Ruthenium Polypyridyl Complexes Research Articles

Computational Exploration of the Mechanism of Action of a Sorafenib-Containing Ruthenium Complex as an Anticancer Agent for Photoactivated Chemotherapy.

Ruthenium(II) polypyridyl complexes are being tested as potential anticancer agents in different therapies, which include conventional chemotherapy and light-activated approaches. A mechanistic study on a recently synthesized dual-action Ru(II) complex [Ru(bpy)2(sora)Cl]+ is described here. It is characterized by two mono-dentate leaving ligands, namely, chloride and sorafenib ligands, which make it possible to form a di-aquo complex able to bind DNA. At the same time, while the released sorafenib can induce ferroptosis, the complex is also able to act as a photosensitizer according to type II photodynamic therapy processes, thus generating one of the most harmful cytotoxic species, 1O2. In order to clarify the mechanism of action of the drug, computational strategies based on density functional theory are exploited. The photophysical properties of the complex, which include the absorption spectrum, the kinetics of ISC, and the character of all the excited states potentially involved in 1O2 generation, as well as the pathway providing the di-aquo complex, are fully explored. Interestingly, the outcomes show that light is needed to form the mono-aquo complex, after releasing both chloride and sorafenib ligands, while the second solvent molecule enters the coordination sphere of the metal once the system has come back to the ground-state potential energy surface. In order to simulate the interaction with canonical DNA, the di-aquo complex interaction with a guanine nucleobase as a model has also been studied. The whole study aims to elucidate the intricate details of the photodissociation process, which could help with designing tailored metal complexes as potential anticancer agents.

Exploring the DNA-binding and anticancer potential of polypyridyl ruthenium(II) complexes

Organometallic medicines based on ruthenium (Ru) have attracted interest as chemotherapeutic and bioimaging agents due to their low toxicity and superior physical optical characteristics. However, there are still no ideal candidates in clinical trials due to the lack of understanding of the structure-activity relationships (SARs) of polypyrodyl Ru(II) complexes. Though increasing the electron-donating ability of the ligands has been proven to benefit bioactivity due to the fast hydroxylation rate between chlorine and DNA, the total electronic effects are much more important, especially for the binding modes between Ru(II)-polypyridyl complexes and DNA. By evaluating the electron-donating ability of the ligand complexes 1 - 4 through density functional theory (DFT) calculations, bioactivities tests, and docking studies, we investigated the relationship between the structures of Ru(II) complexes and cytotoxicity. Our findings showed that it was insufficient to merely consider the impact of electron-donating effects on biological activities in place of interaction modes. Furthermore, the cellular imaging study investigated the complex with phenyl substituents (1) and confirmed that the main target was DNA. Besides, the “off-on” emission phenomena of complex 1 indicated that there is also covalent interaction with DNA. These findings offer valuable insight into the development of SARs of polypyrodyl Ru(II) complexes.

Computational Assessment of Novel Ruthenium Phenoxazine‐Based Complexes as Photosensitizers in Photodynamic Therapy

A computational examination of two new polypyridyl ruthenium complexes, containing meldola blue (MDB) and nile blue (NB) chromophores, is here reported in order to assess the applicability of phenoxazine‐containing complexes in photodynamic therapy (PDT). The designed complexes, named Ru‐3ENB and Ru‐3EMDB, are based on a recently synthesized Ru(II)‐based complex bearing a bipyridyl‐ethynyl‐Nile Red (NR) ligand and proposed for PDT applications. DFT outcomes elucidated how the replacement of NR with MDB induces a red shift of the maximum absorption wavelength within the therapeutic window, up to 638 nm. A change in the molecular orbitals involved in the population of excited states was observed upon chromophore substitution that results in ISC kinetic significantly faster than that computed for the synthesized complex Ru‐3ENR.

