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1.
Inorg Chem ; 58(16): 10778-10790, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31386351

RESUMO

A new family of cyclometalated ruthenium(II) complexes [Ru(N^N)2(C^N)]+ derived from the π-extended benzo[h]imidazo[4,5-f]quinolone ligand appended with thienyl groups (n = 1-4, compounds 1-4) was prepared and its members were characterized for their chemical, photophysical, and photobiological properties. The lipophilicities of 1-4, determined as octanol-water partition coefficients (log Po/w), were positive and increased with the number of thienyl units. The absorption and emission bands of the C^N compounds were red-shifted by up to 200 nm relative to the analogous Ru(II) diimine systems. All of the complexes exhibited dual emission with the intraligand fluorescence (1IL, C^N-based) shifting to lower energies with increasing n and the metal-to-ligand charge transfer phosphorescence (3MLCT, N^N-based) remaining unchanged. Compounds 1-3 exhibited excited state absorption (ESA) profiles consistent with lowest-lying 3MLCT states when probed by nanosecond transient absorption (TA) spectroscopy with 532 nm excitation and had contributions from 1IL(C^N) states with 355 nm excitation. These assignments were supported by the lifetimes observed (<10 ns for the 1IL states and around 20 ns for the 3MLCT states) as well as a noticeable ESA for 3 with 355 nm excitation that did not occur with 532 nm excitation. Compound 4 was the only member of the family with two 3MLCT emissive lifetimes (15, 110 ns), and the TA spectra collected with both 355 and 532 nm excitation was assigned to the 3IL state, which was corroborated by its 4-6 µs lifetime. The ESA for 4 had a rise time of approximately 10 ns and an initial decay of 110 ns, which suggests a possible 3MLCT-3IL excited state equilibrium that results in delayed emission from the 3MLCT state. Compound 4 was nontoxic toward human skin melanoma cells (SKMEL28) in the dark (EC50 = >300 µM); 1-3 were cytotoxic and yielded EC50 values between 1 and 20 µM. The photocytotoxicites with visible light ranged from 87 nM with a phototherapeutic index (PI) of 13 for 1 to approximately 1 µM (PI = >267) for 4. With red light, EC50 values varied from 270 nM (PI = 21) for 3 to 12 µM for 4 (PI = >25). The larger PIs for 4, especially with visible light, were attributed to the much lower dark cytotoxicity for this compound. Because the dark cytotoxicity contributes substantially to the observed photocytotoxicity for 1-3, it was not possible to assess whether the 3IL state of 4 led to a much more potent phototoxic mechanism in the absence of dark toxicity. There was no stark contrast in cellular uptake and accumulation by laser scanning confocal and differential interference contrast microscopy to explain the large differences in dark toxicities between 1-3 and 4. Nevertheless, the study highlights a new family of Ru(II) C^N complexes where π-conjugation beyond a certain point results in low dark cytotoxicity with high photocytotoxicity, opposing the notion that cyclometalated Ru(II) systems are too toxic to be phototherapeutic agents.


Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Quinolonas/farmacologia , Rutênio/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Ligantes , Luz , Estrutura Molecular , Processos Fotoquímicos , Fotoquimioterapia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Quinolonas/química , Rutênio/química
2.
Chemistry ; 25(55): 12789-12794, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31385356

RESUMO

Ruthenium-arene complexes are a unique class of organometallic compounds that have been shown to have prominent therapeutic potencies. Here, we have investigated the interactions of Ru-cymene complexes with a zinc-finger protein NCp7, aiming to understand the effects of various ligands on the reaction. Five different binding modes were observed on selected Ru-complexes. Ru-cymene complex can bind to proteins through either noncovalent binding alone or through a combination of covalent and noncovalent binding modes. Moreover, the noncovalent interaction can promote the coordination of RuII to NCp7, resulting synergistic effects of the different ligands. The binding of Ru(Cym) complexes leads to dysfunction of NCp7 through zinc-ejection and structural perturbation. These results indicate that the reactivity of Ru-complexes can be modulated by ligands through different approaches, which could be closely correlated to their different therapeutic effects.


