Characteristics of catalytic destruction of dichloromethane and ethyl acetate mixture over HxPO4-RuOx/CeO2 catalyst.

Catalytic destruction is an ascendant technology for the abatement of volatile organic compounds (VOCs) originating from solvent-based industrial processes. The varied composition tends to influence each VOC's catalytic behavior in the reaction mixture. We investigated the catalytic destruction of multi-component VOCs including dichloromethane (DCM) and ethyl acetate (EA), as representatives from pharmaceutical waste gases, over co-supported HxPO4-RuOx/CeO2 catalyst. A mutual inhibitory effect relating to concentrations because of competitive adsorption was verified in the binary VOCs oxidation and EA posed a more negative effect on DCM oxidation owing to EA's superior adsorption capacity. Preferential adsorption of EA on acidic sites (HxPO4/CeO2) promoted DCM activation on basic sites (O2-) and the dominating EA oxidation blocked DCM's access to oxidation centers (RuOx/CeO2), resulting in boosted monochloromethane yield and increased chlorine deposition for DCM oxidation. The impaired redox ability of Ru species owing to chlorine deposition in turn jeopardized deep oxidation of EA and its by-products, leading to increased gaseous by-products such as acetic acid originating from EA pyrolysis. Notably, DCM at low concentration slightly promoted EA conversion at low temperatures with or without water, consistent with the enhanced EA adsorption in co-adsorption analyses. This was mainly due to that DCM impeded the shielding effect of hydrolysate deposition from rapid EA hydrolysis depending on the decreased acidity. Moreover, water benefited EA hydrolysis but decreased CO2 selectivity while the generated water derived from EA was likely to affect DCM transformation. This work may provide theoretical guidance for the promotion of applied catalysts toward industrial applications.

High-Sensitivity Homogeneous Detection of miRNA-155 Governed by DNA Walker-Regulated Surface DNA Density of Magnetic Electrochemiluminescence Nanoparticles.

Homogeneous electrochemiluminescence (ECL) has gained attention for its simplicity and stability. However, false positives due to solution background interference pose a challenge. To address this, magnetic ECL nanoparticles (Fe3O4@Ru@SiO2 NPs) were synthesized, offering easy modification, magnetic separation, and stable luminescence. These were utilized in an ECL sensor for miRNA-155 (miR-155) detection, with locked DNAzyme and substrate chain (mDNA) modified on their surface. The poor conductivity of long-chain DNA significantly impacts the conductivity and electron transfer capability of Fe3O4@Ru@SiO2 NPs, resulting in weaker ECL signals. Upon target presence, unlocked DNAzyme catalyzes mDNA cleavage, leading to shortened DNA chains and reduced density. In contrast, the presence of short-chain DNA has minimal impact on the conductivity and electron transfer capability of Fe3O4@Ru@SiO2 NPs. Simultaneously, the material surface's electronegativity decreases, weakening the electrostatic repulsion with the negatively charged electrode, resulting in the system detecting stronger ECL signals. This sensor enables homogeneous ECL detection while mitigating solution background interference through magnetic separation. Within a range of 100 fM to 10 nM, the sensor exhibits a linear relationship between ECL intensity and target concentration, with a 26.91 fM detection limit. It demonstrates high accuracy in clinical sample detection, holding significant potential for clinical diagnostics. Future integration with innovative detection strategies may further enhance sensitivity and specificity in biosensing applications.

Contrasting Photosensitized Processes of Ru(II) Polypyridyl Structural Isomers Containing Linear and Hooked Intercalating Ligands Bound to Guanine-Rich DNA.