Unveiling the key role of metal coordination mode and ligand's side groups on the performance of deep-red light-emitting electrochemical cell

Three novel deep-red to near-infrared (DR to NIR) emitters based on mononuclear and dinuclear ruthenium(II) complexes with bulky structures were presented herein. For the first time, the unusual effects of metal coordination mode on the electroluminescence properties of a binuclear emitter were investigated. Unexpectedly, the mononuclear complexes showed superior performance in deep-red light-emitting electrochemical cells (DR-LEC) compared to the dinuclear complex. Likewise, substituting various ancillary ligands improved the radiance and lifetime of devices by 2.5 and 1.5 times, respectively. To the best of our knowledge, the obtained efficiency is among the best reported to date for DR-LECs based on ruthenium polypyridyl complexes.

Identification of mitochondrial ATP synthase as the cellular target of Ru-polypyridyl-β-carboline complexes by affinity-based protein profiling.

Ruthenium polypyridyl complexes are promising anticancer candidates, while their cellular targets have rarely been identified, which limits their clinical application. Herein, we design a series of Ru(II) polypyridyl complexes containing bioactive β-carboline derivatives as ligands for anticancer evaluation, among which Ru5 shows suitable lipophilicity, high aqueous solubility, relatively high anticancer activity and cancer cell selectivity. The subsequent utilization of a photo-clickable probe, Ru5a, serves to validate the significance of ATP synthase as a crucial target for Ru5 through photoaffinity-based protein profiling. Ru5 accumulates in mitochondria, impairs mitochondrial functions and induces mitophagy and ferroptosis. Combined analysis of mitochondrial proteomics and RNA-sequencing shows that Ru5 significantly downregulates the expression of the chloride channel protein, and influences genes related to ferroptosis and epithelial-to-mesenchymal transition. Finally, we prove that Ru5 exhibits higher anticancer efficacy than cisplatin in vivo. We firstly identify the molecular targets of ruthenium polypyridyl complexes using a photo-click proteomic method coupled with a multiomics approach, which provides an innovative strategy to elucidate the anticancer mechanisms of metallo-anticancer candidates.

Synthesis and structural characterizations of three carbonyl(α-diimine)hydrido(triphenylphosphine)ruthenium(II) complexes with derivatives of 1,10-phenanthroline.

Three new ruthenium(II) polypyridyl complexes containing α-diimine ligands, namely, carbonylhydrido(1,10-phenanthroline-κ2N,N)bis(triphenylphosphine-κP)ruthenium(II) hexafluorophosphate, [RuH(C12H8N2)(C18H15P)2(CO)]PF6, carbonylhydrido(2,9-dimethyl-1,10-phenanthroline-κ2N,N)bis(triphenylphosphine-κP)ruthenium(II) hexafluorophosphate, and carbonylhydrido(4,7-dimethyl-1,10-phenanthroline-κ2N,N)bis(triphenylphosphine-κP)ruthenium(II) hexafluorophosphate, both [RuH(C14H12N2)(C18H15P)2(CO)]PF6, were synthesized and characterized by spectroscopic and X-ray diffraction methods. In these complexes, the ruthenium(II) ion adopts a distorted octahedral geometry. There are no intermolecular hydrogen bonds in the crystal structures of the analysed complexes and Hirshfeld surface analysis showed that the H...H contacts constitute a high percentage, close to 50%, of the intermolecular interactions.

Tetranuclear Polypyridylruthenium(II) Complexes as Selective Nucleic Acid Stains for Flow Cytometric Analysis of Monocytic and Epithelial Lung Carcinoma Large Extracellular Vesicles.

Selective staining of extracellular vesicles (EVs) is a major challenge for diagnostic and therapeutic applications. Herein, the EV labeling properties of a new class of tetranuclear polypyridylruthenium(II) complexes, Rubb7-TNL and Rubb7-TL, as phosphorescent stains are described. These new stains have many advantages over standard stains to detect and characterize EVs, including: high specificity for EV staining versus cell staining; high phosphorescence yields; photostability; and a lack of leaching from EVs until incorporation with target cells. As an example of their utility, large EVs released from control (basal) or lipopolysaccharide (LPS)-stimulated THP-1 monocytic leukemia cells were studied as a model of immune system EVs released during bacterial infection. Key findings from EV staining combined with flow cytometry were as follows: (i) LPS-stimulated THP-1 cells generated significantly larger and more numerous large EVs, as compared with those from unstimulated cells; (ii) EVs retained native EV physical properties after staining; and (iii) the new stains selectively differentiated intact large EVs from artificial liposomes, which are models of cell membrane fragments or other lipid-containing debris, as well as distinguished two distinct subpopulations of monocytic EVs within the same experiment, as a result of biochemical differences between unstimulated and LPS-stimulated monocytes. Comparatively, the staining patterns of A549 epithelial lung carcinoma-derived EVs closely resembled those of THP-1 cell line-derived EVs, which highlighted similarities in their selective staining despite their distinct cellular origins. This is consistent with the hypothesis that these new phosphorescent stains target RNA within the EVs.

