Synthesis and characterization of half-sandwich Ir and Ru complexes containing Mnt ligand (Mnt = maleonitriledithiolate)

The reaction of [Cp¹IrCl₂]₂ and [(p-Cymene)RuCl₂]₂ with disodium maleonitriledithiolate (Na₂Mnt) yield the 16-electron complexes Cp¹Ir(Mnt) (1) and [(p-Cymene)Ru(Mnt)] (2). Complexes 1 and 2 can further react with PPh₃ to form the corresponding 18-electron complexes Cp¹Ir(Mnt)PPh₃ (3) and [(p-Cymene)Ru(Mnt)PPh₃] (4). All complexes have been fully characterized by IR and NMR spectroscopy, as well as elemental analysis. The molecular structures of 1 and 4 have been confirmed by X-ray crystallography.     

Mitochondrial Fragmentation Is an Important Cellular Event Induced by Ruthenium(II) Polypyridyl Complexes in Osteosarcoma Cells

A series of ruthenium(II) polypyridyl complexes were synthesized and evaluated for their in vitro anticancer activities. The results showed that ruthenium polypyridyl complexes, especially [Ru(bpy)₂(p‐tFPIP)]²⁺ ( 2 a ; bpy=bipyridine, tFPIP=2‐(2‐trifluoromethane phenyl)imidazole[4,5‐f][1,10]phenanthroline), exhibited novel anticancer activity against human cancer cell lines, but with less toxicity to a human normal cell line. The results of flow cytometry and caspase activities analysis indicated that the 2 a ‐induced growth inhibition against MG‐63 osteosarcoma cells was mainly caused by mitochondria‐mediated apoptosis. DNA fragmentation and nuclear condensation as detected by TUNEL–DAPI co‐staining further confirmed 2 a ‐induced apoptotic cell death. Further, fluorescence imaging revealed that ruthenium(II) polypyridyl complexes could target mitochondria to induce mitochondrial fragmentation, accompanied by depletion of mitochondrial membrane potential. Taken together, these findings suggest a potential application of theses ruthenium(II) complexes in the treatment of cancers.     

Ruthenium Complexes Induce HepG2 Human Hepatocellular Carcinoma Cell Apoptosis and Inhibit Cell Migration and Invasion through Regulation of the Nrf2 Pathway

Ruthenium (Ru) complexes are currently the focus of substantial interest because of their potential application as chemotherapeutic agents with broad anticancer activities. This study investigated the in vitro and in vivo anticancer activities and mechanisms of two Ru complexes—2,3,7,8,12,13,17,18-Octaethyl-21H,23H-porphine Ru(II) carbonyl (Ru1) and 5,10,15,20-Tetraphenyl-21H,23H-porphine Ru(II) carbonyl (Ru2)—against human hepatocellular carcinoma (HCC) cells. These Ru complexes effectively inhibited the cellular growth of three human hepatocellular carcinoma (HCC) cells, with IC₅₀ values ranging from 2.7–7.3 μM. In contrast, the complexes exhibited lower toxicity towards L02 human liver normal cells with IC₅₀ values of 20.4 and 24.8 μM, respectively. Moreover, Ru2 significantly inhibited HepG2 cell migration and invasion, and these effects were dose-dependent. The mechanistic studies demonstrated that Ru2 induced HCC cell apoptosis, as evidenced by DNA fragmentation and nuclear condensation, which was predominately triggered via caspase family member activation. Furthermore, HCC cell treatment significantly decreased the expression levels of Nrf2 and its downstream effectors, NAD(P)H: quinone oxidoreductase 1 (NQO1) and heme oxygenase 1 (HO1). Ru2 also exhibited potent in vivo anticancer efficacy in a tumor-bearing nude mouse model, as demonstrated by a time- and dose-dependent inhibition on tumor growth. The results demonstrate the therapeutic potential of Ru complexes against HCC via Nrf2 pathway regulation.     