The DNA binding and cellular uptake of the lambda enantiomer of two bis-tetraazaphenanthrene (TAP) Ru(II) polypyridyl complexes containing either a linear dppn (1) or a hooked bdppz (2) benzodipyridophenazine ligand are reported, and the role of different charge-transfer states of the structural isomers in the photo-oxidation of guanine is explored. Both complexes possess characteristic metal-to-ligand charge-transfer (MLCT) bands between 400 and 500 nm and emission at ca. 630 nm in an aerated aqueous solution. Transient visible absorption (TrA) spectroscopy reveals that 400 nm excitation of 1 yields a dppn-based metal-to-ligand charge-transfer (MLCT) state, which in turn populates a dppn intraligand (3IL) state. In contrast, photoexcitation of 2 results in an MLCT state on the TAP ligand and not the intercalating bdppz ligand. Both 1 and 2 bind strongly to double-stranded guanine-rich DNA with a loss of emission. Combined TrA and time-resolved infrared (TRIR) spectroscopy confirms formation of the guanine radical cation when 2 is bound to the d(G5C5)2 duplex, which is not the case when 1 is bound to the same duplex and indicates a different mechanism of action in DNA. Utilizing the long-lived triplet excited lifetime, we show good uptake and localization of 2 in live cells as well as isolated chromosomes. The observed shortening of the excited-state lifetime of 2 when internalized in cell chromosomes is consistent with DNA binding and luminescent quenching due to guanine photo-oxidation.

Biomolecular Interactions and Anticancer Mechanisms of Ru(II)-Arene Complexes of Cinnamaldehyde-Derived Thiosemicarbazone Ligands: Analysis Combining In Silico and In Vitro Approaches.

Our study focuses on synthesizing and exploring the potential of three N-(4) substituted thiosemicarbazones derived from cinnamic aldehyde, alongside their Ru(II)-(η6 -p-cymene)/(η6-benzene) complexes. The synthesized compounds were comprehensively characterized using a range of analytical techniques, including FT-IR, UV-visible spectroscopy, NMR (1H, 13C), and HRMS. We investigated their electronic and physicochemical properties via density functional theory (DFT). X-ray crystal structures validated structural differences identified by DFT. Molecular docking predicted promising bioactivities, supported by experimental observations. Notably, docking with EGFR suggested an inhibitory potential against this cancer-related protein. Spectroscopic titrations revealed significant DNA/BSA binding affinities, particularly with DNA intercalation and BSA hydrophobic interactions. RuPCAM displayed the strongest binding affinity with DNA (Kb = 6.23 × 107 M-1) and BSA (Kb = 9.75 × 105 M-1). Assessed the cytotoxicity of the complexes on cervical cancer cells (HeLa), and breast cancer cells (MCF-7 and MDA-MB 231), revealing remarkable potency. Additionally, selectivity was assessed by examining MCF-10a normal cell lines. The active complexes were found to trigger apoptosis, a vital cellular process crucial for evaluating their potential as anticancer agents utilizing staining assays and flow cytometry analysis. Intriguingly, complexation with Ru(II)-arene precursors significantly amplified the bioactivity of thiosemicarbazones, unveiling promising avenues toward the creation of powerful anticancer agents.

Cytotoxic and pro-oxidant profile of a photosensitive ruthenium nitrosyl candidate for NO delivery in healthy human fibroblasts.

Ruthenium nitrosyl (Ru-NO) complexes are of interest as photoactive nitric oxide (NO) donor candidates for local therapeutic applications. NO plays a crucial regulatory role in skin homeostasis, concentration-dependently affecting processes like the proliferation, apoptosis, autophagy and redox balance. In this context, we investigated HE-10, a ruthenium-based photoinducible NO donor, for its pro-oxidant and cytotoxic effects under light and dark conditions in VH10 human foreskin fibroblast cells. We also tested its intracellular and extracellular NO-releasing function. Our study reveals a significant dose-dependent cytotoxic effect of HE-10, an increase in intracellular reactive oxygen and nitrogen species, and the occurrence of apoptosis in skin fibroblast cells. Furthermore, exposure to both increasing doses of HE-10 and white LED light led to substantial cellular events, including a significant induction of autophagy and G2/M phase cell cycle arrest. Paradoxically, these effects were not solely attributable to NO release based on DAF2-DA NO probe results, suggesting that intracellular photochemical reactions additional to NO photolysis contribute to HE-10's biological activity. This study shows that HE-10 exhibits both cytotoxic and potential therapeutic effects, depending on concentration and light exposure. These findings are crucial for developing targeted Ru-NO complex treatments for skin diseases and potentially certain types of skin cancer, where controlled NO release could be beneficial.

