Ligand Ru Research Articles

MACE: Automated Assessment of Stereochemistry of Transition Metal Complexes and Its Applications in Computational Catalysis.

Computational chemistry pipelines typically commence with geometry generation, well-established for organic compounds but presenting a considerable challenge for transition metal complexes. This paper introduces MACE, an automated computational workflow for converting chemist SMILES/MOL representations of the ligands and the metal center to 3D coordinates for all feasible stereochemical configurations for mononuclear octahedral and square planar complexes directly suitable for quantum chemical computations and implementation in high-throughput computational chemistry workflows. The workflow is validated through a structural screening of a data set of transition metal complexes extracted from the Cambridge Structural Database. To further illustrate the power and capabilities of MACE, we present the results of a model DFT study on the hemilability of pincer ligands in Ru, Fe, and Mn complexes, which highlights the utility of the workflow for both focused mechanistic studies and larger-scale high-throughput pipelines.

2-Hydroxypyridine-based Ligands as Promoter in Ruthenium(II) Catalyzed C-H Bond Activation/Arylation Reactions.

A class of 2-hydroxypyridine based ligands are explored to achieve enhanced catalytic activity for ortho-C-H bond activation/arylation reaction over [(η6 -p-cymene)RuCl2 ]2 catalyst in water. Extensive studies using a series of substituted 2-hydroxypyridine based ligands (L1-L6) inferred that 5-trifluoromethyl-2-hydroxypyridine (L6) exhibited favorable effects to enhance the catalytic activity of Ru(II) catalyst for ortho C-H bond arylation of 2-phenylpyridine by 8 folds compared to those performed without ligands. The (η6 -p-cymene)Ru - L6 system also exhibited enhanced catalytic activity for ortho C-H bond arylation of 2-phenylpyridine using a variety of aryl halides. NMR and mass investigations inferred the presence of several ligand coordinated Ru(II) species, suggesting the involvement of these species in C-H bond activation reaction. Further in concurrence with the experimental findings, the density functional theory (DFT) calculations also evidenced the prominent role of 2-hydroxypyridine based ligands in Ru(II) catalyzed C-H bond arylation of 2-phenylpyridine with lower energy barrier for the C-H activation step.

Photocontrolled self-assembly based on photoresponsive ruthenium complexes

Abstract Self-assembly, which occurs through noncovalent interactions among molecules, is a ubiquitous phenomenon in the natural world. Light is a particularly attractive stimulus for manipulating self-assembled structures due to its precise and noninvasive nature. Photoresponsive ruthenium (Ru) complexes are emerging as promising candidates for controlling self-assembly due to their unique coordination chemistry and reversible light-triggered behavior. Specifically, Ru complexes can undergo photodissociation of their ligands in aqueous solutions, leading to the formation of Ru-H2O species, and this process can be used to control the disassembly of assembled structures upon illumination. Conversely, upon cessation of the light stimulus, some Ru–ligand coordination bonds can be restored, resulting in reassembly of the structures. Herein, we mainly introduce our recent progress in the use of Ru(Ⅱ) complexes to create photocontrolled self-assemblies with applications ranging from cancer therapy to the manipulation of the morphology and properties of nanoscale materials. Finally, we discuss the challenges and future directions of photocontrolled assemblies with Ru complexes.

Substituent’s Effects of PNP Ligands in Ru(II)-Catalyzed CO2 Hydrogenation to Formate: Theoretical Analysis Considering Steric Hindrance and Promotion of Hydrogen Bonding

This paper investigates the effects of substituents in PNP-type ruthenium complexes in the catalytic hydrogenation of CO2 to formate using the DFT method. Six groups were considered as substituents linked to the P atom of the PNP ligand: hydrogen, methyl, iso-propyl, tert-butyl, cyclopentyl, and cyclohexyl. The substituent effects were analyzed from the perspectives of steric hindrance and promotion of hydrogen bonding. With the joint functions of steric hindrance and hydrogen bonding promotion during the CO2 coordination step, hydride addition step, and HCOO− rotation step, these groups exhibited very different substituent effects. The results showed that the methyl group was the most favorable substituent when the solvent’s effects were not included, as it formed hydrogen bonding with relatively weak steric hindrance. The second favorable substituent was the iso-propyl group, while the tert-butyl group was the most unfavorable one, due to remarkable steric hindrance. When the substituent was cyclopentyl or cyclohexyl, the complex provided a wider open space for the reaction compared with the tert-butyl-substituted complex, because cyclopentyl and cyclohexyl are cyclic groups. Therefore, the principle for choosing the substituent in PNP-type complexes allowing the design of highly efficient catalysts for CO2 hydrogenation indicates that more hydrogen atoms but wider open space are ideal. In addition, the substituent’s effects can be markedly impacted by the solvent used.

