New Ru(II) Complexes for Dual Photoreactivity: Ligand Exchange and ¹O₂ Generation

CONSPECTUS

Uncovering the factors that govern the electronic structure of Ru(II)–polypyridyl complexes is critical in designing new compounds for desired photochemical reactions, and strategies to tune excited states for ligand dissociation and ¹O₂ production are discussed herein. The generally accepted mechanism for photoinduced ligand dissociation proposes that population of the dissociative triplet ligand field (³LF) state proceeds through thermal population from the vibrationally cooled triplet metal-to-ligand charge transfer (³MLCT) state; however, temperature-dependent emission spectroscopy provides varied activation energies using the emission and ligand exchange quantum yields for [Ru(bpy)₂(L)₂]²⁺ (bpy = 2,2′-bipyridine; L = CH₃CN or py). This suggests that population of the ³LF state proceeds from the vibrationally excited ³MLCT state. Because the quantum yield of ligand dissociation for nitriles is much more efficient than that for py, steric bulk was introduced into the ligand set to distort the pseudo-octahedral geometry and lower the energy of the ³LF state. The py dissociation quantum yield with 500 nm irradiation in a series of [Ru(tpy)(NN)(py)]²⁺ complexes (tpy = 2,2′:6′,2″-terpyridine; NN = bpy, 6,6′-dimethyl-2,2′-bipyridine (Me₂bpy), 2,2′-biquinoline (biq)) increases by 2–3 orders of magnitude with the sterically bulky Me₂bpy and biq ligands relative to bpy. Ultrafast transient absorption spectroscopy reveals population of the ³LF state within 3–7 ps when NN is bulky, and density functional theory calculations support stabilized ³LF states. Dual activity via ligand dissociation and ¹O₂ production can be achieved by careful selection of the ligand set to tune the excited-state dynamics. Incorporation of an extended π system in Ru(II) complexes such as [Ru(bpy)(dppn)(CH₃CN)₂]²⁺ (dppn = benzo[i]dipyrido[3,2-a:2′,3′-c]phenazine) and [Ru(tpy)(Me₂dppn)(py)]²⁺ (Me₂dppn = 3,6-dimethylbenzo[i]dipyrido[3,2-a:2′,3′-c]phenazine) introduces low-lying, long-lived dppn/Me₂dppn ³ππ* excited states that generate ¹O₂. Similar to [Ru(bpy)₂(CH₃CN)₂]²⁺, photodissociation of CH₃CN occurs upon irradiation of [Ru(bpy)(dppn)(CH₃CN)₂]²⁺, although with lower efficiency because of the presence of the ³ππ* state. The steric bulk in [Ru(tpy)(Me₂dppn)(py)]²⁺ is critical in facilitating the photoinduced py dissociation, as the analogous complex [Ru(tpy)(dppn)(py)]²⁺ produces ¹O₂ with near-unit efficiency. The ability to tune the relative energies of the excited states provides a means to design potentially more active drugs for photochemotherapy because the photorelease of drugs can be coupled to the therapeutic action of reactive oxygen species, effecting cell death via two different mechanisms. The lessons learned about tuning of the excited-state properties can be applied to the use of Ru(II)–polypyridyl compounds in a variety of applications, such as solar energy conversion, sensors and switches, and molecular machines.

INTRODUCTION

Excited states of Ru(II) complexes have been used in solar energy conversion,^1–5 in charge transfer reactions,^6,7 as sensors and switches,^8,9 and as potential therapeutic agents in photochemotherapy (PCT) and imaging.^10–16 Although many complexes are derived from [Ru(bpy)₃]²⁺ (bpy = 2,2′-bipyridine) (Figure 1a),¹⁷ these applications often have different demands. For example, the excited-state redox potential is crucial in solar energy schemes and charge transfer reactions, which often require long-lived triplet metal-to-ligand charge transfer (³MLCT) excited states, whereas strong luminescence and sensitivity to the environment have been important in sensor applications. In contrast, complexes developed for PCT typically require high yields of photo-induced ligand exchange for prodrug delivery or to achieve binding of the metal to biomolecules, which in turn results in short ³MLCT lifetimes with low luminescence yields. In order to tune the relative energies of the excited states to achieve the desired properties, an understanding of the factors that affect the electronic structure of Ru(II) complexes is necessary.

Figure 1.

(a) Molecular structure and simplified (b) MO and (c) state diagrams of [Ru(bpy)₃]²⁺.