Antimetastatic activity of (arene)ruthenium(II) complex of 4-aryl-4H-naphthopyran.

Metastatic cancer remains a formidable challenge in anticancer therapy. Despite efforts to develop effective antimetastasis drugs over the past half-century, currently approved treatments fall short of expectations. This report highlights the promising antiproliferative activity of a ruthenium-based therapeutic agent, namely dichlorido(p-cymene)[2-amino-4-(pyridin-3-yl)-4H-benzo[h]-chromene-3-carbonitrile]ruthenium(II) (complex 1) against metastatic cell lines. Complex 1 shows significant efficacy in metastatic LoVo and Du-145 cell lines at nanomolar concentrations, being markedly more active than clinically used anticancer cisplatin. Studies on the MDA-MB-231 cell line, which displays invasive characteristics, demonstrated that 1 significantly reduces cell invasion. This efficacy was confirmed by its impact on matrix metalloproteinase production in MDA-MB-231 cells. Given that cell migration drives cancer invasion and metastasis, complex 1's effect on MDA-MB-231 cell migration was evaluated via wound healing assay and vimentin network analysis. Results indicated a strong reduction in migration. A re-adhesion assay further demonstrated that 1 significantly lowers the re-adhesion ability of MDA-MB-231 cells compared to cisplatin. To better simulate the human body environment, a 3D spheroid invasion assay was used. This method showed that 1 effectively inhibits tumor spheroids from infiltrating the surrounding extracellular matrix. This study underscores the potential of (arene)ruthenium(II) complexes with naphthopyran ligands as potent antimetastatic agents for chemotherapy.

η6-Arene Ru(II) Complexes as Modulators of Amyloid Aggregation.

Inorganic medicinal compounds represent a unique and versatile source of potential therapeutics in many diseases and, more recently, in neurodegeneration. Herein we investigated the effects of two η6-arene Ru(II) complexes on the self-aggregation processes of several amyloidogenic peptides endowed with different kinetics and primary sequences. The Ru(II) complexes exhibit, around the metal ion, two chlorides, one NHC = N-heterocyclic carbene, with a glucosyl and a methyl substituent and separately a hexamethylbenzene, which is named Ru1, and one benzene, named Ru2. Both complexes were demonstrated to bind monomeric amyloids suppressing aggregation as evidenced in thioflavin T (ThT) binding assays and autofluorescence experiments. Electrospray ionization mass spectrometry (ESI-MS) indicated the formation of direct adducts between amyloid and metal complexes, which determined the marked conformational variation of peptides and a rescue of cellular viability in SH-SY5Y cells. The complex Ru2 was demonstrated to be a more potent inhibitor of amyloid aggregation compared to Ru1 likely because of the less hindrance of the arene moiety. The presented data strongly support the in vitro ability of η6-arene Ru(II) complexes to suppress amyloid aggregation, providing insights into their potential application as novel therapeutics in neurodegenerative diseases.

Robust Ru/Ce@Co Catalyst with an Optimized Support Structure for Propane Oxidation.

Short carbon chain alkanes, as typical volatile organic compounds (VOCs), have molecular structural stability and low molecular polarity, leading to an enormous challenge in the catalytic oxidation of propane. Although Ru-based catalysts exhibit a surprisingly high activity for the catalytic oxidation of propane to CO2 and H2O, active RuOx species are partially oxidized and sintered during the oxidation reaction, leading to a decrease in catalytic activity and significantly inhibiting their application in industrial processes. Herein, the Ru/Ce@Co catalyst is synthesized with a specific structure, in which cerium dioxide is dispersed in a thin layer on the surface of Co3O4, and Ru nanoparticles fall preferentially on cerium oxide with high dispersity. Compared with the Ru/CeO2 and Ru/Co3O4 catalysts, the Ru/Ce@Co catalyst demonstrates excellent catalytic activity and stability for the oxidation of propane, even under severe operating conditions, such as recycling reaction, high space velocity, a certain degree of moisture, and high temperature. Benefiting from this particular structure, the Ru/Ce@Co (5:95) catalyst with more Ce3+ species leads to the Ru species being anchored more firmly on the CeO2 surface with a low-valent state and has a strong potential for adsorption and activation of propane and oxygen, which is beneficial for RuOx species with high activity and stability. This work provides a novel strategy for designing high-efficiency Ru-based catalysts for the catalytic combustion of short carbon alkanes.

