Ligand Photodissociation Research Articles

Steric Bulk‐Dependent Photoresponse of Sulfonamide Azobenzene Ligand in Arene Ruthenium(II) Complexes

AbstractA series of sulfonamide azobenzenes bearing alkyl substituents of increasing steric bulk at the position ortho to the N=N bond and their corresponding chloro(hexamethylbenzene)ruthenium(II) complexes were synthesized. The latter bearing mono‐substituted ligands exhibited an exocyclic azo bond under the E configuration, and underwent reversible E→Z photoisomerization upon irradiation with visible light, followed by thermal Z→E back isomerization upon resting in the dark at 20 °C. In contrast, the corresponding 2,6‐dimethyl substituted azobenzene complex, while also exhibiting an exocyclic azo bond, was isolated as the Z‐isomer and underwent uncommon solvent dependent irreversible photodissociation of azobenzene ligand upon visible light irradiation. Valuable insights into the photophysical and structural properties of these complexes were gained by combination of computational and X‐ray diffraction studies.

Differences in Photophysical Properties and Photochemistry of Ru(II)-Terpyridine Complexes of CH3CN and Pyridine.

A series of 22 Ru(II) complexes of the type [Ru(tpy)(L)(L')]n+, where tpy is the tridentate ligand 2,2';6,2″-terpyridine, L represents bidentate ligands with varying electron-donating ability, and L' is acetonitrile (1a-11a) or pyridine (1b-11b), were investigated. The dissociation of acetonitrile occurs from the 3MLCT state in 1a-11a, such that it does not require the population of a 3LF state. Electrochemistry and spectroscopic data demonstrate that the ground states of these series do not differ significantly. Franck-Condon line-shape analysis of the 77 K emission data shows no significant differences between the emitting 3MLCT states in both series. Arrhenius analysis of the temperature dependence of 3MLCT lifetimes shows that the energy barrier (Ea) to thermally populating a 3LF state from a lower energy 3MLCT state is significantly higher in the pyridine than in the CH3CN series, consistent with the photostability of complexes 1b-11b, which do not undergo pyridine photodissociation under our experimental conditions. Importantly, these results demonstrate that ligand photodissociation of pyridine in 1b-11b does not take place directly from the 3MLCT state, as is the case for 1a-11a. These findings have potential impact on the rational design of complexes for a number of applications, including photochemotherapy, dye-sensitized solar cells, and photocatalysis.

Ruthenium Pyrazole Complexes: A Family of Highly Active Metallodrugs for Photoactivated Chemotherapy.

Ruthenium complexes bearing bis pyrazole (pzH) ligands, cis-[Ru(bpy)2(R-pzH)2]2+ (bpy = 2,2'-bipyridine, R = -H, -Cl), were examined as photoactivated anticancer prodrugs. A dicationic pyrazole complex deprotonated to give monocationic pyrazole-pyrazolate complexes, cis-[Ru(bpy)2(R-pz-)(R-pzH)]+, in an aqueous solution with pKa values of 9.5 and 7.2 for R = H and R = Cl, respectively. Upon deprotonation, relative quantum yields of photosubstitution decreased while lipophilicity of the complexes increased according to the measurements of water-octanol coefficients. The ruthenium complex with 4-chloropyrazole ligands displayed high cytotoxicity upon light irradiation (IC50 = 0.060 ± 0.016 μM) toward lung cancer cells, which was 7 times higher than that in the dark (IC50 = 0.44 ± 0.07 μM). Additional experiments for the ruthenium R-pyrazole complexes indicated that (1) selective photodissociation of the 4-chloropyrazole ligand occurs from cis-[Ru(bpy)2(4-Clpz-)(4-ClpzH)]+, (2) photoinduced ligand dissociation is dominant rather than photoinduced generation of singlet oxygen (1O2), and (3) induction of cell death occurs via the intrinsic pathway of apoptosis.

Cobalt-catalyzed synthesis of amides from alkenes and amines promoted by light.

