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.

Efficient chlorination reaction of Pt/RuO2/g-C3N4 under visible light irradiation for simultaneous removal of ammonia and bacteria from mariculture wastewater.

The removal of ammonia nitrogen (NH4+-N) and bacteria from aquaculture wastewater holds paramount ecological and production significance. In this study, Pt/RuO2/g-C3N4 photocatalysts were prepared by depositing Pt and RuO2 particles onto g-C3N4. The physicochemical properties of photocatalysts were explored by X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), X-ray diffraction (XRD), and UV-vis diffuse reflectance spectrometer (UV-vis DRS). The photocatalysts were then applied to the removal of both NH4+-N and bacteria from simulated mariculture wastewater. The results clarified that the removals of both NH4+-N and bacteria were in the sequence of g-C3N4 < RuO2/g-C3N4 < Pt/g-C3N4 < Pt/RuO2/g-C3N4. This magnificent photocatalytic ability of Pt/RuO2/g-C3N4 can be interpreted by the transfer of holes from g-C3N4 to RuO2 to facilitate the in situ generation of HClO from Cl- in wastewater, while Pt extracts photogenerated electrons for H2 formation to enhance the reaction. The removal of NH4+-N and disinfection effect were more pronounced in simulated seawater than in pure water. The removal efficiency of NH4+-N increases with an increase in pH of wastewater, while the bactericidal effect was more significant under a lower pH in a pH range of 6-9. In actual seawater aquaculture wastewater, Pt/RuO2/g-C3N4 still exhibits effective removal efficiency of NH4+-N and bactericidal performance under sunlight. This study provides an alternative avenue for removement of NH4+-N and bacteria from saline waters under sunlight.

Recent trends in the design and delivery strategies of ruthenium complexes for breast cancer therapy.

As the most frequent and deadly type of cancer in women, breast cancer has a high propensity to spread to the brain, bones, lymph nodes, and lungs. The discovery of cisplatin marked the beginning of the development of anticancer metal-based medications, although the drug's severe side effects have limited its usage in clinical settings. The remarkable antimetastatic and anticancer activity of different ruthenium complexes such as NAMI-A, KP1019, KP1339, etc. reported in the 1980s has bolstered the discovery of ruthenium complexes with various types of ligands for anticancer applications. The review meticulously elucidates the cytotoxic and antimetastatic potential of reported ruthenium complexes against breast cancer cells. Notably, arene-based and cyclometalated ruthenium complexes emerge as standout candidates, showcasing remarkable potency with notably low IC50 values. These findings underscore the promising therapeutic avenues offered by ruthenium-based compounds, particularly in addressing the challenges posed by conventional treatments in refractory or aggressive breast cancer subtypes. Moreover, the review comprehensively integrates a spectrum of ruthenium complexes, spanning traditional metal complexes to nano-based formulations and light-activated variants, underscoring the versatility and adaptability of ruthenium chemistry in breast cancer therapy.

Bioluminescence Resonance Energy Transfer (BRET)-Mediated Protein Release from Self-Illuminating Photoresponsive Biomaterials.

Phototriggered release of various cargos, including soluble protein factors and small molecules, has the potential to correct aberrant biological events by offering spatiotemporal control over local therapeutic levels. However, the poor penetration depth of light historically limits implementation to subdermal regions, necessitating alternative methods of light delivery to achieve the full potential of photodynamic therapeutic release. Here, we introduce a strategy exploiting bioluminescence resonance energy transfer (BRET)-an energy transfer process between light-emitting Nanoluciferase (NLuc) and a photosensitive acceptor molecule-to drive biomolecule release from hydrogel biomaterials. Through a facile, one-pot, and high-yielding synthesis (60-70%), we synthesized a heterobifunctional ruthenium cross-linker bearing an aldehyde and an azide (CHO-Ru-N3), a compound that we demonstrate undergoes predictable exchange of the azide-bearing ligand under blue-green light irradiation (>550 nm). Following site-specific conjugation to NLuc via sortase-tag enhanced protein ligation (STEPL), the modified protein was covalently attached to a poly(ethylene glycol) (PEG)-based hydrogel via strain-promoted azide-alkyne cycloaddition (SPAAC). Leveraging the high photosensitivity of Ru compounds, we demonstrate rapid and equivalent release of epidermal growth factor (EGF) via either direct illumination or via BRET-based bioluminolysis. As NLuc-originated luminescence can be controlled equivalently throughout the body, we anticipate that this unique protein release strategy will find use for locally triggered drug delivery following systemic administration of a small molecule.

