including some metal complexes, i.e. many metalloporphyrins (48,49). However, this scheme had to be subsequently modified to account for cases in which fT,D was near unity while the value of kq was considerably larger than 1/9 kdiff. Formation of charge-transfer intermediates from the initial triplet excited sensitizer–triplet-oxygen encounter complexes may take place in these cases. Singlet oxygen is then formed from these charge-transfer complexes. Thus, for example, several Re(I), and Ir(III) complexes bearing bipyridine (bpy) ligands have kq values near 1010 M1 s1 (i.e. much larger than 1/9 kdiff) but produce singlet oxygen with quantum yields near unity which implies values of fT,D near unity (21,22). All the biscyclometalated Ir complexes studied by Djurovich et al. (1–10) produce singlet oxygen in moderate-to-high yield (44,45). Singlet oxygen quantum yields were determined directly from the time-resolved 1O2 near-infrared (NIR) emission signal. The authors also reported very large values of triplet-oxygen quenching (kq) by the triplet excited complexes. In one case (Complex 7) the value of kq was over an order of magnitude larger than kdiff (45). They suggested that such high rates may be indicative of quenching by electron transfer [Eq (6)], in addition to an energy-transfer mechanism [Eq. (5)] leading to formation of superoxide anion and a sensitizer radical cation. Singlet oxygen would then be formed from back electron transfer. Support for this hypothesis was derived from the very large observed values of kq for complex 7 at the diffusion-controlled rate limit, which is typical for an electron-transfer process and that the excited states of some tris-cyclometalated Ir(III) complexes are in fact quenched by triplet oxygen via an electron-transfer process (50). Further evidence for this hypothesis was derived from the observation that for (C^N)2Ir(acac) complexes 2–4 and 7–10 there exists a correlation between the decrease in the values of fT,D and the reduction potential of the triplet excited state of these complexes (E1/2 (Sen+/*)) (41). As can be seen for complexes 2–4 and 7–10 in Table 1, singlet oxygen quantum yields (and values of fT,D) decrease with decreasing excited-state reduction potential. If singlet oxygen generation by cyclometalated Ir(III) complexes
N
N
N N N
Ir
N
Ir
+
+
+
N
CO2Et
N
N [Ir(ppy)2(bpy)] + 12
[Ir(dpyx)(phbpy)] + 11
N
Ir
N
N
[Ir(dppy)(tpy-f-CO 2Et)]+ 13
+
N N
N
N N
O Ir
Ir O
N
Ir N
N N
N
+ N N Ir N N
N Ir(pip)2(acac) 14
fac-Ir(ppy) 3 15
263
Ir(ppy)2(phen) + 16
Ir(ppy)2(dmbpy) + 17
Scheme 3. Cationic and neutral cyclometalated Ir(III) sensitizers 11–17.
264
David Ashen-Garry and Matthias Selke
Et2N
NEt2
N
+ Et2HN
Ir N
+ NHEt2
N
N
Ir N
N
N
Ir
Ir
N N
NEt2
N
N
N
HN
NHEt2 +
Ir(deatpy)3 18
N N
[Ir(deatpy)3-H3]3+ 19
O
Si
O
O O O
Scheme 4. Iridium(III) substituted ligands.
triscyclometalated
complexes
with
Mesoporous Silica
+
+
S
S
N N Ir N
S
N
N
S
N
N
Ir
20
S
Se
Ir(Mebib)(ppy) on SBA-15 (22) Ir(Mebib)(ppy) on MCM-48 (23) Ir(Mebib)(ppy) on MCM-41 (24)
S
S
CdSe/ZnS QD [(piq) 2Ir(pypzS2)]-CdSe/ZnS (25)
Scheme 6. Irdium(III) cyclometalated complexes tethered to zeolites or QDs.
N
N S
amino-
N N
N
Se N N 21
Scheme 5. Iridium(III) biscyclometalated complexes with dithione or di-selenone ancillary ligands.
diphenylisobenzofuran (DPBF). Singlet oxygen production by this system was turned on by addition of HCl and turned off by addition of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). Son et al. prepared two interesting biscyclometalated complexes bearing an S-bound dithione (20) and a Se-bound di-selenone (21, Scheme 5; (btpy = bis(2-(2′-benzothienyl)pyridine; biS = bis(imidazoline thione; biSe = bis(imidazoline selone), 20) (54). The authors were able to detect singlet oxygen by its nearinfrared emission signal. While quantum yields were not determined, the authors noted that the singlet oxygen emission intensity from the selenone complex 21 was 2.4 times that of the thione complex 20. The compounds were used for photooxidative couplings of benzylamines to imines. Two groups (Che and Yamashita) evaluated singlet oxygen production of cyclometalated Ir(III) complexes tethered to either zeolites (22–24) (55,56) or quantum dots (QDs) (57) (Scheme 6). Singlet oxygen quantum yields were not determined in most cases except for a system in which the Ir(III) biscyclometalated complex [(piq)2Ir(pypzS2), 25] is attached to the surface of a CdSe/ZnS QD (57). No significant F€orster resonance energy transfer (FRET) was observed from the QD to the Ir complex. Singlet oxygen was thus produced by direct excitation of the complex. Singlet oxygen production of the Ir-CdSe/ZnS QD hybrid material was assessed by monitoring of the singlet oxygen NIR emission in aerated MeOH solution. It appears that the presence of the QD does not significantly reduce production of 1O2 by this system. Using bis(triisobutylsiloxy) silicon-2,3-naphthalocyanine (SiINC) as a reference, the singlet oxygen quantum yield ΦD was estimated to be 0.87 (57). Lo et al. prepared a series of poly(ethylene glycol) (PEG)modified Ir complexes and their free analogs (26–35) for potential use in PDT (Scheme 7) (58). The PEG–Ir complexes are [Ir (ppy)2(bpy-CONH-PEG)](PF6) (26), [Ir(pppy)2(bpy-CONHPEG)](PF6) (28), [Ir(pq)2(bpy-CONH-PEG)](PF6) (30), [Ir (bsn)2(bpy-CONH-PEG)](PF6) (32) and [Ir(pba)2(bpy-CONH-
PEG)](PF6) (34), whereas complexes 27, 29, 31, 33, and 35 are the corresponding free analogs (bpy-CONH-PEG = 4-(N-(2-(xmethoxypoly-(1-oxapropyl))ethyl)aminocarbonyl)-4′-methyl-2,2′-bipyridine; ppy = 2-phenylpyridine; pppy = 2-((1,1′-biphenyl)-4-yl) pyridine; pq = 2-phenylquinoline; bsn = 2-(1-naphthyl)benzothiazole; pba = 4-(2-pyridyl)benzaldehyde). The PEG-free compounds have (bpy-CONH-Et) in place of (bpy-CONH-PEG). Emission data taken for all 10 compounds showed that the PEG–Ir compounds were generally similar to their corresponding PEG-free compounds giving green to red emissions and long triplet lifetimes (58). Singlet oxygen production was determined by monitoring the consumption of DPBF at 418 nm in an aerated DMSO solution. Quantum yields were calculated using methylene blue as a reference. A limiting factor in singlet oxygen production by some of these complexes (i.e. 26 and 27) may be a relatively small value for kq such that the term kq[3O2] in Eq. (2) becomes small enough for other decay processes of the triplet excited complex (i.e. nonradiative decay) to be competitive with triplet-oxygen quenching. Complexes with the longest emission lifetimes (34 and 35) had the highest singlet oxygen quantum yields, indicating that longer triplet lifetimes result in higher quantum yields of singlet oxygen. Steric factors were also found to be important, as quantum yields were slightly higher in the PEG-free complexes most likely due to the inability of oxygen to freely diffuse into and out of the PEG complex, making it more difficult to both form singlet oxygen, and for the singlet oxygen produced to then reach the DPBF (58). Recently, several cyclometalated iridium complexes with dramatically enhanced visible absorption have been reported (59–64). While conventional cyclometalated iridium complexes typically have moderately strong absorption in the visible region (typically, e < 104 M1 cm1), the systems developed by Zhao et al. consist of a cyclometalated Ir complex to which an organic fluorophore is attached which increases visible absorption by at least an order of magnitude. These complexes all possess two cyclometalating 2-phenylpyridine (ppy) ligands, and an ancillary bipyrdine (bpy) ligand to which the fluorophore is attached. Several different fluorophores have been utilized, namely diethylcoumarin and phenyldiethylcoumarin ([(ppy)2Ir(deac)]+ [PF6] (36) (59,62) and [(ppy)2Ir(pdeac)]+ [PF6] (37)), perylenebisimide and an amino-substituted derivative ([(ppy)2Ir (bpy-PBI)]+ [PF6] (38) (61,64) and [(ppy)2Ir(bpy-aPBI)]+ [PF6]
Photochemistry and Photobiology, 2014, 90 +
O N
R
Ir N
Poly(ethylene glycol) (PEG)
N H
N N
R
Ir N
26: R = H
N
N
27: R = H
28: R =
29: R = R
O
R
30: R =
+
O
O
N H
N
265
O
31: R =
H
Ir(bpy-CONH-PEG)]+ (ppy, pppy, pba)
H
Ir(bpy-CONH-Et)]+ (ppy, pppy, pba)
+ +
O N N Ir
N
N H
O
S N
R
N H
N 32: R = PEG 33: R = Et
N
Ir(pq)(bpy-CONH-PEG)]+ and Ir(pq)(bpy-CONH-Et)]+
R
Ir N
34: R = PEG 35: R = Et
N S Ir(bsn)(bpy-CONH-PEG)]+ and Ir(bsn)(bpy-CONH-Et)]+
Scheme 7. Irdium(III) biscyclometalated sensitizers tethered to PEG and their free analogues.
