Ruthenium(II) complexes of curcumin and ß-diketone derivatives: effect of structural modifications on their cytotoxicity.

Ruthenium(II) complexes (Ru1-Ru3) with the general formula [Ru(O-O)(PPh3)2(bipy)]PF6, bearing two triphenylphosphine (PPh3), bipyridine (bipy) and a series of natural and synthetic ß-diketones (O,O) ligands were synthesized and characterized using various analytical techniques. The interaction between the complexes and calf thymus DNA (CT-DNA) was investigated and demonstrated a weak interaction. The cytotoxicity of the complexes was investigated against breast cancer cells (MDA-MB-231 and MCF-7), lung cancer cells (A549), cisplatin-resistant ovarian cancer cells (A2780cis), as well as non-tumour lung (MRC-5) and non-tumour breast (MCF-10A) cell lines. All complexes exhibited cytotoxic activity against all the cell lines studied, with half maximal inhibitory concentration (IC50) values ranging from 0.39 to 13 µM. Notably, the three complexes demonstrated selectivity against the A2780cis cell line, with IC50 ranging from 0.39 to 0.82 µM. Among them, Ru2 exhibited the highest cytotoxicity, with an IC50 value of 0.39 µM. Consequently, this new class of complexes shows good selectivity towards cisplatin-resistant ovarian cancer cells and it is promising for further investigation as anti-cancer agents.

Tuning the Coordination Environment of Ru(II) Complexes with a Tailored Acridine Ligand.

A novel tridentate ligand featuring an acridine core and pyrazole rings, namely 2,7- di-tert-butyl-4,5-di(pyrazol-1-yl)acridine, L, was designed and used to create two ruthenium(II) complexes: [RuL2](PF6)2 and [Ru(tpy)L](PF6)2. Surprisingly, the ligand adopted different coordination modes in the complexes: facial coordination for the homoleptic complex and meridional coordination for the heteroleptic complex. The electronic absorption and electrochemical properties were evaluated. Although both complexes exhibited favorable electronic properties for luminescence, neither emitted light at room temperature nor at 77 K. This study highlights the complex interplay between ligand design, coordination mode, and luminescence in ruthenium(II) complexes.

Insights into the antineoplastic activity and mechanisms of action of coumarin-coordinated 8-hydroxyquinoline ruthenium(II/III) compounds.

Ruthenium(II/III) coordination compounds have gained widespread attention as chemotherapy drugs, photosensitizers, and photodynamic therapy reagents. Herein, a family of 11 novel coumarin-coordinated 8-hydroxyquinoline ruthenium(II/III) compounds, i.e., [RuII2(µ2-Cl)2(QL1a)2(DMSO)4] (YNU-4a = Yulin Normal University-4a), [RuII2(µ2-Cl)2(QL1b)2(DMSO)4] (YNU-4b), [RuII2(µ2-Cl)2(QL1c)2(DMSO)4] (YNU-4c), [RuII2(µ2-Cl)2(QL1d)2(DMSO)4]⋅2CH3OH (YNU-4d), [RuII(QL1e)2(DMSO)2] (YNU-4e), [RuIII(QL1e)2(QL3a)] (YNU-4f), [RuIII(QL1e)2(QL3b)] (YNU-4g), [RuIII(QL1e)2(QL3c)] (YNU-4h), [RuIICl2(H-QL3a)2(DMSO)2] (YNU-4i), [RuIICl2(H-QL3b)2(DMSO)2] (YNU-4j), and [RuIICl2(H-QL3c)2(DMSO)2] (YNU-4k), featuring the coligands 5,7-diiodo-8-hydroxyquinoline (H-QL1a), 5,7-dichloro-8-quinolinol (H-QL1b), 5-chloro-7-iodo-8-hydroxyquinolin (H-QL1c), 5,7-dibromo-8-hydroxyquinoline (H-QL1d), and 5,7-dichloro-8-hydroxy-2-methylquinoline (H-QL1e) and the main ligands 6,7-dichloro-3-pyridin-2-yl-chromen-2-one (H-QL3a), 6-bromo-3-pyridin-2-yl-chromen-2-one (H-QL3b), and 6-chloro-3-pyridin-2-yl-chromen-2-one (H-QL3c), respectively. The structure of compounds YNU-4a-YNU-4k was fully confirmed by conducting various spectroscopic analyses. The anticancer activity of YNU-4a-YNU-4k was evaluated in cisplatin-resistant A549/DDP lung cancer cells (LC549) versus normal embryonic kidney (HEK293) cells. Notably, compound YNU-4f bearing QL1e and QL3a ligands showed a more pronounced antiproliferative effect against LC549 cells (IC50 = 1.75 ± 0.09 µM) with high intrinsic selectivity toward LC549 cancer cells than YNU-4a-YNU-4e, H-QL1a-H-QL1e, cisplatin (PDD), YNU-4g-YNU-4k, and H-QL3a-H-QL3c. Additionally, a colocalization assay analysis of YNU-4e and YNU-4f showed that these two ruthenium(II/III) compounds were subcellularly accumulated in the mitochondria and other regions of the cytoplasm, where they induce mitophagy, adenosine triphosphate (ATP) reduction, mitochondrial respiratory chain complex I/IV(RC1/RC4) inhibition, and mitochondrial dysfunction. Accordingly, compounds YNU-4a-YNU-4k can be regarded as mitophagy inductors for the eradication of cisplatin-resistant LC549 cancer cells.