The electronic structure and excited-state dynamics of [Ru(bpy)₃]²⁺ and related complexes have been the subject of numerous reviews.¹⁷ Figure 1b presents a simplified diagram showing the frontier molecular orbitals (MOs) of [Ru(bpy)₃]²⁺ in a pseudo-octahedral field, for which the lowest-energy ¹MLCT transition has a maximum at 452 nm (ε = 14 600 M⁻¹ cm⁻¹) and the bpy ππ* transitions are observed at 285 nm (ε = 87 000 M⁻¹ cm⁻¹) in water.¹⁷ Ultrafast ¹MLCT → ³MLCT intersystem crossing (ISC) was reported in [Ru(bpy)₃]²⁺ (15–40 fs),^18,19 and to our knowledge, significantly lower ISC rates have not been reported for Ru(II) complexes. Therefore, with the exception of charge injection into semiconductors,²⁰ the excited-state chemistry of Ru(II) complexes takes place from the triplet manifold. The low-lying triplet excited states of [Ru(bpy)₃]²⁺ are schematically shown in Figure 1c, where the metal-centered triplet ligand field (³LF) state(s) involve transitions from the t_2g-type orbitals to the e_g-type orbitals, and the triplet ligand-centered (³LC) states arise from movement of an electron from the bpy(π) MOs to the bpy(π*) MOs. In [Ru(bpy)₃]²⁺, the ³MLCT state is emissive (λ_em = 607 nm, τ = 620 ns, Φ = 0.042 in water at 298 K).¹⁷ The lifetimes of Ru(II) complexes in which the ³LC excited state falls below the ³MLCT state are similar to those of the ³ππ* state of the free ligand, and these complexes generally are not emissive, exhibit long lifetimes, and feature efficient ¹O₂ sensitization.^21–24 In contrast, stabilization of the ³LF states results in photoinduced ligand exchange, which may be accomplished by introducing distortions around the metal center. These distortions reduce the orbital overlap and lower the energy of the e_g-type orbitals,¹⁵ thus decreasing the energy of the ³LF states, sometimes below that of the ³MLCT state.²⁵

The present Account focuses on the effect of structural changes to ruthenium(II) complexes on the excited-state properties and reactivity. Of particular interest are compounds that undergo photoinduced ligand exchange and those that generate ¹O₂, as well as new complexes designed in such a way that both processes are operative in the same complex upon irradiation with low-energy light. This dual reactivity has the potential to be useful in applications related to PCT, where cell death may be achieved via two different mechanisms by the same molecule.

ACTIVATION BARRIER TO PHOTOINDUCED LIGAND EXCHANGE

It is well-established that deactivation of the emissive ³MLCT state in Ru(II) complexes proceeds via thermal population of the ³LF states, which reduces the lifetime of the former. For applications that require charge transfer or high luminescence quantum yields, researchers aim to maximize the gap between the ³MLCT and ³LF states, which minimizes deactivation through the latter. In contrast, maximizing photoinduced ligand exchange of ruthenium(II) complexes, such as in the release of active molecules to biological targets and to gain understanding of their function, to inhibit enzymes, and to generate reactive species that can covalently bind to DNA, requires efficient population of the dissociative ³LF states.^11,13–15 One limitation is the relatively low quantum yield of ligand exchange in some complexes.

It has been generally accepted that the formation of photosubstituted products in Ru(II)–polypyridyl complexes proceeds through thermal population of the dissociative ³LF state(s) from the vibrationally cooled emissive ³MLCT state (³MLCT_v=0).²⁶ It is also established that deactivation of the emissive ³MLCT_v=0 state proceeds via population of the low-lying ³LF state(s), as depicted in Figure 2a. If it is assumed that the only source of photoinduced ligand exchange is population of the ³LF state from ³MLCT_v=0, then Arrhenius plots of both the photochemical yield and the emission intensity should give rise to the same activation energy, E_a (Figure 2a).

Figure 2.

Schematic representation of the potential energy surfaces showing (a) the activation energy, E_a, for going from ³MLCT_v=0 to the ³LF state and (b) the proposed sources of $E_{\mathrm{a}}^{\text{Em}}$ and $E_{\mathrm{a}}^{\mathrm{P}}$.

