Ru Polypyridine Complexes Research Articles

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.

Two-photon phototriggering of ROS storm in ruthenium(II) coordinated carbon nitride for robust cancer immunotherapy

The use of Ru(II) polypyridine complexes for photodynamic therapy is receiving much attention. Despite their promising properties, these compounds are associated with a poor excitation in the biological spectral window, a highly reduced or complete loss of the therapeutic effect under hypoxic conditions, and no immune response, limiting their application. To overcome all these limitations, herein, the coordination of Ru(II) polypyridine complexes to graphitic carbon nitride nanosheets for oxygen-self-sufficient two-photon photodynamic immunotherapy is presented. The conjugates were found with an exceptionally strong two-photon absorption and could self-sufficiently produce an ROS storm consisting of •O2-, •OH, and 1O2. Upon two-photon irradiation, the nanomaterial induced cell death in hypoxic monolayer cancer cells and multicellular tumor spheroids by a combination of apoptosis, paraptosis, ferroptosis, and immunogenic cell death. The nanomaterial was found with a strong tumor growth inhibition against the primary and secondary distant tumor in a melanoma-bearing mouse model through activation of the immune system.

Polycationic Ru(II) Luminophores: Syntheses, Photophysics, and Application in Electrostatically Driven Sensitization of Lanthanide Luminescence.

A series of photoluminescent Ru(II) polypyridine complexes have been synthesized in a manner that varies the extent of the cationic charge. Two ligand systems (L1 and L2), based upon 2,2'-bipyridine (bipy) mono- or difunctionalized at the 5- or 5,5'-positions using N-methylimidazolium groups, were utilized. The resulting Ru(II) species therefore carried +3, +4, +6, and +8 complex moieties based on a [Ru(bipy)3]2+ core. Tetra-cationic [Ru(bipy)2(L2)][PF6]4 was characterized using XRD, revealing H-bonding interactions between two of the counteranions and the cationic unit. The ground-state features of the complexes were found to closely resemble those of the parent unfunctionalized [Ru(bipy)3]2+ complex. In contrast, the excited state properties produce a variation in emission maxima, including a bathochromic 44 nm shift of the 3MLCT band for the tetra-cationic complex; interestingly, further increases in overall charge to +6 and +8 produced a hypsochromic shift in the 3MLCT band. Supporting DFT calculations suggest that the trend in emission behavior may, in part, be due to the precise nature of the LUMO and its localization. The utility of a photoactive polycationic Ru(II) complex was then demonstrated through the sensitization of a polyanionic Yb(III) complex in free solution. The study shows that electrostatically driven ion pairing is sufficient to facilitate energy transfer between the 3MLCT donor state of the Ru(II) complex and the accepting 2F5/2 excited state of Yb(III).

Binding and stabilizating effect of RNA triplex poly(U)⋅poly(A)*poly(U) by enantiomers of ruthenium(II) polypyridyl complex [Ru(bpy)2(dppx)]2.

Two chiral ruthenium(II) polypyridyl complexes, Λ-[Ru(bpy)2(dppx)]2+ (bpy = 2,2'-bipyridine, dppx = 7,8-dimethyldipyridophenazine; Λ-1) and Δ-[Ru(bpy)2(dppx)]2+ (Δ-1) have been synthesized and characterized in this work. Interactions of Λ-1 and Δ-1 with the RNA triplex poly(U)⋅poly(A)*poly(U) have been investigated by various biophysical techniques. Spectrophotometric titrations and viscosity measurements suggested that enantiomers Λ-1 and Δ-1 bind with the triplex through intercalation, while the binding strengths of the two enantiomers toward the triplex differed only slightly from each other. Fluorescence titrations showed that although enantiomers Λ-1 and Δ-1 exhibited molecular "light switch" effects toward the triplex, the effect of Δ-1 was more marked. Furthermore, Furthermore, thermal denaturation showed that the two enantiomers have significantly different stabilizing effects on the triplex. The obtained results indicate that the racemic complex [Ru(bpy)2(dppx)]2+ is similar to a non-specific metallointercalator for the triplex investigated in this study, and chiralities of Ru(II) polypyridine complexes have an important influence on the binding and stabilizing effects of enantiomers toward the triplex. Two chiral ruthenium(II) polypyridyl complexes, Λ-[Ru(bpy)2(dppx)]2+ (bpy = 2,2'-bipyridine, dppx = 7,8-dimethyldipyridophenazine; Λ-1) and Δ-[Ru(bpy)2(dppx)]2+ (Δ-1) have been synthesized and characterized in this work. Interactions of Λ-1 and Δ-1 with the RNA triplex poly(U)⋅poly(A)*poly(U) have been investigated by various biophysical techniques. The obtained results indicate that the racemic complex [Ru(bpy)2(dppx)]2+ is similar as a non-specific metallointercalator for the triplex investigated in this study, and chiralities of Ru(II) polypyridine complexes have an important influence on the binding and stabilizing effects of enantiomers toward the triplex.