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.

Insights into the photoactivatable CO releasing properties of dicarbonyl Ru(II) complex with 8-amino quinoline ligand: Experimental and theoretical studies.

Reaction between the polymeric [RuCl2(CO)2]n and the N,N-bidentate ligand, 8-amino-quinoline (Quin), in methanol, afforded the photoactivated CO releasing molecule with the formula of trans-(Cl,Cl)-[RuCl2(CO)2Quin]. In the presence of biomolecules or in solvents with varying polarity and coordinating abilities, the solvatochromic characteristics and dark stability were investigated. A new board band emerged in the visible spectrum during the illumination, and its position varies according to the type of solvent used, indicating the role of the solvent in controlling the nature of the CO-depleted species. Spectral methods were used in combination with density functional theory simulations to get insight into the local minimum structure and the electronic properties of the Ru(II) complex. The results of the myoglobin assay showed that within the first two hours of illumination, one of the two CO molecules was released. The cytotoxic properties of the Ru(II)-based complex were investigated against normal mice bone marrow stromal cells and malignant human acute monocytic leukaemia cells.

Microwave-Assisted Atom Transfer Radical Cyclization in the Synthesis of 3,3-Dichloro-γ- and δ-Lactams from N-Alkenyl-Tethered Trichloroacetamides Catalyzed by RuCl2(PPh3)3 and Their Cytotoxic Evaluation.

An expeditious synthesis of γ- and δ-lactams from tethered alkenyl trichloroacetamides in the presence of 5% of RuCl2(PPh3)3 is reported. In this investigation we have demonstrated that microwave activation significantly enhances reaction rates, leading to the formation of the corresponding lactams in yields ranging from good to excellent. Thus, we have been able to prepare a wide range of lactams, including indole and morphan bicyclic scaffolds, where the corresponding reactions were completely diastereoselective. This process was successfully extended to α,α-dichloroamides without affecting either their yield or their diastereoselectivity. Some of the lactams prepared in this work were evaluated for their hemolytic and cytotoxic responses. All compounds were found to be non-hemolytic at the tested concentration, indicating their safety profile in terms of blood cell integrity. Meanwhile, they exhibited interesting cytotoxicity responses that depend on both their lactam structure and cell line. Among the molecules tested, γ-lactam 2a exhibited the lowest IC50 values (100-250 µg/mL) as a function of its cell line, with promising selectivity against squamous carcinoma cells (A431) in comparison with fibroblasts (3T3 cell line).

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.

Multiple signal-enhanced electrochemiluminescence aptamer sensors based on carboxylated ruthenium (II) complexes for acetamiprid detection.