Plots of ln(Φ) versus 1/T for the photoanation reactions of [Ru(bpy)₂(L)₂]²⁺ (L = py, CH₃CN) to generate the corresponding [Ru(bpy)₂(L)Cl]⁺ product in the presence of excess tetrabutylammonium chloride (TBACl) in CH₂Cl₂ were reported to result in E_a ≈ 700 cm⁻¹,²⁷ whereas changes in the emission lifetime of [Ru(bpy)₂(py)₂]²⁺ with temperature result in E_a = 2758 cm^−1.28 However, these activation barriers were measured in two different temperature regimes, which can account for the different values. In addition, there have been other reports on the discrepancy between the magnitudes of E_a determined from emission and photochemical yields as well as from emission intensity and lifetime data.^28,29 The concluding remarks in both reports point to possible direct population of the ³LF state from the ¹MLCT state together with population of the emissive ³MLCT state.^28,29

To gain further understanding of the photoinduced ligand exchange in [Ru(bpy)₂(L)₂]²⁺ (L = CH₃CN, py), the activation energies for photoanation to generate the corresponding complexes [Ru(bpy)₂(L)Cl]⁺, $E_{\mathrm{a}}^{\mathrm{P}}$, were measured over the same temperature range as for the value from the changes in emission intensity, $E_{\mathrm{a}}^{\text{Em}}$, in 4:1 ethanol/methanol above the glass transition temperature.³⁰ The experiments were conducted in a cryostat placed in the sample compartment of the fluorimeter, and the decrease in the emission intensity as the temperature was raised was monitored in the absence of anion immediately after excitation to determine $E_{\mathrm{a}}^{\text{Em}}$. The change in emission intensity as a function of irradiation time in the presence of 20 mM TBACl was used to calculate the value of $E_{\mathrm{a}}^{\mathrm{P}}$, and the results are listed in Table 1.³⁰ It is evident from Table 1 that for both complexes the value of $E_{\mathrm{a}}^{\mathrm{P}}$ is significantly lower than that of $E_{\mathrm{a}}^{\text{Em}}$. It may be concluded that the ligand exchange does not proceed from ³MLCT_v=0, as shown in Figure 2a. Instead, the population of the dissociative ³LF state must have a different origin, as previously proposed by us,³¹ and may include direct ISC from the Franck–Condon ¹MLCT state, internal conversion (IC) from a higher-energy ³MLCT state, or IC from the vibrationally excited lowest-energy ³MLCT state (³MLCT_v≫1). The latter situation is depicted in Figure 2b, where vibrational cooling competes with IC from a vibrational level well above v = 0, as previously proposed from ultrafast work.³²

Table 1.

Quantum Yields of Photoinduced Ligand Exchange for [Ru(bpy)₂(L)₂]²⁺ Complexes, Absorption Maxima, and Activation Barriers with the Corresponding Temperature Ranges

L	ΦCla	λabs/nmb	$E_{\mathrm{a}}^{\text{Em}}/{\text{cm}}^{-1}$ c	$E_{\mathrm{a}}^{\mathrm{P}}/{\text{cm}}^{-1}$ c	T/K
CH3CN	0.31	420	1310 ± 65	515 ± 100	130–170
py	0.17	460	2040 ± 100	940 ± 85	180–230

^aAt 25 °C in CH₂Cl₂ with 20 mM TBACl (λ_irr = 400 nm).

^bIn H₂O.

^cIrradiated at the absorption maximum.

In order for efficient ligand dissociation to be observed, population of the ³LF state must compete with generation of ³MLCT_v=0. In systems such as [Ru(bpy)₂(CH₃CN)₂]²⁺, there must be strong vibrational coupling between the MLCT (singlet or triplet) and ³LF states, which is reduced in [Ru(bpy)₂(py)₂]²⁺. For example, strong vibrational coupling is believed to play a role in the ultrafast ISC of <100 fs in Cr(acac)₃ (acac = acetylacetonate), but interestingly, it decreases by over an order of magnitude when the ligand’s peripheral methyl groups are replaced by tert-butyl substituents in Cr(t-Bu-acac)₃.³³ In addition to nitriles, thioethers undergo photoinduced ligand dissociation with greater quantum yields than their ammine counterparts, and the ³MLCT states of the former were calculated to exhibit elongated Ru–S bonds, which may be related to MLCT/LF mixing.³⁴