Insight into the intercalating ligands affecting the interactions of ruthenium(II) polypyridyl complexes with RNA poly(A)*poly(U)

A series of ruthenium(II) complexes [Ru(phen)2dppp3]2+ (Ru1, phen = 1,10-phenanthrolline; dppp3 = pyrido[3′,4′:5,6]pyrazino[2,3-f][1,10]phenanthroline), [Ru(phen)2dppp2]2+ (Ru2, dppp2 = pyrido[2′,3′:5,6]pyrazino[2,3-f][1,10]phenanthroline) and [Ru(phen)2bppp]2+ (Ru3, bppp = 10-bromopyrido[2′,3′:5,6]pyrazino-[2,3-f][1,10]phenanthroline) have been synthesized and characterized that helps to further investigate RNA-complex interactions. The viscosity measurement, UV–vis absorption spectrum study as well as EB (ethidium bromide) fluorescence competition have been explored to prove that the binding modes of Ru1, Ru2 and Ru3 with double-stranded RNA were intercalation, and these binding affinities of Ru1, Ru2 and Ru3 toward poly(A)*poly(U) (where “*” denotes the Watson-Crick base) have followed the order of Ru1 > Ru2 > Ru3. The analysis of thermal denaturation results obtained the identical conclusion and revealed that three complexes have positive roles in the stabilization of RNA base pairs. To my knowledge, this study presents the first Ru(Ⅱ) polypyridine complexes with the most effective thermal stabilization of RNA poly(A)*poly(U). All results showed the structural effects of complex main ligands in RNA study, in which the RNA-affinities were impacted greatly by the positions of substituents, and the sizes of functional groups were also key factors controlling the interaction between the complexes and double-stranded RNA.

A Photoactivated Ru (II) Polypyridine Complex Induced Oncotic Necrosis of A549 Cells by Activating Oxidative Phosphorylation and Inhibiting DNA Synthesis as Revealed by Quantitative Proteomics.

The ruthenium polypyridine complex [Ru(dppa)2(pytp)] (PF6)2 (termed as ZQX-1), where dppa = 4,7-diphenyl-1,10-phenanthroline and pytp = 4'-pyrene-2,2':6',2''-terpyridine, has been shown a high and selective cytotoxicity to hypoxic and cisplatin-resistant cancer cells either under irradiation with blue light or upon two-photon excitation. The IC50 values of ZQX-1 towards A549 cancer cells and HEK293 health cells are 0.16 ± 0.09 µM and >100 µM under irradiation at 420 nm, respectively. However, the mechanism of action of ZQX-1 remains unclear. In this work, using the quantitative proteomics method we identified 84 differentially expressed proteins (DEPs) with |fold-change| ≥ 1.2 in A549 cancer cells exposed to ZQX-1 under irradiation at 420 nm. Bioinformatics analysis of the DEPs revealed that photoactivated ZQX-1 generated reactive oxygen species (ROS) to activate oxidative phosphorylation signaling to overproduce ATP; it also released ROS and pyrene derivative to damage DNA and arrest A549 cells at S-phase, which synergistically led to oncotic necrosis and apoptosis of A549 cells to deplete excess ATP, evidenced by the elevated level of PRAP1 and cleaved capase-3. Moreover, the DNA damage inhibited the expression of DNA repair-related proteins, such as RBX1 and GPS1, enhancing photocytotoxicity of ZQX-1, which was reflected in the inhibition of integrin signaling and disruption of ribosome assembly. Importantly, the photoactivated ZQX-1 was shown to activate hypoxia-inducible factor 1A (HIF1A) survival signaling, implying that combining use of ZQX-1 with HIF1A signaling inhibitors may further promote the photocytotoxicity of the prodrug.