Boosting Catalytic and Anti-fluorination Performance of the Ru/Vanadia-Titania Catalyst for the Oxidative Destruction of Freon by Sulfuric Acid Modification.

Chlorofluorocarbons (CFCs) exert a strong greenhouse effect and constitute the largest contributor to ozone depletion. Catalytic removal is considered an effective pathway for eliminating low-concentration CFCs under mild conditions. The key issue is the easy deactivation of the catalysts due to their surface fluorination. We herein report a comparative investigation on catalytic dichlorodifluoromethane (CFC-12) removal in the absence or presence of water over the sulfuric-acid-modified three-dimensionally ordered macroporous vanadia-titania-supported Ru (S-Ru/3DOM VTO) catalysts. The S-Ru/3DOM VTO catalyst exhibited high activity (T90% = 278 °C at space velocity = 40 000 mL g-1 h-1) and good stability within 60 h of on-stream reaction in the presence of 1800 ppm of water due to the improvements in acid site amount and redox ability that promoted the adsorption of CFC-12 and the activation of C-F bonds. Compared with the case under dry conditions, catalytic performance for CFC-12 removal was better over the S-Ru/3DOM VTO catalyst in the presence of water. Water introduction mitigated surface fluorination by the replenishment of hydroxyl groups, inhibited the formation of halogenated byproducts via the surface fluorine species cleaning effect, and promoted the reaction pathway of COX2 (X = Cl/F) → carboxylic acid → CO2.

Spontaneous aggregation-enhanced electrochemiluminescence via galvanic strategy.

Researchers unremittingly strive to develop innovative luminophores to enhance intrinsic electrochemiluminescence (ECL) performance. However, the potential to harness facile strategies, such as manipulating the physical properties of luminophores while retaining functional chemical properties to fabricate cost-effective ECL complexes, remains underexplored. Herein, we reported a novel and efficient one-step galvanic technique to actualize aggregation-enhanced ECL (AEECL) of ruthenium complexes. It marked the first instance of the galvanic process being employed to synthesize aggregate luminophores through electrostatic attraction. The ECL intensity and efficiency of the prepared ruthenium complexes with AEECL properties surpassed traditional ruthenium complexes by 8.9 and 13.6 times, respectively, outperforming most reported luminophores. Remarkably, the target luminophore exhibited high stability across varied scan rates and temperatures. Furthermore, a binder-free and carbon paper-based AEECL analytical device for lidocaine detection was fabricated, achieving a satisfactory detection limit (0.34 nM) and selectivity. The convenient modulation strategy of aggregate structure, along with the transformative leap from insufficient ECL to AEECL, bring forth a new revenue in aggregate science. This research also promises a universally applicable and versatile protocol for future biological analysis and bioimaging applications.

A half sandwich Ru(II)-p-cymene nitrite complex selectively induces cell death in cisplatin-resistant malignant melanoma cells.

The Ru(II)-nitrite complex, Ru4, is explored to release nitric oxide (NO) under acidic conditions and selectively induce a cytotoxic effect towards SK-MEL-28 cisplatin-resistant malignant melanoma cells. These findings suggest that targeting the tumor-associated pHe level could be an effective strategy for the drug function of Ru(II)-nitrite compounds.

Anti-bacterial, anti-biofilm and synergistic effects of phenazine-based ruthenium(II) complexes.