Lattice expansion in ruthenium nanozymes improves catalytic activity and electro-responsiveness for boosting cancer therapy.

Nanozymes have been attracting widespread interest for the past decade, especially in the field of cancer therapy, due to their intrinsic catalytic activities, strong stability, and ease of synthesis. However, enhancing their catalytic activity in the tumor microenvironment (TME) remains a major challenge. Herein, we manipulate catalytic activities of Ru nanozymes via modulating lattice spacing in Ru nanocrystals supported on nitrogen-doped carbon support, to achieve improvement in multiple enzyme-like activities that can form cascade catalytic reactions to boost cancer cell killing. In addition, the lattice expansion in Ru nanocrystals improve the responsiveness of the nanozymes to self-powered electric field, achieving maximized cancer therapeutic outcome. Under the electrical stimulation provided by a human self-propelled triboelectric device, the Ru-based nanozyme (Ru1000) with a lattice expansion of 5.99% realizes optimal catalytic performance and cancer therapeutic outcome of breast cancer in female tumor-bearing mice. Through theoretical calculations, we uncover that the lattice expansion and electrical stimulation promote the catalytic reaction, simultaneously, by reducing the electron density and shifting the d-band center of Ru active sites. This work provides opportunities for improving the development of nanozymes.

Biotin-Pt(IV)-Ru(II)-Boron-Dipyrromethene Prodrug as "Platin Bullet" for Targeted Chemo- and Photodynamic Therapy.

Using the principle of "Magic Bullet", a cisplatin-derived platinum(IV) prodrug heterobimetallic Pt(IV)-Ru(II) complex, cis,cis,trans-[Pt(NH3)2Cl2{Ru(tpy-BODIPY)(tpy-COO)}(biotin)]Cl2 (Pt-Ru-B, 2), having two axial ligands, namely, biotin as water-soluble B-vitamin for enhanced cellular uptake and a BODIPY-ruthenium(II) (Ru-B, 1) photosensitizer having N,N,N-donor tpy (4'-phenyl-2,2':6',2″-terpyridine) bonded to boron-dipyrromethene (BODIPY), is developed as a "Platin Bullet" for targeted photodynamic therapy (PDT). Pt-Ru-B exhibited intense absorption near 500 nm and emission near 513 nm (λex = 488 nm) in a 10% dimethyl sulfoxide-Dulbecco's phosphate-buffered saline medium (pH 7.2). The BODIPY complex on light activation generates singlet oxygen as the reactive oxygen species (ROS) giving a quantum yield (ΦΔ) of ∼0.64 from 1,3-diphenylisobenzofuran experiments. Pt-Ru-B exhibited preferential cellular uptake in cancer cells over noncancerous cells. The dichlorodihydrofluorescein diacetate assay confirmed the generation of cellular ROS. Confocal images revealed its mitochondrial internalization. Pt-Ru-B showed submicromolar photocytotoxicity in visible light (400-700 nm) in A549 and multidrug-resistant MDA-MB-231 cancer cells. It remained nontoxic in the dark and less toxic in nontumorigenic cells. Cellular apoptosis and alteration of the mitochondrial membrane potential were evidenced from the respective Annexin V-FITC/propidium iodide assay and JC-1 dye assay. A wound healing assay using A549 cells and Pt-Ru-B revealed inhibition of cancer cell migration, highlighting its potential as an antimetastatic agent.

Rational design of a red-light absorbing ruthenium polypyridine complex as a photosensitizer for photodynamic therapy.