(39)) and BODIPY (63). Both the PBI and BODIPY ligands were attached via an acetylene linker to the bpy ligand of (ppy)2Ir(bpy). Two different modes of attachment were used for the BODIPY moiety: attachment via the mesophenyl group to afford [(ppy)2Ir (pBodipy)]+ [PF6] (40) and attachment via the two positions of the core p-system giving [(ppy)2Ir(2Bodipy)]+ [PF6] (41) (Scheme 8). All the complexes 36–41 have considerably longer emission lifetimes than conventional cyclometalated Ir complexes (columns 3 and 4 in Table 1). Thus, the perylenebisimide complex 38 has triplet lifetime of 22.3 ls, and a singlet oxygen quantum yield ΦD of 0.91. Addition of the amino group caused a redshift in absorption from 546 nm in compound 38 to 675 nm in the amino-substituted derivative 39. Unfortunately, the aminosubstituted complex 39 has a shorter triplet-state lifetime (8.7 ls), and a significantly reduced singlet oxygen quantum yield (ΦD = 0.15). For the BODIPY complexes, conjugation of the BODIPY with the core (i.e. 2Bodipy, 41) provides more efficient population of the excited triplet state, and thus more efficient singlet oxygen generation compared with pBodipy (40). Complex 40 has a triplet lifetime of 23.7 ls and a singlet oxygen quantum yield of 0.52. Complex 41 has a redshifted maximum absorbance at 534 nm (compared to 504 nm for complex 40), an exceptionally long triplet lifetime of 87.2 ls and a singlet oxygen quantum yield of 0.97. All these quantum yields were calculated using DPBF as a singlet oxygen scavenger and Rose Bengal as a standard. Cyclometalated platinum (II) complexes as singlet oxygen sensitizers The second group of cyclometalated complexes that has been studied for the production of singlet oxygen are square planar d8
O + N Ir N
N
H N
N
N
O
36: R =
N +
-
[ppy)2Ir(deac)] [PF6]
O
R 37: R =
O N
[(ppy)2Ir(pdeac)] + [PF6]-
38: R' =
O
O
N
N
O
O
[(ppy)2Ir(bpy-PBI] + [PF6]-
+ R' N Ir N
O
HN
O
N
N
N
N
O
O
39: R' = [(ppy)2Ir(bpy-aPBI)] + [PF6]-
40: R' = [(ppy)2Ir(pBodipy)]+ [PF6]-
N F B N F
41: R' =
N N B F F + [(ppy)2Ir(2Bodipy) [PF6]-
Scheme 8. Iridium(III) sensitizers with organic fluorophores.
266
David Ashen-Garry and Matthias Selke
Pt(II) complexes. Similar to the octahedral Ir(III) complexes, these compounds can be prepared from the corresponding dichloride-bridged dimers bearing a cyclometalating ligand on each Pt atom by reaction with a variety of compounds such as acetonyl actetonate to bipyridines, quinolines, quinoline thiols as well as many monodentate ligands ranging from triphenylphosphine to pyridine. Tridentate cyclometalating ligands such as C-deprotonated 6-phenyl-2,2′-bipyridine [C^N^N] have also been used to prepare cationic complexes of the type [Pt(C^N^N)R1]n+ (66–71). The photophysical properties of these complexes are quite similar to their Ir counterparts. However, in many cases, the lowest excited state is a triplet intraligand charge-transfer (ILCT) state formed when the HOMO is located on the cyclometalating ligand and the LUMO on an ancillary ligand such as a quinoline. The triplet ILCT state of such complexes is the emissive state with a long lifetime in the microsecond range (72). Mixed triplet MLCT and ILCT states have also been reported (66,69,73). Recent theoretical investigation found that for Pt complexes with a cyclometalating 2-phenylpyridine ligand and a quinoline ligand, the energy gap between the ground state and the triplet excited state exceeds the excitation energy of singlet oxygen (22.5 kcal mol1), indicating that such complexes can indeed produce 1O2 (74). The first report of singlet oxygen production by Pt cyclometalated complexes was by Weinstein et al. in 2006 (75). Singlet oxygen quantum yields were determined directly from the time-resolved 1O2 NIR emission signal, using phenanelone (76) as a reference compound. The cyclometalated complexes studied by Weinstein et al. (42–50) are depicted in Scheme 9. Singlet oxygen quantum yields for these compounds range from 0.5 to 0.9, both in toluene and methylene chloride. The authors also determined the quenching rates of the triplet excited states by triplet oxygen. Unlike for some of the Ir (III) complexes discussed elsewhere in the study (especially 7, 8, 10), these were found to be approximately 1/9 of kdiff, indicating that most likely singlet oxygen production by these complexes occurs only by energy transfer. Subsequently, Djurovich et al. reported singlet oxygen generation from six different Pt(II) cyclometalated complexes (51–56, Scheme 10) (77) with quantum yields near unity in all cases (45). The cyclometalating ligands were the same as those used for Ir complexes 1–10. Measurements were accomplished via excitation at 355 nm and monitoring the 1O2 (NIR) emission sigR
R
R'
N O Pt N
R'
S
R N O Pt N
R'
N O Pt N
(thpy)Pt(QO)
(ppy)Pt(QO)
(dba)Pt(QO)
42: R = R' = H 45: R = Cl, R' = H 48: R = R' = CH3
43: R = R' = H 46: R = R' = CH3
44: R = R' = H 47: R = R' = CH3
N S Pt N
S
(thpy)Pt(QS) 49
N S Pt N (ppy)Pt(QS) 50
Scheme 9. Platinum(II) cyclometalated sensitizers 42–50.
S N Pt O O
N Pt O O
R
R (ppy)Pt 51: R = Me 52: R = t-Bu
[(bt)Pt(dpm)] 53
N Pt O O
N Pt O
S
O
R
R (btp)Pt 55: R = Me 56: R = t-Bu
[(pq)Pt(dpm)] 54
Scheme 10. Platinum(II) cyclometalated sensitizers 51–56. n+ N Pt
n+ N
PPh3
Pt
R
S
R
S
N S
[Pt(Thpy)(PPh 3)R]
[Pt(Thpy)(HThpy)R]
57: R = Cl, n = 0 58: R = NCCH3, n = 1 59: R = pyridine, n = 1
60: R = Cl, n = 0 61: R = pyridine, n = 1
2+ N S
Pt
Cl PPh2
OnBu
Cl Pt PPh2
N
N S
OnBu OnBu OnBu
[(PtThpyCl) 2Calix OnBu)] 62
S
NCMe NCMe N Pt Pt PPh2 PPh 2
OnBu
S
n OnBuO Bu OnBu
[{PtThpy(CH3CN)} 2Calix (O nBu)] 63
Scheme 11. Platinum (II) complexes with a cyclometalating 2-(20 thienyl) pyridyl ligand.