Interaction of ruthenium(Ⅱ) polypyridyl complexes [Ru(phen)2(L)]2+ (L = PIP, p-HPIP and m-HPIP) with RNA poly(A)•poly(U): Each complex unexpectedly exhibiting a destabilizing effect on RNA

To further explore the binding properties of Ru(Ⅱ) polypyridine complexes with RNA, three Ru(Ⅱ) complexes [Ru(phen)2(PIP)]2+ (Ru1), [Ru(phen)2(p-HPIP)]2+ (Ru2), and [Ru(phen)2(m- HPIP)]2+ (Ru3) have been synthesized and characterized in this work. The binding properties of three Ru(Ⅱ) complexes with RNA duplex poly(A)•poly(U) have been investigated by spectral and viscosity experiments. These studies all support that these three Ru(Ⅱ) complexes bind to poly RNA duplex poly(A)•poly(U) by intercalation, and Ru1 without substituents has a stronger binding affinity for poly(A)•poly(U). Interestingly, the thermal melting experiments show that these three Ru(Ⅱ) complexes all destabilize RNA duplex poly(A)•poly(U), and the destabilizing effect can be explained by the conformational changes of duplex structure induced by intercalating agents. To the best of our knowledge, this work report for the first time a small molecule capable of destabilizing an RNA duplex, which reflects that the substitution effect of intercalated ligands has an important influence on the affinity of Ru(Ⅱ) complexes to RNA duplex, and that not all Ru(Ⅱ) complexes show thermal stability effects on an RNA duplex.

Encapsulation of Ru(II) Polypyridine Complexes for Tumor-Targeted Anticancer Therapy.

Ru(II) polypyridine complexes have attracted much attention as anticancer agents because of their unique photophysical, photochemical, and biological properties. Despite their promising therapeutic profile, the vast majority of compounds are associated with poor water solubility and poor cancer selectivity. Among the different strategies employed to overcome these pharmacological limitations, many research efforts have been devoted to the physical or covalent encapsulation of the Ru(II) polypyridine complexes into nanoparticles. This article highlights recent developments in the design, preparation, and physicochemical properties of Ru(II) polypyridine complex-loaded nanoparticles for their potential application in anticancer therapy.

Pyrimidoquinazolinophenanthroline Opens Next Chapter in Design of Bridging Ligands for Artificial Photosynthesis.

The synthesis and detailed characterization of a new Ru polypyridine complex containing a heteroditopic bridging ligand with previously unexplored metal‐metal distances is presented. Due to the twisted geometry of the novel ligand, the resultant division of the ligand in two distinct subunits leads to steady state as well as excited state properties of the corresponding mononuclear Ru(II) polypyridine complex resembling those of prototype [Ru(bpy)3]2+ (bpy=2,2'‐bipyridine). The localization of the initially optically excited and the nature of the long‐lived excited states on the Ru‐facing ligand spheres is evaluated by resonance Raman and fs‐TA spectroscopy, respectively, and supported by DFT and TDDFT calculations. Coordination of a second metal (Zn or Rh) to the available bis‐pyrimidyl‐like coordination sphere strongly influences the frontier orbitals, apparent by, for example, luminescence quenching. Thus, the new bridging ligand motif offers electronic properties, which can be adjusted by the nature of the second metal center. Using the heterodinuclear Ru−Rh complex, visible light‐driven reduction of NAD+ to NADH was achieved, highlighting the potential of this system for photocatalytic applications.

A Photoelectrochemical Study of Hybrid Organic and Donor—Acceptor Dyes as Sensitizers for Dye-Sensitized Solar Cells

An investigation on the photoelectrochemical and sensitizing properties of two different hybrid organic dyes, anchored as sensitizers on mesoporous TiO2, in Grätzel solar cells, is presented. Firstly, we studied the absorption properties of the C106 sensitizer, a Ru polypyridine complex, and of the Y123, an organic push and pull dye. In this work, we characterized these two dyes, employing two different electrolytes, with similar experimental condition and device parameters. From the J–V curves and IPCE photo action spectra, we performed an inedited bifacial study based on the comparison of their photovoltaic performances, exploiting several backgrounds (black or white). Among the obtained results from this study, we found the best bifaciality factor of 93% for C106 and the best power conversion efficiency of 12.8% for Y123. These results represent, concerning these two dyes and to the best of our knowledge, some of the highest values in literature.