Mechanism of cytotoxicity and cellular uptake of lipophilic inert dinuclear polypyridylruthenium(II) complexes

The accumulation, uptake mechanism, cytotoxicity, cellular localisation of—and mode of cell death induced by—dinuclear ruthenium(II) complexes ΔΔ/ΛΛ‐[{Ru(phen)₂}₂{μ‐bb_n}]⁴⁺ (Rubb_n), where phen is 1,10‐phenanthroline, bb_n is bis[4(4′‐methyl‐2,2′‐bipyridyl)]‐1,n‐alkane (n=2, 5, 7, 10, 12 or 16), and the corresponding mononuclear complexes containing the bb_n ligands, were studied in L1210 murine leukaemia cells. Cytotoxicity increased with linker chain length, and the ΔΔ‐Rubb₁₆ complex displayed the highest cytotoxicity of the series, with an IC₅₀ value of 5 μM , similar to that of carboplatin in the L1210 murine leukaemia cell line. Confocal microscopy and flow cytometry studies indicated that the complexes accumulate in the mitochondria of L1210 cells, with the magnitude of cellular uptake and accumulation increasing with linking chain length in the bb_n bridge of the metal complex. ΔΔ‐Rubb₁₆ entered the L1210 cells by passive diffusion (with a minor contribution from protein‐mediated active transport), inducing cell death via apoptosis. Additionally, metal‐complex uptake in leukaemia cells was approximately 16‐times that observed in healthy B cells highlighting that the bb_n series of complexes may have potential as selective anticancer drugs.     

Investigation of inducing apoptosis in human lung cancer A549 cells and related mechanism of a ruthenium(II) polypyridyl complex

Two Ru(II) polypyridyl complexes [Ru(bpy)₂(pztp)]^2 + (Ru1) and [Ru(bpy)₂(pytp)]^2 + (Ru2) were synthesized and characterized. Our data demonstrated that Ru2 displayed relatively higher cytotoxic activity against lung cancer A549 cells and had higher selectivity between tumor and normal cells in comparison with cisplatin. Studies on the molecular mechanism revealed that Ru2 caused cell cycle arrest at G2/M in A549 cells and induced apoptosis through a ROS-mediated mitochondrial dysfunction pathway. The further studies by comet assay at single cell level indicated that DNA damage in A549 cells was triggered by Ru2, following with the up-regulation of phosphorylated ATM (Ser1984), Histone H2A.X (Ser139) and p53 (Ser15). Western blot analysis suggested that MAPKs signaling pathways, especially ERK, were involved in Ru2-induced apoptosis. Moreover, both DNA damage and MAPKs signaling pathways were regulated by the level of ROS. To our knowledge, this is the first report of the ruthenium (II) polypyridyl complex which induces apoptosis partly through the activation of ERK.     

[Ru(L)2(3-tppp)]2 + (L = bpy,phen) stabilizes two different forms of the human telomeric G-quadruplex DNA

The binding properties of new complexes [Ru(L)₂(3-tppp)]^2 + (L = bpy, phen) towards two different forms of the human telomeric G-quadruplexes DNA have been investigated by UV–Vis spectroscopy, fluorescent indicator displacement (FID) assays, fluorescence resonance energy transfer (FRET) melting assays and molecular docking studies. The molecular docking studies indicated that both complexes interacted with 22AG with the stoichiometric ratio of 1:1, but the two complexes showed different G-quadruplexed DNA binding affinity. Complex 2 bound to the G-quadruplexes DNA more tightly than complex 1 did. Moreover, the FRET melting assay revealed that both complexes could be potential stabilizers for G-quadruplex architectures. These studies are useful not only for better understanding of the interaction between the target G-quadruplexes DNA and metal complexes but also valuable in defining the best strategy to prepare metal complexes as potential anticancer drugs.     

Trinuclear Ru(II) polypyridyl complexes as human telomeric quadruplex DNA stabilizers

Two new trinuclear ruthenium(II) complexes [(bpy)₆Ru₃(tpbip)]⁶⁺ (1) and [(bpy)₆Ru₃(tptaip)]⁶⁺ (2) (bpy = 2,2′-bipyridine, tpbip = 1,3,5-tris(1,10-phenanthroline-[5,6-d]imidazol-2-yl)-benzene, tptaip = 2,4,6-tri(1,10-phenanthroline-[5,6-d]imidazol-2-yl)-1,3,5-triazine) have been synthesized and characterized. The interaction of human telomeric DNA with Ru(II) complexes was explored by means of CD spectroscopy, fluorescence titration, ITC and FRET melting. Results indicated that two complexes not only induce a remarkable conformational change of human telomeric DNA, but also have the ability to stabilize the G-quadruplex.     