Assuntos
Rutênio/química , Dedos de Zinco/fisiologia , Antineoplásicos/química , Ligantes , Monoterpenos
4.
Chem Commun (Camb) ; 55(73): 10972-10975, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31453611

RESUMO

Platinum-resistant cancer cells are sensitive to changes in the levels of reactive oxidative species (ROS). Herein, we design a biotin-modified Ru(ii) complex as a photosensitizer (denoted as Ru-Biotin). Ru-Biotin can selectively target cancer cells and produce vast amounts of singlet oxygen under two-photon excitation at 820 nm leading to cell apoptosis. Ru-Biotin is therefore an excellent candidate to overcome platinum resistance via two-photon photodynamic therapy.


Assuntos
Antineoplásicos/farmacologia , Biotina/análogos & derivados , Biotina/farmacologia , Complexos de Coordenação/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Rutênio/química , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/efeitos da radiação , Apoptose/efeitos dos fármacos , Biotina/síntese química , Biotina/efeitos da radiação , Caspase 3/metabolismo , Caspase 7/metabolismo , Linhagem Celular Tumoral , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Complexos de Coordenação/efeitos da radiação , Humanos , Raios Infravermelhos , Fotoquimioterapia/métodos , Fótons , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/efeitos da radiação , Oxigênio Singlete/metabolismo
5.
Inorg Chem ; 58(18): 12334-12347, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31464130

RESUMO

Lysosomal cysteine peptidase cathepsin B (catB) is an important tumor-promoting factor involved in tumor progression and metastasis representing a relevant target for the development of new antitumor agents. In the present study, we synthesized 11 ruthenium compounds bearing either the clinical agent nitroxoline that was previously identified as potent selective reversible inhibitor of catB activity or its derivatives. We demonstrated that organoruthenation is a viable strategy for obtaining highly effective and specific inhibitors of catB endo- and exopeptidase activity, as shown using enzyme kinetics and microscale thermophoresis. Furthermore, we showed that the novel metallodrugs by catB inhibition significantly impair processes of tumor progression in in vitro cell based functional assays at low noncytotoxic concentrations. Generally, by using metallodrugs we observed an improvement in catB inhibition, a reduction of extracellular matrix degradation and tumor cell invasion in comparison to free ligands, and a correlation with the reactivity of the monodentate halide leaving ligand.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Catepsina B/antagonistas & inibidores , Invasividade Neoplásica/prevenção & controle , Nitroquinolinas/farmacologia , Rutênio/farmacologia , Antineoplásicos/química , Neoplasias da Mama/patologia , Catepsina B/metabolismo , Linhagem Celular Tumoral , Feminino , Humanos , Modelos Moleculares , Invasividade Neoplásica/patologia , Nitroquinolinas/química , Inibidores de Proteases/química , Inibidores de Proteases/farmacologia , Rutênio/química
6.
Chem Commun (Camb) ; 55(67): 9904-9914, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31360938

RESUMO

The successful clinical application of the three generation platinum anticancer drugs, cisplatin, carboplatin and oxaliplatin, has promoted research interest in metallodrugs; however, the problems of drug resistance and adverse effects have hindered their further application and effects. Thus, scientists are searching for new anticancer metallodrugs with lower toxicity and higher efficacy. The ruthenium complexes have emerged as the most promising alternatives to platinum-based anticancer agents because of their unique multifunctional biochemical properties. In this review, we first focus on the anticancer applications of various ruthenium complexes in different signaling pathways, including the mitochondria-mediated pathway, the DNA damage-mediated pathway, and the death receptor-mediated pathway. We then discuss the functionalization and cancer-targeting designs of different ruthenium complexes in conjunction with other therapies such as photodynamic therapy, photothermal therapy, radiosensitization, targeted therapy and nanotechnology for precise cancer therapy. This review will help in designing and accelerating the research progress regarding new anticancer ruthenium complexes.