A DFT study of the second-order nonlinear optical properties of Ru(II) polypyridine complexes.

It is important to search for efficient nonlinear optical (NLO) materials due to their potential applications in electro-optic devices. Theoretical investigations into the second-order NLO responses of ten novel Ru(II) polypyridyl complexes based on [Ru(phen)2(bipy)]2+ and [Ru(bphen)2(bipy)]2+ have been performed using density functional theory. The effects on the second-order NLO response of introducing a substituent to the bipy group and of varying the ligand from phen to bphen are studied. The introduction of an electron-withdrawing/donating group improves the static first hyperpolarizability (βtot) for [Ru(phen)2(bipy)]2+ derivatives, where the introduction of a strong electron-donating group, vinyl dimethylamine, increases the βtot value from 10 a.u. for an unsubstituted complex to 16 425 a.u. However, substituting the phen ligand for a bphen group has only a slight effect on the βtot values. Research into the electronic structures, UV-vis absorption spectra, and charge transfer properties was also carried out to further understand the second-order NLO properties of the ten complexes. The frontier orbital energy gap, electron density distribution, and charge-transfer direction and quantity are crucial elements impacting the second-order NLO responses of the complexes. Varying the electronic properties is considered to be an effective method for tuning the second-order NLO responses of materials. We hope our work will provide some helpful information for designing and synthesizing cost-effective and high-performance NLO materials.

An Alkynyl-Dangling Ru(II) Polypyridine Complex for Targeted Antimicrobial Photodynamic Therapy.

To realize clinical application of antibacterial photodynamic therapy (aPDT), one of the most arduous challenges is how to render aPDT agents high selectivity against bacterial pathogens. In light of the fact that amino group-containing lipids are rich on the outer surfaces of Gram-positive bacteria, we herein constructed an alkynyl-dangling ruthenium(II) polypyridine complex (Ru2) to preferentially label Staphylococcus aureus (S. aureus) and methicillin-resistant Staphylococcus aureus (MRSA) over mammalian cells via the amino-yne bio-orthogonal click reaction. Thanks to the strong singlet oxygen generation ability, Ru2 could photo-inactivate S. aureus and MRSA effectively and specifically. Phosphatidylethanolamine (PE) molecules also exist in mammalian cells but are not accessible for Ru2, leading to its poor binding/uptake and negligible cytotoxicity in the dark and upon irradiation towards mammalian cells as well as low hemolysis, all favorable for aPDT application.

Switching the Mechanism of NADH Photooxidation by Supramolecular Interactions.

A series of three Ru(II) polypyridine complexes was investigated for the selective photocatalytic oxidation of NAD(P)H to NAD(P)+ in water. A combination of (time‐resolved) spectroscopic studies and photocatalysis experiments revealed that ligand design can be used to control the mechanism of the photooxidation: For prototypical Ru(II) complexes a 1O2 pathway was found. Rudppz ([(tbbpy)2Ru(dppz)]Cl2, tbbpy=4,4'‐di‐tert‐butyl‐2,2'‐bipyridine, dppz=dipyrido[3,2‐a:2′,3′‐c]phenazine), instead, initiated the cofactor oxidation by electron transfer from NAD(P)H enabled by supramolecular binding between substrate and catalyst. Expulsion of the photoproduct NAD(P)+ from the supramolecular binding site in Rudppz allowed very efficient turnover. Therefore, Rudppz permits repetitive selective assembly and oxidative conversion of reduced naturally occurring nicotinamides by recognizing the redox state of the cofactor under formation of H2O2 as additional product. This photocatalytic process can fuel discontinuous photobiocatalysis.

Polymeric Encapsulation of a Ru(II)-Based Photosensitizer for Folate-Targeted Photodynamic Therapy of Drug Resistant Cancers.

The currently used photodynamic therapy (PDT) photosensitizers (PSs) are generally associated with a poor cancer cell selectivity, which is responsible for some undesirable side effects. To overcome these problems, there is an urgent need for a selective drug delivery system for PDT PSs. Herein, the encapsulation of a promising Ru(II) polypyridine complex in a polymer with terminal folate groups to form nanoparticles is presented. While the Ru(II) complex itself has a cytotoxic effect in the dark, the encapsulation is able to overcome this drawback. Upon light exposure, the nanoparticles were found to be highly phototoxic in 2D monolayer cells as well as 3D multicellular tumor spheroids upon 480 or 595 nm irradiation. Importantly, the nanoparticles demonstrated a high selectivity for cancerous cells over noncancerous cells and were found to be active in drug resistant cancer cells lines, indicating that they are able to overcome drug resistances.