Catalytic methods to couple alkene and amine feedstocks are valuable in synthetic chemistry. The direct carbonylative coupling of alkenes and amines holds promise as a perfectly atom-economical approach to amide synthesis, but general methods remain underdeveloped. Herein, we report an alkene hydroaminocarbonylation catalyzed by unmodified, inexpensive cobalt carbonyl under mild conditions and low pressure promoted by light. Silane addition after the reaction enables sequential cobalt-catalyzed amide reduction, constituting a formal alkene hydroaminomethylation. These methods exhibit exceptional scope across both alkene and amine components with high chemo- and regioselectivity and proceed efficiently even in the absence of solvent. The formation of a hydridocobalt through photodissociation of a carbonyl ligand is proposed to enable catalytic activity under mild conditions, which addresses a long-standing challenge in catalysis.

Discovery of Divergent, Light-Controlled Catalysis Triggered by Ligand Photodissociation from Cobalt Complexes

AbstractPhotochemistry has become a key area of research in synthetic chemistry over the last few decades. More recently, interest has grown in merging this area with transition metal catalysis to develop new reactivity. One key photoinduced step in this context is ligand dissociation from transition metal complexes. This has been used to develop light-gated catalysis, allowing for on/off control over a reaction. However, this concept can only result in a single product outcome. Our group has focused on the development of cobalt-catalyzed reactivity switches, enabled by a simple photodissociation step, which promotes one mechanistic path or another. As such, we can use a single catalytic platform to yield two different outcomes depending on whether the reaction is irradiated with light or not. This short review will focus on works in this area by our group and others.1 Introduction2 Photocontrolled Hydroboration3 Hydrogenation and Hydroformylation4 Conclusion

Acetonitrile Ligand Photosubstitution in Ru(II) Complexes Directly from the 3MLCT State.

The excited states of the series [Ru(tpy)(L)(CH3CN)]n+ (1-11) (n = 1, 2) containing bidentate ligands L with varying electron-donating ability were characterized through Arrhenius analysis of the temperature dependence of their excited-state lifetimes. Complexes 1-11 undergo photoinduced CH3CN dissociation upon 450 nm irradiation with ligand exchange quantum yields that increase with the energy barrier to populating a dissociative triplet ligand field (3LF) state from the lowest-energy triplet metal-to-ligand charge transfer (3MLCT) excited state. Combined with DFT calculations, the data indicate that ligand photodissociation in 1-11 occurs directly from the 3MLCT state instead of a 3LF state. This finding is in contrast to the generally accepted mechanism for ligand photodissociation in Ru(II) complexes and indicates that alternative pathways for photoinduced ligand dissociation are available. These results can widely impact design principles for applications that require ligand photodissociation, such as photochemotherapy and photocatalysis, as well as for those where photosubstitution is undesirable, such as solar energy conversion.

Synthesis and Coordination Chemistry of a Benzannulated Bipyridine: 6,6'-Biphenanthridine.

The synthesis, characterization, and coordination chemistry of a doubly π-extended bipyridine analogue, 6,6'-biphenanthridine (biphe), is presented. The structure of the molecule has been determined in the solid state by X-ray diffraction, showing an angle of 72.6° between the phenanthridine planes. The free, uncoordinated organic molecule displays blue fluorescence in solution. It can be singly protonated with strong acids, and the protonated form displays more intense yellow emission. The effect of acid on the excited states is interpreted with the aid of TDDFT calculations. Two Ru(II) coordination complexes, tris(6,6'-biphenanthridine)ruthenium(II) dichloride, [Ru(biphe)3]Cl2, and bis(2,2'-bipyridine)(6,6'-biphenanthridine)ruthenium(II) tetraphenylborate, [Ru(bpy)2(biphe)](BPh4)2, are also reported and their structures determined in the solid state by X-ray diffraction. Both complexes display emission at 77 K that is strongly bathochromically shifted by almost 200 nm compared to that of the archetypal 3MLCT emitter [Ru(bpy)3]2+. Such a red shift is consistent with the more extended conjugation and lower-energy π* orbitals associated with the biphe ligand, lowering the energy of the 3MLCT excited state, as revealed by TDDFT calculations. The efficient non-radiative decay that is typical of such low-energy emitters renders the phosphorescence extremely weak and short-lived at ambient temperature, and rapid ligand photodissociation also competes with radiative decay, especially in the heteroleptic complex. Electrochemical analysis illustrates the effect of biphe's stabilized vacant π* manifold, with multiple reversible reductions evident at much less negative potentials than those observed for [Ru(bpy)3]2+.

