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.

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.

A unique and biocompatible corneal collagen crosslinking in vivo.

Corneal crosslinking (CXL) is a widely applied technique to halt the progression of ectatic diseases through increasing the thickness and mechanical stiffness of the cornea. This study investigated the biocompatibility and efficiency of a novel CXL procedure using ruthenium and blue light in rat corneas and evaluated parameters important for clinical application. To perform the CXL procedure, the corneal epithelium of rats was removed under anaesthesia, followed by the application of a solution containing ruthenium and sodium persulfate (SPS). The corneas were then exposed to blue light at 430 nm at 3 mW/cm2 for 5 min. Rat corneas were examined and evaluated for corneal opacity, corneal and limbal neovascularization, and corneal epithelial regeneration on days 0, 1, 3, 6, 8, and 14. On day 28, the corneas were isolated for subsequent tissue follow-up and analysis. CXL with ruthenium and blue light showed rapid epithelial healing, with 100% regeneration of the corneal epithelium and no corneal opacity on day 6. The ruthenium group also exhibited significantly reduced corneal (p < 0.01) and limbal neovascularization (p < 0.001). Histological analysis revealed no signs of cellular damage or apoptosis, which further confirms the biocompatibility and nontoxicity of our method. Confocal and scanning electron microscopy (SEM) images confirmed high density of collagen fibrils, indicating efficient crosslinking and enhanced structural integrity. This study is unique that demonstrates in vivo safety, biocompatibility, and functionality of ruthenium and blue light CXL. This approach can prevent toxicity caused by UV-A light and can be an immediate alternative compared to the existing crosslinking procedures that have side effects and clinical risks for the patients.

Ru@UiO-66-NH2 MOFs-Based Dual Emission Ratiometric Fluorescence for Sensitive Sensing of Arginine.

Arginine has been widely applied in the food industry as coloring agents, flavoring agents, and nutritional fortifiers. It is also one of the major components of feed additives. Currently, methods for the highly selective detection of arginine remain absent. For accurate and sensitive detection of L-arginine, a novel ratiometric fluorescence assay based on Ru@UiO-66-NH2 was developed and demonstrated in this study. Under optimized detection conditions, the limit of detection (LOD) of this assay for L-arginine was 2.32 µM, which is superior to most assays reported to date. Meanwhile, Ru@UiO-66-NH2 showed good stability within 30 days, demonstrating the wide applicability of the proposed assay. The spike-and-recovery rates of the proposed assay for L-arginine in real samples (e.g., tea, grape juice, and serum) were 84.27-113.09%. Overall, the proposed assay showed high sensitivity, good reproducibility, and excellent stability in the detection of L-arginine in both buffer and real samples.

The Thermodynamic and Kinetic Properties of the dA-rU DNA-RNA Hybrid Base Pair Investigated via Molecular Dynamics Simulations.

DNA-RNA hybrid duplexes play essential roles during the reverse transcription of RNA viruses and DNA replication. The opening and conformation changes of individual base pairs are critical to their biological functions. However, the microscopic mechanisms governing base pair closing and opening at the atomic level remain poorly understood. In this study, we investigated the thermodynamic and kinetic parameters of the dA-rU base pair in a DNA-RNA hybrid duplex using 4 µs all-atom molecular dynamics (MD) simulations at different temperatures. Our results showed that the thermodynamic parameters of the dA-rU base pair aligned with the predictions of the nearest-neighbor model and were close to those of the AU base pair in RNA. The temperature dependence of the average lifetimes of both the open and the closed states, as well as the transition path times, were obtained. The free-energy barrier for a single base pair opening and closing arises from an increase in enthalpy due to the disruption of the base-stacking interactions and hydrogen bonding, along with an entropy loss attributed to the accompanying restrictions, such as torsional angle constraints and solvent viscosity.

Novel tris-bipyridine based Ru(II) complexes as type-I/-II photosensitizers for antitumor photodynamic therapy through ferroptosis and immunogenic cell death.

Ru(II) complexes have attracted attention as photosensitizers for their promising photodynamic properties. Herein, novel tris-bipyridine based Ru(II) complexes (6a-e) were synthesized by introducing saturated heterocycles to improve photodynamic properties and lipid-water partition coefficients. Among them, 6d demonstrated significant phototoxicity towards three cancer cells, with IC50 values of 5.66-7.17 µM, exceeding values in dark (IC50s > 100 µM). Under hypoxic conditions, 6d maintained excellent photodynamic activity in A549 cells, with PI values exceeding 24, highlighting its potential for highly effective type-I/-II photodynamic therapy by inducing ROS generation, oxidative stress, and mitochondrial damage. Additionally, it induced ferroptosis and immunogenic cell death of A549 cells by regulating the expression of relevant markers. Finally, 6d remarkably inhibited the growth of A549 transplanted tumor growth by 95.4 %. This Ru(II) complex shows great potential for cancer treatment with its potent photodynamic activity and diverse mechanisms of tumor cell death.

DFT Computational Analysis of the Mechanism of Action of Ru(II) Polypyridyl Complexes as Photoactivated Chemotherapy Agents: From Photoinduced Ligand Solvolysis to DNA Binding.