Polyphosphoester-stabilized cubosomes encapsulating a Ru(II) complex for the photodynamic treatment of lung adenocarcinoma

The clinical translation of photosensitizers based on ruthenium(II) polypyridyl complexes (RPCs) in photodynamic therapy of cancer faces several challenges. To address these limitations, we conducted an investigation to assess the potential of a cubosome formulation stabilized in water against coalescence utilizing a polyphosphoester analog of Pluronic F127 as a stabilizer and loaded with newly synthesized RPC-based photosensitizer [Ru(dppn)2(bpy-morph)](PF6)2 (bpy-morph = 2,2′-bipyridine-4,4′-diylbis(morpholinomethanone)), PS-Ru. The photophysical characterization of PS-Ru revealed its robust capacity to induce the formation of singlet oxygen (1O2). Furthermore, the physicochemical analysis of the PS-Ru-loaded cubosomes dispersion demonstrated that the encapsulation of the photosensitizer within the nanoparticles did not disrupt the three-dimensional arrangement of the lipid bilayer. The biological tests showed that PS-Ru-loaded cubosomes exhibited significant phototoxic activity when exposed to the light source, in stark contrast to empty cubosomes and to the same formulation without irradiation. This promising outcome suggests the potential of the formulation in overcoming the drawbacks associated with the clinical use of RPCs in photodynamic therapy for anticancer treatments.

Binding properties of ruthenium(II) polypyridyl complexes [Ru(bpy)2(L)]2+(L=7-F-dppz and 7OCH3–-dppz) with poly(A)-poly(U) under dilute and molecular crowding conditions

Two ruthenium(II) polypyridyl complexes, [Ru(bpy)2(7-F-dppz)]2+ (Ru1, bpy = 2,2′-bipyridine, 7-F-dppz = 7-fluorodipyrido[3,2-a:2′,3′-c]phenazine) and [Ru(bpy)2(7OCH3–-dppz)]2+ (Ru2, 7OCH3–-dppz = 7‑methoxy-dipyrido-[3,2-a,2′,3′-c]-phenazine), were synthesized. The binding properties of Ru1 and Ru2 to duplex RNA poly(A)-poly(U) have been explored through spectroscopic techniques and viscometry. Spectral titration and viscosity experiments show that the binding mode of Ru1 and Ru2 to double-stranded RNA(dsRNA) in dilute solution and molecular crowded environment are intercalation, and that the binding affinity of Ru1 for poly(A)-poly(U) is greater than that of Ru2. Thermal denaturation experiments showed that two complexes have good thermal stability for dsRNA in two environments. Fluorescence titrations showed that Ru1 and Ru2 could act as molecular "light switch" for duplex poly(A)-poly(U) in both environments. Surprisingly, the binding effect of ligands and poly(A)-poly(U) was significantly reduced under crowded condition, and the thermal stability of RNA duplex was less significant than that of dilute solution. The reason of this result is due to the water activity in molecular crowded environment, the increased viscosity of the medium leading to a decrease in the affinity of the ligand for the RNA duplex, and also the electronic effect of the ligand on the binding affinity of the poly(A)-poly(U). Results of the present work facilitate our understanding of the two environments as well as the interaction between ruthenium(II) polypyridyl complexes and dsRNA is influenced by the electronegativity of the substituents.