Binding properties of ruthenium(II) complexes [Ru(phen)2(7-R-dppz)]2+ (R = methyl or bromine) toward poly(U)•poly(A) RNA duplex

Two Ru(II) complexes containing different substituents, [Ru(phen)2(7-CH3-dppz)]2+ (Ru1) and [Ru(phen)2(7-Br-dppz)]2+ (Ru2), have been synthesized in this study. The binding properties of Ru1 and Ru2 with the duplex RNA poly(U)•poly(A) (where “•” denotes the Watson – Crick base pairing) have been researched by biophysical techniques and viscosity measurements. Analysis of spectral titrations and viscosity measurements indicate that Ru1 and Ru2 bind to the duplex via intercalative, and the binding affinity of Ru1 with the duplex is remarkably higher than that of Ru2. Furthermore, fluorescence emission spectra demonstrates that although complexes Ru1 and Ru2 can act as molecular “light switches” for the duplex RNA, alters in fluorescence emission of Ru1 and Ru2 are prominent differences, and the effectiveness of Ru1 is more remarkable compared with that of Ru2. The melting experiments suggest that the duplex RNA stabilizing effects of Ru1 and Ru2 differ from each other, among them, complex Ru1 can obviously enhance the stability of the duplex RNA, while Ru2 has only a slightly stabilizing effect for the duplex RNA, indicating that Ru1 preferentially binds to RNA duplex over Ru2. The obtained results indicate that subtle modifications of the intercalative ligand of Ru(II) polypyridyl complex with either methyl or bromide group have a significant effect on the duplex-binding discrimination.

Plasmon-catalysed decarboxylation of dicarboxybipyridine ligands in Ru(II) complexes chemisorbed on Ag nanoparticles: conditions, proposed mechanism and role of Ag(0) adsorption sites.

Plasmon-catalyzed decarboxylation reactions of Ru(II) bis(2,2'-bipyridine)(4,4'-dicarboxy-bipyridine) denoted as Ru(bpy)2(dcbpy) and Ru(II) tris(4,4'-dicarboxy-bipyridine) denoted as Ru(dcbpy)3 complexes in hydrosol systems with Ag nanoparticles (NPs) conditioned by the presence of Ag(0) adsorption sites on Ag NP surfaces have been revealed by surface-enhanced (resonance) Raman scattering (SERRS and/or SERS) spectral probing and monitoring further supported by factor analysis. Interpretation of the experimental results was based on an identification of specific marker bands of the Ru-dcbpy and of the Ru-bpy units. Furthermore, by a series of specifically targeted SERRS and/or SERS experiments complemented by UV/vis spectral measurements and TEM imaging of deposited Ag NPs, plasmon catalysis by charge carriers, namely hot electrons (e-) and hot holes (h+), has been established as the most probable mechanism of decarboxylation reactions undergone by the carboxylate-chemisorbed Ru-dcbpy units of the complexes. The presence of Ag(0) adsorption sites on Ag NP surfaces as the necessary condition of the reaction progress is in full accord with the charge carrier mechanism of plasmon catalysis. In particular, the neutral Ag(0) sites create the interface required for the transport of hot e- to H+ co-reactants complementing thus the C-C bond breaking and CO2 formation caused by hot h+.

Insights into the Protein Ruthenation Mechanism by Antimetastatic Metallodrugs: High-Resolution X-ray Structures of the Adduct Formed between Hen Egg-White Lysozyme and NAMI-A at Various Time Points.

The pharmacological profile of medicinally relevant Ru(III) coordination compounds has been ascribed to their interactions with proteins, as several studies have provided evidence that DNA is not the primary target. In this regard, numerous spectroscopic and crystallographic studies have indicated that the Ru(III) ligands play an important role in determining the metal binding site, acting as the recognition element in the early stages of the protein-complex formation. Herein, we present a series of near-atomic-resolution X-ray crystal structures of the adducts formed between the antimetastatic metallodrug imidazolium trans-[tetrachlorido(S-dimethyl sufoxide)(1H-imidazole)ruthenate(III)] (NAMI-A) and hen egg-white lysozyme (HEWL). These structures elucidate a series of binding events starting from the noncovalent interaction of intact NAMI-A ions with HEWL (1.5 h), followed by the stepwise exchange of all Ru ligands except for 1H-imidazole (26 h) to the final "ruthenated" protein comprising one aquated Ru ion coordinated to histidine-15 of HEWL (98 h). Our structural data clearly support a two-step mechanism of protein ruthenation, illustrating the ligand-mediated recognition step of the process.

