Ru Polypyridyl Complexes Research Articles

Application of bioorganometallic B12 in green organic synthesis.

Bioorganometallic structure found in coenzyme B12 is a key component in B12-dependent enzymatic reactions in natural enzymes. Cleavage of a cobalt-carbon bond in organometallic B12 compound provide reactive intermediate for molecular transformations. Application of the bioorganometallic B12 in organic synthesis have been developed using natural vitamin B12 as well as synthetic vitamin B12 derivatives as a bioinspired catalyst in organic solvent. Vitamin B12 derivatives composed of corrinoid structure should form stable organometallic compound having a cobalt-carbon bond. Using the unique property of the organometallic vitamin B12 derivatives, various catalytic reactions have been developed in synthetic organic chemistry. The dual catalytic system of vitamin B12 derivatives and photocatalyst, such as Ru(II) polypyridyl complex or titanium oxide, could construct light-driven molecular transformations. The B12-dependent enzymes mimic reactions, such as the dechlorination of organic halides and the radical mediated isomerization reactions, catalytically proceed in the dual catalyst system. Electroorganic syntheses mediated by the vitamin B12 derivatives have been developed as green molecular transformations. The redox active vitamin B12 derivatives shows a unique catalysis in the electroorganic synthesis, such as alkene and alkyne reductions.

Physico-Chemical Characterization Studies of Collagen Labelled with Ru(II) Polypyridyl Complex

Physico-Chemical Characterization Studies of Collagen Labelled with Ru(II) Polypyridyl Complex

Increasing the cytotoxicity of Ru(II) polypyridyl complexes by tuning the electron-donating ability of 1,10-phenanthroline ligands.

Ruthenium (Ru)-based chemotherapeutic agents are a choice to replace traditional platinum-containing metallodrugs due to fewer side effects. It has been proved that the mechanism of Ru complex drugs is to highly likely bind with DNA and certain proteins, which also highly depends on the electronic structures of Ru complexes. However, the relationship between electronic properties and chemotherapeutic activities has not yet been completely systemically investigated, which limits the effective drug design strategies. Herein, we propose that increasing the electron densities of Ru would enhance the nucleophilic substitution rate of chlorine atoms (Cl) on Ru, providing better bioactivity against both amino acids and nucleic acids. A series of complexes with various optimized electron-donating groups (EDGs) were synthesized according to DFT calculations. In addition, kinetics substitution with L-histidine, DNA binding experiments, and cell cytotoxicity studies verified our assumptions. Surprisingly, these complexes could also be potential cellular imaging probes via an unprecedented "off-on" light-switching mechanism of living cells, which was caused by the "HOMO-LUMO" distribution changes of Ru complexes after interaction with DNA. Accordingly, the reactivity and selectivity demonstrated by these compounds support the further development of these Ru complexes in cancer treatments and afford strategic perspectives on the development of metal complexes as chemotherapeutic agents and bioimaging probes.

Ru(II)-Based Acetylacetonate Complexes Induce Apoptosis Selectively in Cancer Cells.

The synthesis, chemical and biological characterization of seven Ru(II) polypyridyl complexes containing acetylacetonate (acac) ligands are reported. Electronic absorption spectra were determined and electrochemical potentials consistent with Ru(III/II) couples ranging from +0.60 to +0.73 V vs Ag/AgCl were measured. A series of complexes were screened against MDA-MB-231, DU-145, and MCF-10A cell lines to evaluate their cytotoxicities in cancer and normal cell lines. Although most complexes were either nontoxic or equipotent in cancer cells and normal cell lines, compound 1, [Ru(dpqy)(acac)(py)](PF6), where dqpy is 2,6-di(quinolin-2-yl)pyridine, showed up to 2.5:1.0 selectivity for cancer as compared to normal cells, along with nanomolar EC50 values in MDA-MB-231 cells. Lipophilicity, determined as the octanol/water partition coefficient, log Po/w, ranged from -0.33 (0.06) to 1.15 (0.10) for the complexes. Although cytotoxicity was not correlated with electrochemical potentials, a moderate linear correlation between lipophilicity and toxicities was observed. Cell death mechanism studies indicated that several of the Ru-acac compounds, including 1, induce apoptosis in MDA-MB-231 cells.