ENHANCED PHOTOINDUCED LIGAND EXCHANGE WITH STERIC BULK

To increase the quantum yield for pyridine exchange through enhanced population of the ³LF state, sterically bulky ligands were incorporated to distort the pseudo-octahedral geometry around the metal center. The decrease in the energy of the ³LF state(s) as a function of increasing steric bulk was demonstrated for a series of complexes [Ru(NN)₃]²⁺ with NN = bpy, 6-methyl-2,2′-bipyridine (6-Mebpy), and 4,4′,6,6′-tetramethyl-2,2′-bipyridine (Me₄bpy) using ultrafast transient absorption (TA) spectroscopy.²⁵ On the basis of the difference in the decay of the ³MLCT state and recovery of the ground state, it was shown that the rate of population of a ³LF state from the ³MLCT state increased by an order of magnitude in going from [Ru(6-Mebpy)₃]²⁺ to the more sterically demanding [Ru-(Me₄bpy)₃]²⁺, with ³MLCT lifetimes of 1.6 and 0.16 ps, respectively.²⁵ Distortions around the metal lead to a decrease in the calculated energy of the ³LF state by ~4000 cm⁻¹ in [Ru(6-Mebpy)₃]²⁺ and ~7000 cm⁻¹ in [Ru(Me₄bpy)₃]²⁺ relative to that in [Ru(bpy)₃]²⁺. Therefore, while the ³LF state lies above the ³MLCT state in the latter, it falls below the ³MLCT state in the former, resulting in fast ³MLCT decay to populate the ³LF state.

The enhanced population of the ³LF state(s) in ruthenium-(II) complexes with bulky ligands leads to greater photo-induced ligand exchange. For example, photodissociation of 2,2′-biquinoline (biq) from [Ru(biq)(phen)₂]²⁺ (phen = 1,10-phenathroline) and [Ru(biq)₂(phen)]²⁺ in H₂O occurs with λ_irr ≥ 600 nm, while this photoactivity is not observed in [Ru(phen)₃]^2+.35 The crystal structures of the biq complexes reveal lengthened Ru–N bonds compared with those in [Ru(phen)₃]²⁺ as well as significant twisting of biq along the C–C bond connecting the two quinoline moieties and bending of biq by ~20° out of the normal plane. Similar photoreactivity was reported for [Ru(biq)₂(bpy)]²⁺ in CH₃CN.³⁶ The presence of methyl, phenyl, or chloro substituents positioned toward the Ru(II) center also induces geometric distortions and facilitates photosubstitution of the bulky bidentate ligands with solvent molecules.^15,37,38

To increase the photodissociation quantum yield of pyridine from pseudo-octahedral ruthenium(II) complexes, steric bulk was introduced in the series [Ru(tpy)(NN)(py)]²⁺ (tpy = 2,2′:6′,2″-terpyridine; NN = bpy, 6,6′-dimethyl-2,2′-bipyridinep(Me₂bpy), biq) (Figure 3).³⁹ The lowest-energy electronic transition observed in [Ru(tpy)(NN)(py)]²⁺ (NN = bpy, Me₂bpy) is the Ru(dπ) → tpy(π*) ¹MLCT transition with maxima at 468 nm (8120 M⁻¹ cm⁻¹) and 471 nm (8020 M⁻¹ cm⁻¹), respectively, whereas that in [Ru(tpy)(biq)(py)]²⁺ is assigned as the Ru(dπ) → biq(π*) ¹MLCT transition at 530 nm (9020 M⁻¹ cm⁻¹). Photoinduced exchange of py is not observed in [Ru(tpy)(bpy)(py)]²⁺ (Φ₅₀₀ < 0.0001), but irradiation of [Ru(tpy)(Me₂bpy)(py)]²⁺ and [Ru(tpy)(biq)-(py)]²⁺ in CH₃CN generates the corresponding products [Ru(tpy)(NN)(CH₃CN)]²⁺ (NN = Me₂bpy, biq) with Φ₅₀₀ = 0.16(1) and 0.033(1), respectively (Table 2). All three complexes are stable in CH₃CN and H₂O solutions in the dark for at least 24 h at room temperature.

Figure 3.

Structural representations of [Ru(tpy)(L)(py)]²⁺ (NN = bpy, Me₂bpy, biq).

Table 2.

Quantum Yields of Ligand Exchange, Φ_LE, and ¹O₂ production, Φ_Δ, for Selected Complexes

complex	ΦLEa	ΦΔb
[Ru(tpy)(bpy)(py)]2+	<10−4
[Ru(tpy)(Me2bpy)(py)]2+	0.16(1)
[Ru(tpy)(biq)(py)]2+	0.033(1)
[Ru(tpy)(dppn)(py)]2+	<10−4	0.98(6)
[Ru(tpy)(Me2dppn)(py)]2+	0.053(1)	0.69(9)

^aCH₃CN, λ_irr = 500 nm.

^bMeOH, λ_irr = 460 nm.