Studies on interactions of ruthenium(II) polypyridyl complexes [Ru(bpy)2(btip)]2+ and [Ru(dmb)2(btip)]2+ with double-stranded RNA poly(A)·poly(U) under molecular crowding conditions

Ruthenium(II) polypyridyl complexes have emerged as excellent nucleic acid binders based on the easy-to-construct three-dimensional structures and rich photophysical and photochemical properties. However, most studies are usually performed under dilute conditions, which might be disturbed by the crowding environment of cells. Herein, two ruthenium(II) polypyridyl complexes, [Ru(bpy)2(btip)]2+ (Ru1, bpy = 2,2′-bipyridine, btip = 2-benzo[b]thien-2-yl-1H-imidazo[4,5-f]-[1,10]phenanthroline) and [Ru(dmb)2(btip)]2+ (Ru2, dmb = 4,4′-dimethyl-2,2′-bipyridine) have been synthesized and characterized. Interactions of the two complexes with double-stranded RNA poly(A)·poly(U) in dilute solution and molecular crowding environment have been studied by spectroscopic techniques and viscosity measurements, respectively. Spectral titration and viscosity experiments show that both Ru1 and Ru2 combine with poly(A)·poly(U) through an intercalative mode in both environments, and the binding affinity in crowding environment is significantly lower than that in dilute solution, but still comparatively high. Moreover, thermal denaturation experiments show that the abilities of Ru1 and Ru2 to poly(A)·poly(U) are significantly reduced under crowding condition, which are attributed to the reduced binding affinity of the complexes to poly(A)·poly(U) in crowding environment.

Ruthenium(II) Polypyridyl Complexes with Benzoxazole Derivatives and Non-Innocent Ligands as Effective Antioxidants in Human Neuroblasts.

Ruthenium(II) polypyridyl complexes continue to raise increasing interest for the encouraging results in several biomedical areas. Considering their vast chemical-physical repertoire, in particular the possibility to switch from the sensitization of reactive oxygen species (ROS) to ROS-scavenging abilities by tuning the nature of their ligands, it is therefore surprising that their potential as antioxidants has not been largely investigated so far. Herein, we explored the antioxidant behaviour of the novel ruthenium compound [Ru(dbpy)(2,3-DAN)Cl]PF6 (Ru1), featuring a benzoxazole derivative (dpby=2,6-bis(4-methyl-2-benzoxazolyl)pyridine) and the non-innocent 2,3-diamminonaftalene (2,3-DAN) ligand, along with the reference tpy-containing analogue [Ru(tpy)(2,3-DAN)Cl]PF6 (Ru2) (tpy=2,2':6',2''-terpyridine). Following the synthesis and the electrochemical characterization, chemical antioxidant assays highlighted the beneficial role of dpby for the ROS-scavenging properties of Ru1. These data have been corroborated by the highest protective effect of Ru1 against the oxidative stress induced in SH-SY5Y human neuroblastoma, which exerts pro-survival and anti-inflammatory actions. The results herein reported highlight the potential of Ru1 as pharmacological tool in neurodegenerative diseases and specially prove that the antioxidant properties of such compounds are likely the result of a non-trivial synergetic action involving the bioactive ligands in their chemical architectures.

Aminoquinoline-based ruthenium(II) and iridium(III) polypyridyl complexes: Investigating potential photosensitisers for cancer treatment via photodynamic therapy

Cancer is a devastating noncommunicable disease that remains one of the most pressing health challenges of the twenty-first century. Chemotherapy stands as one of the most common and effective cancer treatment methods. However, severe side effects and acquired drug resistance in many cancers have significantly diminished the efficacy of current chemotherapeutic agents. The urgent demand for novel treatment modalities has led to the development of photodynamic therapy (PDT) for the treatment of various cancer types. In this work, the synthesis of aminoquinoline-based transition metal complexes containing two PGMs (Ir(III) and Ru(II)) as potential photosensitisers is described. Mononuclear N,N-chelated Ru(II) and Ir(III) transition metal complexes were synthesized by reacting 4-aminoquinoline Schiff base ligands, which contain either a pyridyl or a quinolyl entity. The photostable Ru(II) and Ir(III) polypyridyl complexes were investigated for their potential use as PDT agents. In vitro cytotoxicity screenings conducted against a melanoma cell line (501mel) both in the absence and presence of light confirmed that all complexes demonstrated increased biological activity when exposed to visible light at 455 nm. Overall, the Ru(II) complexes are superior phototoxic agents in comparison with their Ir(III) congenors.