Recent Approaches towards the Development of Ru(II) Polypyridyl Complexes for Anticancer Photodynamic Therapy.

Photodynamic therapy (PDT) is a remarkable alternative or complementary technique to chemotherapy, radiotherapy or immunotherapy to treat certain forms of cancer. The synergistic effect of light, photosensitizer (PS) and oxygen allows for the treatment of tumours with an extremely high spatio-tumoral control, therefore minimizing the severe side effects usually observed in chemotherapy. The currently employed PDT PSs based on porphyrins have, in some cases, some limitations, which include a low absorbance in the therapeutic window, a low body clearance, photobleaching, among others. In this context, Ru(ii) polypyridyl complexes are interesting alternatives. They have low lying excited energy states and the presence of a heavy metal increases the possibility of spin-orbit coupling. Moreover, their photophysical properties are relatively easy to tune and they have very low photobleaching rates. All of these make them attractive candidates for further development as therapeutically suitable PDT PSs. In this review, after having presented this field of research, we discuss the developments made by our group in this field of research since 2017. We notably describe how we tuned the photophysical properties of our complexes from the visible region to the therapeutically suitable red region. This was accompanied by the preparation of PSs with enhanced phototoxicity and high phototoxicity index. We also discuss the use of two-photon excitation to eradicate tumours in nude mice. Furthermore, we describe our approach for the selective delivery of our complexes using targeting agents. Lastly, we report on our very recent synergistic approach to treat cancer using bimetallic Ru(ii)-Pt(iv) prodrug candidates.

Inhibition of Matrix Metalloproteinases and Cancer Cell Detachment by Ru(II) Polypyridyl Complexes Containing 4,7-Diphenyl-1,10-phenanthroline Ligands-New Candidates for Antimetastatic Agents.

Primary tumor targeting is the dominant approach in drug development, while metastasis is the leading cause of cancer death. Therefore, in addition to the cytotoxic activity of a series of Ru(II) polypyridyl complexes of the type [Ru(dip)2L]2+ (dip: 4,7-diphenyl-1,10-phenanthroline while L = dip; bpy: 2,2′-bipyridine; bpy-SC: bipyridine derivative bearing a semicarbazone 2-formylopyridine moiety; dpq, dpq(CH3)2, dpb: quinoxaline derivatives) their ability to inhibit cell detachment was investigated. In vitro studies performed on lung cancer A549 cells showed that they accumulate in cells very well and exhibit moderate cytotoxicity with IC50 ranging from 4 to 13 µM. Three of the studied compounds that have dip, bpy-SC, or dpb ligands after treatment of the cells with a non-toxic dose (<1/2IC50) enhanced their adhesion properties demonstrated by lower detachment in the trypsin resistance assay. The same complexes inhibited both MMP-2 and MMP-9 enzyme activities with IC50 ranging from 2 to 12 µM; however, the MMP-9 inhibition was stronger. More detailed studies for [Ru(dip)2(bpy-SC)]2+, which induced the greatest increase in cell adhesion, revealed that it is predominately accumulated in the cytoskeletal fraction of A549 cells. Moreover, cells treated with this compound showed the localization of MMP-9 to a greater extent also in the cytoskeleton. Taken together, our results indicate the possibility of a reduction of metastatic cells escaping from the primary lesion to the surrounding tissue by prevention of their detachment and by influencing the activity of MMP-2 and MMP-9.

Effect of Alkyl Chain Length on the Photophysical, Photochemical, and Photobiological Properties of Ruthenium(II) Polypyridyl Complexes for Their Application as DNA-Targeting, Cellular-Imaging, and Light-Activated Therapeutic Agents.