Photorelease of a metal-binding pharmacophore from a Ru(II) polypyridine complex.

The adoption of compounds that target metalloenzymes comprises a relatively low (<5%) percentage of all FDA approved therapeutics. Metalloenzyme inhibitors typically coordinate to the active site metal ions and therefore contain ligands with charged or highly polar functional groups. While these groups may generate highly water-soluble compounds, this functionalization can also limit their pharmacological properties. To overcome this drawback, drug candidates can be formulated as prodrugs. While a variety of protecting groups have been developed, increasing efforts have been devoted towards the use of caging groups that can be removed upon exposure to light to provide spatial and temporal control over the treatment. Among these, the application of Ru(ii) polypyridine complexes is receiving increased attention based on their attractive biological and photophysical properties. Herein, a conjugate consisting of a metalloenzyme inhibitor and a Ru(ii) polypyridine complex as a photo-cage is presented. The conjugate was designed using density functional theory calculations and docking studies. The conjugate is stable in an aqueous solution, but irradiation of the complex with 450 nm light releases the inhibitor within several minutes. As a model system, the biochemical properties were investigated against the endonucleolytic active site of the influenza virus. While showing no inhibition in the dark in an in vitro assay, the conjugate generated inhibition upon light exposure at 450 nm, demonstrating the ability to liberate the metalloenzyme inhibitor. The presented inhibitor-Ru(ii) polypyridine conjugate is an example of computationally-guided drug design for light-activated drug release and may help reveal new avenues for the prodrugging of metalloenzyme inhibitors.

Polymeric Encapsulation of a Ruthenium Polypyridine Complex for Tumor Targeted One- and Two-Photon Photodynamic Therapy.

Photodynamic therapy is a medical technique, which is gaining increasing attention to treat various types of cancer. Among the investigated classes of photosensitizers (PSs), the use of Ru(II) polypyridine complexes is gaining momentum. However, the currently investigated compounds generally show poor cancer cell selectivity. As a consequence, high drug doses are needed, which can cause side effects. To overcome this limitation, there is a need for the development of a suitable drug delivery system to increase the amount of PS delivered to the tumor. Herein, we report the encapsulation of a promising Ru(II) polypyridyl complex into polymeric nanoparticles with terminal biotin groups. Thanks to this design, the particles showed much higher selectivity for cancer cells in comparison to noncancerous cells in a 2D monolayer and 3D multicellular tumor spheroid model. As a highlight, upon intravenous injection of an identical amount of the Ru(II) polypyridine complex of the nanoparticle formulation, an improved accumulation inside an adenocarcinomic human alveolar basal epithelial tumor of a mouse up to a factor of 8.7 compared to the Ru complex itself was determined. The nanoparticles were found to have a high phototoxic effect upon one-photon (500 nm) or two-photon (800 nm) excitation with eradication of adenocarcinomic human alveolar basal epithelial tumor inside a mouse model. Overall, this work describes, to the best of our knowledge, the first in vivo study demonstrating the cancer cell selectivity of a very promising Ru(II)-based PDT photosensitizer encapsulated into polymeric nanoparticles with terminal biotin groups.

Position isomers of Ru(II) polypyridine complexes with tunable photophysical properties, aggregation-induced phosphorescence enhancement and application in triplet-triplet annihilated upconversion

Three Ru(II) polypyridine complex isomers (Ru-2-DP, Ru-3-DP and Ru-5-DP) have been synthesized using phenanthroline-based isomers containing 4-(2,2-diphenyl-vinyl)-phenyl unit. Their photophysical properties are systematically investigated. Notably, three coordination isomers exhibit much longer triplet lifetimes compared to the model complex [Ru(bpy)2(Phen)]2+. The density function theory calculations reveal that the extension of triplet lifetimes is attributed to the establishment of an excited-state equilibrium between the intraligand (3IL) state and the metal-to-ligand charge-transfer (3MLCT) state. In aggregates, Ru-2-DP shows an interesting aggregation-induced phosphorescence enhancement (AIPE) property. The phosphorescence intensity of Ru-2-DP increases by 16.2-fold from acetonitrile solution to aggregated state. However, Ru-3-DP and Ru-5-DP are AIPE-inactive. Single-crystal analyses show substituent position has a dramatic effect on intramolecular steric hindrance, leading to different molecular conformation and packing pattern. Using three coordination isomers as triplet sensitizers for triplet-triplet annihilated (TTA) upconversion, Ru-3-DP and Ru-5-DP display obvious upconversion properties, but it's quite the opposite for Ru-2-DP. Experimental data demonstrate 3- and 5-positions of phenanthroline, especially 3-position, are beneficial to enhance intersystem crossing and triplet-triplet energy transfer and for the resulting upconverted efficiency enhancement. This work definitely suggests that minor structural change may have major effects upon the solid-state spectroscopic properties and TTA upconversion performances, which provides a rational basis for designing excellent solid phosphorescent materials and triplet sensitizers.

