Beyond the First Coordination Sphere─Manipulating the Excited-State Landscape in Iron(II) Chromophores with Protons.

Molecular transition metal chromophores play a central role in light harvesting and energy conversion. Recently, earth-abundant transition-metal-based chromophores have begun to challenge the dominance of platinum group metal complexes in this area. However, the development of new chromophores with optimized photophysical properties is still limited by a lack of synthetic methods, especially with respect to heteroleptic complexes with functional ligands. Here, we demonstrate a facile and efficient method for the combination of strong-field carbenes with the functional 2,2'-bibenzimidazole ligand in a heteroleptic iron(II) chromophore complex. Our approach yields two isomers that differ predominantly in their excited-state lifetimes based on the symmetry of the ligand field. Deprotonation of both isomers leads to a significant red-shift of the metal-to-ligand charge transfer (MLCT) absorption and a shortening of excited-state lifetimes. Femtosecond transient absorption spectroscopy in combination with quantum chemical simulations and resonance Raman spectroscopy reveals the complex relationship between protonation and photophysical properties. Protonation is found to tip the balance between MLCT and metal-centered (MC) excited states in favor of the former. This study showcases the first example of fine-tuning of the excited-state landscape in an iron(II) chromophore through second-sphere manipulations and provides a new perspective to the challenge of excited-state optimizations in 3d transition metal chromophores.

A Carbon Nanodot Based Near-Infrared Photosensitizer with a Protein-Ruthenium Shell for Low-Power Photodynamic Applications.

Near-infrared (NIR) light-activated photosensitization represents an encouraging therapeutic method in photodynamic therapy, especially for deep tissue penetration. In this context, two-photon activation, i.e., utilization of photons with relatively low energy but high photon flux for populating a virtual intermediate state leading to an excited state, is attractive. This concept would be highly advantageous in photodynamic therapy due to its minimal side effects. Herein, we propose that the combination of plasma protein serum albumin (HSA) containing several Ru complexes and NIR two-photon excitable carbon nanodots (Cdots), termed HSA-Ru-Cdots, provides several attractive features for enhancing singlet oxygen formation within the mitochondria of cancer cells stimulated by two-photon excitation in the NIR region. HSA-Ru-Cdot features biocompatibility, water solubility, and photostability as well as uptake into cancer cells with an endosomal release, which is an essential feature for subcellular targeting of mitochondria. The NIR two-photon excitation induced visible emission of the Cdots allows fluorescence resonance energy transfer (FRET) to excite the metal-to-ligand charge transfer of the Ru moiety, and fluorescence-lifetime imaging microscopy (FLIM) has been applied to demonstrate FRET within the cells. The NIR two-photon excitation is indirectly transferred to the Ru complexes, which leads to the production of singlet oxygen within the mitochondria of cancer cells. Consequently, we observe the destruction of filamentous mitochondrial structures into spheroid aggregates within various cancer cell lines. Cell death is induced by the long-wavelength NIR light irradiation at 810 nm with a low power density (7 mW/cm2), which could be attractive for phototherapy applications where deeper tissue penetration is crucial.

Pyrimidoquinazolinophenanthroline Opens Next Chapter in Design of Bridging Ligands for Artificial Photosynthesis.

The synthesis and detailed characterization of a new Ru polypyridine complex containing a heteroditopic bridging ligand with previously unexplored metal-metal distances is presented. Due to the twisted geometry of the novel ligand, the resultant division of the ligand in two distinct subunits leads to steady state as well as excited state properties of the corresponding mononuclear Ru(II) polypyridine complex resembling those of prototype [Ru(bpy)3 ]2+ (bpy=2,2'-bipyridine). The localization of the initially optically excited and the nature of the long-lived excited states on the Ru-facing ligand spheres is evaluated by resonance Raman and fs-TA spectroscopy, respectively, and supported by DFT and TDDFT calculations. Coordination of a second metal (Zn or Rh) to the available bis-pyrimidyl-like coordination sphere strongly influences the frontier orbitals, apparent by, for example, luminescence quenching. Thus, the new bridging ligand motif offers electronic properties, which can be adjusted by the nature of the second metal center. Using the heterodinuclear Ru-Rh complex, visible light-driven reduction of NAD+ to NADH was achieved, highlighting the potential of this system for photocatalytic applications.