nal. Again, quenching rates of the triplet excited states of these complexes by triplet oxygen were found to be approximately 1/9 of kdiff, and, as ΦΔ is unity, fT,D must be unity as well, indicating that most likely singlet oxygen production occurs by energy transfer. Singlet oxygen quenching rates (kT) by Pt complexes 51–56 were also determined, and found to be somewhat higher (6.9 9 106–2.2 9 107 M1 s1) than those of the analogous Ir complexes, but still moderately low, and lower than sensitizers such as tetraphenyl porphyrine (kT = 4.4 9 107 M1 s1) (78). The authors also noted that steric bulk on the ancillary ligands does not appear to affect the singlet oxygen quantum yield (45). Lai et al. reported singlet oxygen quantum yields for a series of 2-(2′-thienyl)pyridyl platinum(II) complexes bearing various ancillary ligands such as Cl, PPh3 and pyridine (57–63, Thpy = 2-(2′-thienyl)pyridyl) (79). The lowest excited state of complexes 57–63 (Scheme 11) is a triplet ILCT state, as is common for cyclometalated Pt complexes. The quantum yields for singlet oxygen production were obtained by time-resolved laser measurements of NIR signal intensity of 1O2 at an excitation wavelength of 355 nm in
Photochemistry and Photobiology, 2014, 90 deuterated acetonitrile and dichloromethane (Table 2) using C60 (ΦD = 1) (80) as a reference. The cationic complexes 58 and 59 had a notably higher singlet oxygen quantum yield compared with their neutral counterparts. The triplet excited states of these cationic compounds also have a considerably longer lifetime, indicating a smaller value for the nonradiative decay rate con-
267
stant, and hence a larger value for the term PT,O2 in Eqs. (2) and (3). The authors also investigated two binuclear Pt complexes linked via a 5,17-bis(diphenylphosphino)-25,26,27,28-tetra-n-butoxycalix[4]arene group (62 and 63) (81). They found that neither the large calixarene nor the second metal center significantly decrease the singlet oxygen quantum yield (79).
Table 2. Singlet oxygen generation and related photophysical data for Pt cyclometallated complexes.
Compound
Solvent
[(thpy)Pt(QOH)] 42 [(ppy)Pt(QOH)] 43 [(dba)Pt(QOH)] 44 [(thpy)Pt(QOCl)] 45 [(thpy)Pt(QOMe)] 46 [(ppy)Pt(QOMe)] 47 [(dba)Pt(QOMe)] 48 [(thpy)Pt(QS)] 49 [(ppy)Pt(QS)] 50 [(ppy)Pt(acac)] 51 [(ppy)Pt(dpm)] 52 [(bt)Pt(dpm)] 53 [(pq)Pt(dpm)] 54 [(btp)Pt(acac)] 55 [(btp)Pt(dpm)] 56 [Pt(Thpy) (PPh3)Cl] 57 [Pt(Thpy)(PPh3) CH3CN] ClO4 58 [Pt(Thpy)(PPh3) py]ClO4 59 [Pt(Thpy) (HThpy)Cl] 60 [Pt(Thpy)(Hthpy)py]ClO4 61 [(PtThpyCl)2Calix (OnBu)] 62 [{PtThpy(CH3CN)}2Calix (OnBu)](ClO4)2 63 (acac)Pt(deac) 64 (acac)Pt(coumarin) 65 Pt(dpbpy)SBA-15 66 PolyPt(pbp)L 67
CH2Cl2 Toluene CH2Cl2 Toluene CH2Cl2 Toluene CH2Cl2 Toluene CH2Cl2 Toluene CH2Cl2 Toluene CH2Cl2 Toluene CH2Cl2 Toluene CH2Cl2 Toluene Toluene MeOD Toluene MeOD Toluene MeOD Toluene MeOD Toluene MeOD Toluene MeOD CH3CN CD2Cl2 CH3CN CD2Cl2 CH3CN CD2Cl2 CH3CN CD2Cl2 CH3CN CD2Cl2 CH3CN CD2Cl2 CH3CN CD2Cl2
Fraction of triplet quenched by 3 O2 leading to formation of 1 O2 (fT,D)
Emission lifetime (degassed) (s, ls)
Emission lifetime (aerated) (s, ls)
5.3
0.26
4.3
0.26
4.4
0.23
2.4
0.3
1.8
0.26
1.3
0.1
0.6
0.17
1.6
0.21
1.6
0.21
2.9
0.155
3.1
1.03
2.52
0.15
3.3
1.01
5.65
0.272
1.9
1.05
7.08
0.333
1.8
1.01
8.85
0.179
1.9
1.02
9.87
0.177
1.9
1.02
6.8
Invited Review Singlet Oxygen Generation by Cyclometalated Complexes and Applications† David Ashen-Garry and Matthias Selke* Department of Chemistry and Biochemistry, California State University Los Angeles, Los Angeles, CA Received 20 August 2013, accepted 28 October 2013, DOI: 10.1111/php.12211
ABSTRACT
involved in apoptosis (8), and the chemistry of catalytic antibodies (9,10). Given these very diverse contexts and applications, it is not surprising that a number of different methods for thermal and photochemical singlet oxygen generation have been developed, and, despite the apparent abundance of thermal and photochemical sources of singlet oxygen, this has remained an active area of research. For thermal singlet oxygen generation, the most important group of precursors are arguably aromatic endoperoxides, several hundred of which have been prepared and found to release 1O2 upon heating (11). Among the aromatic endoperoxides, anthracene derivatives have been most thoroughly investigated. Unfortunately, not all these endoperoxides release 1O2 in high yield. In a classic study, Turro et al. showed that the activation barrier for release of dioxygen from 9,10-anthracene endoperoxides via a retro-[4 + 2] cycloaddition is ca. 38 kcal mol1 (12,13). As the excitation energy of singlet oxygen is 22.5 kcal mol1, dioxygen could be released either in the singlet or triplet state. Turro et al. demonstrated that 9,10-endoperoxides may undergo stepwise release of dioxygen, leading to a biradical intermediate which undergoes intersystem crossing (ISC) to a triplet biradical which then loses 3O2 rather than 1O2. On the other hand, the retro[4 + 2] cycloaddition in 1,4-endoperoxides is a concerted process leading only to singlet oxygen and the parent anthracene derivative. In general, attaching various substituents to 1,4-anthracene derivatives allows for control over solubility, stability and thus the temperature and yield of singlet oxygen release during the cycloreversion of the corresponding anthracene endoperoxides, making these compounds the most common thermal source of singlet oxygen in the laboratory (11). In addition to these thermal sources, singlet oxygen can be produced photochemically by various dyes, including porphyrins and related compounds by photosensitization. Just as aromatic endoperoxides can be fine-tuned to affect the parameters of thermal singlet oxygen release, porphyrins and porphyrin derivatives as well as phthalocyanines can be fine-tuned to control the solubility, excitation wavelength and singlet oxygen quantum yield. Several reviews have been published on singlet oxygen generation by these compounds (14–16). One drawback of these sensitizers is that synthetic modification to attach them to other materials or biomolecules is usually not trivial; aggregation of porphyrin-type sensitizers in solution is also a common problem. As an alternative, during the past decade, a number of borondipyrromethene (BODIPY)-based photosensitizers for production
While cyclometalated complexes have been extensively studied for optoelectronic applications, these compounds also represent a relatively new class of photosensitizers for the production of singlet oxygen. Thus far, singlet oxygen generation from cyclometalated Ir and Pt complexes has been studied in detail. In this review, photophysical data for singlet oxygen generation from these complexes are presented, and the mechanism of 1O2 generation is discussed, including evidence for singlet oxygen generation via an electron-transfer mechanism for some of cyclometalated Ir complexes. The period from the first report of singlet oxygen generation by a cyclometalated Ir complex in 2002 through August 2013 is covered in this review. This new class of singlet oxygen photosensitizers may prove to be rather versatile due to the ease of substitution of ancillary ligands without loss of activity. Several cyclometalated complexes have been tethered to zeolites, polystyrene, or quantum dots. Applications for photooxygenation of organic molecules, including “traditional” singlet oxygen reactions (ene reaction, [4 + 2] and [2 + 2] cycloadditions) as well as oxidative coupling of amines are presented. Potential biomedical applications are also reviewed.