Modulating Excited State Properties and Ligand Ejection Kinetics in Ruthenium Polypyridyl Complexes Designed to Mimic Photochemotherapeutics.

Ruthenium(II) polypyridyl complexes have gained significant interest as photochemotherapeutics (PCTs) due to their synthetic viability, strong light absorption, well understood excited state properties, and high phototoxicity indexes. Herein, we report the synthesis, characterization, electrochemical, spectrochemical, and preliminary cytotoxicity analyses of three series of ruthenium(II) polypyridyl complexes designed to mimic PCTs. The three series have the general structure of [Ru(bpy)2(N-N)]2+ (Series 1), [Ru(bpy)(dmb)(N-N)]2+ (Series 2), and [Ru(dmb)2(N-N)]2+ (Series 3, where N-N is a bidentate polypyridyl ligand, bpy = 2,2'-bipyridine, and dmb = 6,6'-dimethyl-2,2'-bipyridine). In the three series, the N-N ligand was systematically modified to incorporate increased conjugation and/or electronegative heteroatoms to increase dπ-π* backbonding, red-shifting the lowest energy metal-to-ligand charge transfer (MLCT) absorptions from λmax = 454 to λmax = 580 nm, nearing the therapeutic window for PCTs (600-1100 nm). In addition, steric bulk was systematically introduced through the series, distorting the Ru(II) octahedra, making the dissociative 3dd* state thermally accessible at room and body temperatures. This resulted in a 4 orders of magnitude increase in photoinduced ligand ejection kinetics, and demonstrates the ability to modulate both the MLCT* and dd* manifolds in the complexes, which is critical in PCT drug design. Preliminary cell viability assays suggest that the increased steric bulk to lower the 3dd* states may interfere with the cytotoxicity mechanism, limiting photoinitiated toxicity of the complexes. This work demonstrates the importance of understanding both the MLCT* and dd* manifolds and how they impact the ability of a complex to act as a PCT agent.

Photophysical Studies of Helicate and Mesocate Double-Stranded Dinuclear Ru(II) Complexes.

The metal-ligand charge transfer (3MLCT) and phosphorescence-quenching metal-centered (3MC) states of the helicate and mesocate diastereoisomers of a double-stranded dinuclear polypyridylruthenium(II) complex have been investigated using ultrafast transient absorption spectroscopy. At 294 K, transient signals of the helicate decayed significantly slower than those of the mesocate, whereas at 77 K, no clear contrast in kinetics was observed. Contributions to excited-state decay from high-lying 3MLCT states were identified at both temperatures. Spectroscopic data (294 K) suggest that the 3MC state of the helicate lies above the 3MLCT and that the reverse is true for the mesocate; this was further validated by density functional theory calculations. The stabilization of the 3MC state relative to the 3MLCT state in the mesocate was explained by a reduction in ligand field strength due to distortion near the ligand bridge, which causes further deviation from octahedral geometry compared to the helicate. This work illustrates how minor structural differences can significantly influence excited state dynamics.

Application of Novel Ruthenium (II) Polypyridyl Complexes as Robust DNA Probes, Optical Material and Antimicrobials-An Experimental and DFT Approach.