Evaluation of 1H-NMR Spectroscopy-Based Quantification Methods of the Supramolecular Aggregation of a Molecular Photosensitizer†.

The supramolecular dimerization of a ruthenium polypyridyl precursor of a well-developed family of hydrogen-evolving photocatalysts via π-π interactions of the polyheteroaromatic bridging ligand was quantified with concentration-dependent 1 H-NMR spectroscopy. The data sets were analyzed with different calculation and fit methods. A comparison between the results of direct calculation and linear and nonlinear approaches showed that the application of a global nonlinear fit procedure yields the best results. The presented methods are also applicable for dimerization processes in the solution of other molecular moieties.

Transforming Escherichia coli Proteomembranes into Artificial Chloroplasts Using Molecular Photocatalysis.

During the light-dependent reaction of photosynthesis, green plants couple photoinduced cascades of redox reactions with transmembrane proton translocations to generate reducing equivalents and chemical energy in the form of NADPH (nicotinamide adenine dinucleotide phosphate) and ATP (adenosine triphosphate), respectively. We mimic these basic processes by combining molecular ruthenium polypyridine-based photocatalysts and inverted vesicles derived from Escherichia coli. Upon irradiation with visible light, the interplay of photocatalytic nicotinamide reduction and enzymatic membrane-located respiration leads to the simultaneous formation of two biologically active cofactors, NADH (nicotinamide adenine dinucleotide) and ATP, respectively. This inorganic-biologic hybrid system thus emulates the cofactor delivering function of an active chloroplast.

Merging of a Perylene Moiety Enables a RuII Photosensitizer with Long-Lived Excited States and the Efficient Production of Singlet Oxygen.

Multichromophoric systems based on a RuII polypyridine moiety containing an additional organic chromophore are of increasing interest with respect to different light-driven applications. Here, we present the synthesis and detailed characterization of a novel RuII photosensitizer, namely [(tbbpy)2 Ru((2-(perylen-3-yl)-1H-imidazo[4,5-f][1,10]-phenanthrolline))](PF6 )2 RuipPer, that includes a merged perylene dye in the back of the ip ligand. This complex features two emissive excited states as well as a long-lived (8 µs) dark state in acetonitrile solution. Compared to prototype [(bpy)3 Ru]2+ -like complexes, a strongly altered absorption (ϵ=50.3×103  M-1 cm-1 at 467 nm) and emission behavior caused by the introduction of the perylene unit is found. A combination of spectro-electrochemistry and time-resolved spectroscopy was used to elucidate the nature of the excited states. Finally, this photosensitizer was successfully used for the efficient formation of reactive singlet oxygen.

Merging of a Perylene Moiety Enables a RuII Photosensitizer with Long-Lived Excited States and the Efficient Production of Singlet Oxygen.

Invited for the front cover of this issue are Stefanie Tschierlei, Sven Rau and co-workers. The image shows the fusion of an organic chromophore with a RuII polypyridine moiety resulting in a unique bichromophoric photosensitizer. Read the full text of the article at 10.1002/chem.202103609.

Switching the Mechanism of NADH Photooxidation by Supramolecular Interactions.

A series of three Ru(II) polypyridine complexes was investigated for the selective photocatalytic oxidation of NAD(P)H to NAD(P)+ in water. A combination of (time-resolved) spectroscopic studies and photocatalysis experiments revealed that ligand design can be used to control the mechanism of the photooxidation: For prototypical Ru(II) complexes a 1 O2 pathway was found. Rudppz ([(tbbpy)2 Ru(dppz)]Cl2 , tbbpy=4,4'-di-tert-butyl-2,2'-bipyridine, dppz=dipyrido[3,2-a:2',3'-c]phenazine), instead, initiated the cofactor oxidation by electron transfer from NAD(P)H enabled by supramolecular binding between substrate and catalyst. Expulsion of the photoproduct NAD(P)+ from the supramolecular binding site in Rudppz allowed very efficient turnover. Therefore, Rudppz permits repetitive selective assembly and oxidative conversion of reduced naturally occurring nicotinamides by recognizing the redox state of the cofactor under formation of H2 O2 as additional product. This photocatalytic process can fuel discontinuous photobiocatalysis.

Molecular Scylla and Charybdis: Maneuvering between pH Sensitivity and Excited-State Localization in Ruthenium Bi(benz)imidazole Complexes.