INTRODUCTION Some sources of singlet oxygen—A brief overview Singlet oxygen (1Δg), the lowest excited state of the dioxygen molecule, can be produced thermally or photochemically (1–5). The former method involves loss of dioxygen in its singlet state from various precursors such as phosphite ozonites or various peroxides while the latter method involves either photochemically induced loss of 1O2 from a peroxide or, much more commonly, excitation of a photosensitizer followed by energy transfer to ground-state (triplet) dioxygen. Singlet oxygen is widely used for oxyfunctionalizations of organic molecules. It is also involved in a variety of biological and biomedical processes: It is the major cytotoxic species in photodynamic therapy (PDT) (6) and some photoactive antiviral drugs (7). It may also be *Corresponding author email: [email protected] (Matthias Selke) †This paper is part of the Special Issue honoring the Memory of Nicholas J. Turro. © 2013 The American Society of Photobiology
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David Ashen-Garry and Matthias Selke
of singlet oxygen have been developed. This new class of sensitizers has recently been reviewed (17,18). Yet another major class of singlet oxygen photosensitizers is various metal complexes. Numerous diimine transition metal complexes derived from Ru(II), Os(II) and Pt(II) as well as Ir(III) are singlet oxygen sensitizers (19–26). Perhaps the most promising group of metal-based singlet oxygen sensitizers is cyclometalated complexes of late transition metals. Just like porphyrins and phthalocyanines, the photophysical parameters of these compounds can be systematically manipulated by changes in the electronic properties of the complex (27). In addition, unlike other sensitizers, cyclometalated complexes often possess ancillary ligands that can easily be replaced, thereby allowing facile attachment of the sensitizer to other molecules, including nanomaterials or biomolecules such as DNA bases or proteins. This review will focus on singlet oxygen generation by cyclometalated complexes, and various applications of this relatively new class of sensitizers. All cyclometalated complexes which have thus far been evaluated as singlet oxygen sensitizers are either octahedral d6 Ir(III) complexes or square planar d8 Pt(II) complexes. Photophysical properties of cyclometalated complexes During the past two decades, cyclometalated complexes have been primarily studied for applications in optoelectronic materials, especially organic light-emitting devices (28–31). The emissive properties of the excited states of all these complexes include high luminescence efficiencies and long excited-state lifetimes. Cyclometalating ligands are strong-field ligands as the metal–carbon bond of the cyclometalating ligand enhances splitting of the d orbitals of the metal. Upon excitation of a cyclometalated complex, this large splitting of the metal d orbitals leads to preferential formation of metal-to-ligand charge-transfer (MLCT) states instead of metal-centered excited states. The large extended p system of the cyclometalating ligand may also undergo excitation of an electron to a p* orbital thereby generating a purely ligand-based excited state. The high Z metal center promotes rapid ISC to a triplet p-p* ligand-based excited state. Consistent with this analyses, a computational study by Hay has shown that the LUMO and LUMO + 1 are indeed p* orbitals located on the ligands (32). As the ligand-based MLCT and p-p* states are close in energy, there appears to be significant overlap between these two excited states, leading to a mixed MLCT-3[p-p*] state. In general, this mixed triplet excited state is the long-lived (usually in the microsecond range) emissive state of these complexes (33–36), although interligand energy transfer from the 3MLCT state to an ancillary ligand (which thereby becomes the emitting center) may occur in some cases (37). Ancillary ligands can be used to fine-tune the emission wavelength. For example, Yersin et al. have studied the photophysical properties of two biscyclometalated Ir complexes bearing identical cyclometalating ligands (2-(4′,6′-difluorophenyl)pyridine) (38). These complexes differ only in that one complex has an acetonylacetonato ancillary ligand, whereas the second complex has an N,O-bound picolinato ligand. The nitrogen atom possesses higher ligand field strength than the oxygen atom, thereby lowering the energy of the three occupied d orbitals of the t2g level (HOMO). This increases the d-p* energy gap, thereby causing a blueshift in the emission, as the energy of the MLCT transition is raised (39). The effect of electron-withdrawing substituents on the cyclometalating ligand is somewhat harder to
predict. While such substituents lower the energy of the LUMO (i.e. the p* orbital on the cyclometalating ligand), they also withdraw electron density from the metal-based HOMO (i.e. the t2g manifold), thereby raising its energy level. Usually the latter effect predominates (39). Synthesis of cyclometalated iridium (III) complexes Octahedral Ir(III) complexes can possess one, two, or three cyclometalating ligands. Biscyclometalated complexes of the type Ir(C^N)2L2 (C^N=cyclometalating ligand, L=ancillary ligand) are most common, but mono- and tris-cyclometalated Ir(III) complexes (Ir[C^N]3) can be prepared as well. Monocyclometalated Ir(III) complexes are comparatively rare, and have not yet been investigated as sensitizers for the production of singlet oxygen. Most Ir(III) complexes that have been investigated as singlet oxygen sensitizers are biscyclometalated complexes; in addition to the two cyclometalating ligands, they posses either two singly bound ancillary ligands or one chelating ancillary ligand. The synthesis of such biscyclometalated Ir(III) complexes is rather facile, and is usually accomplished by simply refluxing IrCl3 in the presence of four equivalents of the cyclometalating ligand (33). This leads to a chloro-bridged dimer with two cyclometalating ligands on each Ir atom. The dimer can then be cleaved with an ancillary ligand. A wide range of compounds can be used to cleave the chloride-bridged dimer, ranging from 2,4-pentadione in the presence of base to bipyridine to amino acids which can be N,O-bound. Monoamines can also be used to cleave the dimer, in which case each of the monomers retains one of the two bridging chloride atoms. The latter reaction allows for facile linking of these sensitizers with spacers to biomolecules or nanomaterials (33,39). The synthesis of tris-cyclometalated Ir(III) complex is also rather straightforward, as these compounds can be prepared from biscyclometalated precursors via displacement of an ancillary ligand. For example, for complexes containing 2-phenylpyridine as the cyclometalating ligand, displacement of the acetonylacetate (acac) ligand from the biscyclometalated complex with another cyclometalating ligand and reflux at high temperature (>200°C) leads to the facial (fac) isomer of the triscyclometalated complex. The meridional (mer) isomer can be obtained by simply decreasing the reflux temperature after addition of the 2-phenylpyridine to the biscyclometalated complex to 140°C. Alternatively, refluxing Ir(acac)3 with three equiv. of the cyclometalating ligand represents a direct pathway to the fac isomer of the tris-cyclometalated complex (33,40–42). The various routes to bis- and tris-cyclometalated complexes bearing 2-phenylpyridine ligands are shown in Scheme 1 below. Recently, Swager et al. have developed another simple route to a wide range of cyclometalated Ir(III) complexes using a Cu (I) trazolide intermediate for the transmetalation step (43). This simple procedure allows a one-pot procedure for ligand synthesis and cyclometalation, thereby again allowing facile preparation of a wide range of these complexes with different ancillary ligands and substituents on the cyclometalating ligands. Overall, from a synthetic point of view, cyclometalated complexes are a class of singlet oxygen sensitizers that are quite easy to prepare and fine-tune both for different absorption profiles and for different applications. Literally hundreds of different complexes have been prepared during the past decade, and a review of the detailed synthesis and characterization of each of these complexes would be beyond the scope of this study. We will focus on complexes
Photochemistry and Photobiology, 2014, 90
259
Scheme 1. Synthesis of bis- and triscyclometalated Ir(III) complexes.
for which photosensitized generation of singlet oxygen has been experimentally demonstrated.
SINGLET OXYGEN GENERATION BY CYCLOMETALATED COMPLEXES Iridium (III) complexes as sensitizers—mechanistic aspects In 2002, the groups of Thompson and Selke reported that several Ir(III) biscyclometalated complexes are excellent photosensitizers for the production of singlet oxygen (44). This was followed by a full paper in 2007 which explored the mechanism of singlet oxygen generation by these complexes (45). The structures of the Ir complexes (1–10) are depicted in Scheme 2. They all possess two cyclometalating ligands, and several different ancillary ligands, including N,O-bound glycine (Complex 5). Several different cyclometalating ligands were employed in this study, namely 2-phenylpyridine (ppy); 1-naphtylpyridine (1np); 2-phenylquinoline (pq); 2-(1-naphthyl)benzothiazole (bsn); 2-phenylbenzothiazole (bt); 2-phenylbenzo-oxazole (bo) and (2-pyridyl)benzothiophene) (btp). Table 1 gives an overview of the photophysical data for all cyclometalated Ir(III) complexes that have been investigated for the production of singlet oxygen to date (August 2013). Many of these complexes produce singlet oxygen in high yield, with quantum yields approaching unity in some cases. As discussed earlier, cyclometalated complexes possess a long-lived triplet state of mixed MLCT-p-p* character. This triplet state is rapidly quenched by triplet (ground-state) oxygen. The fraction of triplet quenched by ground-state oxygen (PT,O2) can easily be determined by comparison of the triplet lifetime in degassed samples vs in air [Eq. (1)]
Scheme 2. Biscyclometalated Ir(III) complexes 1–10 that produce singlet oxygen.
