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1.
Yakugaku Zasshi ; 140(8): 955-960, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32741867

RESUMO

A nickel-aluminium-zirconium complex-layered hydroxide (NAZ), which was synthesized using each inorganic sulfate mixing ratio of 0.9 : 1.0 : 0.1, was prepared and calcined at different temperatures. The physicochemical properties of the NAZ were analyzed by scanning electron microscopy, specific surface area, number of hydroxyl groups, and pore volume. The specific surface area, number of hydroxyl groups, and pore volume of NAZ was 51.9 m2/g, 1.08 mmol/g, and 0.27 µL/g, respectively. The amount of phosphate ion adsorbed onto NAZ was higher than that onto calcined NAZ at different temperatures. Therefore, the interaction between phosphate ions and NAZ was assessed using the elemental distribution analysis and the binding energy. After adsorption, the intensity of phosphorus atoms increased, indicating that the phosphate ions were adsorbed onto the NAZ surface. Additionally, phosphorus peaks (189 eV for 2s and 130 eV for 2p), which were not detected before adsorption, were clearly detected after adsorption. On the other hand, the intensity of the sulfur peak (165 eV for 2p) decreased after adsorption. Thus, we evaluated the ion exchange between phosphate ion and sulfate ion in the interlayer space of the NAZ. As a result, the correlation coefficient between the amount of phosphate ion adsorbed and the amount of sulfate ion released was positively correlated (r=0.960). Therefore, it can be clearly stated that one of the adsorption mechanisms of phosphate ions was related to ion exchange in the interlayer space of the NAZ. These findings are useful for preventing the eutrophication and recovery of phosphate ion in water environments.


Assuntos
Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Hidróxidos/química , Hidróxidos/síntese química , Fosfatos/química , Adsorção , Alumínio , Fenômenos Químicos , Eutrofização , Troca Iônica , Íons , Microscopia Eletroquímica de Varredura , Níquel , Zircônio
2.
Nat Commun ; 11(1): 3262, 2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32591538

RESUMO

The use of photodynamic therapy (PDT) against cancer has received increasing attention over recent years. However, the application of the currently approved photosensitizers (PSs) is limited by their poor aqueous solubility, aggregation, photobleaching and slow clearance from the body. To overcome these limitations, there is a need for the development of new classes of PSs with ruthenium(II) polypyridine complexes currently gaining momentum. However, these compounds generally lack significant absorption in the biological spectral window, limiting their application to treat deep-seated or large tumors. To overcome this drawback, ruthenium(II) polypyridine complexes designed in silico with (E,E')-4,4'-bisstyryl-2,2'-bipyridine ligands show impressive 1- and 2-Photon absorption up to a magnitude higher than the ones published so far. While nontoxic in the dark, these compounds are phototoxic in various 2D monolayer cells, 3D multicellular tumor spheroids and are able to eradicate a multiresistant tumor inside a mouse model upon clinically relevant 1-Photon and 2-Photon excitation.


Assuntos
Complexos de Coordenação/uso terapêutico , Desenho de Fármacos , Fotoquimioterapia , Fótons , Rutênio/química , Animais , Proliferação de Células , Sobrevivência Celular , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Feminino , Células HeLa , Humanos , Camundongos Nus , Oxigênio Singlete/química , Análise Espectral , Esferoides Celulares/patologia
3.
Chemistry ; 26(34): 7595-7601, 2020 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-32302020

RESUMO

We propose post-metalation modification as a useful strategy to control the guest recognition behavior of a metal-containing macrocyclic host. This is based on the ligand exchange of the axial ligands of a cobalt(III) dinuclear macrocyclic host, [LCo2 X4 ]2+ (X=axial amine ligand). Four piperidine ligands in [LCo2 (pip)4 ]2+ (pip=piperidine) were site-selectively replaced with primary amines. The competitive experiments revealed that the order of the affinity toward the cobalt centers in [LCo2 X4 ]2+ is primary amine > secondary amine > tertiary amine and that the piperidine-coordinating complex, [LCo2 (pip)4 ]2+ , was reasonably reactive among the isolable complexes. Indeed, two piperidine ligands at the diagonal positions in [LCo2 (pip)4 ]2+ were site-selectively replaced with pyridine or acetate ion. The replacement of piperidine with acetate ion significantly enhanced the recognition ability towards Na+ .