Bi(benz)imidazoles (b(b)im) acting as N,N-chelates in ruthenium complexes represent a unique class of ligands. They do not harbor metal-to-ligand charge-transfer (MLCT) excited states in ruthenium polypyridyl complexes upon visible-light excitation provided that no substitution is introduced at the N atoms. Hence, they can be used to steer light-driven electron-transfer pathways in a desired direction. Nonetheless, the free N atoms are susceptible to protonation and, hence, introduce highly pH-dependent properties into the complexes. Previous results for ruthenium complexes containing R2bbim ligands with alkylic or arylic N,N'-substitution indicated that, although pH insensitivity was accomplished, unexpected losses of spectator ligand features incurred simultaneously. Here, we report the synthesis and photophysical characterization of a series of differently N,N'-alkylated b(b)im ligands along with their corresponding [(tbbpy)2Ru(R2b(b)im)](PF6)2 complexes (tbbpy = 4,4'-tert-butyl-2,2'-bipyridine). The data reveal that elongation of a rigid ethylene bridge by just one methylene group drastically increases the emission quantum yield, emission lifetime, and photostability of the resultant complexes. Quantum-chemical calculations support these findings and allow us to rationalize the observed effects based on the energetic positions of the respective excited states. We suggest that N,N'-propylene-protected 1H,1'H-2,2'-biimidazole (prbim) is a suitable spectator ligand because it stabilizes sufficiently long-lived MLCT excited states exclusively localized at auxiliary bipyridine ligands. This ligand represents, therefore, a vital building block for next-generation photochemical molecular devices in artificial photosynthesis.

Intracellular Photophysics of an Osmium Complex bearing an Oligothiophene Extended Ligand.

This contribution describes the excited-state properties of an Osmium-complex when taken up into human cells. The complex 1 [Os(bpy)2 (IP-4T)](PF6 )2 with bpy=2,2'-bipyridine and IP-4T=2-{5'-[3',4'-diethyl-(2,2'-bithien-5-yl)]-3,4-diethyl-2,2'-bithiophene}imidazo[4,5-f][1,10]phenanthroline) can be discussed as a candidate for photodynamic therapy in the biological red/NIR window. The complex is taken up by MCF7 cells and localizes rather homogeneously within in the cytoplasm. To detail the sub-ns photophysics of 1, comparative transient absorption measurements were carried out in different solvents to derive a model of the photoinduced processes. Key to rationalize the excited-state relaxation is a long-lived 3 ILCT state associated with the oligothiophene chain. This model was then tested with the complex internalized into MCF7 cells, since the intracellular environment has long been suspected to take big influence on the excited state properties. In our study of 1 in cells, we were able to show that, though the overall model remained the same, the excited-state dynamics are affected strongly by the intracellular environment. Our study represents the first in depth correlation towards ex-vivo and in vivo ultrafast spectroscopy for a possible photodrug.

Somatostatin receptor mediated targeting of acute myeloid leukemia by photodynamic metal complexes for light induced apoptosis.

Acute myeloid leukemia (AML) is characterized by relapse and treatment resistance in a major fraction of patients, underlining the need of innovative AML targeting therapies. Here we analysed the therapeutic potential of an innovative biohybrid consisting of the tumor-associated peptide somatostatin and the photosensitizer ruthenium in AML cell lines and primary AML patient samples. Selective toxicity was analyzed by using CD34 enriched cord blood cells as control. Treatment of OCI AML3, HL60 and THP1 resulted in a 92, and 99 and 97% decrease in clonogenic growth compared to the controls. Primary AML cells demonstrated a major response with a 74 to 99% reduction in clonogenicity in 5 of 6 patient samples. In contrast, treatment of CD34+ CB cells resulted in substantially less reduction in colony numbers. Subcellular localization assays of RU-SST in OCI-AML3 cells confirmed strong co-localization of RU-SST in the lysosomes compared to the other cellular organelles. Our data demonstrate that conjugation of a Ruthenium complex with somatostatin is efficiently eradicating LSC candidates of patients with AML. This indicates that receptor mediated lysosomal accumulation of photodynamic metal complexes is a highly attractive approach for targeting AML cells.

Two Emissive Long-Lived Excited States of an Imidazole-Functionalized Ruthenium Dipyridophenazine Complex.