A family of six Ru(II) polypyridyl complexes (1-6) which contain phenanthroline-based ligands functionalized with alkyl chains of different lengths (one methyl group, 10 and 21 carbon alkyl chains) and either 1,10-phenanthroline (phen) or 1,4,5,8-tetraazaphenanthrene (TAP) as ancillary ligands have been synthesized and characterized. The influence of the alkyl chain length on their photophysical and photochemical properties as well as in their photobiological applications has been elucidated by monitoring the changes in their MLCT-centered absorption and emission bands. The presence of one methyl group or 10 carbon alkyl chains does not seem to significantly affect the photophysical and photochemical properties of the resulting Ru(II) complexes when compared to the well-known [Ru(phen)3]2+ and [Ru(TAP)2phen]2+. However, an effect on their emission properties and in their ability to photosensitize singlet oxygen is observed for the Ru(II) complexes containing 21 carbon alkyl chains. The binding of these complexes to salmon testes DNA (stDNA) was investigated by observing the changes in the photophysical properties. Complexes 1, 2, 4, and 5 all showed changes in their MLCT bands that could be analyzed using conventional fitting methods, such as the Bard equation. In contrast, complexes 3 and 6, possessing long aliphatic chains, gave rise to nonclassic behavior. In addition to these analyses, both thermal denaturation and circular dichroism studies of 1-6 were carried out in the presence of stDNA which confirmed that these complexes bind to DNA. Confocal microscopy and viability studies in HeLa cervical cancer cells reveal an alkyl chain-length dependence on the cellular uptake and cytotoxicity of the resulting Ru(II) complexes due to an enhancement of their lipophilicity with increasing alkyl chain length. Thus, complexes containing 10 and 21 carbon alkyl chains are rapidly taken up into HeLa cells and, in particular, those with 21 carbon alkyl chains show a significant phototoxicity against the same cell line. Therefore, this study provides further insight into the possible modulation of the photophysical, photochemical, and photobiological properties of Ru(II) polypyridyl complexes by varying the length of the alkyl chains attached to the polypyridyl ligands coordinated to the Ru(II) center and the nature of the auxiliary groups, which we show has a significant effect on photophysical and biological properties.

Biological Investigations of Ru(II) Complexes With Diverse β-diketone Ligands.

The β-diketone scaffold is a commonly used synthetic intermediate, and is a functional group found in natural products such as curcuminoids. This core structure can also act as a chelating ligand for a variety of metals. In order to assess the potential of this scaffold for medicinal inorganic chemistry, seven different κ2-O,O'-chelating ligands were used to construct Ru(II) complexes with polypyridyl co-ligands, and their biological activity was evaluated. The complexes demonstrated promising structure-dependent cytotoxicity. Three complexes maintained high activity in a tumor spheroid model, and all complexes demonstrated low in vivo toxicity in a zebrafish model. From this series, the best compound exhibited a ~ 30-fold window between cytotoxicity in a 3-D tumor spheroid model and potential in vivo toxicity. These results suggest that κ2-O,O'-ligands can be incorporated into Ru(II)-polypyridyl complexes to create favorable candidates for future drug development.

Probing the acetylcholinesterase inhibitory activity of a novel Ru(II) polypyridyl complex and the supramolecular interaction by (STD)-NMR

Currently, acetylcholinesterase (AChE) inhibitors are the only anti-Alzheimer drugs commercially available. Despite their wide use those drugs are all dose dependent and their effect last for no longer than two years, with several side effects. The search of novel acetylcholinesterase (AChE) inhibitors remains as the main scientific route. Here we describe the synthesis, characterization, biological activity and an NMR binding-target study of a novel cis-[Ru(Bpy)2(EtPy)2]2+, (RuEtPy), Bpy = 2,2′-bipyridine and EtPy = 4,2-Ethylamino-pyridine) as a potential AChE inhibitor. The classic Ellman's colorimetric assay suggests that the RuEtPy exhibits a high inhibitory activity, following a competitive mechanism, with a remarkable low inhibition constant (Ki ≈ 16.8 μM), together with a IC50 = 39 μM. Hence, we have studied the spatial interactions for this novel candidate towards the human acetylcholinesterase (hAChE) using saturation transfer difference (STD)-NMR, in order to describe the mechanism of the interaction. NMR binding-target results shows that the 4,2-Ethylamino-Pyridine group is spatially closer to hAChE surface chemical arrangement than 2,2′ bipyridine counterpart, exerting an efficient intermolecular interaction, with a low dissociation constant (KD ≈ 55 μM), probing that 4,2-Ethylamino-pyridine motif plays a key role in the inhibitory action.