Comparative DFT Study on Dehydrogenative C(sp)–H Elementation (E = Si, Ge, and Sn) of Terminal Alkynes Catalyzed by a Cationic Ruthenium(II) Thiolate Complex

Described herein is a comparative theoretical study of dehydrogenative C(sp)-H functionalizations of a terminal alkyne with group-14-based hydrides (HEEt3; E = Si, Ge, Sn) catalyzed by an Ohki-Tatsumi complex-a cationic Ru(II) complex with a tethered thiolate ligand ([Ru-S] = [(DmpS)Ru(PiPr3)][BAr4F]; Dmp = 2,6-(dimesityl)2C6H3; ArF = 3,5-(CF3)2C6H3). The calculations indicate that the energy barriers for heterolytic cleavage of the H-EEt3 bonds at the Ru-S sites of the Ohki-Tatsumi complex highly vary depending on the group 14 elements from 3.8 kcal/mol (E = Sn) to 10.5 kcal/mol (E = Ge) and 18.5 kcal/mol (E = Si), where Ru and S elements cooperatively serve as the Lewis acid and base, respectively. Likewise, the transfer of the group 14 cation (Et3E+) to the C-C triple bond to generate the β-element-stabilized vinyl cations-the rate-determining step (RDS) of the overall reaction-is predicted to be susceptible to the element's identity [Ea = 36.8 for Sn < 42.9 and Ge < 50.7 for Si (kcal/mol)]. The key transition states involved in the RDS are compared in terms of energy and structure within each system of the group 14 hydrides. The distortion/interaction-activation strain (DIAS) model analysis of the transition states responsible for dehydrogenative stannylation and hydrostannation of a terminal alkyne sheds light on the origin of the experimentally observed kinetic preference toward dehydrogenative C-H stannylation over hydrostannation.

A novel quinoxalinedione-bicapped tri-ruthenium carbonyl cluster [Ru3(μ-H)2(CO)6(μ3-HDCQX)2]: synthesis, characterization, anticancer activity and theoretical investigation of Ru–Ru and Ru–Ligand bonding interactions

A new tri-ruthenium dihydrido cluster, [Ru3(μ-H)2(CO)6(HDCQX)2] (1), in which two HDCQX (H2DCQX = 6,7-dichloroquinoxaline-2,3-dione) ligands cap both faces of the tri-ruthenium triangle similarly through oxygen atoms, has been synthesized and characterized by mass, IR, NMR (1H and 13C) and electronic spectroscopy. DFT calculations, in both gas and solution (CPCM/DMSO) phases, were performed to analyze the electronic structure of the cluster and interpret its vibrational and NMR spectra. The presence of non-equivalent bridging hydrides was assigned by 1H NMR as two singlet resonances at δ −16.85 and −17.67 ppm and confirmed by theoretical DFT-GIAO calculations at δ −12.92 and −14.48 ppm. Time-dependent density functional theory (TD-DFT) calculations, performed to characterize the frontier orbitals and interpret the electronic spectrum, indicated that the lowest-energy transition of 1 originates from a highly delocalized HOMO with Ru–Ru (σ), Ru–CO (π) and Ru–CO (σ*) contributions and ends in the LUMO with Ru1–Ru2–Ru3 (σ*) and QX/QX′ (π*) anti-bonding character. The natural transition orbital (NTO) corresponding to this transition revealed a decrease of the electron density on the Ru1Ru2(CO)4 fragment and an increase of the electron density on the Ru1–Ru2–Ru3 unit and the HDCQX ligands. The Ru–Ru and Ru–ligand bonding was studied by the quantum theory of atoms in molecules (QTAIM) and electron localization function (ELF) methods. Both confirmed the presence of unique bonding between the Ru1 and Ru2 atoms and not between Ru3 and the other Ru atoms. While the QTAIM assigned the Ru1–Ru2 bonding as a transit between pure closed-shell and pure shared-shell interactions, the ELF analysis suggested that this bond is dominated by a fluctuation of electron density. The covariance analysis indicated that the core basin populations C(Ru1) and C(Ru2) account for 76% of the V(Ru1, Ru2) variance. Natural bond orbital (NBO) analysis of the Ru3(µ-H)2O4(CO)6 unit indicated a 2c–2e bonding type for the Ru–O, Ru–C and Ru–Ru bonds with orbital occupations of 1.88–1.95, 1.95–1.96, and 1.57 e, respectively, and a 3c–2e bonding for the Ru–H–Ru bonds with an orbital occupation of ca. 1.7 e. NBO second-order perturbative energy analysis was performed to estimate the strength of the Ru–CO π-back-donation and to establish a correlation between the stabilization energy (E(2)) and the spectroscopic data. Although the calculated stabilization energy (E(2)total) follows the expected trend of decreasing the CO stretching frequency (νCO) and increasing the 13CO chemical shift with the extent of the Ru–CO π-back-donation, the latter parameter was more consistent in estimating the strength of such interactions. The in vitro anticancer activities of the title compound and cisplatin were determined against three common types of human cancer cell lines, HCT-116 (colon), HELA (cervix) and MCF-7 (breast). The IC50 values of 3.18 ± 0.40, 4.21 ± 0.29 and 5.39 ± 0.52 μM, respectively, represent 4- and 2-times improvement in potency relative to cisplatin (12.06 ± 1.28, 10.34 ± 2.08 and 6.29 ± 1.68 μM, respectively) against the HCT-116 and HeLa cancer cell lines.