BACKGROUND: Rapid and sensitive detection for acetamiprid, a kind of widely used neonicotinoid insecticide, is very meaningful for the development of modern agriculture and the protection of human health. Highly stable electrochemiluminescence (ECL) materials are one of the key factors in ECL sensing technology. ECL materials prepared by porous materials (e.g., MOFs) coated with chromophores have been used for ECL sensing detection, but these materials have poor stability because the chromophores escape when they are in aqueous solution. Therefore, the development of highly stable ECL materials is of great significance to improve the sensitivity of ECL sensing technology. RESULTS: In this work, by combining etched metal-organic frameworks (E-UIO-66-NH2) as carrier with Tris(4,4'-dicarboxylic acid-2,2'-bipyridine)Ru(II) chloride (Ru(dcbpy)32+) as signal probe via amide bonds, highly stable nanocomposites (E-UIO-66-NH2-Ru) with excellent ECL performance were firstly prepared. Then, using MoS2 loaded with AuNPs as substrate material and co-reactant promoter, a signal off-on-off ECL aptamer sensor was prepared for sensitive detection of acetamiprid. Due to the excellent catalytic activity of E-UIO-66-NH2-Ru and MoS2@Au towards K2S2O8, the ECL signals can be enhanced by multiple signal enhancement pathways, the prepared ECL aptamer sensor could achieve sensitive detection of acetamiprid in the linear range of 10-13 to10-7 mol L-1, with the limit of detection (LOD) of 2.78ⅹ10-15 mol L-1 (S/N = 3). After the evaluation of actual sample testing, this sensing platform was proven to be an effective method for the detection of acetamiprid in food and agricultural products. SIGNIFICANCE AND NOVELTY: The E-UIO-66-NH2-Ru prepared by linking Ru(dcbpy)32+ to E-UIO-66-NH2 via amide bonding has very high stability. The synergistic catalytic effect of MoS2 and AuNPs enhanced the ECL signal. By exploring the sensing mechanism and evaluating the actual sample tests, the proposed signal "on-off" ECL sensing strategy was proved to be an effective and excellent ECL sensing method for sensitive and stable detection of acetamiprid.

Ferrocene-modified half-sandwich iridium(III) and ruthenium(II) propionylhydrazone complexes and anticancer application.

Ferrocene, ruthenium(II) and iridium(III) organometallic complexes, potential substitutes for platinum-based drugs, have shown good application prospects in the field of cancer therapy. Therefore, in this paper, six ferrocene-modified half-sandwich ruthenium(II) and iridium(III) propionylhydrazone complexes were prepared, and the anticancer potential was evaluated and compared with cisplatin. These complexes showed potential in-vitro anti-proliferative activity against A549 cancer cells, especially for Ir-based complexes, and showing favorable synergistic anticancer effect. Meanwhile, these complexes showed little cytotoxicity and effective anti-migration activity. Ir3, the most active complex (ferrocene-appended iridium(III) complex), could accumulate in the intracellular mitochondria, disturb the cell cycle (S-phase), induce the accumulation of reactive oxygen species, and eventually cause the apoptosis of A549 cells. Then, the design of these complexes provides a good structural basis for the multi-active non­platinum organometallic anticancer complexes.

Effect of ruthenium(II) complexes on MDA-MB-231 cells and lifespan/tumor growth in gld-1mutant, Daf-16 TF and stress productive genes: A perspective study.

Pincer type coumarin based N-substituted semicarbazone ligands HL1-4 and their corresponding ruthenium(II) complexes (1-4) were synthesized, analyzed and confirmed by various spectro analytical techniques. The molecular structure of the ligand HL3 and complex 3 was confirmed by single crystal X-ray diffraction analysis. The stoichiometry of complexes 1, 2 and 4 was confirmed by high resolution mass spectroscopy (HRMS). The binding affinity of the compounds with CT-DNA (Calf Thymus DNA) and BSA (Bovine Serum Albumin) was established by absorption and emission titration methods. The results of In vitro cytotoxicity showed the significant cytotoxic potential of the complexes against MDA-MB-231 cells (TNBC- Triple-negative breast cancer). Among the complexes, 1 and 4 have shown appreciable results. Further, antimigratory activity against the MDA-MB-231 cells was studied for the complexes 1 and 4. The percentage cell cycle arrest, apoptosis and necrosis were explored by flow cytometry. The in vivo anti-tumor activity of the complexes 1 and 4 using C. elegans as model organism was established by using the tumoral C. elegans strain JK1466 (gld-1(q485)), which bears a mutation in the gld-1 tumor suppressor gene. We have determined the effect of our complexes on tumor gonad reduction and found to be non toxic to the JK1466 worms and they have prolonged their mean lifespan with potential antioxidant ability by overcoming stress responses. Overall, our study reported herein demonstrated that the complexes 1 and 4 could be established as potential metallo-drugs substantiating further exploration.