The cell-impermeable Ru(II) polypyridyl complex as a potent intracellular photosensitizer under visible light irradiation via ion-pairing with suitable lipophilic counter-anions

Developing the cell-impermeable Ru(II) polypyridyl cationic complexes as effective photosensitizers (PS) which have high cellular uptake and photo-toxicity, but low dark toxicity, is quite challenging. Here we found that the highly reactive singlet oxygen (1O2) can be generated by the irradiation of a typical Ru(II) polypyridyl complex Ru(II)tris(tetramethylphenanthroline) ([Ru(TMP)3]2+) under visible light irradiation by ESR with TEMPO (2,2,6,6-tetramethyl-4-piperidone-N-oxyl) as 1O2 probe. Effective cellular and nuclear delivery of cationic [Ru(TMP)3]2+ was achieved through our recently developed ion-pairing method, and 2,3,4,5-tetrachlorophenol (2,3,4,5-TeCP) was found to be the most effective among all chlorophenols tested. The accelerated cellular, especially nuclear uptake of [Ru(TMP)3]2+ results in the formation of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and DNA strand breaks, caspase 3/7 activation and cell apoptosis in HeLa cells upon light irradiation. More importantly, compared with other traditional photosensitizers, [Ru(TMP)3]2+ showed significant photo-toxicity but low dark toxicity. Similar effects were observed when 2,3,4,5-TeCP was substituted by the currently clinically used anti-inflammatory drug flufenamic acid. This represents the first report that the cell-impermeable Ru(II) polypyridyl complex ion-paired with suitable lipophilic counter-anions functions as potent intracellular photosensitizer under visible light irradiation mainly via a 1O2-mediated mechanism. These findings should provide new perspectives for future investigations on other metal complexes with similar characteristics as promising photosensitizers for potential photodynamic therapy.

Chiral ruthenium(II) complexes as stabilizers for an RNA triplex: In contrast to Λ-enantiomer, Δ-enantiomer stabilizes the Watson-Crick duplex and the Hoogsteen strand without significant preference

To further determine the factors governing the triplex stabilization by chiral ruthium(II) polypyridyl complexes, two new dppz-beased binding reagents, Δ-[Ru(bpy)2(6-NO2-dppz)]2+ (Δ-1; bpy = 2,2′-bipyridine; 6-NO2-dppz = 6-nitro-dipyrido-3,2-a,2′,3′-c]phenazine) and Λ-[Ru(bpy)2(6-NO2-dppz)]2+ (Λ-1), have been synthesized and characterized in this work. Binding properties of the two enantiomers Δ-1 and Λ-1 with the RNA poly(U)•poly(A)*poly(U) triplex have been studied by spectroscopic technologies and viscosity measurements as well as melting measurements. Spectral titrations and viscosity experiments as well as light-scattering experiments show that although the two enantiomers bind to the triplex through an intercalative mode, the binding affinity of Δ-1 toward the triplex is slightly higer than that of Λ-1. Moreover, melting measurements show that the two enantiomers exhibit different stabilization effects on the triplex under the same conditions. The enantiomer Δ-1 stabilizes the triplex without significant preference, thereby almost equally stabilizing the Watson-Crick base-paired duplex (the template duplex) and the Hoogsteen base-paired strand (third-strand) of the triplex. In contrast to Δ-1, Λ-1 shows preference for stabilizing the template duplex rather than third-strand to a large extent. This suggests that the racemic complex [Ru(bpy)2(6-NO2-dppz)]2+ is similar as a non-specific metallointercalator for the triplex investigated in this study. The results obtained in this work show that in addition to chiralities of Ru(II) polypyridyl complexes, substituent effects of the main ligands also play important roles in altering the ability and selectivity of the metal complex enantiomers to stabilize the triplex.

Photoactive Zr and Ti Metal‐Organic‐Frameworks for Solid‐State Solar Cells

Solid-state photovoltaic cells based on robust metal-organic frameworks (MOFs), MIL-125(Ti), MIL-125(Ti)-NH2 , UiO-67, Ru(bpy)2 -UiO-67, (bpy 2,2'-bipyridine) as active components and spiro-MeOTAD (MeOTAD 2,2',7,7'-tetrakis[N,N-di(p-methoxyphenyl)amino]-9,9'-spirobifluorene) as hole transporting layer have been prepared., The photovoltaic response of this material increases in the presence of bathochromic -NH2 groups on the linker or Ru (II) polypyridyl complexes light harvester. These results show that the strategies typically employed in photocatalysis to enhance the photocatalytic activity of MOFs can also be applied in the field of photovoltaic devices.