Reconfigurable Materials Based on Photocontrolled Metal–Ligand Coordination

Photoresponsive materials have attracted growing interest because of their potential applications in materials science, such as photoswitches, photopatterning, information storage, and so on. However, there are some challenges for photoresponsive materials for certain applications: 1) Only a few photoresponsive surfaces are transformed into multiple states after photoreactions to adapt to changing environmental conditions; 2) Photoresponsive materials may not function properly in cold environments, especially for gels. To address these problems, we have recently developed photoresponsive materials based on ruthenium (Ru) complexes. Such Ru complexes showed a photoinduced ligand substitution under visible light irradiation. Reconfigurable surfaces that can adapt to environmental changes and photoresponsive organohydrogels that function effectively at sub‐zero temperatures have been fabricated using photoresponsive Ru complexes. Herein, it is demonstrated that based on photocontrolled Ru–ligand coordination, reconfigurable surfaces can be modified for user‐defined functions via visible light irradiation and that photoresponsive gels can function even at –20 °C. As a perspective, Ru‐containing photoresponsive complexes could open up pathways for a variety of applications.

4,5-Diazafluorene and 9,9'-Dimethyl-4,5-Diazafluorene as Ligands Supporting Redox-Active Mn and Ru Complexes.

4,5-diazafluorene (daf) and 9,9’-dimethyl-4,5-diazafluorene (Me2daf) are structurally similar to the important ligand 2,2’-bipyridine (bpy), but significantly less is known about the redox and spectroscopic properties of metal complexes containing Me2daf as a ligand than those containing bpy. New complexes Mn(CO)3Br(daf) (2), Mn(CO)3Br(Me2daf) (3), and [Ru(Me2daf)3](PF6)2 (5) have been prepared and fully characterized to understand the influence of the Me2daf framework on their chemical and electrochemical properties. Structural data for 2, 3, and 5 from single-crystal X-ray diffraction analysis reveal a distinctive widening of the daf and Me2daf chelate angles in comparison to the analogous Mn(CO)3(bpy)Br (1) and [Ru(bpy)3]2+ (4) complexes. Electronic absorption data for these complexes confirm the electronic similarity of daf, Me2daf, and bpy, as spectra are dominated in each case by metal-to-ligand charge transfer bands in the visible region. However, the electrochemical properties of 2, 3, and 5 reveal that the redox-active Me2daf framework in 3 and 5 undergoes reduction at a slightly more negative potential than that of bpy in 1 and 4. Taken together, the results indicate that Me2daf could be useful for preparation of a variety of new redox-active compounds, as it retains the useful redox-active nature of bpy but lacks the acidic, benzylic C–H bonds that can induce secondary reactivity in complexes bearing daf.

Complexation and bonding studies on [Ru(NO)(H2O)5]3+ with nitrate ions by using density functional theory calculation.