Photoproduct formation in coenzyme B12-dependent CarH via a singlet pathway

The CarH photoreceptor exploits of the light-sensing ability of coenzyme B12 ( adenosylcobalamin=AdoCbl) to perform its catalytic function, which includes large-scale structural changes to regulate transcription. In daylight, transcription is activated in CarH via the photo-cleavage of the Co-C5' bond of coenzyme B12. Subsequently, the photoproduct, 4',5'-anhydroadenosine (anhAdo) is formed inducing dissociation of the CarH tetramer from DNA. Several experimental studies have proposed that hydridocoblamin (HCbl) may be formed in process with anhAdo. The photolytic cleavage of the Co-C5' bond of AdoCbl was previously investigated using photochemical techniques and the involvement of both singlet and triplet excited states were explored. Herein, QM/MM calculations were employed to probe (1) the photolytic processes which may involve singlet excited states, (2) the mechanism of anhAdo formation, and (3) whether HCbl is a viable intermediate in CarH. Time-dependent density functional theory (TD-DFT) calculations indicate that the mechanism of photodissociation of the Ado ligand involves the ligand field (LF) portion of the lowest singlet excited state (S1) potential energy surface (PES). This is followed by deactivation to a point on the S0 PES where the Co-C5' bond remains broken. This species corresponds to a singlet diradical intermediate. From this point, the PES for anhAdo formation was explored, using the Co-C5' and Co-C4' bond distances as active coordinates, and a local minimum representing anhAdo and HCbl formation was found. The transition state (TS) for the formation of the Co-H bond of HCbl was located and its identity was confirmed by a single imaginary frequency of i1592 cm-1. Comparisons to experimental studies and the potential role of rotation around the N-glycosidic bond of the Ado ligand were discussed.

Improving the Photostability of [Ru(bpy)3]2+ by Embedment in Silica

AbstractAs a classical photosensitizer model, [Ru(bpy)3]2+ possesses excellent photochemical properties and plays a critical role in photocatalysis. Improving the photostability of [Ru(bpy)3]2+ is still a challenge, as its ligands are easily lost upon light irradiation. It is thus of importance to understand the mechanisms of photo‐instability and to explore counter measures. Herein, we demonstrate that loading [Ru(bpy)3]2+ in silica could greatly suppress its photodissociation of ligands, thus improving its photocatalytic activity. By integrating nano‐stirbars with [Ru(bpy)3]2+‐silica nanocomposites, the heterogeneous catalysis showed improved activity and recyclability. We believe that the preservation of the ligand sphere in embedded complexes would facilitate regioselectivity and enantioselectivity in conventional heterogeneous catalysis.

Light-Gated Cobalt(I) Hydride Catalysed Alkyne Hydroboration

We report a light-gated, catalytic protocol for hydroboration of terminal alkynes based on a bench-stable cobalt(I) hydride complex which undergoes ligand photodissociation with visible light. The products are obtained in good yields and with excellent E-selectivity.

Capturing Atom-Specific Electronic Structural Dynamics of Transition-Metal Complexes with Ultrafast Soft X-Ray Spectroscopy.

The atomic specificity of X-ray spectroscopies provides a distinct perspective on molecular electronic structure. For 3d metal coordination and organometallic complexes, the combination of metal- and ligand-specific X-ray spectroscopies directly interrogates metal-ligand covalency-the hybridization of metal and ligand electronic states. Resonant inelastic X-ray scattering (RIXS), the X-ray analog of resonance Raman scattering, provides access to all classes of valence excited states in transition-metal complexes, making it a particularly powerful means of characterizing the valence electronic structure of 3d metal complexes. Recent advances in X-ray free-electron laser sources have enabled RIXS to be extended to the ultrafast time domain. We review RIXS studies of two archetypical photochemical processes: charge-transfer excitation in ferricyanide and ligand photodissociation in iron pentacarbonyl. These studies demonstratefemtosecond-resolution RIXS can directly characterize the time-evolving electronic structure, including the evolution of the metal-ligand covalency.

Unlocking the Potential of Ru(II) Dual-action Compounds with the Power of the Heavy-atom Effect.