Antimicrobial resistance has become a global threat to human health, which is coupled with the lack of novel drugs. Metallocompounds have emerged as promising diverse scaffolds for the development of new antibiotics. Herein, we prepared some metal compounds mainly focusing on cis-[Ru(bpy)(dppz)(SO3)(NO)](PF6) (PR02, bpy = 2,2'-bipyridine, dppz = dipyrido[3,2-a:2',3'-c]phenazine), in which phenazinic and nitric oxide ligands along with sulfite conferred some key properties. This compound exhibited a redox potential for bound NO+/0 of -0.252 V (vs. Ag|AgCl) and a high pH for nitrosyl-nitro conversion of 9.16, making the nitrosyl ligand the major species. These compounds were still able to bind to DNA structures. Interestingly, reduced glutathione (GSH) was unable to promote significant NO/HNO release, an uncommon feature of many similar systems. However, this reducing agent was essential to generate superoxide radicals. Antimicrobial studies were carried out using six bacterial strains, where none or very low activity was observed for Gram-negative bacteria. However, PR02 and PR (cis-[Ru(bpy)(dppz)Cl2]) showed high antibacterial activity in some Gram-positive strains (MBC for S. aureus up to 4.9 µmol L-1), where the activity of PR02 was similar to or at least 4-fold better than that of PR. Besides, PR02 showed capacity to inhibit bacterial biofilm formation, a major health issue leading to bacterial tolerance to antibiotics. Interestingly, we also showed that PR02 can function in synergism with the known antibiotic ampicillin, improving their action up to 4-fold even against resistant strains. Altogether, these results showed that PR02 is a promising antimicrobial nitrosyl ruthenium compound combining features beyond its killing action, which deserves further biological studies.

Ruthenium(II) Complex-Based Tetradentate Schiff Bases: Synthesis, Spectroscopic, Antioxidant, and Antibacterial Investigations.

In this work, we describe the synthesis of novel Ruthenium (II) complex-based salen Schiff bases. The obtained Ruthenium (II) complexes are characterized using usual spectroscopic and spectrometric techniques, viz., IR, UV-Vis, NMR (1H and 13C), powder X-ray diffraction, and HRMS. Further techniques, such as DTA-TGA and elemental analysis, are used to well establish the structure of the obtained complexes. Octahedral geometries are tentatively proposed for the new Ru(II) complexes. The measured molar conductance for the Ruthenium (II) complexes shows their electrolytic nature (4.24-4.44 S/m). The new Ru(II) complexes are evaluated for their antioxidant and antibacterial activities. The DPPH radical scavenging, FRAP, and total antioxidant capacity (TAC) assays show that the obtained complexes are more potent than the used positive control. They also exhibit promising antibacterial responses against pathogen bacteria: [RuH2L3Cl2] exhibits an important inhibition against Bacillus subtilis DSM 6633, with an inhibition zone of 21 ± 1.41 mm with an MIC value of 0.39 mg/mL, and Proteus mirabilis INH, with 16.50 ± 0.70 mm and an MIC value of 0.78 mg/mL, while [RuH2L2Cl2] exerts interesting antibacterial effects versus Bacillus subtilis DSM 6633 (21 ± 1.41 mm) and Proteus mirabilis INH (25.5 ± 0.70 mm) with equal MIC values of 0.97 mg/mL.

In Vitro Encapsulation of Functionally Active Abiotic Photosensitizers Inside a Bacterial Microcompartment Shell.

Bacterial microcompartments (BMCs) are self-assembling, selectively permeable protein shells that encapsulate enzymes to enhance catalytic efficiency of segments of metabolic pathways through means of confinement. The modular nature of BMC shells' structure and assembly enables programming of shell permeability and underscores their promise in biotechnology engineering efforts for applications in industry, medicine, and clean energy. Realizing this potential requires methods for encapsulation of abiotic molecules, which have been developed here for the first time. We report in vitro cargo loading of BMC shells with ruthenium photosensitizers (RuPS) by two approaches─one involving site-specific covalent labeling and the other driven by diffusion, requiring no specific interactions between cargo molecules and shell proteins. The highly stable shells retain encapsulated cargo over 1 week without egress and preserve RuPS photophysical activity. This study is an important foundation for further work that will converge biological BMC architecture with synthetic chemistry to facilitate biohybrid photocatalysis.