Substituent effects on the interactions of ruthenium(II) polypyridyl complexes [Ru(bpy)2(6-R-dppz)]2+ (R = hydroxy and fluorine) with the RNA triplex poly(rU)·poly(rA) × poly(rU)

Two new ruthenium(II) polypyridyl complexes, [Ru(bpy)2(6-OH-dppz)]2+ (Ru1, bpy = 2,2′-bipyridine, 6-OH-dppz = 6-hydroxydipyrido[3,2-a:2′,3′-c]phenazine) and [Ru(bpy)2(6-F-dppz)]2+ (Ru2, 6-F-dppz = 6-fluorodipyrido[3,2-a:2′,3′-c]-phenazine), have been synthesized and characterized in this work. The interactions of Ru1 and Ru2 with the RNA triplex poly(rU)·poly(rA) × poly(rU) have been investigated by spectroscopic and viscometric techniques. Spectral titrations and viscosity experiments show that the binding modes of Ru1 and Ru2 to the triplex are intercalation, with the binding affinity for Ru2 being greater than that for Ru1. Fluorescence titrations indicate that Ru2, unlike Ru1, can act as a “molecular light switch” for the triplex. Furthermore, thermal denaturation experiments suggest that Ru1 and Ru2 stabilize the Hoogsteen base-paired strand (third-strand) of the triplex without significant differences, while the two complexes exhibit different selective stabilizing effects toward the triplex. In contrast to Ru1, Ru2 shows a preference for stabilizing the template duplex under the conditions used in this study. Results of the present work demonstrate that the electronic effects of substituents on the main ligands can significantly affect the binding and stabilization effects of Ru(II) polypyridyl complexes toward the RNA triplex poly(rU)·poly(rA) × poly(rU).

Ruthenium polypyridyl complex-containing bioconjugates

• Bioconjugation improves some of the features of Ru(II) polypyridyl complexes • The intrinsic properties of the complexes are not usually altered by the bioconjugation. • Peptides are among the most common biomolecules used in bioconjugation with Ru(II) complexes. • The bioconjugates were used for different purposes. In the last decades, the number of articles describing the synthesis, characterization and applications of ruthenium polypyridyl complexes has significantly increased. One of the reasons is their tuneable, outstanding luminescent properties. However, ruthenium polypyridyl complexes usually have no intrinsic selectivity towards cancer cells, making them impractical, for example, in certain biological applications. To overcome this drawback, these complexes have been conjugated to biomolecules. In this review, we describe the different ruthenium polypyridyl complex-containing bioconjugates reported so far and their applications as, for example, anticancer drug candidates, sensors or biocatalysts. However, we are not reviewing ruthenium-containing nucleotides and DNA conjugates since these topics were recently reported. The multiple ways of attaching the biomolecules (i.e., peptides, antibodies, carbohydrates, lipids and vitamins) to the ruthenium core are also summarized.

Recent developments in metal‐free organic sensitizers derived from carbazole, triphenylamine, and phenothiazine for dye‐sensitized solar cells

In the present context of increasing population, renewable and sustainable energy alternatives are very much essential to satisfy the necessities of the world. To satisfy this growing demand, scientists are prioritizing the production of cost-effective and high-performance clean energy appliances. Dye-sensitized solar cells (DSSCs) are one such material that is at the forefront of modern solar cell technologies. Being one of the main components of DSSCs, metal-free organic dyes play a crucial role in light processing and electron injection. In recent times, carbazole (CZ)-, triphenylamine (TPA)-, and phenothiazine (PTZ)-based derivatives have been identified as suitable alternatives to Ru(II) polypyridyl complexes because they are easy to synthesize and exhibit excellent thermal and electronic properties. This review focuses largely on the latest developments in the use of monoanchored and multianchored CZ, TPA, and PTZ scaffolds for DSSC applications and focuses especially on the correlation between molecular design and photovoltaic performance. The physical properties of devices can be adjusted through the sensitizer's strategic design that helps to improve the performance of the devices. We tabulated the photovoltaic parameters corresponding to all dyes presented in this review. Also, applications of additives are presented after the systematic review on CZ-, TPA-, and PTZ-based dyes.