We report the synthesis, photochemical and biological characterization of two new Ru(II) photoactivated complexesbased on [Ru(tpy)(Me2 bpy)(L)]2+ (tpy = 2,2':6',2''-terpyridine, Me2 bpy = 6,6'-dimethyl-2,2'-bipyridine), where L = pyridyl-BODIPY (pyBOD). Two pyBOD ligands were prepared bearing flanking hydrogen or iodine atoms. Ru(II)-bound BODIPY dyes show a red-shift of absorption maxima relative to the free dyes and undergo photodissociation of BODIPY ligands with green light irradiation. Addition of iodine into the BODIPY ligand facilitates intersystem crossing, which leads to efficient singlet oxygen production in the free dye, but also enhances quantum yield of release of the BODIPY ligand from Ru(II). This represents the first report of a strategy to enhance photodissociation quantum yields through the heavy-atom effect in Ru(II) complexes. Furthermore, Ru(II)-bound BODIPY dyes display fluorescence turn-on once released, with a lead analog showing nanomolar EC50 values against triple negative breast cancer cells, >100-fold phototherapeutic indexes under green light irradiation, and higher selectivity toward cancer cells as compared to normal cells than the corresponding free BODIPY photosensitizer. Conventional Ru(II) photoactivated complexes require nonbiorthogonal blue light for activation and rarely show submicromolar potency to achieve cell death. Our study represents an avenue for the improved photochemistry and potency of future Ru(II) complexes.

Photoactivated Osmium Arene Anticancer Complexes

Half-sandwich Os-arene complexes exhibit promising anticancer activity, but their photochemistry has hardly been explored. To exploit the photocytotoxicity and photochemistry of Os-arenes, O,O-chelated complexes [Os(η6-p-cymene)(Curc)Cl] (OsCUR-1, Curc = curcumin) and [Os(η6-biphenyl)(Curc)Cl] (OsCUR-2), and N,N-chelated complexes [Os(η6-biphenyl)(dpq)I]PF6 (OsDPQ-2, dpq = pyrazino[2,3-f][1,10]phenanthroline) and [Os(η6-biphenyl)(bpy)I]PF6 (OsBPY-2, bpy = 2,2'-bipyridine), have been investigated. The Os-arene curcumin complexes showed remarkable photocytotoxicity toward a range of cancer cell lines (blue light IC50: 2.6-5.8 μM, photocytotoxicity index PI = 23-34), especially toward cisplatin-resistant cancer cells, but were nontoxic to normal cells. They localized mainly in mitochondria in the dark but translocated to the nucleus upon photoirradiation, generating DNA and mitochondrial damage, which might contribute toward overcoming cisplatin resistance. Mitochondrial damage, apoptosis, ROS generation, DNA damage, angiogenesis inhibition, and colony formation were observed when A549 lung cancer cells were treated with OsCUR-2. The photochemistry of these Os-arene complexes was investigated by a combination of NMR, HPLC-MS, high energy resolution fluorescence detected (HERFD), X-ray adsorption near edge structure (XANES) spectroscopy, total fluorescence yield (TFY) XANES spectra, and theoretical computation. Selective photodissociation of the arene ligand and oxidation of Os(II) to Os(III) occurred under blue light or UVA excitation. This new approach to the design of novel Os-arene complexes as phototherapeutic agents suggests that the novel curcumin complex OsCUR-2, in particular, is a potential candidate for further development as a photosensitizer for anticancer photoactivated chemotherapy (PACT).

Selective and Efficient Photoinactivation of Intracellular Staphylococcus aureus and MRSA with Little Accumulation of Drug Resistance: Application of a Ru(II) Complex with Photolabile Ligands.

Novel antibacterial agents capable of efficiently sterilizing intracellular Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) but with low cytotoxicity and low resistance development are quite appealing. In this work, three Ru(II) complexes with photolabile ligands were explored to realize such a goal. Complex 3 (5 μM) can inhibit more than 90% growth of S. aureus/MRSA that has invaded in J774A.1 cells upon visible light irradiation, being much more efficient than vancomycin. In similar conditions, negligible dark- and phototoxicity were found toward the host cells. The bactericidal activity is highly correlated with DNA covalent binding by the Ru(II) fractions generated after ligand photodissociation. Moreover, S. aureus quickly developed resistance toward vancomycin, while negligible resistance toward complex 3 even after 700 generations was obtained. These appealing results may pave a new way for fighting against intracellular antibiotic-resistant pathogens.