Assuntos
Antineoplásicos/química , Complexos de Coordenação/química , Rutênio/química , Animais , Antineoplásicos/uso terapêutico , Complexos de Coordenação/uso terapêutico , Descoberta de Drogas , Humanos , Estrutura Molecular , Terapia de Alvo Molecular , Nanopartículas/química , Fotoquimioterapia/métodos , Medicina de Precisão , Relação Estrutura-Atividade
7.
Photochem Photobiol Sci ; 18(8): 2012-2022, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31282525

RESUMO

Organic-metal complexes are promising molecules for use in photodynamic therapy (PDT). The aim of this study was to investigate in vitro effects of novel Ru(ii) and Ir(iii) BODIPY complexes for PDT. These hybrid organic-metal molecules (Ru-BD and Ir-BD) have been synthesized via reactions of a BODIPY precursor (BD) with a phenanthroline unit bearing Ru(ii) (3) and novel Ir(iii) (4) compounds. The crystal structures of the new distyryl BODIPY (BD) and Ru(ii) complex (3) are also reported. The photophysical and singlet oxygen generation properties of Ru-BD and Ir-BD were investigated in comparison with unsubstituted BODIPY (BD). Moreover, Ru-BD and Ir-BD have been biologically evaluated in vitro in chronic myeloid leukemia and cervical cancer cell lines in terms of photodynamic therapy efficacy in the presence of BD control. These complexes were not toxic in the dark but red light was needed to induce cell death. These data support the fact that Ru-BD could be accepted as a valuable photosensitizer-drug for further PDT treatment.


Assuntos
Antineoplásicos/farmacologia , Compostos de Boro/farmacologia , Corantes/farmacologia , Compostos Organometálicos/farmacologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Compostos de Boro/síntese química , Compostos de Boro/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Corantes/síntese química , Corantes/química , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Irídio/química , Irídio/farmacologia , Modelos Moleculares , Estrutura Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Rutênio/química , Rutênio/farmacologia , Oxigênio Singlete/análise , Oxigênio Singlete/metabolismo , Células Tumorais Cultivadas
8.
J Phys Chem Lett ; 10(14): 4123-4128, 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31287699

RESUMO

Delivering potential theranostic metal complexes into preferential cellular targets is becoming of increasing interest. Here we report that nuclear uptake of a cell-impermeable DNA "light-switching" Ru(II)-polypyridyl complex can be significantly facilitated by chlorophenolate counter-anions, which was found, unexpectedly, to be correlated positively with the binding stability but inversely with the lipophilicity of the formed ion pairs.


Assuntos
Clorofenóis/química , Complexos de Coordenação/química , DNA/química , Piridinas/química , Rutênio/química , Química Física , Células HeLa , Humanos , Íons/química , Estrutura Molecular , Polímeros/química
9.
Inorg Chem ; 58(14): 9452-9459, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31247836

RESUMO

The biexponential excited-state emission decay characteristic of DNA intercalated tris-bidentate dppz-based ruthenium complexes of the general form Ru(L)2dppz2+ has previously been explained by a binding model with two distinct geometry orientations of the bound ligands, with a distinct lifetime associated with each orientation. However, it has been found that upon DNA binding of Ru(phen)2dppz2+ the fractions of short and long lifetimes are strongly dependent on environmental factors such as salt concentration and, in particular, temperature. Analyzing isothermal titration calorimetry for competitive binding of Ru(phen)2dppz2+ enantiomers to poly(dAdT)2, we find that a consistent binding model must assume that the short and long lifetimes states of intercalated complexes are in equilibrium and that this equilibrium is altered when neighboring bound ligands affect each other. The degree of intercomplex binding is found to be a subtle manifestation of several attractive and repulsive factors that are highly likely to directly reflect the strong diastereomeric difference in the binding enthalpy and entropy values. In addition, as the titration progresses and the binding sites on the DNA lattice become increasingly occupied, a general resistance for the saturation of the binding sites is observed, suggesting diastereomeric crowding of the neighboring bound ligands.