Minimal Functionalization of Ruthenium Compounds with Enhanced Photoreactivity against Hard-to-Treat Cancer Cells and Resistant Bacteria.

Metallocompounds have emerged as promising new anticancer agents, which can also exhibit properties to be used in photodynamic therapy. Here, we prepared two ruthenium-based compounds with a 2,2'-bipyridine ligand conjugated to an anthracenyl moiety. These compounds coded GRBA and GRPA contain 2,2'-bipyridine or 1,10-phenathroline as auxiliary ligands, respectively, which provide quite a distinct behavior. Notably, compound GRPA exhibited remarkably high photoproduction of singlet oxygen even in water (Ï•Δ = 0.96), almost twice that of GRBA (Ï•Δ = 0.52). On the other hand, this latter produced twice more superoxide and hydroxyl radical species than GRPA, which may be due to the modulation of their excited state. Interestingly, GRPA exhibited a modest binding to DNA (Kb = 4.51 × 104), while GRBA did not show a measurable interaction only noticed by circular dichroism measurements. Studies with bacteria showed a great antimicrobial effect, including a synergistic effect in combination with commercial antibiotics. Besides that, GRBA showed very low or no cytotoxicity against four mammalian cells, including a hard-to-treat MDA-MB-231, triple-negative human breast cancer. Potent activities were measured for GRBA upon blue light irradiation, where IC50 of 43 and 13 nmol L-1 were seen against hard-to-treat triple-negative human breast cancer (MDA-MB-231) and ovarian cancer cells (A2780), respectively. These promising results are an interesting case of a simple modification with expressive enhancement of biological activity that deserves further biological studies.

Anticancer Activity of Metallodrugs and Metallizing Host Defense Peptides-Current Developments in Structure-Activity Relationship.

This article provides an overview of the development, structure and activity of various metal complexes with anti-cancer activity. Chemical researchers continue to work on the development and synthesis of new molecules that could act as anti-tumor drugs to achieve more favorable therapies. It is therefore important to have information about the various chemotherapeutic substances and their mode of action. This review focuses on metallodrugs that contain a metal as a key structural fragment, with cisplatin paving the way for their chemotherapeutic application. The text also looks at ruthenium complexes, including the therapeutic applications of phosphorescent ruthenium(II) complexes, emphasizing their dual role in therapy and diagnostics. In addition, the antitumor activities of titanium and gold derivatives, their side effects, and ongoing research to improve their efficacy and reduce adverse effects are discussed. Metallization of host defense peptides (HDPs) with various metal ions is also highlighted as a strategy that significantly enhances their anticancer activity by broadening their mechanisms of action.

Ligand Characterization and DNA Intercalation of Ru(II) Polypyridyl Complexes: A Local Vibrational Mode Study.

We investigated in this work ruthenium-ligand bonding across the RuN framework in 12 Ru(II) polypyridyl complexes in the gas phase and solution for both singlet and triplet states, in addition to their affinity for DNA binding through π-π stacking interactions with DNA nucleobases. As a tool to assess the intrinsic strength of the ruthenium-ligand bonds, we determined local vibrational force constants via our local vibrational mode analysis software. We introduced a novel local force constant that directly accounts for the intrinsic strength of the π-π stacking interaction between DNA and the intercalated Ru(II) complex. According to our findings, [Ru(phen)2(dppz)]2+ and [Ru(phen)2(11-CN-dppz)]2+ provide an intriguing trade-off between photoinduced complex excitation and the strength of the subsequent π-π stacking interaction with DNA. [Ru(phen)2(dppz)]2+ displays a small singlet-triplet splitting and a strong π-π stacking interaction in its singlet state, suggesting a favorable photoexcitation but potentially weaker interaction with DNA in the excited state. Conversely, [Ru(phen)2(11-CN-dppz)]2+ exhibits a larger singlet-triplet splitting and a stronger π-π stacking interaction with DNA in its triplet state, indicating a less favorable photoinduced transition but a stronger interaction with DNA postexcitation. We hope our study will inspire future experimental and computational work aimed at the design of novel Ru-polypyridyl drug candidates and that our new quantitative measure of π-π stacking interactions in DNA will find a general application in the field.