Tuning the lability of a series of Ru(II) polypyridyl complexes: a comparison of experimental-kinetic and DFT-predicted reaction mechanisms

This report deals with a comparison of experimentally obtained kinetic and activation parameter data, and theoretical DFT computations, in terms of mechanistic information on the water exchange and water displacement reactions by thiourea for a series of complexes of the type [RuII(terpy)(N^N)(H2O)]2+, where terpy = 2,2′:6′,2″-terpyridine and N^N represents ethylenediamine (en), 2-(aminomethyl)pyridine (ampy), 2,2′-bipyridine (bipy), 1,10-phenantroline (phen), and N,N,N′,N′-tetramethylethylenediamine (tmen). The complexes were all isolated in the form of [Ru(terpy)(N^N)Cl]X (X = Cl– or ClO4 –) compounds and fully characterized in both the solid state and in solution. The DFT calculations revealed further mechanistic insight into the water exchange reactions as well as the water displacement reactions by thiourea. Both the experimental activation parameters and the DFT calculations suggest the operation of an associative interchange (Ia ) mechanism for both reaction types studied.

Practical considerations in the application of a polypyridyl complex of Ru(II) in physiological and biochemical studies of Pectobacterium spp. and other bacteria

Assessment of bacterial growth is an essential tool in many fields of study. Numerous methods are available for that purpose, but they are not without disadvantages. The present study aimed to investigate the application of a water soluble oxygen sensor [Ru(dpp(SO3Na)2)3]Cl2x6H2O (RuBPS) in physiological and biochemical studies of Pectobacterium spp. and other bacteria in 96-well microplate systems. The method was optimized with respect to compound concentration, microplate type, and measurement parameters. The growth of bacteria was assessed under increased salinity, acidic and alkaline pH, decreased water availability, and osmotic stress. Utilization of various sugars by bacteria as the only carbon source and the usefulness of RuBPS in antibiotic susceptibility assays were also investigated. The studies confirmed that the respirometry assay can be successfully used to assess bacterial growth in place of the optical density measurement and the resazurin assay, or in conjugation with those methods. The assay is of special value when growth media are non-homogeneous, bacteria produce reductive compounds during growth, or when bacteria do not grow well in the medium of choice. It may be used to study adaptation potential of plant pathogenic bacteria and other bacteria, and their possible spread into new ecological niches.

Mechanistic investigation of the aerobic oxidation of 2-pyridylacetate coordinated to a Ru(II) polypyridyl complex.

A new ruthenium polypyridyl complex, [Ru(bpy)2(acpy)]+ (acpy = 2-pyridylacetate, bpy = 2,2'-bipyridine), was synthesized and fully characterized. Distinct from the previously reported analog, [Ru(bpy)2(pic)]+ (pic = 2-pyridylcarboxylate), the new complex is unstable under aerobic conditions and undergoes oxidation to yield the corresponding α-keto-2-pyridyl-acetate (acpyoxi) coordinated to the RuII center. The reaction is one of the few examples of C-H activation at mild conditions using O2 as the primary oxidant and can provide mechanistic insights with important implications for catalysis. Theoretical and experimental investigations of this aerobic oxidative transformation indicate that it takes place in two steps, first producing the α-hydroxo-2-pyridyl-acetate analog and then the final product. The observed rate constant for the first oxidation was in the order of 10-2 h-1. The reaction is hindered in the presence of coordinating solvents indicating the role of the metal center in the process. Theoretical calculations at the M06-L level of theory were performed for multiple reaction pathways in order to gain insights into the most probable mechanism. Our results indicate that O2 binding to [Ru(bpy)2(acpy)]+ is favored by the relative instability of the six-ring chelate formed by the acpy ligand and the resulting RuIII-OO˙- superoxo is stabilized by the carboxylate group in the coordination sphere. C-H activation by this species involves high activation free energies (ΔG‡ = 41.1 kcal mol-1), thus the formation of a diruthenium μ-peroxo intermediate, [(RuIII(bpy)2(O-acpy))2O2]2+via interaction of a second [Ru(bpy)2(acpy)]+ was examined as an alternative pathway. The dimer yields two RuIVO centers with a low ΔG‡ of 2.3 kcal mol-1. The resulting RuIVO species can activate C-H bonds in acpy (ΔG‡ = 23.1 kcal mol-1) to produce the coordinated α-hydroxo-2-pyridylacetate. Further oxidation of this intermediate leads to the α-keto-2-pyridyl-acetate product. The findings provide new insights into the mechanism of C-H activation catalyzed by transition-metal complexes using O2 as the sole oxygen source.