Herein, the computer-guided design, chemical synthesis, and biological evaluation of a RuC polypyridine complex, that could eradicate cancerous cells upon excitation with red light at 630 nm, is reported.

Total Synthesis of the Phenylnaphthacenoid Type II Polyketide Antibiotic Formicamycin H via Regioselective Ruthenium-Catalyzed Hydrogen Auto-Transfer [4 + 2] Cycloaddition.

The first total synthesis of the pentacyclic phenylnaphthacenoid type II polyketide antibiotic formicamycin H is described. A key feature of the synthesis involves the convergent, regioselective assembly of the tetracyclic core via ruthenium-catalyzed α-ketol-benzocyclobutenone [4 + 2] cycloaddition. Double dehydration of the diol-containing cycloadduct provides an achiral enone, which upon asymmetric nucleophilic epoxidation and further manipulations delivers the penultimate tetracyclic trichloride in enantiomerically enriched form. Subsequent chemo- and atroposelective Suzuki cross-coupling of the tetracyclic trichloride introduces the E-ring to complete the total synthesis. Single-crystal X-ray diffraction analyses of two model compounds suggest that the initially assigned stereochemistry of the axially chiral C6-C7 linkage may require revision.

Mixed Ru(II)-Ir(III) Complexes as Photoactive Inhibitors of the Major Human Drug Metabolizing Enzyme CYP3A4.

Cytochrome P450 3A4 (CYP3A4) is a crucial enzyme in human drug metabolism. To garner photochemical control over the inhibition of CYP3A4, a potent Ir(III)-based inhibitor of CYP3A4 was complexed with two Ru(II)-based photocaging groups. Chemical, photochemical, and biological properties of the photocaged inhibitors were characterized. Importantly, mixed Ru(II)-Ir(III) complexes strongly absorb green light, which facilitates the photochemical release of the Ir(III) inhibitor from the Ru(II) caging fragment [Ru(tpy)(Me2bpy)]2+, where tpy = 2,2':6',2″-terpyridine and Me2bpy = 6,6'-dimethyl-2,2'-bipyridine. Emission turn on, type II heme binding, and more potent inhibition under light vs dark conditions were observed. The study also demonstrated that a Ru(II)-Ir(III) conjugate can be photoactivated to exert cytotoxic effects on MCF-7 breast cancer cells upon green light exposure. Additionally, a synthesized analogue with one [Ru(TPA)]2+ fragment (TPA = tris(pyridin-2-ylmethyl)amine) and two Ir(III) centers, although resistant to photochemical release, showed strong inhibition of CYP3A4 both in purified form and in CYP3A4-overexpressing HepG2 cells, with nanomolar potency. These mixed Ru(II)-Ir(III) compounds can permeate cell membranes and inhibit CYP3A4, presenting a new class of bioactive compounds.

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.

Ratiometric Imaging Detection of Amyloid-ß Fibrils by a Dual-Emissive Tris-Heteroleptic Ruthenium Complex.

Two dual fluorescent/phosphorescent tris-heteroleptic mononuclear Ru(ΙΙ) complexes (2 and 3) were designed and applied in amyloid-ß (Aß) sensing. These complexes have a general formula of [Ru(phen)(dppz)(L)](PF6)2, where L is (2-pyrazinyl)(2-pyridyl)(methyl)amine (H-L) with different substituents (-OMe for 2, -H for 3), phen is 1,10-phenanthroline, and dppz is dipyridophenazine, respectively. Compared with the previously reported ratiometric probe 1 with a di(pyrid-2-yl)(methyl)amine ligand, complex 2 can be employed for not only ratiometric emissive detection of Aß aggregation but also ratiometric imaging detection of Aß fibrils. In ratiometric emissive detection, as the incubation time of the Aß sample (Aß40 and Aß42) was prolonged, a new phosphorescence emission band appeared with gradual enhancement of the emission intensity, while the fluorescence emission was basically unchanged, which could be treated as an intrinsic internal reference signal. In comparison, a larger ratiometric photoluminescence enhancement (I640/I440) was observed for Aß40 aggregation with respect to Aß42. In ratiometric imaging detection, the imaging signals obtained from the phosphorescence emission are much brighter than the fluorescence emission in both Aß40 and Aß42 fibrils. As indicated by molecular docking results, stronger interactions were found between complex 2 with Aß40 fibrils, which included π/π, π/C-H, and π/H interactions between bidentate ligands dppz and phen with amino acid residues. Moreover, computational calculations were carried out to assist the interpretation of these experimental findings.