A ruthenium(II) polypyridine-type complex based on the dipyridophenazine ligand with a directly fused imidazole unit (L1, dipyrido[3,2-a:2',3'-c]phenazine-10,11-imidazole) has been synthesized, and its electrochemical and photophysical properties have been studied. The cyclic voltammogram of [Ru(tbbpy)2(L1)]2+ (C1) (tbbpy is 4,4'-tert-butyl-2,2'-bipyridine) shows a cathodic shift of the phenazine-based reduction process compared to similar molecules, while the first detected reduction wave (-1.34 V vs Fc/Fc+) is assigned to the imidazole unit within the molecule. On the basis of the TD-DFT calculations, the strong visible absorption band exhibited by C1 is assigned to a metal-to-ligand charge transfer (MLCT) transition with a concurrent ligand-centered (LC) transition. At room-temperature, C1 features emission (Φ = 0.04) from its lowest excited states with time constants of 1.2 and 18.3 µs. These lifetimes are assigned to emission processes from the 3MLCT and 3LC state, respectively. This is the first time that a long-lived dual emission has been observed for a ruthenium(II) complex bearing a directly fused extended π-system. Furthermore, the emission of C1 is quenched upon water addition. In contrast to related compounds based on a dipyridophenazine ligand, the excited state energy is not shifted, and the lifetime is drastically decreased to 169 ns.

Mitochondria Targeted Protein-Ruthenium Photosensitizer for Efficient Photodynamic Applications.

Organelle-targeted photosensitization represents a promising approach in photodynamic therapy where the design of the active photosensitizer (PS) is very crucial. In this work, we developed a macromolecular PS with multiple copies of mitochondria-targeting groups and ruthenium complexes that displays highest phototoxicity toward several cancerous cell lines. In particular, enhanced anticancer activity was demonstrated in acute myeloid leukemia cell lines, where significant impairment of proliferation and clonogenicity occurs. Finally, attractive two-photon absorbing properties further underlined the great significance of this PS for mitochondria targeted PDT applications in deep tissue cancer therapy.

Subtle Changes to Peripheral Ligands Enable High Turnover Numbers for Photocatalytic Hydrogen Generation with Supramolecular Photocatalysts.

The photocatalytic generation of hydrogen (H2) from protons by two cyclometalated ruthenium-platinum polypyridyl complexes, [Ru(bpy)2(2,5-bpp)PtIS](2+) (1) and [Ru(dceb)2(2,5-bpp)PtIS](2+) (2) [where bpy = 2,2'-bipyridine, 2,5-bpp = 2,2',5',2″-terpyridine, dceb = 4,4'-di(carboxyethyl)bipyridine, and S = solvent], is reported. Turnover numbers (TONs) for H2 generation were increased by nearly an order of magnitude by the introduction of carboxyethyl ester units, i.e., from 80 for 1P to 650 for 2P after 6 h of irradiation, with an early turnover frequency (TOF) increasing from 15 to 200 h(-1). The TON and TOF values for 2P are among the highest reported to date for supramolecular photocatalysts. The increase correlates with stabilization of the excited states localized on the peripheral ligands of the light-harvesting Ru(II) center.

CuAAC click reactions for the design of multifunctional luminescent ruthenium complexes.

CuAAC (Cu(i) catalyzed azide-alkyne cycloaddition) click chemistry has emerged as a versatile tool in the development of photoactive ruthenium complexes with multilateral potential applicability. In this contribution we discuss possible synthetic approaches towards CuAAC reactions with ruthenium(ii) polypyridine complexes and their differences with respect to possible applications. We focus on two main application possibilities of the click-coupled ruthenium assemblies. New results within the development of ruthenium based photosensitizers for the field of renewable energy supply, i.e. DSSCs (dye-sensitized solar cells) and artificial photocatalysis for the production of hydrogen, or for anticancer photodynamic therapeutic applications are reviewed.

Receptor selective ruthenium-somatostatin photosensitizer for cancer targeted photodynamic applications.

The efficient conjugation of a ruthenium complex and the peptide hormone somatostatin is presented. The resultant biohybrid offers valuable features for photodynamic therapy such as remarkable cellular selectivity, rapid cell uptake by receptor-mediated endocytosis, efficient generation of (1)O2 upon irradiation, potent phototoxicity as well as low cytotoxicity in the "off"-state.