[(bsn)2Ir(acac)] 1 [(bsn)2Ir(dpm)] 2 [(pq)2Ir(acac)] 3 [(bt)2Ir(acac)] 4 [(bsn)2Ir(gly)] 5 [(bt)2Ir(py)Cl] 6 [(ppy)2Ir(acac)] 7 [(bo)2Ir(acac)] 8 [(1np)2Ir(acac)] 9 [(btp)2Ir(acac)] 10 [Ir(dpyx) (phbpy)]+ 11 [Ir(ppy)2(bpy)]+ 12 [Ir(ppy)2(bpy)]+ 12 [(ppy)2Ir(bpy)]+ 12 [Ir(dppy)(tpy-CO2Et)]+ 13 [(pip)2Ir(acac)] 14 [fac-Ir(ppy)3] 15 [(ppy)2Ir(phen)]+ 16 [(ppy)2Ir (dmbpy)]+ 17 [Ir(deatpy)3] 18 [Ir(deatpy)3-H3]3+ 19 [Ir(btpy)2(biS)]+ 20
Compound
None detected
1.5
DMSO/H2O/HCl
CH2Cl2
0.78 1.2
27
0.78
0.93
+
†
+
None detected
0.78
0.93
CH2Cl2:MeOH (9:1) CH3CN DMSO/H2O
33
0.5
0.5
46
1.9 1.6 0.88
CH2Cl2:MeOH (9:1) Toluene CH2Cl2:MeOH (9:1) 0.036
0.26
CH2Cl2:MeOH (9:1)
54
53
52 34 53
52 65 52
52
51
52
51
45 33 51
0.6 0.05
0.98
0.5 0.05
1.25
CH3CN
43
6.4
0.049
0.68
45 33 45 33 45
44
44,45 33 44,45 33 44
44 33 44,45
Ref.
54
0.34
CH2Cl2:MeOH (9:1)
6.8
0.079
1.35
1.31
1.63
1.27
1.28
1.06
E1/2 (Sen+/*) (V)*
0.97
0.18
THF
CH3CN
None detected
0.72 0.06
5.66 5.8 0.12
Toluene 2MeTHF CH3CN
0.97
0.81
0.4 0.05
None detected
0.76 0.05
5.2
0.104
0.18 0.03
0.76 0.06
7.1
0.076
None detected
0.92
0.90 0.05
23
1.43 1.6 1.31 1.1 3.45
Toluene 2MeTHF Toluene 2MeTHF Toluene
0.026
None detected
0.95 0.09
1.0 0.2
4.0 0.3
6.3 0.2
C6H6
0.92
5.9 0.6
0.085
0.62 0.05
0.60 0.06
0.59 0.07
O2 quantum yield (ΦD)
2.1 0.5
0.65
7.2 0.3
0.071
1
1 O2 quenching rate (kT, 106 M1 s1)
0.54 0.02
0.73
2.9 0.1
0.165
Emission quenching by 3O2 (kq, 109 M1 s1)
0.5 0.2
1.5 2 1.41 1.8
1.8 1.49
Emission lifetime (aerated) (s, ls)
Fraction of T1 quenched by 3O2 leading to formation of 1O2 (fT,D)
0.86 0.07
C6H6 2MeTHF C6H6 2MeTHF C6H6
C6H6 2MeTHF C6H6
Solvent
Emission lifetime (degassed) (s, ls)
Table 1. Singlet oxygen generation and related photophysical data for Ir-cyclometallated complexes.
260 David Ashen-Garry and Matthias Selke
[(ppy)2Ir(deac)] 36
[(bsn)2Ir(bpy-CONH-Et)]+ 35
[(bsn)2Ir(bpy-CONH-PEG)]+ 34
[(pq)2Ir(bpy-CONH-Et)]+ 33
[(pq)2Ir(bpy-CONH-PEG)]+ 32
[(pba)2Ir(bpy-CONH-Et)]+ 31
[(pba)2Ir(bpy-CONH-PEG)]+ 30
[(pppy)2Ir(bpy-CONH-Et)]+ 29
[(pppy)2Ir(bpy-CONH-PEG)]+ 28
[(ppy)2Ir(bpy-CONH-Et)]+ 27
[Ir(btpy)2(biSe)]+ 21 [Ir(Mebib)(ppy)]+ on SBA-15 22 [Ir(Mebib)(ppy)]+ on MCM48 23 [Ir(Mebib)(ppy)]+on MCM-41 24 [(piq)2Ir(pypzS2)]–CdSe/ZnS 25 [(ppy)2Ir(bpy-CONH-PEG)]+ 26
Compound
Table 1. (continued)
CH2Cl2 CH3CN DMSO CH2Cl2 CH3CN DMSO CH2Cl2 CH3CN DMSO CH2Cl2 CH3CN DMSO CH2Cl2 CH3CN DMSO CH2Cl2 CH3CN DMSO CH2Cl2 CH3CN DMSO CH2Cl2 CH3CN DMSO CH2Cl2 CH3CN DMSO CH2Cl2 CH3CN DMSO CH3CN 2-Propanol 4:1 75.5
4.26 3.72
4.1 3.76
0.67 0.54
2.08(10%) 0.78(90%) 2.16(15%) 0.54(85%)
2.86 3.72
4.26 2.86
0.50 0.33
0.49 0.34
0.40 0.23
0.78
0.80
0.29
0.31
0.54
0.54
0.21
0.24
0.16
0.83 +§
0.69
0.58
0.51
0.79
0.58
0.50
0.38
0.38
0.24
0.87
MeOH
58 58 58 58 58 58 58 58 58 58 58 58 58 58 58 58 58 58 58 58 58 58 58 58 58 58 58 58 58 58 62
57
56
+‡
CH3CN
56
54
56
None detected
Ref.
++‡
‡
E1/2 (Sen+/*) (V)*
CH3CN
0.17
O2 quantum yield (ΦD)
++†
1
1 O2 quenching rate (kT, 106 M1 s1)
+++
0.38 0.21
Emission lifetime (aerated) (s, ls)
Fraction of T1 quenched by 3O2 leading to formation of 1O2 (fT,D)
CH3CN
CH2Cl2
Solvent
Emission lifetime (degassed) (s, ls)
Emission quenching by 3O2 (kq, 109 M1 s1)
Photochemistry and Photobiology, 2014, 90 261
0.97
0.52
0.15 0.177
0.133
87.2 MeOH
23.7 MeOH
8.7 CH2Cl2/MeOH
22.3
CH3CN 2-Propanol 4:1 MeOH
[(ppy)2Ir(pdeac)] 37 [(ppy)2Ir(bpy-PBI)]+[PF6] 38 [(ppy)2Ir(bpy-aPBI)]+[PF6] 39 [(ppy)2Ir(pBodipy)]+[PF6] 40 [(ppy)2Ir(2Bodipy)]+[PF6] 41
Compound
Solvent
73.6
Emission lifetime (degassed) (s, ls) Table 1. (continued)
*E(Sen+/0*) = E(Sen+/0) E0-0; †not quantified, but [Ir(btpy)2(biSe)]+ had 2.4 times larger 1O2 emission intensity than [Ir(btpy)2(biS)]+; ‡not quantified, but relative singlet oxygen levels were SBA15 > MCM-48 > MCM-41; §not quantified, but efficient photooxidation of 1,5-dihydroxynaphthalene to 5-hydroxy 1,4-naphthalenedione (juglone).
63
63
64
64 0.91
+
§
Emission lifetime (aerated) (s, ls)
Emission quenching by 3O2 (kq, 109 M1 s1)
Fraction of T1 quenched by 3O2 leading to formation of 1O2 (fT,D)
1
O2 quantum yield (ΦD)
1 O2 quenching rate (kT, 106 M1 s1)
E1/2 (Sen+/*) (V)*
62
David Ashen-Garry and Matthias Selke Ref.