Strategically Engineered Ru(II) Complexes with Enhanced ROS Activity Enabling Potent Sonodynamic Effect against Multidrug-Resistant Biofilms.

Sonodynamic therapy (SDT) can generate reactive oxygen species (ROS) to combat multidrug-resistant biofilms, which pose significant challenges to human health. As the key to producing ROS in SDT, the design of sonosensitizers with optimal molecular structures for sufficient ROS generation and activity in complex biofilm matrix is essential. In this study, we propose a π-expansion strategy and synthesize a series of small-molecule metal Ru(II) complexes (Ru1-Ru4) as sonosensitizers (Ru1-Ru4) to enhance the efficacy of SDT. Among these complexes, Ru4 demonstrates remarkable ROS generation capability (∼65.5-fold) that surpasses most commercial sonosensitizers (1.3- to 6.7-fold). Through catalyzing endogenous H2O2 decomposition, Ru4 facilitates the production of abundant O2 as a resource for 1O2 and the generation of new ROS (i.e., •OH) for improving SDT. Furthermore, Ru4 maintains the sustained ROS activity via consuming the interferences (e.g., glutathione) that react with ROS. Due to these unique advantages, Ru4 exhibits potent biofilm eradication ability against methicillin-resistant Staphylococcus aureus (MRSA) both in vitro and in vivo, underscoring its potential use in clinical settings. This work introduces a new approach for designing effective sonosensitizers to eliminate biofilm infections, addressing a critical need in healthcare management.

DNA-Directed Activation of Photocatalytic Labeling at Cell-Cell Contact Sites.

Cell-cell interactions govern diverse biological activities, necessitating molecular tools for understanding and regulating these interactions. Photoredox chemistry can detect cell-cell interactions by anchoring photocatalysts on cellular membranes to generate reactive species that tag closely contacting cells. However, the activation of photocatalysts lacks precise spatial resolution for selectively labeling intercellular interfaces. Herein, we report a DNA-based approach to selectively activate photocatalytic reactions at cell-cell contacts. Two cell populations are coated with distinct DNA strands, which interact at intercellular contacts, mediating the site-specific turn-on of a Ru(bpy)3-type photocatalyst. We demonstrate high spatial specificity for intercellular chemical labeling in cultured mammalian cells. Furthermore, as a proof of concept, we activate the dynamic DNA catalyst at cell-cell contacts in response to customized DNA triggers. This study lays the foundation for designing versatile chemical tools with high spatial precision and programmable responsiveness, along with the temporal resolution afforded by photoirradiation, to investigate and manipulate cell-cell interactions.

Toxicological Implications of Platinum Group Elements (PGEs): A Systematic Review of In Vivo and In Vitro Studies Using Mammalian Models.