Modification of amyloid-beta peptide aggregation via photoactivation of strained Ru(ii) polypyridyl complexes.

Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by progressive and irreversible damage to the brain. One of the hallmarks of the disease is the presence of both soluble and insoluble aggregates of the amyloid beta (Aβ) peptide in the brain, and these aggregates are considered central to disease progression. Thus, the development of small molecules capable of modulating Aβ peptide aggregation may provide critical insight into the pathophysiology of AD. In this work we investigate how photoactivation of three distorted Ru(ii) polypyridyl complexes (Ru1–3) alters the aggregation profile of the Aβ peptide. Photoactivation of Ru1–3 results in the loss of a 6,6′-dimethyl-2,2′-bipyridyl (6,6′-dmb) ligand, affording cis-exchangeable coordination sites for binding to the Aβ peptide. Both Ru1 and Ru2 contain an extended planar imidazo[4,5-f][1,10]phenanthroline ligand, as compared to a 2,2′-bipyridine ligand for Ru3, and we show that the presence of the phenanthroline ligand promotes covalent binding to Aβ peptide His residues, and in addition, leads to a pronounced effect on peptide aggregation immediately after photoactivation. Interestingly, all three complexes resulted in a similar aggregate size distribution at 24 h, forming insoluble amorphous aggregates as compared to significant fibril formation for peptide alone. Photoactivation of Ru1–3 in the presence of pre-formed Aβ1–42 fibrils results in a change to amorphous aggregate morphology, with Ru1 and Ru2 forming large amorphous aggregates immediately after activation. Our results show that photoactivation of Ru1–3 in the presence of either monomeric or fibrillar Aβ1–42 results in the formation of large amorphous aggregates as a common endpoint, with Ru complexes incorporating the extended phenanthroline ligand accelerating this process and thereby limiting the formation of oligomeric species in the initial stages of the aggregation process that are reported to show considerable toxicity.

Synthesis and Characterization of Ru(II) Polypyridyl Complexes with 2-(4-Methylbenzoate)-1H-imidazo[4,5-f][1,10]phenantroline Ligand, and Their DNA Binding, Photocleavage, Physico-Chemical Properties, and Cytotoxicity

In search for efficient chemotherapeutic agents, we have synthesized a novel MBIP 2-(4-methylbenzoate)-1H-imidazo[4,5-f][1,10]phenantroline and its Ru(II) polypyridyl complexes of the general formula [Ru(N–N)2(L)]2+ (where N–N = phen (1,10-phenanthroline), bpy (2,2ʹ-bipyridine), dmb (4,4ʹ-dimethyl-2,2ʹ-bipyridine), and L = MBIP. All complexes have been characterized by analytical and spectroscopic methods. Physico-chemical properties of the synthesized complexes such as stability and lipophilicity have been studied. Interaction of Ru(II) complexes with calf-thymus DNA (CT-DNA) has been explored by different spectrophotometric methods. Spectral and viscosity data indicate that all the complexes are probably involved in intercalative binding with DNA. These complexes can cleave pBR322 DNA efficiently via oxidative pathway involving singlet oxygen under photoirradiation. The DNA molecular light switch on and off performance of Ru(II) complexes has been studied. According to antimicrobial activity assays the complexes are potential agents against gram positive and gram negative bacteria. In vitro cytotoxicity has been evaluated by MTT assay against HeLa cell lines, being compared to cisplatin. The live cell imaging and lipophilicity results have revealed that the complexes can possibly cross the cell membranes and accumulate in the nucleus. The cellular localization of Ru(II) complexes determined by their lipophilicity can probably affect their anticancer efficacy and mechanism of action.