The modification of a pyrene group makes a Ru(ii) complex versatile.

In this work, the simple modification of a pyrene group on the labile ligand gives the resultant complex 1 versatility, for example, "turn-on" fluorescence after photo-dissociation, dual PDT and PACT activity, and a large two-photon absorption cross section.

Intramolecular Hydrogen Bonding: A Key Factor Controlling the Photosubstitution of Ruthenium Complexes.

Photosubstitution reactions of ruthenium complexes with pyrazole ligands, cis-[Ru(bpy)2(pzH)2]2+ (1a), cis-[Ru(bpy)2(pz)(pzH)]+ (1b), and cis-[Ru(bpy)2(pz)2]0 (1c) (pzH = pyrazole, bpy = 2,2'-bipyridine), were investigated. Dicationic complex 1a was deprotonated to 1b using moderate base (pKa = 15.2, MeCN), while the second deprotonation to give 1c required more severe conditions (pKa = 26.9). Monocationic complex 1b possessed an N-H···N-type intramolecular hydrogen bond between the pyrazole and pyrazolate ligands, as corroborated by the solid-state crystal structure. The photosubstitution quantum yield of 1a (Φ = 0.26) was comparable to that of cis-[Ru(bpy)2(pyridine)2]2+ (Φ = 0.24) in acetonitrile solution. In contrast, the photodissociation of a pzH ligand was strongly suppressed by the deprotonation of a pyrazole ligand N-H group. In the presence of 10 000 equiv of 4,4'-dimethylaminopyridine, the quantum yield dropped to ∼2 × 10-6 in acetonitrile. The photosubstitution quantum yield of 1b was even smaller than that of neutral complex 1c, although 1c had a smaller HOMO-LUMO energy gap than monocationic complex 1b. The small quantum yield of 1b was attributed to intramolecular hydrogen bonding between pyrazole and pyrazolate ligands. The apparent rate constants for the photosubstitution of 1b were highly solvent-dependent. The photosubstitution of 1b was suppressed in aprotic solvents, while the reaction was accelerated by 2 orders of magnitude in protic solvents with strong proton donor abilities.

Ligand photodissociation in Ru(ii)–1,4,7-triazacyclononane complexes enhances water oxidation and enables electrochemical generation of surface active species

Ligand transformations involved in metal complexes during water oxidation (WO), such as ligand decomposition, partial oxidation, or complete dissociation have been reported, however, ligand photodissociation has not been reported yet.

Ultrafast Structural Changes Decomposed from Serial Crystallographic Data.

Direct visualization of electronic and molecular events during biochemical reactions is essential to mechanistic insights. This Letter presents an in-depth analysis of the serial crystallographic data sets collected by Barends and Schlichting et al. ( Science 2015 , 350 , 445 ) that probe the ligand photodissociation in carbonmonoxy myoglobin. This analysis reveals electron density changes caused by the formation of high-spin 3d atomic orbitals of the heme iron upon photolysis and their dynamic behaviors within the first few picoseconds. The heme iron is found popping out of and recoiling back into the heme plane in succession. These findings provide long-awaited visual validations for previous works using ultrafast spectroscopy and molecular dynamics simulations. Electron density variations are also found largely in the solvent during the first period of a low-frequency oscillation. This work demonstrates the importance of the analytical methods in detecting and isolating weak, transient signals of electronic changes arising from chemical reactions.

Ru(II) Polypyridyl Complexes Derived from Tetradentate Ancillary Ligands for Effective Photocaging.