BACKGROUND: The six Platinum group metal elements (PGEs) comprising Ruthenium, Rhodium, Palladium, Platinum, Iridium and Osmium are grouped together in the periodic table. Human activities are mostly responsible for releasing PGEs into the environment. This systematic review focused on three PGEs with the greatest anthropogenic use, including in vehicle catalytic converters: Platinum (Pt), Palladium (Pd), and Rhodium (Rh). Consequently, these represent the greatest contributors to environmental pollution. The current review of in vivo toxicological studies (mammalian models) and in vitro cell exposure studies examined the potential harmful effects of these metalloids to mammalians, and their possible toxicity to human health. METHODS: We applied Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology to conduct a comprehensive search and evaluation of records in the available literature published between 01/01/2009 and 01/15/2024 in four databases. PROSPERO code ID: CRD42024471558. Results concerning the health effects of PGEs were extracted from articles according to the inclusion and exclusion criteria. After screening the records for eligibility, 22 studies were included in the final analysis. RESULTS: This systematic review revealed that airborne PGEs significantly increased the activation of pathologic pathways in several human organs and/or perturbed various metabolic pathways. In view of the known pro-inflammatory and organ-degenerative effects of PGEs, the paucity of studies on the effect of PGEs on the central nervous system and on possible correlations with neurodegenerative diseases were particularly evident. CONCLUSIONS: The clinical complexity and chronic nature of PGE-related pathologies indicate that targeted research is essential. In light of the increasing incidence of non-communicable diseases, particular attention should be paid to the design of epidemiological studies and to environmental monitoring services.

Ru-terpyridine complexes containing clotrimazole as potent photoactivatable selective antifungal agents.

The overuse of antimicrobial agents in medical and veterinary applications has led to the development of antimicrobial resistance in some microorganisms and this is now one of the major concerns in modern society. In this context, the use of transition metal complexes with photoactivatable properties, which can act as drug delivery systems triggered by light, could become a potent strategy to overcome the problem of resistance. In this work several Ru complexes with terpyridine ligands and the clotrimazole fragment, which is a potent antimycotic drug, were synthesized. The main goal was to explore the potential photoactivated activity of the complexes as antifungal agents and evaluate the effect of introducing different substituents on the terpyridine ligand. The complexes were capable of delivering the clotrimazole unit upon irradiation with visible light in a short period of time. The influence of the substituents on the photodissociation rate was explained by means of TD-DFT calculations. The complexes were tested against three different yeasts, which were selected based on their prevalence in fungal infections. The complex in which a carboxybenzene unit was attached to the terpyridine ligand showed the best activity against the three species under light, with minimal inhibitory concentration values of 0.88 µM and a phototoxicity index of 50 achieved. The activity of this complex was markedly higher than that of free clotrimazole, especially upon irradiation with visible light (141 times higher). The complexes were more active on yeast species than on cancer cell lines.

Enhanced DNA damage and anti-proliferative activity of a novel ruthenium complex with a chlorambucil-decorated ligand.

Triphenylphosphine substitution reactions of [RuCl(PPh3)2(tpm)]Cl, 1, featuring tris(pyrazolyl)methane (tpm) as ligand, with the chlorambucil-decorated pyridine ligand PyCA, 3-aminopyridine (PyNH2) and 4-pyridinemethanol (PyOH) afforded the corresponding pyridine complexes 2-4 in high yields. PyCA was preliminarily obtained via esterification of 4-pyridinemethanol with chlorambucil. The new compounds PyCA and 2-3 were characterized by IR and multinuclear NMR spectroscopy. Additionally, the structure of 3 was ascertained by single crystal X-ray diffraction. The in vitro anti-proliferative activity of 2-4 and PyCA was determined against a panel of cancer cell lines, outlining 2 as the most performing compound. Targeted studies were subsequently undertaken using 2 to elucidate mechanistic aspects, including the assessment of ruthenium cellular uptake, cell cycle arrest, production of reactive oxygen species (ROS), western blotting and DNA damage (comet test). Overall, data highlight that the anticancer activity provided by 2 primarily affects the mitochondria pathway with a potential additional contribution from DNA damage.

RAPTA-coordinated polydiacetylene self-assembly: A chameleon-like prodrug with a dual-lock strategy for real-time release monitoring of metallodrug.

Herein, we report the first-ever design strategy of modifying RAPTA-C into a self-reporting prodrug candidate based on Ru-coordinated polydiacetylene self-assembly. This nanosystem exhibits a dual lock strategy that responds to visible light and pH-stimuli sequentially one by one with a concomitant color change for controlled RAPTA-C release and real-time release monitoring in human gastric cancer cells.

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.

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.