Complexation reactions of ruthenium–nitrosyl complexes in HNO3 solution were investigated by density functional theory (DFT) calculations in order to predict the stability of Ru species in high-level radioactive liquid waste (HLLW) solution. The equilibrium structure of [Ru(NO)(NO3)3(H2O)2] obtained by DFT calculations reproduced the experimental Ru–ligand bond lengths and IR frequencies reported previously. Comparison of the Gibbs energies among the geometrical isomers for [Ru(NO)(NO3)x(H2O)5−x](3−x)+/− revealed that the complexation reactions of the ruthenium–nitrosyl complexes with NO3− proceed via the NO3− coordination to the equatorial plane toward the Ru–NO axis. We also estimated Gibbs energy differences on the stepwise complexation reactions to succeed in reproducing the fraction of Ru–NO species in 6 M HNO3 solution, such as in HLLW, by considering the association energy between the Ru–NO species and the substituting ligands. Electron density analyses of the complexes indicated that the strength of the Ru–ligand coordination bonds depends on the stability of the Ru species and the Ru complex without NO3− at the axial position is more stable than that with NO3−, which might be attributed to the difference in the trans influence between H2O and NO3−. Finally, we demonstrated the complexation kinetics in the reactions x = 1 → x = 2. The present study is expected to enable us to model the precise complexation reactions of platinum-group metals in HNO3 solution.

Tuning acylthiourea ligands in Ru(II) catalysts for altering the reactivity and chemoselectivity of transfer hydrogenation reactions, and synthesis of 3-isopropoxy-1H-indole through a new synthetic approach

Ru(II)-p-cymene complexes (1–3) containing picolyl based pseudo-acylthiourea ligands (L1-L3) were synthesized and characterized. The crystallographic study confirmed the molecular structures of all the ligands (L1-L3) and complex 3. The catalytic activity of the complexes was tested mainly towards TH of carbonyl compounds and nitroarenes. The influence of steric and electronic effects of the ligands on the chemoselectivity and reactivity were reported. The catalytic activity was enhanced and chemoselectivity was switched after tuning the ligands in the catalysts, compared to their corresponding unmodified Ru(II)-p-cymene complexes. The catalysis was extended to a broad range of substrates including some challenging systems like furfural, benzoylpyridine, benzoquinone, chromanone, etc. The strategy of tuning the bifunctional ligands in the catalysts for effective and selective catalysis worked nicely. Further, the catalysis was extended to one pot synthesis of 3-isopropoxyindole from 2-nitrocinnamaldehyde, the first synthetic route similar to Baeyer Emmerling indole synthesis. All the catalytic experiments exhibited high conversion and selectivity.

Indoles from Alkynes and Aryl Azides: Scope and Theoretical Assessment of Ruthenium Porphyrin-Catalyzed Reactions.

A symbiotic experimental/computational study analyzed the Ru(TPP)(NAr)2 -catalyzed one-pot formation of indoles from alkynes and aryl azides. Thirty different C3 -substituted indoles were synthesized and the best performance, in term of yields and regioselectivities, was observed when reacting ArC≡CH alkynes with 3,5-(EWG)2 C6 H3 N3 azides, whereas the reaction was less efficient when using electron-rich aryl azides. A DFT analysis describes the reaction mechanism in terms of the energy costs and orbital/electronic evolutions; the limited reactivity of electron-rich azides was also justified. In summary, PhC≡CH alkyne interacts with one NAr imido ligand of Ru(TPP)(NAr)2 to give a residually dangling C(Ph) group, which, by coupling with a C(H) unit of the N-aryl substituent, forms a 5+6 bicyclic molecule. In the process, two subsequent spin changes allow inverting the conformation of the sp2 C(Ph) atom and its consequent electrophilic-like attack to the aromatic ring. The bicycle isomerizes to indole via a two-step outer sphere H-migration. Eventually, a 'Ru(TPP)(NAr)' mono-imido active catalyst is reformed after each azide/alkyne reaction.