262
PT;O2 ¼ 1 ðsair =sN2 Þ
ð1Þ
where sair and sN2 are the triplet lifetimes in air and under nitrogen respectively. PT,O2 can also be expressed as the fraction of the rate of triplet quenching (kq) by triplet oxygen relative to the intrinsic rate of decay of the triplet state under anaerobic conditions (i.e. sN21) [Eq. (2)]. PT;O2 ¼ kq ½3 O2 =ðsN2 1 þ kq ½3 O2 Þ
ð2Þ
In the absence of any chemical reaction, the rate of decay of the triplet state is the sum of the rate constants for nonradiative decay and phosphorescence, and hence Eq. (2) can be rewritten as PT;O2 ¼ kq ½3 O2 =ðkq ½3 O2 þ knr þ kp Þ
ð3Þ
where knr and kp are the rate constant for nonradiative decay and phosphorescence respectively. The overall quantum yield of singlet oxygen production (ΦD) is given by Eq. (3). UD ¼ UT PT;O2 fT;D
ð4Þ
where ΦT is the quantum yield of triplet formation and fT,D is the fraction of triplet quenched by ground-state oxygen leading to formation of singlet oxygen. In cyclometalated complexes, the value of ΦT is usually unity, as the heavy metal atom of these complexes facilitates intersystem crossing to the triplet mixed MLCT-p-p* state. On the other hand, the values of the fraction of triplet quenched by ground-state oxygen leading to formation of singlet oxygen fT,D may vary considerably. Triplet oxygen may quench the triplet excited MLCT-p-p* state of the cyclometalated Ir complex by three different mechanisms, namely energy transfer which directly leads to formation of singlet oxygen 1O2 [Eq. (5)], or electron transfer leading to formation of superoxide anion [O2•, Eq. (6)], or simple physical deactivation [Eq. (7)]. ½Ir(C^ N)2 L2 þ3 O2 ! 1 O2 þ ½Ir(C^ N)2 L2
ð5Þ
þ ^ ½Ir(C^ N)2 L2 þ3 O2 ! O 2 þ ½Ir(C N)2 L2
ð6Þ
½Ir(C^ N)2 L2 þ3 O2 ! 3 O2 þ ½Ir(C^ N)2 L2
ð7Þ
A classic scheme for singlet oxygen generation by energy transfer [Eq. (5)] developed originally by Gijzeman et al. (46,47) correlates the values of the rate constant for quenching of triplet excited states by triplet oxygen [kq, Eq. (2)] with values of fT,D, i.e. the fraction of triplet quenched by ground-state oxygen leading to formation of singlet oxygen. A triplet excited sensitizer and triplet oxygen reversibly form an encounter complex of (T13Σ) spin configuration. There are four unpaired electrons, and hence nine different spin configurations for this encounter complex, but only the singlet (1[T13Σ]) state of the encounter complex can dissociate to form singlet oxygen and ground-state sensitizer. Quenching rates of 1/9 of the diffusioncontrolled rate limit (kdiff) thus imply exclusive quenching of the triplet excited sensitizer by energy transfer and a value of unity for fT,D. Larger values for kq should lead to fT,D values of less than unity, as quenching from other states besides the singlet (1[T13Σ]) state of the encounter complex must occur.
Photochemistry and Photobiology, 2014, 90
occurs at least partly by an electron-transfer/back electron-transfer mechanism, it follows that the singlet oxygen quantum yield should decrease as an unfavorable excited-state reduction potential diminishes formation of such electron-transfer or charge-transfer intermediates. Several other groups have determined singlet oxygen quantum yields for cyclometalated iridium complexes. In 2008, Williams et al. reported singlet oxygen generation by two interesting Ir(III) complexes possessing two terdentate ligands of the type Ir (N^C^N)(N^N^C, 11) and Ir(C^N^C)(N^N^N, 13), as well as the biscyclometalated complex 12 which has an ancillary bipyridine ligand (Scheme 3) (51). Time-resolved measurements of singlet oxygen luminescence (excitation wavelength at 355 nm) gave singlet oxygen quantum yields of 0.4–0.6. The reason for the somewhat lower quantum yields (compared with complexes 1–10) is not known. Murata et al. subsequently studied singlet oxygen generation by a number of neutral and cationic cyclometalated complexes (12 and 14–17, Scheme 3) (52). This includes cationic complexes 12, 16 and 17 as well as the tris-cyclometalated complex fac(Ir(ppy)3) (15). Singlet oxygen quantum yields were measured by a chemical method, namely trapping of 1O2 by 1,5dihydroxynaphthalene. They also determined values for quenching of the triplet state of these complexes by triplet oxygen, and obtained values near the diffusion-controlled rate limit. However, only the cationic complexes—except complex 17—gave very high singlet oxygen yields, whereas those for the neutral complexes were lower. The reduced quantum yield of 17 was attributed to a steric blocking effect of the methyl groups on the bipyridine moiety. For the neutral complexes, the authors suggested that although electron transfer from the excited complex to triplet oxygen (Eq. (6)) is extremely rapid, the back electron transfer required to produce singlet oxygen by the electron-transfer mechanism is unfavorable (52). Aoki et al. prepared tris-cyclometalated Ir complexes bearing amino-substituted 2-phenyl pyridine ligands (18–19, Scheme 4) (53). They reported that the neutral complex 18 does not produce any singlet oxygen while the triprotonated complex 19 does, although the quantum yield is not known at this time. Singlet oxygen production was monitored by a chemical trap, i.e. 1,3-
Empirically, quenching rates near 1/9 kdiff and very high singlet oxygen quantum yields have been observed for many different sensitizers, including some metal complexes, i.e. many metalloporphyrins (48,49). However, this scheme had to be subsequently modified to account for cases in which fT,D was near unity while the value of kq was considerably larger than 1/9 kdiff. Formation of charge-transfer intermediates from the initial triplet excited sensitizer–triplet-oxygen encounter complexes may take place in these cases. Singlet oxygen is then formed from these charge-transfer complexes. Thus, for example, several Re(I), and Ir(III) complexes bearing bipyridine (bpy) ligands have kq values near 1010 M1 s1 (i.e. much larger than 1/9 kdiff) but produce singlet oxygen with quantum yields near unity which implies values of fT,D near unity (21,22). All the biscyclometalated Ir complexes studied by Djurovich et al. (1–10) produce singlet oxygen in moderate-to-high yield (44,45). Singlet oxygen quantum yields were determined directly from the time-resolved 1O2 near-infrared (NIR) emission signal. The authors also reported very large values of triplet-oxygen quenching (kq) by the triplet excited complexes. In one case (Complex 7) the value of kq was over an order of magnitude larger than kdiff (45). They suggested that such high rates may be indicative of quenching by electron transfer [Eq (6)], in addition to an energy-transfer mechanism [Eq. (5)] leading to formation of superoxide anion and a sensitizer radical cation. Singlet oxygen would then be formed from back electron transfer. Support for this hypothesis was derived from the very large observed values of kq for complex 7 at the diffusion-controlled rate limit, which is typical for an electron-transfer process and that the excited states of some tris-cyclometalated Ir(III) complexes are in fact quenched by triplet oxygen via an electron-transfer process (50). Further evidence for this hypothesis was derived from the observation that for (C^N)2Ir(acac) complexes 2–4 and 7–10 there exists a correlation between the decrease in the values of fT,D and the reduction potential of the triplet excited state of these complexes (E1/2 (Sen+/*)) (41). As can be seen for complexes 2–4 and 7–10 in Table 1, singlet oxygen quantum yields (and values of fT,D) decrease with decreasing excited-state reduction potential. If singlet oxygen generation by cyclometalated Ir(III) complexes
N
N
N N N
Ir
N
Ir
+
+
+
N
CO2Et
N
N [Ir(ppy)2(bpy)] + 12
[Ir(dpyx)(phbpy)] + 11
N
Ir
N
N
[Ir(dppy)(tpy-f-CO 2Et)]+ 13
+
N N
N
N N
O Ir
Ir O
N
Ir N
N N
N
+ N N Ir N N
N Ir(pip)2(acac) 14
fac-Ir(ppy) 3 15
263
Ir(ppy)2(phen) + 16
Ir(ppy)2(dmbpy) + 17
Scheme 3. Cationic and neutral cyclometalated Ir(III) sensitizers 11–17.
264
David Ashen-Garry and Matthias Selke
Et2N
NEt2
N
+ Et2HN
Ir N
+ NHEt2
N
N
Ir N
N
N
Ir
Ir
N N
NEt2
N
N
N
HN
NHEt2 +
Ir(deatpy)3 18
N N
[Ir(deatpy)3-H3]3+ 19
O
Si
O
O O O
Scheme 4. Iridium(III) substituted ligands.
triscyclometalated
complexes
with
Mesoporous Silica
+
+
S
S
N N Ir N
S
N
N
S
N
N
Ir
20
S
Se
Ir(Mebib)(ppy) on SBA-15 (22) Ir(Mebib)(ppy) on MCM-48 (23) Ir(Mebib)(ppy) on MCM-41 (24)
S
S
CdSe/ZnS QD [(piq) 2Ir(pypzS2)]-CdSe/ZnS (25)
Scheme 6. Irdium(III) cyclometalated complexes tethered to zeolites or QDs.