The crystal structures reveal key structural distortions in [Ru(tpy)(Me₂bpy)(py)]²⁺ and [Ru(tpy)(biq)(py)]²⁺ afforded by steric bulk from the bidentate ligands compared with [Ru(tpy)(bpy)(py)]²⁺. In particular, the angle between the plane defined by the bidentate ligand and that of the tpy ligand, determined to be 83.34° in [Ru(tpy)(bpy)(py)]²⁺, is reduced to 67.87° and 61.89° in [Ru(tpy)(Me₂bpy)(py)]²⁺ and [Ru(tpy)(biq)(py)]²⁺, respectively, similar to distortions reported for related complexes.^35,40,41 More importantly, the pyridine ligand in the Me₂bpy and biq complexes is distorted relative to that in [Ru(tpy)(bpy)(py)]²⁺. The enhanced photoinduced ligand exchange efficiency is correlated to structural distortions, which are believed to stabilize ³LF states and weaken the Ru–py σ bond.

Ultrafast TA spectroscopy reveals the consequences of added steric bulk on the excited-state dynamics of [Ru(tpy)(Me₂bpy)-(py)]²⁺ compared with [Ru(tpy)(bpy)(py)]²⁺ (Figure 4). For both complexes, the spectra feature a ground-state bleach centered at ~470 nm as well as positive transient absorption signals at ~375 and >500 nm associated with the Ru(dπ) → tpy(π*) ³MLCT state.⁴² While the spectral features are similar for the two complexes, stark differences are observed in the kinetics. The absorption changes of the bleach signal at 470 nm for [Ru(tpy)(bpy)(py)]²⁺ in CH₃CN (Figure 4a) can be fitted to a biexponential decay with τ₁ = 28 ps (8%) and τ₂ = 544 ps (92%). The absorption changes associated with the reduced ligands in the ³MLCT states in the 350–420 nm range display a broad maximum at ~370 nm at 1–10 ps delay but sharpen and red-shift to ~375 nm with a shoulder at ~390 nm at later times. These changes are accompanied by biexponential decays at 375 and 575 nm with τ₁ ≈ 3 ps and a long component with τ₂ ≈ 500 ps. The Ru → bpy ¹MLCT state is preferentially excited at 350 nm, resulting in fast ISC to the corresponding Ru → bpy ³MLCT state with maximum at ~370 nm associated with reduced bpy. This state decays to populate the Ru → tpy ³MLCT state within ~23 ps, with a maximum at ~375 nm and a shoulder at ~410 nm, similar to the spectral features for [Ru(tpy)₂]^2+.43,44 Since the 28 ps component represents a minor fraction (8%) of the bleach recovery, it corresponds to changes in absorption during ³MLCT(bpy) → ³MLCT(tpy) IC. The 23 ps component for the ³MLCT(bpy) → ³MLCT-(tpy) IC is consistent with the value of 26 ps previously reported for a related complex with two low-lying ³MLCT states.⁴⁵

Figure 4.

Transient absorption spectra of (a) [Ru(tpy)(bpy)(py)]²⁺ (λ_exc = 350 nm) and (b) [Ru(tpy)(Me₂bpy)(py)]²⁺ (λ_exc = 568 nm) in CH₃CN collected 1, 5, 10, 20, 40, 60, 100, 200, 500, 1000, and 2000 ps following the laser pulse (fwhm = 300 fs, baseline collected at −10 ps).

Excitation of the red edge of the Ru → tpy ¹MLCT absorption band of [Ru(tpy)(bpy)(py)]²⁺ with λ_exc = 568 nm produces a bleach signal that can be fitted to τ₁ = 6 ps (12%) and τ₂ = 437 ps (88%); similar kinetics are observed at 375 nm. The 6 ps component is attributed to vibrational relaxation in the Ru → tpy ³MLCT state, which then decays to regenerate the ground state with τ = 470 ps (Figure 5a). As expected, the 23–28 ps component is not present with 568 nm excitation. The 470 ps lifetime of the Ru → tpy ³MLCT state compares well to those of [Ru(tpy)₂]²⁺ (120 ps in CH₃CN and 250 ps in H₂O).^42–44

Figure 5.

Jablonski diagrams for (a) [Ru(tpy)(bpy)(py)]²⁺ and (b) [Ru(tpy)(Me₂bpy)(py)]²⁺.