Synthesis and Characterization of an Epidermal Growth Factor Receptor-Selective RuII Polypyridyl–Nanobody Conjugate as a Photosensitizer for Photodynamic Therapy

There is a current surge of interest in the development of novel photosensitizers (PSs) for photodynamic therapy (PDT), as those currently approved are not completely ideal. Among the tested compounds, we have previously investigated the use of Ru^II polypyridyl complexes with a [Ru(bipy)₂(dppz)]²⁺ and [Ru(phen)₂(dppz)]²⁺ scaffold (bipy=2,2′-bipyridine; dppz=dipyrido[3,2-a:2′,3′-c]phenazine; phen=1,10-phenanthroline). These complexes selectively target DNA. However, because DNA is ubiquitous, it would be of great interest to increase the selectivity of our PDT PSs by linking them to a targeting vector in view of targeted PDT. Herein, we present the synthesis, characterization, and in-depth photophysical evaluation of a nanobody-containing Ru^II polypyridyl conjugate selective for the epidermal growth factor receptor (EGFR) in view of targeted PDT. Using ICP-MS and confocal microscopy, we could demonstrate that our conjugate has high selectivity for the EGFR receptor, which is a crucial oncological target because it is overexpressed and/or deregulated in a variety of solid tumors. However, in contrast to expectations, this conjugate was found to not produce reactive oxygen species (ROS) in cancer cells and is therefore not phototoxic.     

Antheraea pernyi Silk Fibroin-Coated PEI/DNA Complexes for Targeted Gene Delivery in HEK 293 and HCT 116 Cells

Polyethylenimine (PEI) has attracted much attention as a DNA condenser, but its toxicity and non-specific targeting limit its potential. To overcome these limitations, Antheraea pernyi silk fibroin (ASF), a natural protein rich in arginyl-glycyl-aspartic acid (RGD) peptides that contains negative surface charges in a neutral aqueous solution, was used to coat PEI/DNA complexes to form ASF/PEI/DNA ternary complexes. Coating these complexes with ASF caused fewer surface charges and greater size compared with the PEI/DNA complexes alone. In vitro transfection studies revealed that incorporation of ASF led to greater transfection efficiencies in both HEK (human embryonic kidney) 293 and HCT (human colorectal carcinoma) 116 cells, albeit with less electrostatic binding affinity for the cells. Moreover, the transfection efficiency in the HCT 116 cells was higher than that in the HEK 293 cells under the same conditions, which may be due to the target bonding affinity of the RGD peptides in ASF for integrins on the HCT 116 cell surface. This result indicated that the RGD binding affinity in ASF for integrins can enhance the specific targeting affinity to compensate for the reduction in electrostatic binding between ASF-coated PEI carriers and cells. Cell viability measurements showed higher cell viability after transfection of ASF/PEI/DNA ternary complexes than after transfection of PEI/DNA binary complexes alone. Lactate dehydrogenase (LDH) release studies further confirmed the improvement in the targeting effect of ASF/PEI/DNA ternary complexes to cells. These results suggest that ASF-coated PEI is a preferred transfection reagent and useful for improving both the transfection efficiency and cell viability of PEI-based nonviral vectors.     

Study of the anticancer properties of tin(IV) carboxylate complexes on a panel of human tumor cell lines

A group of organotin(IV) complexes were prepared: [SnCy₃(DMNI)] ( 1 ), [SnCy₃(BZDO)] ( 2 ), [SnCy₃(DMFU)] ( 3 ), and [SnPh₂(BZDO)₂] ( 4 ), for which DMNIH=2,6‐dimethoxynicotinic acid, BZDOH=1,4‐benzodioxane‐6‐carboxylic acid, and DMFUH=2,5‐dimethyl‐3‐furoic acid. The cytotoxic activities of compounds 1 – 4 were tested against pancreatic carcinoma (PANC‐1), erythroleukemia (K562), and two glioblastoma multiform (U87 and LN‐229) human cell lines; they show very high antiproliferative activity, with IC₅₀ values in the 150–700 nM range after incubation for 72 h. Distribution of cellular DNA upon treatment with 1 – 4 revealed that whereas compounds 1 – 3 induce apoptosis in most of the cell lines, compound 4 does not affect cell viability in any cell line tested, indicating a possible difference in cytotoxic mechanism. Studies with the daunomycin‐resistant K562/R cell line expressing P‐glycoprotein (Pgp) showed that compounds 1 – 4 are not substrates of this protein efflux pump, indicating that these compounds do not induce acquisition of multidrug resistance, which is associated with the overexpression of Pgp.     