N
N S
amino-
N N
N
Se N N 21
Scheme 5. Iridium(III) biscyclometalated complexes with dithione or di-selenone ancillary ligands.
diphenylisobenzofuran (DPBF). Singlet oxygen production by this system was turned on by addition of HCl and turned off by addition of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). Son et al. prepared two interesting biscyclometalated complexes bearing an S-bound dithione (20) and a Se-bound di-selenone (21, Scheme 5; (btpy = bis(2-(2′-benzothienyl)pyridine; biS = bis(imidazoline thione; biSe = bis(imidazoline selone), 20) (54). The authors were able to detect singlet oxygen by its nearinfrared emission signal. While quantum yields were not determined, the authors noted that the singlet oxygen emission intensity from the selenone complex 21 was 2.4 times that of the thione complex 20. The compounds were used for photooxidative couplings of benzylamines to imines. Two groups (Che and Yamashita) evaluated singlet oxygen production of cyclometalated Ir(III) complexes tethered to either zeolites (22–24) (55,56) or quantum dots (QDs) (57) (Scheme 6). Singlet oxygen quantum yields were not determined in most cases except for a system in which the Ir(III) biscyclometalated complex [(piq)2Ir(pypzS2), 25] is attached to the surface of a CdSe/ZnS QD (57). No significant F€orster resonance energy transfer (FRET) was observed from the QD to the Ir complex. Singlet oxygen was thus produced by direct excitation of the complex. Singlet oxygen production of the Ir-CdSe/ZnS QD hybrid material was assessed by monitoring of the singlet oxygen NIR emission in aerated MeOH solution. It appears that the presence of the QD does not significantly reduce production of 1O2 by this system. Using bis(triisobutylsiloxy) silicon-2,3-naphthalocyanine (SiINC) as a reference, the singlet oxygen quantum yield ΦD was estimated to be 0.87 (57). Lo et al. prepared a series of poly(ethylene glycol) (PEG)modified Ir complexes and their free analogs (26–35) for potential use in PDT (Scheme 7) (58). The PEG–Ir complexes are [Ir (ppy)2(bpy-CONH-PEG)](PF6) (26), [Ir(pppy)2(bpy-CONHPEG)](PF6) (28), [Ir(pq)2(bpy-CONH-PEG)](PF6) (30), [Ir (bsn)2(bpy-CONH-PEG)](PF6) (32) and [Ir(pba)2(bpy-CONH-
PEG)](PF6) (34), whereas complexes 27, 29, 31, 33, and 35 are the corresponding free analogs (bpy-CONH-PEG = 4-(N-(2-(xmethoxypoly-(1-oxapropyl))ethyl)aminocarbonyl)-4′-methyl-2,2′-bipyridine; ppy = 2-phenylpyridine; pppy = 2-((1,1′-biphenyl)-4-yl) pyridine; pq = 2-phenylquinoline; bsn = 2-(1-naphthyl)benzothiazole; pba = 4-(2-pyridyl)benzaldehyde). The PEG-free compounds have (bpy-CONH-Et) in place of (bpy-CONH-PEG). Emission data taken for all 10 compounds showed that the PEG–Ir compounds were generally similar to their corresponding PEG-free compounds giving green to red emissions and long triplet lifetimes (58). Singlet oxygen production was determined by monitoring the consumption of DPBF at 418 nm in an aerated DMSO solution. Quantum yields were calculated using methylene blue as a reference. A limiting factor in singlet oxygen production by some of these complexes (i.e. 26 and 27) may be a relatively small value for kq such that the term kq[3O2] in Eq. (2) becomes small enough for other decay processes of the triplet excited complex (i.e. nonradiative decay) to be competitive with triplet-oxygen quenching. Complexes with the longest emission lifetimes (34 and 35) had the highest singlet oxygen quantum yields, indicating that longer triplet lifetimes result in higher quantum yields of singlet oxygen. Steric factors were also found to be important, as quantum yields were slightly higher in the PEG-free complexes most likely due to the inability of oxygen to freely diffuse into and out of the PEG complex, making it more difficult to both form singlet oxygen, and for the singlet oxygen produced to then reach the DPBF (58). Recently, several cyclometalated iridium complexes with dramatically enhanced visible absorption have been reported (59–64). While conventional cyclometalated iridium complexes typically have moderately strong absorption in the visible region (typically, e < 104 M1 cm1), the systems developed by Zhao et al. consist of a cyclometalated Ir complex to which an organic fluorophore is attached which increases visible absorption by at least an order of magnitude. These complexes all possess two cyclometalating 2-phenylpyridine (ppy) ligands, and an ancillary bipyrdine (bpy) ligand to which the fluorophore is attached. Several different fluorophores have been utilized, namely diethylcoumarin and phenyldiethylcoumarin ([(ppy)2Ir(deac)]+ [PF6] (36) (59,62) and [(ppy)2Ir(pdeac)]+ [PF6] (37)), perylenebisimide and an amino-substituted derivative ([(ppy)2Ir (bpy-PBI)]+ [PF6] (38) (61,64) and [(ppy)2Ir(bpy-aPBI)]+ [PF6]
Photochemistry and Photobiology, 2014, 90 +
O N
R
Ir N
Poly(ethylene glycol) (PEG)
N H
N N
R
Ir N
26: R = H
N
N
27: R = H
28: R =
29: R = R
O
R
30: R =
+
O
O
N H
N
265
O
31: R =
H
Ir(bpy-CONH-PEG)]+ (ppy, pppy, pba)
H
Ir(bpy-CONH-Et)]+ (ppy, pppy, pba)
+ +
O N N Ir
N
N H
O
S N
R
N H
N 32: R = PEG 33: R = Et
N
Ir(pq)(bpy-CONH-PEG)]+ and Ir(pq)(bpy-CONH-Et)]+
R
Ir N
34: R = PEG 35: R = Et
N S Ir(bsn)(bpy-CONH-PEG)]+ and Ir(bsn)(bpy-CONH-Et)]+
Scheme 7. Irdium(III) biscyclometalated sensitizers tethered to PEG and their free analogues.
(39)) and BODIPY (63). Both the PBI and BODIPY ligands were attached via an acetylene linker to the bpy ligand of (ppy)2Ir(bpy). Two different modes of attachment were used for the BODIPY moiety: attachment via the mesophenyl group to afford [(ppy)2Ir (pBodipy)]+ [PF6] (40) and attachment via the two positions of the core p-system giving [(ppy)2Ir(2Bodipy)]+ [PF6] (41) (Scheme 8). All the complexes 36–41 have considerably longer emission lifetimes than conventional cyclometalated Ir complexes (columns 3 and 4 in Table 1). Thus, the perylenebisimide complex 38 has triplet lifetime of 22.3 ls, and a singlet oxygen quantum yield ΦD of 0.91. Addition of the amino group caused a redshift in absorption from 546 nm in compound 38 to 675 nm in the amino-substituted derivative 39. Unfortunately, the aminosubstituted complex 39 has a shorter triplet-state lifetime (8.7 ls), and a significantly reduced singlet oxygen quantum yield (ΦD = 0.15). For the BODIPY complexes, conjugation of the BODIPY with the core (i.e. 2Bodipy, 41) provides more efficient population of the excited triplet state, and thus more efficient singlet oxygen generation compared with pBodipy (40). Complex 40 has a triplet lifetime of 23.7 ls and a singlet oxygen quantum yield of 0.52. Complex 41 has a redshifted maximum absorbance at 534 nm (compared to 504 nm for complex 40), an exceptionally long triplet lifetime of 87.2 ls and a singlet oxygen quantum yield of 0.97. All these quantum yields were calculated using DPBF as a singlet oxygen scavenger and Rose Bengal as a standard. Cyclometalated platinum (II) complexes as singlet oxygen sensitizers The second group of cyclometalated complexes that has been studied for the production of singlet oxygen are square planar d8
O + N Ir N
N
H N
N
N
O
36: R =
N +
-
[ppy)2Ir(deac)] [PF6]
O
R 37: R =
O N
[(ppy)2Ir(pdeac)] + [PF6]-
38: R' =
O
O
N
N
O
O
[(ppy)2Ir(bpy-PBI] + [PF6]-
+ R' N Ir N
O
HN
O
N
N
N
N
O
O
39: R' = [(ppy)2Ir(bpy-aPBI)] + [PF6]-
40: R' = [(ppy)2Ir(pBodipy)]+ [PF6]-
N F B N F
41: R' =
N N B F F + [(ppy)2Ir(2Bodipy) [PF6]-
Scheme 8. Iridium(III) sensitizers with organic fluorophores.