Design, synthesis and in vitro bioactivity of mixed ligand Ru(II) complexes bearing the fluoroquinolone antibacterial agents

Mixed ligand Ru(II) phenanthroline complexes of the type [Ru(1,10-phen)2Flq]ClO4 (RPFlq-1-3) and “piano-stool”-type Ru(II) arene complexes [Ru(η6-p-cymene)Cl(Flq)] (RAFlq-1-3), where Flq = fluoroquinolone, have been synthesized, characterized and studied for their anticancer potential. DFT calculations were in line with the proposed structures, wherein the fluoroquinolones are coordinated to the metal through the ring carbonyl and one of the carboxylic oxygen atoms in a bidentate fashion. Binding efficacies of the synthesized complexes with bovine serum albumin (BSA) and CT-DNA were studied spectroscopically, and it has been established that the arene complexes, though have moderate binding propensities to CT-DNA (Kb = 0.8–1.7 × 103 M−1), have 102–103-fold better binding efficacies toward BSA (Ka = 3.2 × 105–2.1 × 106 M−1) due to the presence of the hydrophobic arene moiety. These results further prompted a study in their in vitro cytotoxicity assay on A-549 non-small cell lung cancer and MCF7 breast cancer cell lines. Furthermore, gene expression studies on BAX and BCL-2 genes and FACS analysis confirmed apoptosis as the mode of cell death.

Probing the antibacterial and anticancer potential of tryptamine based mixed ligand Schiff base Ruthenium(III) complexes

Development of new chemotherapeutic agents to treat microbial infections and recurrent cancers is of pivotal importance. Metal based drugs particularly ruthenium complexes have the uniqueness and desired properties that make them suitable candidates for the search of potential chemotherapeutic agents. In this study, two mixed ligand Ru(III) complexes [Ru(Cl)2(SB)(Phen] (RC-1) and [Ru(Cl)2(SB)(Bipy)] (RC-2) were synthesised and characterized by elemental analysis, IR, UV–Vis, 1H, 13C NMR spectroscopic techniques and their molecular structure was confirmed by X-ray crystallography. Antibacterial activity evaluation against two Gram-positive (S. pneumonia and E. faecalis) and four Gram-negative strains (P. aurogenosa, K. pneumoniae, S. enterica, and E. coli) revealed their moderate antibacterial activity with MIC value of ≥250 μg/mL. Anticancer activity evaluation against a non-small lung cancer cell line (H1299) revealed the tremendous anticancer activity of these complexes which was further validated by DNA binding and docking results. DNA binding profile of the complexes studied by UV–Visible and fluorescence spectroscopy showed an intercalative binding mode with CT-DNA and an intrinsic binding constant in the range of 3.481–1.015× 105 M−1. Both the complexes were also found to exert weak toxicity to human erythrocytes by haemolytic assay compared to cisplatin. Potential of these complexes as anticancer agents will be further delineated by in vivo studies.

Synthesis, characterization and cytotoxic activity of naturally isolated naringin-metal complexes

High-purity naringin was isolated from the fruit peels of Citrus maxima and characterized by various spectroscopic methods like UV and NMR. The isolated compound ligand (HL) was used as ligand-metal complexes synthesis after using Ag (I), Y (III) and Ru (III) metals. These ligand-metal complexes were characterized by elemental analysis, FT-IR, UV–VIS, TGA, molar conductance and magnetic properties. Cytotoxic activity of the isolated naringin and its metal complexes were investigated against two human cancer cell lines namely, white breast Adenocarcinoma (MCF7) and Lung carcinoma (A549) using cell viability assay. Transition metal increased the cytotoxic activity of naringin when they were conjugated. LC50 of Ag ligand complex demonstrated strong cytotoxicity against MCF-7 and A549 cell line that was found higher active more than three and four times the strength, respectively when compared to LC50 of Adriamycin. While LC50 of Adriamycin compound was slightly more active only about 30% and twice the strength of the Ru ligand complex against MCF-7 and A549 cell line, respectively.

Fluorination on non-photolabile dppz ligands for improving Ru(ii) complex-based photoactivated chemotherapy.

Ru(ii) polypyridine complexes which can undergo photo-induced ligand dissociation and subsequent DNA covalent binding may potentially serve as photoactivated chemotherapeutic (PACT) agents. In this paper, three fluorinated dppz ligand coordinated Ru(ii) complexes (2-4) containing four monodentate pyridine ligands were studied. All complexes released one pyridine and covalently bound to DNA upon 470 nm irradiation. Compared with the parent complex [Ru(dppz)(py)4]2+ (1), 2-4 displayed enhanced phototoxicity but diminished dark cytotoxicity, more favorable for PACT application. Complex 3 is the most efficient one with IC50 values of about 8 μM toward HeLa and SKOV-3 cell lines, and also has a much higher IC50 value toward normal L-02 cells. Our results indicate that fluorination on the retaining ligand may be an efficient way to improve the drug activity of Ru(ii) PACT agents.