Assuntos
Complexos de Coordenação/química , DNA/química , Substâncias Intercalantes/química , Modelos Moleculares , Estrutura Molecular , Fenantrolinas/química , Rutênio/química
10.
Chem Asian J ; 14(15): 2662-2675, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31149777

RESUMO

Chicken feather-derived high-surface-area porous activated carbon (CFAC) material was prepared using chemical activation. A new composite composed of Ru-Pd nanoparticles supported on CFAC (Ru-Pd@CFAC) has been prepared by microwave-thermal reduction in the presence of the support. Characterization by XRD, Raman, BET, FE-SEM/TEM, FT-IR, TGA, XPS, HAADF-STEM-EDS, H2 -chemisorption, H2 -TPR, and ICP-AES was used to analyze the catalyst. This catalyst is found to be efficient for the reduction of hexavalent chromium (CrVI ), potassium ferricyanide (K3 [Fe(CN)6 ]), 4-nitrophenol (4-NP), and pendimethalin (PDM), at room temperature, and remains stable, even after several repeated runs. Moreover, it showed excellent catalytic activity compared with the monometallic counterparts.


Assuntos
Ligas/química , Carbono/química , Nanopartículas Metálicas/química , Paládio/química , Rutênio/química , Compostos de Anilina/química , Animais , Catálise , Galinhas , Cromo/química , Ferricianetos/química , Nitrofenóis/química , Oxirredução , Porosidade , Reciclagem , Espectrofotometria , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura Ambiente , Eliminação de Resíduos Líquidos
11.
Chem Biodivers ; 16(8): e1900243, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31207061

RESUMO

The new complex compounds [RuLCl(p-cymene)] ⋅ 3H2 O and [NiL2 (H2 O)2 ] ⋅ 3H2 O (L: 1-{4-[(2-hydroxy-3-methoxybenzylidene)amino]phenyl}ethanone) were prepared and characterized using FT-IR, 1 H- and 13 C-NMR, mass spectroscopy, TGA, elemental analysis, X-ray powder diffraction and magnetic moment techniques. Octahedral geometry for new Ni(II) and Ru(II) complexes was proposed. Thermal decomposition confirmed the existence of lattice and coordinated water molecule in the complexes. To determine the antioxidant properties of Schiff base ligand and its Ni(II), Ru(II) metal complexes, FRAP, CUPRAC, ABTS and DPPH methods of antioxidant assays were used. Moreover, enzyme inhibition of complexes was evaluated against carbonic anhydrase I and II isoenzymes (CA I and CA II) and acetylcholinesterase (AChE). For CA I and CA II, the best inhibition enzymes, was the Ni(II) complex with 62.98±18.41, 86.17±23.62 Ki values, whereas this inhibition effect showed ligand with 24.53±2.66 Ki value for the AChE enzyme.


Assuntos
Antioxidantes/química , Complexos de Coordenação/química , Inibidores Enzimáticos/química , Níquel/química , Rutênio/química , Bases de Schiff/química , Acetilcolinesterase/química , Acetilcolinesterase/metabolismo , Anidrase Carbônica I/antagonistas & inibidores , Anidrase Carbônica I/metabolismo , Anidrase Carbônica II/antagonistas & inibidores , Anidrase Carbônica II/metabolismo , Complexos de Coordenação/farmacologia , Inibidores Enzimáticos/metabolismo , Concentração Inibidora 50 , Espectrofotometria Infravermelho
12.
Int J Nanomedicine ; 14: 4157-4165, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31239674

RESUMO

Background: During decades, all improvements and developments in radiation therapy technologies have been focused on its main goal: maximize the dose in the tumor and minimize it in surrounding normal tissues. Recently, scientists have some approaches to nanoparticles, especially gold nanoparticles (GNPs), for dose localization. Purpose: Herein, the effect of GNPs in combination with electron brachytherapy in a model of eye tumor has been investigated. Materials and methods: Monte Carlo simulation was utilized and a complete anatomical model of the eye, a tumor with 5 mm thick, and a type of Ruthenium-106 beta emitter ophthalmic plaque were simulated. Simulation results have been validated by a Plexiglas eye phantom and film dosimetry, experimentally. Results: The results showed using GNPs causes the dose amplification in 2 mm from the plaque surface which the higher concentration has the higher enhancement. At more distances, Dose Enhancement Factors (DEFs) have the negative amounts, so that total delivered dose to the tumor has decreased with increasing of Au concentrations and the dose of organ at risk like sclera has increased. Conclusion: Therefore, using of GNPs along with a 106Ru/106Rh ocular plaque, as an electron emitter source, is a good choice only for superficial lesions, and it is not recommended for deeper tumors due to the parameters of radiation treatment and delivered dose to the tissues.