Photoactivated chemotherapy (PACT) is a form of target-oriented cancer therapy that exploits light of the proper wavelength to selectively activate the drug. Among the prodrugs used for this purpose, ruthenium-based complexes are particularly interesting, as when irradiated by light, they can release ligands by forming aquo-complexes able to bind DNA in both single and double strand fashions, causing its distortion. Using as model system a Ru(II) polypyridyl complex that has been demonstrated to be a promising photochemotherapeutic agent, all of the key aspects of the photoinduced solvolysis process and subsequent DNA interaction have been scrutinized using density functional theory (DFT) and time-dependent-DFT (TDDFT). Photoexcitation, intersystem crossing, internal conversion, mechanism by which photoinduced ligand release, and subsequent aquation steps occur have been examined. Pathways leading to the formation of both cis and trans biaquated photoproducts have been described, and the formation of the cis form of the biaquated photoproduct being the most favorable one, its reaction with a guanine base has also been reported in order to account for DNA binding.

On-Site Visualization Assay for Tumor-Associated miRNAs: Using Ru@TiO2 as a Peroxidase-like Nanozyme.

Accurate diagnosis of highly aggressive and deadly tumors is essential for effective treatment and improved patient outcomes, and microRNAs (miRNAs) have emerged as crucial biomarkers for their roles in tumor initiation, progression, and metastasis. Herein, we present an on-site visualization colorimetric assay for tumor-associated miRNAs using ruthenium nanoparticle decorated titanium dioxide nanoribbon (Ru@TiO2) as a peroxidase-like (POD) nanozyme. Remarkably, the Ru@TiO2 nanozyme can catalyze the oxidation of chromogenic substrates through its POD-like activity, which is effectively inhibited by pyrophosphate generated during the rolling circle amplification process, thereby enabling miRNA detection through a visible colorimetric readout. This approach provides a highly sensitive and specificity assay for miRNAs in diluted human serum with a detection limit of 100 pM. It shows great potential for clinical diagnostics and biological research, offering a promising tool for early cancer diagnosis and molecular diagnostics.

Photodynamic Therapy against Colorectal Cancer Using Porphin-Loaded Arene Ruthenium Cages.

Colorectal cancer (CRC) is the third most common cancer in the world, with an ongoing rising incidence. Despite secure advancements in CRC treatments, challenges such as side effects and therapy resistance remain to be addressed. Photodynamic therapy (PDT) emerges as a promising modality, clinically used in treating different diseases, including cancer. Among the main challenges with current photosensitizers (PS), hydrophobicity and low selective uptake by the tumor remain prominent. Thus, developing an optimal design for PS to improve their solubility and enhance their selective accumulation in cancer cells is crucial for enhancing the efficacy of PDT. Targeted photoactivation triggers the production of reactive oxygen species (ROS), which promote oxidative stress within cancer cells and ultimately lead to their death. Ruthenium (Ru)-based compounds, known for their selective toxicity towards cancer cells, hold potential as anticancer agents. In this study, we investigated the effect of two distinct arene-Ru assemblies, which lodge porphin PS in their inner cavity, and tested them as PDT agents on the HCT116 and HT-29 human CRC cell lines. The cellular internalization of the porphin-loaded assemblies was confirmed by fluorescence microscopy. Additionally, significant photocytotoxicity was observed in both cell lines after photoactivation of the porphin in the cage systems, inducing apoptosis through caspase activation and cell cycle progression disruptions. These findings suggest that arene-Ru assemblies lodging porphin PS are potent candidates for PDT of CRC.

Bombesin-Targeted Delivery of ß-Carboline-Based Ir(III) and Ru(II) Photosensitizers for a Selective Photodynamic Therapy of Prostate Cancer.

Despite advances in Ir(III) and Ru(II) photosensitizers (PSs), their lack of selectivity for cancer cells has hindered their use in photodynamic therapy (PDT). We disclose the synthesis and characterization of two pairs of Ir(III) and Ru(II) polypyridyl complexes bearing two ß-carboline ligands (N^N') functionalized with -COOMe (L1) or -COOH (L2), resulting in PSs of formulas [Ir(C^N)2(N^N')]Cl (Ir-Me: C^N = ppy, N^N' = L1; Ir-H: C^N = ppy, N^N' = L2) and [Ru(N^N)2(N^N')](Cl)2 (Ru-Me: N^N = bpy, N^N' = L1; Ru-H: N^N = bpy, N^N' = L2). To enhance their selectivity toward cancer cells, Ir-H and Ru-H were coupled to a bombesin derivative (BN3), resulting in the metallopeptides Ir-BN and Ru-BN. Ir(III) complexes showed higher anticancer activity than their Ru(II) counterparts, particularly upon blue light irradiation, but lacked cancer cell selectivity. In contrast, Ir-BN and Ru-BN exhibited selective photocytoxicity against prostate cancer cells, with a lower effect against nonmalignant fibroblasts. All compounds generated ROS and induced severe mitochondrial toxicity upon photoactivation, leading to apoptosis. Additionally, the ability of Ir-Me to oxidize NADH was demonstrated, suggesting a mechanism for mitochondrial damage. Our findings indicated that the conjugation of metal PSs with BN3 creates efficient PDT agents, achieving selectivity through targeting bombesin receptors and local photoactivation.

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.

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.

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.

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.

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.

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.

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.

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.

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.