Unravelling the aggregation induced emission enhancement in Tris(4,7-diphenyl-1,10-phenanthroline)ruthenium(II) complex

For the first time, we unearthed the aggregation induced emission enhancement of well-known ruthenium(II) complex attached with bathophenanthroline ligand, Ru(dpphen)32+ (dpphen = 4,7-diphenyl-1,10-phenanthroline). Complex Ru(dpphen)32+ displayed a weak emission at 613 nm in CH3CN while exciting at its MLCT band (464 nm). However, upon response with incremental addition of poor and viscous solvents into the CH3CN solution of Ru(dpphen)32+, the emission intensity drastically increased due to the formation of nanoaggregates. Restricted intramolecular rotation (RIR) of peripheral phenyl rings attached to the bathophenanthroline ligands in Ru(dpphen)32+ complex is responsible for this unique phenomenon, thereby stimulates the emission intensity. The formation of these nanoaggregates was confirmed by TEM studies.

Ru(II) Polypyridyl Complexes Derived from Tetradentate Ancillary Ligands for Effective Photocaging.

Metal complexes have many proven applications in the caging and photochemical release of biologically active compounds. Photocaging groups derived from Ru(II) traditionally have been composed of ancillary ligands that are planar and bi- or tridentate, such as 2,2'-bipyridine (bpy), 2,2':6',2″-terpyridine (tpy), and 1,10-phenanthroline (phen). Complexes bearing ancillary ligands with denticities higher than three represent a new class of Ru(II)-based photocaging groups that are grossly underdeveloped. Because high-denticity ancillary ligands provide the ability to increase the structural rigidity and control the stereochemistry, our groups initiated a research program to explore the applications of such ligands in Ru(II)-based photocaging. Ru(TPA), bearing the tetradentate ancillary ligand tris(2-pyridylmethyl)amine (TPA), has been successfully utilized to effectively cage nitriles and aromatic heterocycles. Nitriles and aromatic heterocycles caged by the Ru(TPA) group show excellent stability in aqueous solutions in the dark, and the complexes can selectively release the caged molecules upon irradiation with light. Ru(TPA) is applicable as a photochemical agent to offer precise spatiotemporal control over biological activity without undesired toxicity. In addition, Ru(II) polypyridyl complexes with desired photochemical properties can be synthesized and identified by solid-phase synthesis, and the resulting complexes show properties to similar to those of complexes obtained by solution-phase synthesis. Density functional theory (DFT) calculations reveal that orbital mixing between the π* orbitals of the ancillary ligand and the Ru-N dσ* orbital is essential for ligand photodissociation in these complexes. Furthermore, the introduction of steric bulk enhances the photoliability of the caged molecules, validating that steric effects can largely influence the quantum efficiency of photoinduced ligand exchange in Ru(II) polypyridyl complexes. Recently, two new photocaging groups, Ru(cyTPA) and Ru(1-isocyTPQA), have been designed and synthesized for caging of nitriles and aromatic heterocycles, and these complexes exhibit unique photochemical properties distinct from those derived from Ru(TPA). Notably, the unusually greater quantum efficiency for the ligand exchange in [Ru(1-isocyTPQA)(MeCN)2](PF6)2, Φ400 = 0.033(3), uncovers a trans-type effect in the triplet metal-to-ligand charge transfer (3MLCT) state that enhances photoinduced ligand exchange in a new manner. DFT calculations and ultrafast transient spectroscopy reveal that the lowest-energy triplet state in [Ru(1-isocyTPQA)(MeCN)2](PF6)2 is a highly mixed 3MLCT/3ππ* excited state rather than a triplet metal-centered ligand-field (3LF) excited state; the latter is generally accepted for ligand photodissociation. In addition, Mulliken spin density calculations indicate that a majority of the spin density in [Ru(1-isocyTPQA)(MeCN)2](PF6)2 is localized on the isoquinoline arm, which is opposite to the cis MeCN, rather than on the ruthenium center. This significantly weakens the Ru-N6 ( cis MeCN) bond, which then promotes the ligand photodissociation. This newly discovered effect gives a clearer perception of the interplay between the 3MLCT and 3LF excited states of Ru(II) polypyridyl complexes, which may be useful in the design and applications of ruthenium complexes in the areas of photoactivated drug delivery and photosensitizers.