The TA spectra that result from 568 nm excitation of [Ru(tpy)(Me₂bpy)(py)]²⁺ are shown in Figure 4b, where selective population of the Ru → tpy ¹MLCT state results in observation of the Ru → tpy ³MLCT absorption signals at ~375 and ~400 nm with monoexponential decay of τ = 6 ps and a biexponential bleach recovery at 470 nm with τ₁ = 7 ps (16%) and τ₂ = 38 ps (84%). The 6–7 ps component can be ascribed to IC from the Ru → tpy ³MLCT state to populate the ³LF state, which competes with vibrational cooling in the former, and the ³LF state regenerates the ground state with time constant of 38 ps (Figure 5b). Excitation of [Ru(tpy)-(Me₂bpy)(py)]²⁺ at 350 nm provides similar kinetics but with an additional ~3 ps component associated with decay of the Ru → Me₂bpy ³MLCT state (Figure 5b). These experiments are consistent with generation of the ³LF state within 3–7 ps, which then deactivates via ligand dissociation and thermal decay to the ground state. It is evident in the ultrafast TA data for [Ru(tpy)(Me₂bpy)(py)]²⁺ in Figure 4b that the ground state does not fully recover in the final trace (2 ns), consistent with formation of the monosubstituted CH₃CN photoproduct, [Ru(tpy)(Me₂bpy)(CH₃CN)]²⁺. However, the kinetics of the photoproduct formation cannot be determined because of its spectral overlap with the ground and excited states of the starting compound and the relatively small quantity of photoproduct formed.

Distortions around the metal center in [Ru(tpy)(Me₂bpy)-(py)]²⁺ compared with [Ru(tpy)(bpy)(py)]²⁺ can explain the differences in excited-state dynamics, resulting in a lower-energy ³LF state in the former that falls below the Ru → tpy ³MLCT state (Figure 5). The lower-energy ³LF state leads to enhanced ligand exchange for the Me₂bpy complex; the ³LF lifetime of [Ru(tpy)(Me₂bpy)(py)]²⁺ is similar to those of Ru(II) complexes with sterically bulky ligands, 45 ps for [Ru(6-Mebpy)₃]²⁺ and 7.5 ps for [Ru(Me₄bpy)₃]^2+.25 The formation of a pentacoordinate intermediate (PCI) from the ³LF state is possible, such that the dynamics of the ground-state regeneration are due to geminate recombination of the PCI and pyridine. However, the cage escape and geminate recombination kinetics for the related complex [Ru-(bpy)₂(NA)₂]²⁺ (NA = nicotinamide) in water were reported as 377 and 263 ps, respectively.³² This order of magnitude difference between the bleach recovery of [Ru(tpy)(Me₂bpy)-(py)]²⁺ and [Ru(bpy)₂(NA)₂]²⁺ is inconsistent with the 38 ps component assigned as geminate recombination. Ultrafast population of the ³LF state from the Ru → tpy ¹MLCT or vibrationally excited ³MLCT state, ³MLCT_vΔ1, to afford py dissociation is supported by efficient ligand exchange for [Ru(tpy)(Me₂bpy)(py)]²⁺ with low-energy light (λ_irr ≥ 600 nm) and the excited-state dynamics measured with 568 nm excitation. This finding is also consistent with the differences in $E_{\mathrm{a}}^{\text{Em}}$ and $E_{\mathrm{a}}^{\mathrm{P}}$ measured for [Ru(bpy)₂(py)₂]²⁺ (Table 1).

Density functional theory (DFT) calculations on [Ru(tpy)-(NN)(py)]²⁺ (NN = bpy, Me₂bpy) show that the unoccupied d_x²–y² orbital, directed along the Ru–py bond, is at a lower energy than the d_z² orbital in each complex. Therefore, population of the lowest-energy LF state results in additional electron density in the d_x²–² orbital, weakening the Ru–py bond. The distortions in [Ru(tpy)(Me₂bpy)(py)]²⁺ lower the calculated d_x²–² orbital energy by 0.82 eV relative to [Ru(tpy)(bpy)(py)]²⁺, consistent with stabilization of the LF states with Ru–py(σ*) character.

DUAL ACTIVITY: PHOTOINDUCED LIGAND EXCHANGE AND ¹O₂ GENERATION

[Ru(bpy)(dppn)(CH₃CN)₂]²⁺ (dppn = benzo[i]dipyrido[3,2-a:2′,3′-c]phenazine) (Figure 6) combines the ligand exchange photochemistry of [Ru(bpy)₂(CH₃CN)₂]²⁺ and the ¹O₂ production of [Ru(bpy)₂(dppn)]²⁺ to enhance cellular photo-toxicity.⁴⁶ The electronic absorption spectrum of [Ru(bpy)-(dppn)(CH₃CN)₂]²⁺ features a ¹MLCT maximum at 430 nm (11 000 M⁻¹ cm⁻¹) and dppn-centered ¹ππ* transitions at 382 nm (11 100 M⁻¹ cm⁻¹) and 405 nm (13 500 M⁻¹ cm⁻¹). The lowest-energy excited state of the complex is the dppn-centered ³ππ* state with τ = 20 μs in CH₃CN, similar to those of [Ru(bpy)₂(dppn)]²⁺ (τ = 33 μs in CH₃CN) and free dppn (τ = 18 μs in CHCl₃).²¹ In [Ru(bpy)₂(CH₃CN)₂]²⁺, both the lowest-energy ³MLCT excited state (τ = 51 ps) and the low-lying ³LF state are populated upon ultrafast excitation, and the complex undergoes efficient photoinduced ligand exchange.³¹

Figure 6.