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.

cis,cis,cis-Di-chlorido-bis-(N4,N4-di-methyl-pyridin-4-amine-κN1)bis-(dimethyl sulfoxide-κS)ruthenium(II).

The structure of the title compound, [RuCl2(C7H10N2)2(C2H6OS)2], has monoclinic (P21/n) symmetry. The Ru-N distances of the coordination compound are influenced by the trans chloride or di-methyl-sulfoxide-κS ligands. The mol-ecular structure exhibits disorder for two of the terminal methyl groups of a dimethyl sulfoxide ligand.

Bis[2,6-bis-(1H-benzimidazol-2-yl)pyridine]ruthenium(II) bis(hexa-fluorido-phosphate) diethyl ether tris-olvate.

The title compound, [Ru(C19H13N5)2](PF6)2·3C4H10O, was obtained from the reaction of Ru(bimpy)Cl3 [bimpy is 2,6-bis-(1H-benzimidazol-2-yl)pyridine] and bimpy in refluxing ethanol followed by recrystallization from diethyl ether/aceto-nitrile. At 125 K the complex has ortho-rhom-bic (Pca21) symmetry. It is remarkable that the structure is almost centrosymmetric. However, refinement in space group Pbcn leads to disorder and definitely worse results. It is of inter-est with respect to potential catalytic reduction of CO2. The structure displays N-H⋯O, N-H⋯F hydrogen bonding and significant π-π stacking and C-H⋯π stacking inter-actions.

Aqua-bis-(2,2'-bi-pyridine-κ2N,N')(isonicotinamide-κN)ruthenium(II) bis-(trifluoromethanesulfonate).

In the title complex, [Ru(C10H8N2)2(C6H6N2O)(H2O)](CF3SO3)2, the central RuII atom is sixfold coordinated by two bidentate 2,2'-bi-pyridine, an isonic-otinamide ligand, and a water mol-ecule in a distorted octa-hedral environment with tri-fluoro-methane-sulfonate ions completing the outer coordination sphere of the complex. Hydrogen bonding involving the water mol-ecule and weak π-π stacking inter-actions between the pyridyl rings in adjacent mol-ecules contribute to the alignment of the complexes in columns parallel to the c axis.

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.

Electrochemiluminescence detection of diazinon in vegetables based on the synergistic interaction of WO3-x dots with Au@SiO2 nanocapsules.

In this work, a simple synthesis of low-toxicity transition metal material of WO3-x dots was used as a co-reactant with Au@SiO2 as a core-shell material and a signal amplification factor to collaboratively promote Ru(bpy)32+ electrochemiluminescence (ECL) for the construction of a highly sensitive aptasensor for the detection of diazinon (DZN) in vegetables. Electrodes modified with multi-walled carbon nanotubes-chitosan composite membranes (MWCNTs-CS) were used to load and immobilize more Ru(bpy)32+.can load more Ru(bpy)32+. WO3-x dots synthesized by a simple method showed excellent ECL efficiency as a novel co-reactant for Ru(bpy)32+. Under optimized conditions, this aptasensor for DZN has a wide detection range (10 pg mL-1 - 1 µg mL-1.) and a low detection limit (0.0197 ng L-1). The aptasensor has shown good results in the analysis of real samples in the experiment. This work provides a new approach to the construction of a novel electrochemiluminescence sensor for the detection of pesticides.

Fabrication of alginate-based hydrogel microparticle via ruthenium-catalyzed photocrosslinking.

In this study, we developed an alginate-based microparticle production process via sodium ruthenium(II) tris-bipyridyl dication (Ru)/ammonium persulfate (SPS)-mediated visible light crosslinking system using a microfluidic device. Microparticles were prepared by crosslinking phenolic-substituted alginate (AlgPh) and incorporated gelatin (GelPh) in an aqueous solution containing SPS, which flowed into an ambient immiscible liquid paraffin-containing Ru using coaxial double orifice microfluidic device. The hydrogel microparticles appeared with the desired geometries and dimensions under optimal conditions. The concentration of AlgPh and light intensity were the most critical parameters for harvesting spherical microparticles with homogeneous size distribution. The physical properties of the prepared AlgPh microparticles were characterized and compared with Alg-Ca microparticles. Cell viability and proliferation preserved on AlgPh/GelPh hydrogel surfaces. Also, encapsulated cells in microparticles were also viable and proliferated well over 13 days after encapsulation. In brief, the results proved the feasibility of fabricating AlgPh vehicles via Ru/SPS-mediated system and visible light irradiation as a simple and efficient three-dimensional platform, which are applicable for various tissue engineering and cell delivery purposes.