Assuntos
Braquiterapia , Elétrons , Neoplasias Oculares/radioterapia , Ouro/uso terapêutico , Nanopartículas Metálicas/uso terapêutico , Simulação por Computador , Relação Dose-Resposta à Radiação , Olho/patologia , Olho/efeitos da radiação , Humanos , Método de Monte Carlo , Imagens de Fantasmas , Dosagem Radioterapêutica , Reprodutibilidade dos Testes , Rutênio/química , Prata/uso terapêutico
13.
Eur J Med Chem ; 175: 269-286, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31096151

RESUMO

Organometallic complexes have widely been used for the treatment of various diseases viz., malaria, arthritis, syphilis, pernicious anemia, tuberculosis and particular in cancers. Recent decades have witnessed an upsurging interest in the application of organometallic compounds to treat various phenotypes of cancers with multiple etiologies. The unique and exceptional properties of organometallic compounds, intermediate between classical inorganic and organic materials provide new insight in the progress of inorganic medicinal chemistry. Herein, we have selectively focused on various organometallic sandwich and half-sandwich complexes of ruthenium (Ru), titanium (Ti), gold (Au) and iron (Fe) exhibiting promising activity towards a panel of cancer cell lines and resistant cancer cell lines. These complexes exhibit novel mechanisms of drug action through incorporation of outer-sphere recognition of molecular targets and controlled activation features based on ligand substitution along with monometallic and heterometallic redox processes. Furthermore, they are usually found to be uncharged or neutral possessing metals in a low oxidation state, exhibit kinetic stability, relative lipophilicity and are amenable to a host of various chemical transformations. This review mainly sheds light on the successful advancement of organometallic complexes as anticancer drug aspirants in relation to their versatile structural chemistry and innovative mechanisms of action targeting nucleic acids, several enzymes viz; thioredoxin reductases (Thrx), EGFR, transferrin, cathepsin B, topoisomerases etc.


Assuntos
Antineoplásicos/farmacologia , Neoplasias/tratamento farmacológico , Compostos Organometálicos/farmacologia , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Catepsina B/efeitos dos fármacos , Linhagem Celular , Linhagem Celular Tumoral , DNA Topoisomerases/efeitos dos fármacos , Receptores ErbB/efeitos dos fármacos , Ouro/química , Humanos , Neoplasias/patologia , Ácidos Nucleicos/efeitos dos fármacos , Compostos Organometálicos/química , Compostos Organometálicos/uso terapêutico , Rutênio/química , Tiorredoxina Dissulfeto Redutase/efeitos dos fármacos , Titânio/química , Transferrina/efeitos dos fármacos
14.
Inorg Chem ; 58(13): 8587-8595, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31117633

RESUMO

A new N,O-based BODIPY ligand was synthesized and further utilized to develop highly fluorescent and photostable Ru(II), Rh(III), and Ir(III) metal complexes. The complexes were fully characterized by different analytical techniques including single-crystal XRD studies. The photostabilities and live cell imaging capabilities of the complexes were investigated via confocal microscopy. The complexes localized specifically in the mitochondria of live cells and showed negligible cytotoxicities at a concentration used for imaging purposes. They also exhibited high photostabilities, with fluorescence intensities remaining above 50% after 1800 scans.