In Vitro and In Vivo Biological Activity of Ruthenium 1,10-Phenanthroline-5,6-dione Arene Complexes

Ruthenium(II) arene complexes exhibit promising chemotherapeutic properties. In this study, the effect of the counter anion in Ru(II) complexes was evaluated by analyzing the biological effect of two Ru(II) p-cymene derivatives with the 1,10-phenanthroline-5,6-dione ligand of general-formula [(η⁶-arene)Ru(L)Cl][X] X = CF₃SO₃ (JHOR10) and PF₆ (JHOR11). The biological activity of JHOR10 and JHOR11 was examined in the ovarian carcinoma cell line A2780, colorectal carcinoma cell line HCT116, doxorubicin-resistant HCT116 (HCT116-Dox) and in normal human dermal fibroblasts. Both complexes JHOR10 and JHOR11 displayed an antiproliferative effect on A2780 and HCT116 cell lines, and low cytotoxicity in fibroblasts. Interestingly, JHOR11 also showed antiproliferative activity in the HCT116-Dox cancer cell line, while JHOR10 was inactive. Studies in A2780 cells showed that JHOR11 induced the production of reactive oxygen species (ROS) that trigger autophagy and cellular senescence, but no apoptosis induction. Further analysis showed that JHOR11 presented no tumorigenicity, with no effect in the cellular mobility, as evaluated by thye wound scratch assay, and no anti- or pro-angiogenic effect, as evaluated by the ex-ovo chorioallantoic membrane (CAM) assay. Importantly, JHOR11 presented no toxicity in chicken and zebrafish embryos and reduced in vivo the proliferation of HCT116 injected into zebrafish embryos. These results show that these are suitable complexes for clinical applications with improved tumor cell cytotoxicity and low toxicity, and that counter-anion alteration might be a viable clinical strategy for improving chemotherapy outcomes in multidrug-resistant (MDR) tumors.     

Arene–RuII Complexes of Curcumin Exert Antitumor Activity via Proteasome Inhibition and Apoptosis Induction

Organometallic ruthenium(II) complexes of general formula [(η⁶‐arene)Ru(curcuminato)Cl], with arene being p‐iPrC₆H₄Me ( 1 ), C₆H₆ ( 2 ), and C₆Me₆ ( 3 ), were synthesized, characterized, and evaluated for their antitumor effects. Specifically, we explored their ability to regulate the proteasome, a validated pharmacological target in cancer treatment. Ruthenium complexes inhibited isolated proteasomes to various extents, with the biological activity of these complexes depending on the nature of the bound arene; in particular, [(η⁶‐arene)Ru(curcuminato)Cl] 2 suppressed proteasomal activities more potently than 1 , 3 , or free curcumin. Each complex also inhibited proteasomes in cultured colon cancer cells and consequently triggered apoptosis, with the [(η⁶‐benzene)Ru(curcuminato)Cl] complex 2 being the most active. The influence on the oxidative status of HCT116 cells and the DNA binding ability of the [(η⁶‐arene)Ru(curcuminato)Cl] complexes were studied. Complex 2 showed the highest antioxidant capacity; moreover, complexes 1 and 2 were shown to bind isolated DNA with higher affinity (up to threefold) than free curcumin. Collectively, our results demonstrate that the complexation of curcumin with ruthenium(II) is a promising starting point for the development of curcumin‐based anticancer drugs.     

Cell‐Selective,Apoptosis‐inducing Rhodium(III) Crown Thiaether Complexes

Half‐sandwich rhodium(III) polypyridyl (pp) complexes with the metal atom capped by the facial crown thiaether 1,4,7‐trithiacyclononane [9]aneS₃ represent a promising class of apoptosis‐inducing potent cytostatic agents. The necrotic damage caused by the complexes is negligible. In vitro cytotoxicity assays with the human cancer cell lines MCF‐7 and HT‐29 and immortalized HEK‐293 cells indicate that the dicationic κ²N(imino) complexes [([9]aneS₃)RhCl(pp)]²⁺ are much more active than monocationic complexes [([9]aneS₃)RhCl₂(L)]⁺ (L=imidazole, CH₃CN). Whereas the κ²N(amino) complex [([9]aneS₃)RhCl(piperazine)]²⁺ is inactive, replacing piperazine with the structurally analogous κ²S (thiaether) ligand 1,4‐dithiane restores cytotoxicity as evidenced by IC₅₀ values in the range 8.1‐11.6 μM . Spectroscopic (CD, UV/Vis, NOESY) and viscosity measurements indicate that the active dppz complex 8 (IC₅₀ values: 4.7–8.9 μM ) exhibits strong intercalative binding towards DNA whereas the even more potent bipyrimidine complex 9 (IC₅₀ values: 0.6–1.9 μM ) causes no alteration of the duplex B conformation. Weaker intercalative binding is observed for the dpq complex 7 . A comparative annexin V–propidium iodide binding assay with lymphoma (BJAB) cells and healthy leukocytes demonstrates that the cytotoxic activity of complex 8 and particularly complex 9 is highly selective towards the malignant cells.     