266
David Ashen-Garry and Matthias Selke
Pt(II) complexes. Similar to the octahedral Ir(III) complexes, these compounds can be prepared from the corresponding dichloride-bridged dimers bearing a cyclometalating ligand on each Pt atom by reaction with a variety of compounds such as acetonyl actetonate to bipyridines, quinolines, quinoline thiols as well as many monodentate ligands ranging from triphenylphosphine to pyridine. Tridentate cyclometalating ligands such as C-deprotonated 6-phenyl-2,2′-bipyridine [C^N^N] have also been used to prepare cationic complexes of the type [Pt(C^N^N)R1]n+ (66–71). The photophysical properties of these complexes are quite similar to their Ir counterparts. However, in many cases, the lowest excited state is a triplet intraligand charge-transfer (ILCT) state formed when the HOMO is located on the cyclometalating ligand and the LUMO on an ancillary ligand such as a quinoline. The triplet ILCT state of such complexes is the emissive state with a long lifetime in the microsecond range (72). Mixed triplet MLCT and ILCT states have also been reported (66,69,73). Recent theoretical investigation found that for Pt complexes with a cyclometalating 2-phenylpyridine ligand and a quinoline ligand, the energy gap between the ground state and the triplet excited state exceeds the excitation energy of singlet oxygen (22.5 kcal mol1), indicating that such complexes can indeed produce 1O2 (74). The first report of singlet oxygen production by Pt cyclometalated complexes was by Weinstein et al. in 2006 (75). Singlet oxygen quantum yields were determined directly from the time-resolved 1O2 NIR emission signal, using phenanelone (76) as a reference compound. The cyclometalated complexes studied by Weinstein et al. (42–50) are depicted in Scheme 9. Singlet oxygen quantum yields for these compounds range from 0.5 to 0.9, both in toluene and methylene chloride. The authors also determined the quenching rates of the triplet excited states by triplet oxygen. Unlike for some of the Ir (III) complexes discussed elsewhere in the study (especially 7, 8, 10), these were found to be approximately 1/9 of kdiff, indicating that most likely singlet oxygen production by these complexes occurs only by energy transfer. Subsequently, Djurovich et al. reported singlet oxygen generation from six different Pt(II) cyclometalated complexes (51–56, Scheme 10) (77) with quantum yields near unity in all cases (45). The cyclometalating ligands were the same as those used for Ir complexes 1–10. Measurements were accomplished via excitation at 355 nm and monitoring the 1O2 (NIR) emission sigR
R
R'
N O Pt N
R'
S
R N O Pt N
R'
N O Pt N
(thpy)Pt(QO)
(ppy)Pt(QO)
(dba)Pt(QO)
42: R = R' = H 45: R = Cl, R' = H 48: R = R' = CH3
43: R = R' = H 46: R = R' = CH3
44: R = R' = H 47: R = R' = CH3
N S Pt N
S
(thpy)Pt(QS) 49
N S Pt N (ppy)Pt(QS) 50
Scheme 9. Platinum(II) cyclometalated sensitizers 42–50.
S N Pt O O
N Pt O O
R
R (ppy)Pt 51: R = Me 52: R = t-Bu
[(bt)Pt(dpm)] 53
N Pt O O
N Pt O
S
O
R
R (btp)Pt 55: R = Me 56: R = t-Bu
[(pq)Pt(dpm)] 54
Scheme 10. Platinum(II) cyclometalated sensitizers 51–56. n+ N Pt
n+ N
PPh3
Pt
R
S
R
S
N S
[Pt(Thpy)(PPh 3)R]
[Pt(Thpy)(HThpy)R]
57: R = Cl, n = 0 58: R = NCCH3, n = 1 59: R = pyridine, n = 1
60: R = Cl, n = 0 61: R = pyridine, n = 1
2+ N S
Pt
Cl PPh2
OnBu
Cl Pt PPh2
N
N S
OnBu OnBu OnBu
[(PtThpyCl) 2Calix OnBu)] 62
S
NCMe NCMe N Pt Pt PPh2 PPh 2
OnBu
S
n OnBuO Bu OnBu
[{PtThpy(CH3CN)} 2Calix (O nBu)] 63
Scheme 11. Platinum (II) complexes with a cyclometalating 2-(20 thienyl) pyridyl ligand.
nal. Again, quenching rates of the triplet excited states of these complexes by triplet oxygen were found to be approximately 1/9 of kdiff, and, as ΦΔ is unity, fT,D must be unity as well, indicating that most likely singlet oxygen production occurs by energy transfer. Singlet oxygen quenching rates (kT) by Pt complexes 51–56 were also determined, and found to be somewhat higher (6.9 9 106–2.2 9 107 M1 s1) than those of the analogous Ir complexes, but still moderately low, and lower than sensitizers such as tetraphenyl porphyrine (kT = 4.4 9 107 M1 s1) (78). The authors also noted that steric bulk on the ancillary ligands does not appear to affect the singlet oxygen quantum yield (45). Lai et al. reported singlet oxygen quantum yields for a series of 2-(2′-thienyl)pyridyl platinum(II) complexes bearing various ancillary ligands such as Cl, PPh3 and pyridine (57–63, Thpy = 2-(2′-thienyl)pyridyl) (79). The lowest excited state of complexes 57–63 (Scheme 11) is a triplet ILCT state, as is common for cyclometalated Pt complexes. The quantum yields for singlet oxygen production were obtained by time-resolved laser measurements of NIR signal intensity of 1O2 at an excitation wavelength of 355 nm in
Photochemistry and Photobiology, 2014, 90 deuterated acetonitrile and dichloromethane (Table 2) using C60 (ΦD = 1) (80) as a reference. The cationic complexes 58 and 59 had a notably higher singlet oxygen quantum yield compared with their neutral counterparts. The triplet excited states of these cationic compounds also have a considerably longer lifetime, indicating a smaller value for the nonradiative decay rate con-
267
stant, and hence a larger value for the term PT,O2 in Eqs. (2) and (3). The authors also investigated two binuclear Pt complexes linked via a 5,17-bis(diphenylphosphino)-25,26,27,28-tetra-n-butoxycalix[4]arene group (62 and 63) (81). They found that neither the large calixarene nor the second metal center significantly decrease the singlet oxygen quantum yield (79).
Table 2. Singlet oxygen generation and related photophysical data for Pt cyclometallated complexes.
Compound
Solvent
[(thpy)Pt(QOH)] 42 [(ppy)Pt(QOH)] 43 [(dba)Pt(QOH)] 44 [(thpy)Pt(QOCl)] 45 [(thpy)Pt(QOMe)] 46 [(ppy)Pt(QOMe)] 47 [(dba)Pt(QOMe)] 48 [(thpy)Pt(QS)] 49 [(ppy)Pt(QS)] 50 [(ppy)Pt(acac)] 51 [(ppy)Pt(dpm)] 52 [(bt)Pt(dpm)] 53 [(pq)Pt(dpm)] 54 [(btp)Pt(acac)] 55 [(btp)Pt(dpm)] 56 [Pt(Thpy) (PPh3)Cl] 57 [Pt(Thpy)(PPh3) CH3CN] ClO4 58 [Pt(Thpy)(PPh3) py]ClO4 59 [Pt(Thpy) (HThpy)Cl] 60 [Pt(Thpy)(Hthpy)py]ClO4 61 [(PtThpyCl)2Calix (OnBu)] 62 [{PtThpy(CH3CN)}2Calix (OnBu)](ClO4)2 63 (acac)Pt(deac) 64 (acac)Pt(coumarin) 65 Pt(dpbpy)SBA-15 66 PolyPt(pbp)L 67
CH2Cl2 Toluene CH2Cl2 Toluene CH2Cl2 Toluene CH2Cl2 Toluene CH2Cl2 Toluene CH2Cl2 Toluene CH2Cl2 Toluene CH2Cl2 Toluene CH2Cl2 Toluene Toluene MeOD Toluene MeOD Toluene MeOD Toluene MeOD Toluene MeOD Toluene MeOD CH3CN CD2Cl2 CH3CN CD2Cl2 CH3CN CD2Cl2 CH3CN CD2Cl2 CH3CN CD2Cl2 CH3CN CD2Cl2 CH3CN CD2Cl2
Fraction of triplet quenched by 3 O2 leading to formation of 1 O2 (fT,D)
Emission lifetime (degassed) (s, ls)
Emission lifetime (aerated) (s, ls)
5.3
0.26
4.3
0.26
4.4
0.23
2.4
0.3
1.8
0.26
1.3
0.1
0.6
0.17
1.6
0.21
1.6
0.21
2.9
0.155
3.1
1.03
2.52
0.15
3.3
1.01
5.65
0.272
1.9
1.05
7.08
0.333
1.8
1.01
8.85
0.179
1.9
1.02
9.87
0.177
1.9
1.02
6.8