How Does Peripheral Functionalization of Ruthenium(II)-Terpyridine Complexes Affect Spatial Charge Redistribution after Photoexcitation at the Franck-Condon Point?

Ruthenium polypyridine-type complexes are extensively used sensitizers to convert solar energy into chemical and/or electrical energy, and they can be tailored through their metal-to-ligand charge-transfer (MLCT) properties. Much work has been directed at harnessing the triplet MLCT state in photoinduced processes, from sophisticated molecular architectures to dye-sensitized solar cells. In dye-sensitized solar cells, strong coupling to the semiconductor exploits the high reactivity of the (hot) singlet/triplet MLCT state. In this work, we explore the nature of the (1) MLCT states of remotely substituted Ru(II) model complexes by both experimental and theoretical techniques. Two model complexes with electron-withdrawing (i.e. NO2 ) and electron-donating (i.e. NH2 ) groups were synthesized; these complexes contained a phenylene spacer to serve as a spectroscopic handle and to confirm the contribution of the remote substituent to the (1) MLCT transition. [Ru(tpy)2 ](2+) -based complexes (tpy=2,2':6',2''-terpyridine) were further desymmetrized by tert-butyl groups to yield unidirectional (1) MLCTs with large transition dipole moments, which are beneficial for related directional charge-transfer processes. Detailed comparison of experimental spectra (deconvoluted UV/Vis and resonance Raman spectroscopy data) with theoretical calculations based on density functional theory (including vibronic broadening) revealed different properties of the optically active bright (1) MLCT states already at the Franck-Condon point.

Palladium versus platinum: the metal in the catalytic center of a molecular photocatalyst determines the mechanism of the hydrogen production with visible light.

To develop highly efficient molecular photocatalysts for visible light-driven hydrogen production, a thorough understanding of the photophysical and chemical processes in the photocatalyst is of vital importance. In this context, in situ X-ray absorption spectroscopic (XAS) investigations show that the nature of the catalytically active metal center in a (N^N)MCl2 (M=Pd or Pt) coordination sphere has a significant impact on the mechanism of the hydrogen formation. Pd as the catalytic center showed a substantially altered chemical environment and a formation of metal colloids during catalysis, whereas no changes of the coordination sphere were observed for Pt as catalytic center. The high stability of the Pt center was confirmed by chloride addition and mercury poisoning experiments. Thus, for Pt a fundamentally different catalytic mechanism without the involvement of colloids is confirmed.

Modified bibenzimidazole ligands as spectator ligands in photoactive molecular functional Ru-polypyridine units? Implications from spectroscopy.

The photophysical properties of Ruthenium-bipyridine complexes bearing a bibenzimidazole ligand were investigated. The nitrogens on the bibenzimidazole-ligand were protected, by adding either a phenylene group or a 1,2-ethandiyl group, to remove the photophysical dependence of the complex on the protonation state of the bibenzimidazole ligand. This protection results in the bibenzimidazole ligand contributing to the MLCT transition, which is experimentally evidenced by (resonance) Raman scattering in concert with DFT calculations for a detailed mode assignment in the (resonance) Raman spectra.

Protonation effects on the resonance Raman properties of a novel (terpyridine)Ru(4H-imidazole) complex: an experimental and theoretical case study.

The optically active states in a novel (terpyridine)Ru(4H-imidazole) complex displaying an unusually broad and red-shifted absorption in the visible range are investigated experimentally and theoretically. Since this property renders the complex promising for an application as sensitizer in dye-sensitized solar cells, a detailed knowledge on the correlation between features in the absorption spectrum and structural elements is indispensable in order to develop strategies for spectroscopy/theory-guided design of such molecular components. To this aim, time-dependent density functional theory calculations, including solvent effects, are employed to analyze the experimental UV-vis absorption and resonance Raman (RR) spectra of the unprotonated and protonated forms of the complex. This provides a detailed photophysical picture for a complex belonging to a novel class of Ru-polypyridine black absorbers, which can be tuned by external pH stimuli. The complex presents two absorption maxima in the visible region, which are assigned by the calculations to metal-to-ligand charge transfer (MLCT) and intra-ligand states, respectively. RR simulations are performed in resonance with both bands and are found to correctly reproduce the observed effects of protonation. Finally, the examination of the molecular orbitals and of the RR spectra for the MLCT state shows that protonation favors a charge transfer excitation to the 4H-imidazole ligand.