The nature of the interaction of DNA with heteroleptic Ruthenium (II) Polypyridyl complexes of the type [Ru (A)2TPIP]2+, where TPIP = 2-(1-p-tolyl-1H pyrazol-4 -yl)-1H-imidazo [4, 5-f[1. 10] phenanthroline and A = 1,10 phenanthroline (1),4,4'-dimethyl-1,10-ortho Phenanthroline (2),2,2' - bipyridine(3) and 4, 4' dimethyl 2, 2'- bipyridine (4), has been investigated by experimentaland molecular docking approaches. The order of the DNA binding affinities of the synthesised complexes is 1 > 2 > 3 > 4. The findings imply that the unsubstitutedcomplex has a better affinity to bind with DNA than the substituted (dmp and dmb) emphasizing the significance of the auxiliary ligand. Additionally, as the medium's ionic strength drops, the DNA/Ru ratio rises, or when water is displaced by glycerol, the intercalation of complexes into DNA increases. DFT calculations at the B3LYP/LANL2MBlevel was used for molecular geometry (Ground State) and electronic characteristic calculations. The HOMO-LUMO gap of the Ru [II]complex is less than the intercalator and hence kinetically labile. Among the complexes, the bpy complex has shown utmost non-linear optical properties (α = -153.9099 10-24esuand β = 3.8498 10-30esu). The docking study shows the significance of the Metal-intercalator's shorter length may increase DNA binding affinity. This study divulges that the Ruthenium (II) polypyridyl complexes bind to DNA preponderantly by intercalation supporting Viscosity studies. All the complexes have a considerable attraction for guanine. The standarddiskdiffusion method reveals that complexes (1,2,3 and 4) have good antibacterial activity.

Trinuclear ruthenium(II) polypyridyl complexes: Evaluation as photosensitizers for enhanced cervical cancer treatment

Trinuclear ruthenium(II) polypyridyl complexes anchored to benzimidazole-triazine / trisamine scaffolds were investigated as photosensitizers for photodynamic therapy. The trinuclear complexes were noted to produce a significant amount of singlet oxygen in both DMF and aqueous media, are photostable and show appreciable emission quantum yields (ɸem). In our experimental setting, despite the moderate phototoxic activity in the HeLa cervical cancer cell line, the phototoxic indices (PI) of the trinuclear complexes are superior relative to the PIs of a clinically approved photosensitizer, Photofrin®, and the pro-drug 5-aminolevulinic acid (PI: >7 relative to PI: >1 and PI: 4.4 for 5-aminolevulinic acid and Photofrin®, respectively). Furthermore, the ruthenium complexes were noted to show appreciable long-term cytotoxicity upon light irradiation in HeLa cells in a concentration-dependent manner. Consequently, this long-term activity of the ruthenium(II) polypyridyl complexes embodies their ability to reduce the probability of the recurrence of cervical cancer. Taken together, this presents a strong motivation for the development of polymetallic complexes as anticancer agents.

Antifungal activity of ruthenium (II) complex combined with fluconazole against drug-resistant Candida albicans in vitro and its anti-invasive infection in vivo

With the abuse of antibiotics and azoles, drug-resistant Candida albicans infections have increased sharply and are spreading rapidly, thereby significantly reducing the antifungal efficacy of existing therapeutics. Several patients die of fungal infections every year. Therefore, there is an urgent requirement to develop new drugs. Accordingly, we synthesized a series of polypyridyl ruthenium (II) complexes having the formula [Ru (NN)2 (bpm)] (PF6)2 (N-N = 2,2′-bipyridine) (bpy, in Ru1), 1,10-phenanthroline (phen, in Ru2), 4,7-diphenyl-1,10-phenanthroline (DIP, in Ru3) (bpm = 2,2′-bipyrimidine) and studied their antifungal activities. Ru3 alone had no effect on the drug-resistant strains, but Ru3 combined with fluconazole (FLC) exhibited significant antifungal activity on drug-resistant strains. A high-dose combination of Ru3 and FLC exhibited direct fungicidal activity by promoting the accumulation of reactive oxygen species and damaging the cellular structure of C. albicans. Additionally, the combination of Ru3 and FLC demonstrated potent antifungal efficacy in vivo in a mouse model of invasive candidiasis. Moreover, the combination significantly improved the survival state of mice, restored their immune systems, and reduced renal injury. These findings could provide ideas for the development of ruthenium (II) complexes as novel antifungal agents for drug-resistant microbial stains.