Ligand dehydrogenation in ruthenium trinitrogen complexes: synthesis,structure and chirality of the cations [Ru(LH4)(L)]2+ [LH4=2,6-bis(pyrrolidin-2-yl)pyridine]

Reaction of 2,6-bis(pyrrolidin-2-yl)pyridine (LH₄) with RuCl₃·3H₂O in refluxing methanol/water mixtures gives rise to the formation of the octahedral complexes [Ru(LH₄)(L)]²⁺, in which one of the two trihapto ligands has been dehydrogenated as 2,6-bis(3,4-dihydro-2H-pyrrol-5-yl)pyridine (L), even if LH₄ was present in excess. With the three stereoisomers of LH₄, the complexes [Ru(R,S-LH₄)(L)]²⁺ (meso), [Ru(R,R-LH₄)(L)]²⁺ and [Ru(S,S-LH₄)(L)]²⁺ have been isolated as the perchlorate salts and characterised by X-ray structure analysis and by CD spectra.     

Synthesis and characterization of ruthenium complexes immobilized on poly(4-vinylpyridine)

The [Ru(NH₃)₅(H₂O)]²⁺ andtrans-[Ru(NH₃)₄SO₂(H₂O)]²⁺ complexes ions were immobilized on poly(4-vinylpyridine) (4-PVP) through reactions in aqueous solutions. The stability of the imobilized complexes was checked in aqueous solution in the pH 2.0–8.0 range. The number of pyridinic nitrogens in the polymer 4-PVP is 2.80±0.05 mmol/g according to nitrogen elemental analysis. Potentiometric titration experiments showed that the accessible nitrogen, in aqueous medium, was 0.94±0.02 mmol/g with a pK _a value of 7.4±0.2. In addition, ruthenium and sulfate analysis has demonstrated that about 15% of the accessible nitrogen sites are able to coordinate to the metal centers. The characterization of the immobilized complexes was made through diffuse electronic and infrared spectroscopies and differential pulse and cyclic voltammetries.     

含柔性插入配体的钌(Ⅱ)配合物的合成及其与DNA作用研究

设计合成一个柔性插入配体dcpip（dcpip=2-（2,3-环己烯基眯唑并[4,5-f]邻菲咯啉）及其钌（Ⅱ）多吡啶配合物[Ru（bpy）2（dcpip）]（ClO4）2（bpy=2,2＇-联吡啶）和[Ru（phen）2（dcpip）]（ClO4）2（phen=1,10-邻菲咯啉）。采用元素分析和质谱对其进行表征。用电子吸收光谱、荧光光谱和粘度测试研究配合物与DNA作用。研究结果表明,配合物与DNA之间通过插入作用结合。     

Synthesis and in vitro Anticancer Activity of Octahedral Platinum(IV) Complexes with Cyclohexyl‐Functionalized Ethylenediamine‐N,N′‐Diacetate‐Type Ligands

The present study describes the synthesis and anticancer activity of novel octahedral Pt^IV complexes with cyclohexyl functionalized ethylenediamine‐N,N′‐diacetate‐type ligands. Molecular mechanics calculations and density functional theory analysis revealed that s‐cis is the preferred geometry of these Pt^IV complexes with tetradentate‐coordinated (S,S)‐ethylenediamine‐N,N′‐di‐2‐(3‐cyclohexyl)propanoate. The viability of cancer cell lines (U251 human glioma, C6 rat glioma, L929 mouse fibrosarcoma, and B16 human melanoma) was assessed by measuring mitochondrial dehydrogenase activity and lactate dehydrogenase release. Cell‐cycle distribution, oxidative stress, caspase activation, and induction of autophagy were analyzed by flow cytometry using appropriate fluorescent reporter dyes. The cytotoxic activity of novel Pt^IV complexes against various cancer cell lines (IC₅₀ range: 1.9–8.7 μM ) was higher than that of cisplatin (IC₅₀ range: 10.9–67.0 μM ) and proceeded through completely different mechanisms. Cisplatin induced caspase‐dependent apoptosis associated with the cytoprotective autophagic response. In contrast, the new Pt^IV complexes caused rapid, caspase‐independent, oxidative stress‐mediated non‐apoptotic cell death characterized by massive cytoplasmic vacuolization, cell membrane damage, and the absence of protective autophagy.     