Assuntos
Compostos de Boro/metabolismo , Complexos de Coordenação/metabolismo , Corantes Fluorescentes/metabolismo , Mitocôndrias/metabolismo , Transporte Biológico , Compostos de Boro/síntese química , Compostos de Boro/efeitos da radiação , Compostos de Boro/toxicidade , Complexos de Coordenação/síntese química , Complexos de Coordenação/efeitos da radiação , Complexos de Coordenação/toxicidade , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/efeitos da radiação , Corantes Fluorescentes/toxicidade , Células HeLa , Humanos , Irídio/química , Ligantes , Microscopia Confocal , Fotodegradação , Ródio/química , Rutênio/química
15.
Artigo em Inglês | MEDLINE | ID: mdl-31081456

RESUMO

Three new Ru(II) polypyridyl complexes [Ru(phen)2CIIP]2+ (1) {CIIP = 2-(5-Chloro-3a H-Isoindol-3-yl)-1H-Imidazo[4,5-f][1, 10]phenantholine} (phen = 1, 10 phenanthroline), [Ru(bpy)2CIIP]2+ (2) (bpy = 2, 2' bipyridine) and [Ru(dmb)2CIIP]2+ (3) (dmb = 4, 4'-dimethyl 2, 2' bipyridine) were synthesized and characterized by different spectral methods. The DNA-binding behavior of these complexes was investigated by absorption, emission spectroscopic titration and viscosity measurements, indicating that these three complexes bind to CT-DNA in an intercalative mode, but binding affinities of these complexes were different. The DNA-binding constants Kb of complexes 1, 2 and 3 were calculated in the order of 106. All three complexes cleave pBR322 DNA in photoactivated cleavage studies and exhibit good antimicrobial activity. Anticancer activity of these Ru(II) complexes was evaluated in MCF7 cells. Cytotoxicity by MTT assay showed growth inhibition in a dose dependent manner. Cell cycle analysis by flow cytometry data showed an increase in Sub G1 population. Annexin V FITC/PI staining confirms that these complexes cause cell death by the induction of apoptosis.


Assuntos
Antibacterianos/química , Antineoplásicos/química , Complexos de Coordenação/química , Substâncias Intercalantes/química , Isoindóis/química , Fenantrolinas/química , Piridinas/química , Rutênio/química , Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Bacillus subtilis/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/farmacologia , DNA/metabolismo , Clivagem do DNA , Escherichia coli/efeitos dos fármacos , Humanos , Substâncias Intercalantes/farmacologia , Isoindóis/farmacologia , Células MCF-7 , Fenantrolinas/farmacologia , Processos Fotoquímicos , Piridinas/farmacologia , Termodinâmica
16.
Chem Commun (Camb) ; 55(60): 8764-8767, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31139806

RESUMO

Ru(ii)-complexes with polyazaaromatic ligands can undergo direct electron transfer with guanine nucleobases on blue light excitation that results in DNA lesions with phototherapeutic potential. Here we use single molecule approaches to demonstrate DNA binding mode heterogeneity and evaluate how multivalent binding governs the photochemistry of [Ru(TAP)3]2+ (TAP = 1,4,5,8-tetraazaphenanthrene).


Assuntos
DNA/química , Substâncias Intercalantes/química , Compostos Organometálicos/química , Fenantrenos/química , Adutos de DNA/síntese química , Guanina/química , Substâncias Intercalantes/efeitos da radiação , Ligantes , Luz , Conformação de Ácido Nucleico , Compostos Organometálicos/efeitos da radiação , Fenantrenos/efeitos da radiação , Fenantrolinas/química , Fenantrolinas/efeitos da radiação , Rutênio/química
17.
Chemistry ; 25(45): 10606-10615, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31107567

RESUMO

A comparative study between two novel, highly water soluble, ruthenium(II) polypyridyl complexes, [Ru(phen)2 L'] and [Ru(phen)2 Cu(II)L'] (L and L-CuII ), containing the polyaazamacrocyclic unit 4,4'-(2,5,8,11,14-pentaaza[15])-2,2'-bipyridilophane (L'), is herein reported. L and L-CuII interact with calf-thymus DNA and efficiently cleave DNA plasmid when light-activated. They also possess great penetration abilities and photo-induced biological activities, evaluated on an A375 human melanoma cell line, with L-CuII being the most effective. Our study highlights the key role of the Fenton active CuII center within the macrocycle framework, that would play a synergistic role with light activation in the formation of cytotoxic ROS species. Based on these results, an optimal design of RuII polypyridyl systems featuring specific CuII -chelating polyamine units could represent a suitable strategy for the development of novel and effective photosensitizers in photodynamic therapy.