Structural representations of [Ru(bpy)(dppn)(CH₃CN)₂]²⁺, [Ru(bpy)₂(dppn)]²⁺, and [Ru(bpy)₂(CH₃CN)₂]²⁺.

Irradiation of [Ru(bpy)(dppn)(CH₃CN)₂]²⁺ in water promotes sequential substitution of the two CH₃CN ligands (λ_irr = 400 nm); the first step forms [Ru(bpy)(dppn)-(CH₃CN)(OH₂)]²⁺ with Φ₄₀₀ = 0.002(3), which is 2 orders of magnitude lower than that in [Ru(bpy)₂(CH₃CN)₂]²⁺ (Φ₄₀₀ = 0.21).³¹ The quantum yield for production of ¹O₂ (Φ_Δ) from the ³ππ* state of [Ru(bpy)(dppn)(CH₃CN)₂]²⁺ is 0.72(2), which is slightly lower than that of [Ru(bpy)₂(dppn)]²⁺ (0.88(2)). The lower yields of ligand exchange and ¹O₂ generation in [Ru(bpy)(dppn)(CH₃CN)₂]²⁺ relative to the parent complexes are explained by competitive population of the ³LF and ³ππ* states. A phthalocyanine Ru(II) complex with bound NO ligands was previously shown to produce ¹O₂ with Φ_Δ = 0.29 and photorelease NO.⁴⁷

Ultrafast TA spectroscopy reveals the excited-state dynamics of [Ru(bpy)(dppn)(CH₃CN)₂]²⁺. Because of spectral overlap of the ¹MLCT and ¹ππ* bands, one cannot be accessed selectively. Excitation in the 300 to 400 nm range results in the observation of both the ³MLCT and ³ππ* states within the laser pulse, with absorption at ~360 and ~540 nm, respectively (Figure 7). Additionally, the lower-lying ³ππ* state is also populated from the ³MLCT state through IC with τ = 22 ps (Figure 7). Although the observed ligand exchange is expected to occur through the ³LF state, the latter was not detected, likely because of its low quantum yield and weak oscillator strength.

Figure 7.

Transient absorption spectra of [Ru(bpy)(dppn)-(CH₃CN)₂]²⁺ in CH₃CN (λ_exc = 300 nm, fwhm = 300 fs).

[Ru(tpy)(Me₂dppn)(py)]²⁺ (Me₂dppn = 3,6-dimethylbenzo-[i]dipyrido[3,2-a:2′,3′-c]phenazine) (Figure 8) undergoes both pyridine dissociation and ¹O₂ production with visible light. The Me₂dppn ligand causes geometric strain similar to that caused by Me₂bpy, but the complex maintains the Me₂dppn ³ππ* lowest-energy excited state.⁴⁸ [Ru(tpy)(Me₂dppn)(py)]²⁺ absorbs strongly in the visible region with dppn-centered ¹ππ* transitions at 382 nm (11 400 M⁻¹ cm⁻¹) and 404 nm (12 400 M⁻¹ cm⁻¹) and a ¹MLCT peak at 486 nm (12 900 M⁻¹ cm⁻¹). When photolyzed in CH₃CN (λ_irr = 500 nm), [Ru(tpy)(Me₂dppn)(CH₃CN)]²⁺ is formed with Φ₅₀₀ = 0.053(1) in the absence of O₂, but ligand exchange is not observed in [Ru(tpy)(dppn)(py)]²⁺ (Φ₅₀₀ < 10⁻⁴), which lacks steric strain (Table 2). Photosensitization of ¹O₂ by [Ru(tpy)-(Me₂dppn)(py)]²⁺ occurs with Φ_Δ = 0.69(9), which is lower than the value of 0.98(6) measured for [Ru(tpy)(dppn)(py)]²⁺ (λ_irr = 460 nm), as listed in Table 2. The reduced quantum yield for [Ru(tpy)(Me₂dppn)(py)]²⁺ can be attributed to competitive deactivation through the ³LF state afforded by distortions around the metal. Competitive population of excited states also explains the lower ligand exchange quantum yield of [Ru(tpy)(Me₂dppn)(py)]²⁺ relative to [Ru(tpy)(Me₂bpy)-(py)]²⁺.

Figure 8.