Differentiated management of ROS level in tumor and kidney to alleviate Cis-platinum induced acute kidney injury with improved efficacy.

Cisplatin (DDP) is a prevalent chemotherapeutic agent used in tumor therapy, yet DDP-induced acute kidney injury (AKI) severely limits its clinical application. Antioxidants as reactive oxygen species (ROS) scavengers can circumvent this adverse effect while leading to the decrease of efficacy to tumor. Herein, we report ultrasmall ruthenium nanoparticles (URNPs) as switchable ROS scavengers/generators to alleviate DDP-induced AKI and improve its therapeutic efficacy. In the physiological environment of the kidney, URNPs mimic multi-enzyme activities, such as superoxide dismutase and catalase, effectively protecting the renal cell and tissue by down-regulating the increased ROS level caused by DDP and alleviating AKI. Specifically, URNPs are oxidized by high levels of H2O2 in the tumor microenvironment (TME), resulting in the generation of oxygen vacancies and Ru3+/Ru4+ ions. This unique structure transformation endows URNPs to generate singlet oxygen (1O2) under laser irradiation and hydroxyl radicals (∙OH) through a Fenton-like reaction in tumor cell and tissue. The simultaneous generation of multifarious ROS effectively improves the efficacy of DDP in vitro and in vivo. This TME-responsive ROS scavenger/generator acts as an adjuvant therapeutic agent to minimize side effects and improve the efficacy of chemotherapy drugs, providing a new avenue to chemotherapy and facilitating clinical tumor therapy.

Ruthenium p-Cymene Complexes Incorporating Substituted Pyridine-Quinoline-Based Ligands: Synthesis, Characterization, and Cytotoxic Properties.

Organometallic complexes of the formula [Ru(N^N)(p-cymene)Cl][X] (N^N = bidentate polypyridyl ligands, p-cymene = 1-methyl-4-(1-methylethyl)-benzene, X = counter anion), are currently studied as possible candidates for the potential treatment of cancer. Searching for new organometallic compounds with good to moderate cytotoxic activities, a series of mononuclear water-soluble ruthenium(II)-arene complexes incorporating substituted pyridine-quinoline ligands, with pending -CH2OH, -CO2H and -CO2Me groups in the 4-position of quinoline ring, were synthesized, for the first time, to study their possible effect to modulate the activity of the ruthenium p-cymene complexes. These include the [Ru(η6-p-cymene)(pqhyme)Cl][X] (X = Cl- (1-Cl), PF6- (1-PF6), pqhyme = 4-hydroxymethyl-2-(pyridin-2-yl)quinoline), [Ru(η6-p-cymene)(pqca)Cl][Cl] ((2-Cl), pqca = 4-carboxy-2-(pyridin-2-yl)quinoline), and [Ru(η6-p-cymene)(pqcame)Cl][X] (X = Cl- (3-Cl), PF6- (3-PF6), pqcame = 4-carboxymethyl-2-(pyridin-2-yl)quinoline) complexes, respectively. Identification of the complexes was based on multinuclear NMR and ATR-IR spectroscopic methods, elemental analysis, conductivity measurements, UV-Vis spectroscopic, and ESI-HRMS techniques. The solid-state structures of 1-PF6 and 3-PF6 have been elucidated by single-crystal X-ray diffraction revealing a three-legged piano stool geometry. This is the first time that the in vitro cytotoxic activities of these complexes are studied. These were conducted in HEK293T (human embryonic kidney cells) and HeLa cells (cervical cancer cells) via the MTT assay. The results show poor in vitro anticancer activities for the HeLa cancer cell lines and 3-Cl proved to be the most potent (IC50 > 80 µΜ). In both cell lines, the cytotoxicity of the ligand precursor pqhyme is significantly higher than that of cisplatin.

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.