Biotin-conjugated Ru(II) complexes with AIE characteristics as mitochondria-targeted photosensitizers for enhancing photodynamic therapy by disrupting cellular redox balance.

The potential use of Ru(II) complexes as photosensitizers (PSs) in photodynamic therapy (PDT) has gained significant attention. In comparison with fluorophores with aggregation-caused quenching (ACQ), fluorophores with aggregation-induced emission (AIE) characteristics exhibit sustained fluorescence and dispersibility in aqueous solutions. PSs with AIE characteristics have received much attention in recent years. Herein, we reported two novel biotin-conjugated Ru(II) polypyridyl complexes (Ru1 and Ru2) with AIE characteristics. When exposed to 460 nm (10 mW cm-2) light, Ru1 and Ru2 exhibited outstanding photostability and photocatalytic activity. Ru1 and Ru2 could efficiently generate singlet oxygen and induce pUC19 DNA photolysis when exposed to 460 nm light. Interestingly, both Ru1 and Ru2 also functioned as catalysts for NADH oxidation when exposed to 460 nm light. The presence of biotin fragments in Ru1 and Ru2 enhanced the specific uptake of these complexes by tumor cells. Both complexes showed minimal toxicity to selected cells in the dark. Nevertheless, the phototoxicity of both complexes significantly increased upon 460 nm light irradiation for 15 min. Further experiments revealed that Ru2 primarily accumulated in mitochondria and might bind to mitochondrial DNA. Under 460 nm light irradiation, Ru2 induced the generation of reactive oxygen species (ROS) and NADH depletion disrupting intracellular redox homeostasis in A549 cells, activating the mitochondrial apoptosis pathway resulting in up-regulation of apoptotic marker caspase-3, effectively damaged A549 cell DNA and arrested A549 cell cycle in the S phase. In vivo anti-tumor experiments were conducted to assess the effects of Ru2 on tumor growth in A549 tumor-bearing mice. The results showed that Ru2 effectively inhibited tumor growth under 460 nm light irradiation conditions. These findings indicate that Ru2 has great potential as a targeted photosensitizer for mitochondrial targeting imaging and photodynamic therapy of tumors.

Ruthenium(II) polypyridyl complexes as emerging photosensitisers for antibacterial photodynamic therapy.

Photodynamic therapy (PDT) has recently emerged as a potential valuable alternative to treat microbial infections. In PDT, singlet oxygen is generated in the presence of photosensitisers and oxygen under light irradiation of a specific wavelength, causing cytotoxic damage to bacteria. This review highlights different generations of photosensitisers and the common characteristics of ideal photosensitisers. It also focuses on the emergence of ruthenium and more specifically on Ru(II) polypyridyl complexes as metal-based photosensitisers used in antimicrobial photodynamic therapy (aPDT). Their photochemical and photophysical properties as well as structures are discussed while relating them to their phototoxicity. The use of Ru(II) complexes with recent advancements such as nanoformulations, combinatory therapy and photothermal therapy to improve on previous shortcomings of the complexes are outlined. Future perspectives of these complexes used in two-photon PDT, photoacoustic imaging and sonotherapy are also discussed. This review covers the literature published from 2017 to 2023.

Asymmetric Ruthenium-Catalyzed C-H Activation by a Versatile Chiral-Amide-Directing Strategy.

A versatile and readily available chiral amide directing group has been developed for the ruthenium(II)-catalyzed asymmetric C-H activation. Asymmetric C-H activation of the related chiral benzamides with various olefins, aldehydes and propargylic alcohols has been accomplished with high stereoselectivities, affording a series of chiral products including 3,4-dihydroisocoumarins (up to 96 % ee), isocoumarins (up to 92 % ee), phthalides (up to 99 % ee), chiral bicyclo[2.2.1]heptanes (>20 : 1 dr), 4-alkylidene-3,4-dihydroisocoumarins (up to 97 % ee) and allenes (>20 : 1 dr). Importantly, our methodologies enabled concise syntheses of many biologically active compounds and natural products (e.g., Montroumarin, Cyclosporone E, Cyclosporone Q, Concentricolide, Chuangxinol, and Eleutherol).