Polypyridyl ruthenium complexes with benzothiazole moiety as membrane disruptors and anti-resistance agents for Staphylococcus aureus

Developing new antimicrobials to combat drug-resistant bacterial infections is necessary due to the increasing problem of bacterial resistance. In this study, four metallic ruthenium complexes modified with benzothiazoles were designed, synthesized and subjected to bio-evaluated. Among them, Ru-2 displayed remarkable inhibitory activity against Staphylococcus aureus (S. aureus) with a minimum inhibitory concentration (MIC) of 1.56 μg/mL. Additionally, it showcased low hemolytic toxicity (HC50 > 200 μg/mL) and the ability to effectively eradicate S. aureus without fostering drug resistance. Further investigation into the antibacterial mechanism suggested that Ru-2 may target the phospholipid component of S. aureus, leading to the disruption of the bacterial cell membrane and subsequent leakage of cell contents (nucleic acid, protein, and ONPG), ultimately resulting in the death of the bacterial cell. In vivo studies, both the G. mellonella larvae and the mouse skin infection models were conducted, indicated that Ru-2 could potentially serve as a viable candidate for the treatment of S. aureus infection. It exhibited no toxic or side effects on normal tissues. The results suggest that benzothiazole-modified ruthenium complexes may have potential as membrane-active antimicrobials against drug-resistant bacterial infections.

PH-Activatable Ruthenium(II) Fluorescein Salphen Schiff Base Photosensitizers for Theranostic Applications.

Ruthenium(II) polypyridyl complexes exhibit a lack of selectivity toward cancer tissues despite extensive studies as photosensitizers for photodynamic therapy (PDT). Here, we report pH-activatable RuII photosensitizers for molecularly targeted PDT by exploiting the higher acidity of tumoral tissue. The fluorescein moiety, well known for its high pH sensitivity, was connected to a RuII center to yield novel photosensitizers for pH-sensitive 1O2 photogeneration. Their ability to photosensitize molecular dioxygen was studied at various pHs and revealed a drastic enhancement from 0.07 to 0.66 of the 1O2 quantum yield under acidic conditions (pH 7.5 to pH 5.5). Their photocytotoxicity against U2OS osteosarcoma cells was also investigated at pH 5.5 and 7.5 through IC50 determination. A strong enhancement of the photocytotoxicity reaching 930 nM was observed at pH 5.5, which showed the potential of such photosensitizers for pH-activatable PDT.

Iron-Sensitized Solar Cells (FeSSCs).

ConspectusThe harvesting and conversion of solar energy have become a burning issue for our modern societies seeking to move away from the exploitation of fossil fuels. In this context, dye-sensitized solar cells (DSSCs) have proven to be trustworthy alternatives to silicon-based cells with advantages in terms of transparency and efficiency under low illumination conditions. These devices are highly dependent on the ability of the sensitizer that they contain to collect sunlight and transfer an electron to a semiconductor after excitation. Ruthenium and polypyridine complexes are benchmarks in this field as they exhibit ideal characteristics such as long-lasting metal-ligand charge transfer (MLCT) states and efficient separation between electrons and holes, limiting recombination at the dye-semiconductor interface. Despite all of these advantages, ruthenium is a noble metal, and the development of more sustainable energy devices based on earth-abundant metals is now a must. A quick glance at the periodic table reveals iron as a potential good candidate, since it belongs to the same group of ruthenium, which suggests similar electronic properties. However, striking photophysical differences exist between ruthenium(II) polypyridyl complexes and their Fe(II) analogues, the latter suffering from short-lived MLCT states resulting of their ultrafast relaxation into metal-centered (MC) states. Pyridyl-N-heterocyclic carbenes (pyridylNHC) brought a strong σ-donor character required to promote a higher ligand field splitting of the iron d orbitals. This induces destabilization of the MC states over the MLCT manifold and a consequent slowdown of the excited states deactivation providing iron(II) complexes with tens of picoseconds lifetimes, making them more promising for applications in DSSCs. This Account highlights our recent advances in the development and characterization of iron-sensitized solar cells (FeSSCs) with a focus on the design of efficient sensitizers going from homoleptic to heteroleptic complexes (bearing different anchoring groups) and the tuning of electrolyte composition. Our rational approach led to the best photocurrent and efficiency ever reported for an iron sensitized solar cell (2% PCE and 9 mA/cm2) using a cosensitization process. This work clearly evidences that the solar energy conversion based on iron complex sensitization is now an opened and fruitful route.