Metal complexes have many proven applications in the caging and photochemical release of biologically active compounds. Photocaging groups derived from Ru(II) traditionally have been composed of ancillary ligands that are planar and bi- or tridentate, such as 2,2'-bipyridine (bpy), 2,2':6',2″-terpyridine (tpy), and 1,10-phenanthroline (phen). Complexes bearing ancillary ligands with denticities higher than three represent a new class of Ru(II)-based photocaging groups that are grossly underdeveloped. Because high-denticity ancillary ligands provide the ability to increase the structural rigidity and control the stereochemistry, our groups initiated a research program to explore the applications of such ligands in Ru(II)-based photocaging. Ru(TPA), bearing the tetradentate ancillary ligand tris(2-pyridylmethyl)amine (TPA), has been successfully utilized to effectively cage nitriles and aromatic heterocycles. Nitriles and aromatic heterocycles caged by the Ru(TPA) group show excellent stability in aqueous solutions in the dark, and the complexes can selectively release the caged molecules upon irradiation with light. Ru(TPA) is applicable as a photochemical agent to offer precise spatiotemporal control over biological activity without undesired toxicity. In addition, Ru(II) polypyridyl complexes with desired photochemical properties can be synthesized and identified by solid-phase synthesis, and the resulting complexes show properties to similar to those of complexes obtained by solution-phase synthesis. Density functional theory (DFT) calculations reveal that orbital mixing between the π* orbitals of the ancillary ligand and the Ru-N dσ* orbital is essential for ligand photodissociation in these complexes. Furthermore, the introduction of steric bulk enhances the photoliability of the caged molecules, validating that steric effects can largely influence the quantum efficiency of photoinduced ligand exchange in Ru(II) polypyridyl complexes. Recently, two new photocaging groups, Ru(cyTPA) and Ru(1-isocyTPQA), have been designed and synthesized for caging of nitriles and aromatic heterocycles, and these complexes exhibit unique photochemical properties distinct from those derived from Ru(TPA). Notably, the unusually greater quantum efficiency for the ligand exchange in [Ru(1-isocyTPQA)(MeCN)2](PF6)2, Φ400 = 0.033(3), uncovers a trans-type effect in the triplet metal-to-ligand charge transfer (3MLCT) state that enhances photoinduced ligand exchange in a new manner. DFT calculations and ultrafast transient spectroscopy reveal that the lowest-energy triplet state in [Ru(1-isocyTPQA)(MeCN)2](PF6)2 is a highly mixed 3MLCT/3ππ* excited state rather than a triplet metal-centered ligand-field (3LF) excited state; the latter is generally accepted for ligand photodissociation. In addition, Mulliken spin density calculations indicate that a majority of the spin density in [Ru(1-isocyTPQA)(MeCN)2](PF6)2 is localized on the isoquinoline arm, which is opposite to the cis MeCN, rather than on the ruthenium center. This significantly weakens the Ru-N6 ( cis MeCN) bond, which then promotes the ligand photodissociation. This newly discovered effect gives a clearer perception of the interplay between the 3MLCT and 3LF excited states of Ru(II) polypyridyl complexes, which may be useful in the design and applications of ruthenium complexes in the areas of photoactivated drug delivery and photosensitizers.

DFT Investigation of Ligand Photodissociation in [RuII(tpy)(bpy)(py)]2+ and [RuII(tpy)(Me2bpy)(py)]2+ Complexes.

Photoinduced ligand dissociation of pyridine occurs much more readily in [Ru(tpy)(Me2bpy)(py)]2+ than in [Ru(tpy)(bpy)(py)]2+ (tpy = 2,2':6',2″-terpyridine; bpy = 2,2'-bipyridine, Me2bpy = 6,6'-dimethyl-2,2'-bipyridine; py = pyridine). The S0 ground state and the 3MLCT and 3MC excited states of these complexes have been studied using BP86 density functional theory with the SDD basis set and effective core potential on Ru and the 6-31G(d) basis set for the rest of the atoms. In both complexes, excitation by visible light and intersystem crossing leads to a 3MLCT state in which an electron from a Ru d orbital has been promoted to a π* orbital of terpyridine, followed by pyridine release after internal conversion to a dissociative 3MC state. Interaction between the methyl groups and the other ligands causes significantly more strain in [Ru(tpy)(Me2bpy)(py)]2+ than in [Ru(tpy)(bpy)(py)]2+, in both the S0 and 3MLCT states. Transition to the dissociative 3MC states releases this strain, resulting in lower barriers for ligand dissociation from [Ru(tpy)(Me2bpy)(py)]2+ than from [Ru(tpy)(bpy)(py)]2+. Analysis of the molecular orbitals along relaxed scans for stretching the Ru-N bonds reveals that ligand photodissociation is promoted by orbital mixing between the ligand π* orbital of tpy in the 3MLCT state and the dσ* orbitals that characterize the dissociative 3MC states. Good overlap and strong mixing occur when the Ru-N bond of the leaving ligand is perpendicular to the π* orbital of terpyridine, favoring the release of pyridine positioned in a cis fashion to the terpyridine ligand.