Structural representations of [Ru(tpy)(Me₂dppn)(py)]²⁺ and [Ru(tpy)(dppn)(py)]²⁺.

Following selective Ru → tpy ¹MLCT excitation of [Ru(tpy)(dppn)(py)]²⁺ and [Ru(tpy)(Me₂dppn)(py)]²⁺ at 568 nm, the Ru → tpy ³MLCT state of [Ru(tpy)(Me₂dppn)-(py)]²⁺ is observed at ~390 and ~415 nm within the laser pulse, along with a strong ground-state bleach centered at ~480 nm (Figure 9a). Although the signal at 535 nm corresponding to the Me₂dppn ³ππ* state is not observed at early times, it evolves with τ₁ = 2 ps (28%) and τ₂ = 17 ps (72%), concomitant with the decay of the ³MLCT signals fitted to τ₁ = 3 ps (13%) and τ₂ = 18 ps (87%) at 415 nm and changes in the bleach signal with τ₁ = 1 ps (16%) and τ₂ = 18 ps (84%). The ~2 ps decay is believed to have contributions from ISC, IC, and vibrational cooling, while the 18 ps component is assigned to population of the ³ππ* state from the ³MLCT state. Similar spectral features and kinetics were measured for [Ru(tpy)-(dppn)(py)]²⁺ in CH₃CN under 568 nm excitation, for which the growth of the 540 nm peak and bleach recovery at 470 nm can be fitted to τ₁ = 1 ps (21%) and τ₂ = 22 ps (79%). The long component is ascribed to IC from the ³MLCT state to the dppn ³ππ* state, while the short component is related to ISC, IC, and vibrational cooling processes.

Figure 9.

(a) Ultrafast transient absorption of [Ru(tpy)(Me₂dppn)-(py)]²⁺ in CH₃CN (λ_exc = 568 nm, fwhm = 300 fs) and (b) the corresponding Jablonski diagram.

The Jablonski diagram of [Ru(tpy)(Me₂dppn)(py)]²⁺, depicted in Figure 9b, shows that IC from the Ru → tpy ³MLCT state to the dppn ³ππ* state occurs with τ = 18 ps in the Me₂dppn complex, as opposed to 22 ps in [Ru(tpy)-(dppn)(py)]²⁺. Since photoinduced ligand exchange is observed in [Ru(tpy)(Me₂dppn)(py)]²⁺ with λ_irr ≥ 550 nm, low-energy light must populate the dissociative ³LF state. The similarity in the ³ππ* lifetimes of [Ru(tpy)(dppn)(py)]²⁺ and [Ru(tpy)(Me₂dppn)(py)]²⁺ (τ = 50 and 47 μs, respectively; λ_exc = 355 nm, fwhm ≈ 8 ns) is consistent with the ³LF state being located at a higher energy, as shown in Figure 9b.

CONCLUSIONS

The ability of Ru(II) complexes to undergo both photoinduced ligand exchange and ¹O₂ generation efficiently provides a means to design potentially more active PCT therapeutics. In particular, photorelease of drugs can be coupled to the activity of reactive oxygen species, enabling these compounds to effect cell death via two different mechanisms upon visible-light irradiation. Steric strain can be used to lower the energy of the metal-centered state(s), resulting in greater yields of ligand photodissociation, even when these states(s) are not the lowest in energy. Mixing between the ³LF state(s) and MLCT and/or LC states is believed to play an important role in efficient photoinduced ligand exchange, which is greater when these states are closer in energy. Work is underway to gain further understanding of the coupling between states with the goal of increasing the ligand exchange yields in these dual-action complexes while retaining relatively high sensitization of ¹O₂ upon irradiation in the photodynamic window (600–900 nm).

Biographies

Jessica D. Knoll received her B.S. in chemistry from the University of Dayton in 2008. In 2013, she earned her Ph.D. from Virginia Tech with Prof. Karen Brewer, and she is currently a postdoctoral researcher with Prof. Claudia Turro at The Ohio State University.

Bryan A. Albani received his B.A. in chemistry from The College of Wooster in 2010. He obtained his Ph.D. in 2015 under the supervision of Prof. Claudia Turro at The Ohio State University and is employed as an Advanced Research Scientist at Owens Corning.

Claudia Turro was born in Argentina and received her B.S. and Ph.D. in chemistry at Michigan State University with Profs. Daniel Nocera and George Leroi. Her graduate work on ultrafast proton-coupled electron transfer and excited states of inorganic complexes was followed by research on the interactions of metal complexes with DNA at Columbia University with Prof. Nicholas Turro as a Jane Coffin Childs Memorial Fellow. She began her independent career as a faculty member at The Ohio State University in 1996.