Assuntos
Complexos de Coordenação/química , Fármacos Fotossensibilizantes/química , Rutênio/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/farmacologia , DNA/química , Clivagem do DNA/efeitos dos fármacos , Humanos , Microscopia Confocal , Fármacos Fotossensibilizantes/farmacologia , Piridinas/química , Oxigênio Singlete/metabolismo
18.
Dalton Trans ; 48(20): 6910-6920, 2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31038129

RESUMO

In order to address outstanding questions about ruthenium complexes in complex biological solutions, 19F NMR spectroscopy was used to follow the binding preferences between fluorinated RuII(η6-arene)(bipyridine) complexes and protected amino acids and glutathione. Reporting what ruthenium compounds bind to in complex environments has so far been restricted to relatively qualitative methods, such as mass spectrometry and X-ray spectroscopic methods; however, quantitative information on the species present in the solution phase cannot be inferred from these techniques. Furthermore, using 1H NMR, in water, to distinguish and monitor a number of different complex RuII(η6-arene) adducts forming is challenging. Incorporating an NMR active heteroatom into ruthenium organometallic complexes provides a quantitative, diagnostic 'fingerprint' to track solution-phase behaviour and allow for unambiguous assignment of any given adduct. The resulting 19F NMR spectra show for the first time the varied, dynamic behaviour of organoruthenium compounds when exposed to simple biomolecules in complex mixtures. The rates of formation of the different observed species are dramatically influenced by the electronic properties at the metal, even in a closely related series of complexes in which only the electron-donating properties of the arene ligand are altered. Preference for cysteine binding is absolute: the first quantitative solution-phase evidence of such behaviour.


Assuntos
Aminoácidos/análise , Complexos de Coordenação/química , Flúor/química , Rutênio/química , Complexos de Coordenação/síntese química , Cisteína/química , Halogenação , Cinética , Ligantes , Estrutura Molecular , Água/química
19.
Chemistry ; 25(38): 9098-9107, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31046169

RESUMO

The understanding of structure-function relationships within synthetic biomimetic systems is a fundamental challenge in chemistry. Herein we report the direct correlation between the structure of short peptoid ligands-N-substituted glycine oligomers incorporating 2,2'-bipyridine groups-varied in their monomer sequence, and the photoluminescence of RuII centers coordinated by these ligands. Based on circular dichroism and fluorescence spectroscopy we demonstrate that while helical peptoids do not affect the fluorescence of the embedded RuII chromophore, unstructured peptoids lead to its significant decay. Transmittance electron microscopy (TEM) revealed significant differences in the arrangements of metal-bound helical versus unstructured peptoids, suggesting that only the latter can have through-space interactions with the ruthenium dye leading to its quenching. High-resolution TEM enabled the remarkable direct imaging of singular ruthenium-bound peptoids and bundles, supporting our explanation for structure-depended quenching. Moreover, this correlation allowed us to fine-tune the luminescence properties of the complexes simply by modifying the sequence of their peptoid ligands. Finally, we also describe the chiral properties of these Ru-peptoids and demonstrate that remote chiral induction from the peptoids backbone to the ruthenium center is only possible when the peptoids are both chiral and helical.


Assuntos
2,2'-Dipiridil/química , Glicina/análogos & derivados , Substâncias Luminescentes/química , Peptoides/química , Rutênio/química , Luminescência , Estereoisomerismo
20.
Org Lett ; 21(9): 3337-3341, 2019 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-31002524

RESUMO

The in situ formed ruthenium catalytic system ([Ru]/L) was found to be highly selective for the dehydrogenative coupling reaction of 2-aminophenyl ketones with amines to form quinazoline products. The deaminative coupling reaction of 2-aminobenzamides with amines led to the efficient formation of quinazolinone products. The catalytic coupling method provides an efficient synthesis of quinazoline and quinazolinone derivatives without using any reactive reagents or forming any toxic byproducts.


Assuntos
Aminas/química , Benzamidas/química , Complexos de Coordenação/química , Cetonas/química , Quinazolinas/síntese química , Rutênio/química , Catálise , Reação de Cicloadição , Ligantes , Quinazolinonas/síntese química
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