Rationally Designed Long-Wavelength Absorbing Ru(II) Polypyridyl Complexes as Photosensitizers for Photodynamic Therapy.

The utilization of photodynamic therapy (PDT) for the treatment of various types of cancer has gained increasing attention over the last decades. Despite the clinical success of approved photosensitizers (PSs), their application is sometimes limited due to poor water solubility, aggregation, photodegradation, and slow clearance from the body. To overcome these drawbacks, research efforts are devoted toward the development of metal complexes and especially Ru(II) polypyridine complexes based on their attractive photophysical and biological properties. Despite the recent research developments, the vast majority of complexes utilize blue or UV-A light to obtain a PDT effect, limiting the penetration depth inside tissues and, therefore, the possibility to treat deep-seated or large tumors. To circumvent these drawbacks, we present the first example of a DFT guided search for efficient PDT PSs with a substantial spectral red shift toward the biological spectral window. Thanks to this design, we have unveiled a Ru(II) polypyridine complex that causes phototoxicity in the very low micromolar to nanomolar range at clinically relevant 595 nm, in monolayer cells as well as in 3D multicellular tumor spheroids.

Steric and electronic tuning of the reactivity of [RuII(terpy)(N^N)Cl]Cl complexes

The substitution behavior of [RuII(terpy)(phen)Cl]Cl and [RuII(terpy)(tmen)Cl]ClO4 (where terpy = 2,2′:6′,2″-terpyridine, phen = 1,10-phennatroline, tmen = N,N,N′,N′-tetramethylethylenediamine) have been investigated. The crystal structures of the complexes were determined by single crystal X-ray diffraction. The structures of the complexes in solution were confirmed by ESI-MS and multinuclear NMR spectroscopy. The stability of [RuII(terpy)(phen)Cl]+ and [RuII(terpy)(tmen)Cl]+ in aqueous solution, acidity and substitution behavior of the corresponding aqua derivatives with chloride, thiourea and N,N′-dimethylthiourea, were studied. The kinetics of the substitution reactions was followed under pseudo-first order conditions using UV–visible spectroscopy as a function of nucleophile concentration and temperature. The reactivity and pKa values of the tmen and phen complexes were compared with the earlier studied Ru(II) polypyridine complexes. The aqueous behavior of all the examined Ru(II) complexes depends on the electronic and steric properties provided by the spectator bidentate ligands.

Fluorination in enhancing photoactivated antibacterial activity of Ru(ii) complexes with photo-labile ligands.

Fluorination in enhancing photoactivated antibacterial activity of Ru(ii) complexes with photo-labile ligands was studied. Ru(ii) polypyridine complexes containing a di-fluorinated dppz (dipyrido[3,2-a:2′,3′-c]phenazine) or mono-trifluoromethylated dppz bidentate ligand and four pyridine monodentate ligands (complexes 3 and 4) were found to show potent photoactivated antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), and Escherichia coli (E. coli) in both normoxic and hypoxic conditions. The bactericidal effect of complexes 3 and 4 under hypoxic conditions may stem from the fluorine-containing Ru(ii) aqua species after photo-induced pyridine dissociation, and DNA may be the potential antibacterial target. Photosensitized singlet oxygen may also account for their antibacterial activity under normoxic conditions. Moreover, negligible hemolysis rates as well as low dark- and photo-cytotoxicity toward human normal liver cells (L-O2) were also observed for both complexes. Our work may provide new insights into the development of novel and efficient Ru(ii) complex based photoactivatable antibacterial agents against antibiotic-resistant bacteria.