Cationic Ruthenium‐Cyclopentadienyl‐Diphosphine Complexes as Catalysts for the Allylation of Phenols with Allyl Alcohol; Relation between Structure and Catalytic Performance in O‐ vs. C‐Allylation

A new catalytic method has been investigated to obtain either O‐ or C‐allylated phenolic products using allyl alcohol or diallyl ether as the allyl donor. With the use of new cationic ruthenium(II) complexes as catalyst, both reactions can be performed with good selectivity. Active cationic Ru(II) complexes, having cyclopentadienyl and bidentate phosphine ligands are generated from the corresponding Ru(II) chloride complexes with a silver salt. The structures of three novel (diphosphine)Ru(II)CpCl catalyst precursor complexes are reported. It appears that the structure of the bidentate ligand has a major influence on catalytic activity as well as chemoselectivity. In addition, a strong cocatalytic effect of small amounts of acid is revealed. Model experiments are described that have been used to build a reaction network that explains the origin and evolution in time of both O‐allylated and C‐allylated phenolic products. Some mechanistic implications of the observed structure vs. performance relation of the [(diphosphine)RuCp]⁺ complexes and the cocatalytic role of added protons are discussed.     

Exploring the Molecular Mechanisms Underlying the in vitro Anticancer Effects of Multitarget-Directed Hydrazone Ruthenium(II)–Arene Complexes

The molecular targets and the modes of action behind the cytotoxicity of two structurally established N,O- or N,N-hydrazone ruthenium(II)–arene complexes were explored in human breast adenocarcinoma cells (MCF-7) and paralleled in non-cancerous and cisplatin-resistant counterparts (MCF-10A and MCF-7CR respectively). Both complexes, [Ru(hmb)(L1)Cl] ( 1 , L1=4-((2-(2,4-dinitrophenyl)hydrazono)(phenyl)methyl)-3-methyl-1-phenyl-1H-pyrazol-5-olate) and [Ru(cym)(L2)Cl] ( 2 , L2=1-((3-methyl-5-oxo-1-phenyl-1H-pyrazol-4(5H)-ylidene)(phenyl)methyl)-2-(pyridin-2-yl)hydrazin-1-ide), reversibly interact with moderate-to-high affinity with a number of molecular targets in cell-free assays, namely serum albumin, DNA, the 20S proteasome and hydroxymethylglutaryl-CoA reductase. Most interestingly, only 2 readily crosses the cell membrane and preserves its binding/modulatory ability toward the targets of interest upon rapid cellular internalization. The resulting action at multiple levels of the cancer cascade is likely the cause for the selective sensitization of tumour cells to p27-mediated apoptotic death, and for the ability of 2 to overcome the drug resistance problem.     

Increased Lipophilicity of Halogenated Ruthenium(II) Polypyridyl Complexes Leads to Decreased Phototoxicity in vitro when Used as Photosensitizers for Photodynamic Therapy

In the fight against cancer, photodynamic therapy is generating great interest thanks to its ability to selectively kill cancer cells without harming healthy tissues. In this field, ruthenium(II) polypyridyl complexes, and more specifically, complexes with dipyrido[3,2-a:2’,3’-c]phenazine (dppz) as a ligand are of particular interest due to their DNA-binding and photocleaving properties. However, ruthenium(II) polypyridyl complexes can sometimes suffer from low lipophilicity, which hampers cellular internalisation through passive diffusion. In this study, four new [Ru(dppz-X₂)₃]²⁺ complexes (X=H, F, Cl, Br, I) were synthesized and their lipophilicity (logP), cytotoxicity and phototoxicity on cancerous and noncancerous cell lines were assessed. This study shows that, counterintuitively, the phototoxicity of these complexes decreases as their lipophilicity increases; this could be due solely to the atomic radius of the halogen substituents.