Assuntos
Aminas/química , Cobalto/química , Complexos de Coordenação/química , Piridinas/química , Complexos de Coordenação/síntese química , Cristalografia por Raios X , Ligantes , Metais , Estrutura Molecular
4.
Inorg Chem ; 59(8): 5662-5673, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32255617

RESUMO

A family of stable anticancer gold(III)-based therapeutic complexes containing cyclometalated triphenylphosphine sulfide ligands have been prepared. The anticancer properties of the newly developed complexes [AuCl2{κ2-2-C6H4P(S)Ph2}] (1), [Au(κ2-S2CNEt2){κ2-2-C6H4P(S)Ph2}]PF6 (2), [AuCl(dppe){κC-2-C6H4P(S)Ph2}]Cl (3), and [Au(dppe){κ2-2-C6H4P(S)Ph2}][PF6]2 (4) were investigated toward five human cancer cell lines [cervical (HeLa), lung (A549), prostate (PC3), fibrosarcoma (HT1080), and breast (MDA-MB-231)]. In vitro cytotoxicity studies revealed that compounds 2-4 displayed potent cell growth inhibition (IC50 values in the range of 0.17-2.50 µM), comparable to, or better than, clinically used cisplatin (0.63-6.35 µM). Preliminary mechanistic studies using HeLa cells indicate that the cytotoxic effects of the compounds involve apoptosis induction through ROS accumulation. Compound 2 also demonstrated significant inhibition of endothelial cell migration and tube formation in the angiogenesis process. Evaluation of the in vivo antitumor activity of compound 2 in nude mice bearing cervical cancer cell (HeLa) xenografts indicated significant tumor growth inhibition (55%) with 1 mg/kg dose (every 3 days) compared with the same dose of cisplatin (28%). These results demonstrate the potential of gold(III) complexes containing cyclometalated triphenylphosphine sulfide ligands as novel metal-based anticancer agents.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Complexos de Coordenação/uso terapêutico , Neoplasias/tratamento farmacológico , Fosfinas/uso terapêutico , Sulfetos/uso terapêutico , Inibidores da Angiogênese/síntese química , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Complexos de Coordenação/síntese química , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/uso terapêutico , Feminino , Ouro/química , Humanos , Ligantes , Camundongos Endogâmicos BALB C , Camundongos Nus , Fosfinas/síntese química , Espécies Reativas de Oxigênio/metabolismo , Sulfetos/síntese química , Tiorredoxina Dissulfeto Redutase/antagonistas & inibidores , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Chemistry ; 26(41): 8875-8878, 2020 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-32237247

RESUMO

The nickel(II)-mediated self-assembly of a multimeric DNA binder is described. The binder is composed of two metal-chelating peptides derived from a bZIP transcription factor (brHis2 ) and one short AT-hook domain equipped with two bipyridine ligands (HkBpy2 ). These peptides reversibly assemble in the presence of NiII ions at selected DNA sequences of 13 base pairs.


Assuntos
Complexos de Coordenação/química , DNA/química , Níquel/química , Peptídeos/química , Fatores de Transcrição/química , Complexos de Coordenação/síntese química , Íons/química , Ligantes
6.
Chem Pharm Bull (Tokyo) ; 68(3): 292-297, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32115537

RESUMO

In this study, the adsorption capability of phosphate ion using a novel tri-metals complex hydroxide was evaluated for preventing the eutrophication in water environment. A nickel-aluminum-zirconium complex hydroxide (NAZ) was synthesized using each inorganic sulfate mixing ratio of 0.9 : 1.0 : 0.1 and was calcined at different temperatures. The characteristics of the NAZ were analyzed by scanning electron microscopy images, X-ray diffraction analysis, elemental distribution, and binding energy. Moreover, the amount adsorbed of phosphate ion onto uncalcined and calcined NAZ was measured. That of phosphate ions onto the uncalcined was the largest of all. These results suggested that the adsorption of phosphate ions tends to depend on the physicochemical properties (e.g., amount of hydroxyl groups, pore volumes, and pH) of the adsorbents. Moreover, the adsorption mechanism of phosphate ions was evaluated on the basis of binding energy and elemental analysis. After adsorption, the binding energy of phosphorus P (2s and 2p) peaked and the sulfur peak intensity S(2s) reduced. This result indicated that the adsorption mechanism of phosphate would be exchanged with sulfate ions.


Assuntos
Alumínio/química , Complexos de Coordenação/química , Hidróxidos/química , Níquel/química , Fosfatos/química , Zircônio/química , Adsorção , Complexos de Coordenação/síntese química , Tamanho da Partícula , Propriedades de Superfície
7.
Chem Commun (Camb) ; 56(20): 3069-3072, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32049075

RESUMO

Niacin-ligated platinum(iv)-ruthenium(ii) chimeric complexes (PtRu 1-4) have been synthesized and evaluated for their antitumor performance. Using the optimal complex, PtRu-1, we show that this water-soluble chimeric prodrug not only potently inhibits the metastasis and proliferation of tumor cells but also has an unexpectedly higher safety margin in animals compared with the traditionally-used, clinically approved drug cisplatin.


Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Niacina/farmacologia , Platina/farmacologia , Rutênio/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Peso Corporal/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cisplatino/química , Cisplatino/farmacologia , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos ICR , Camundongos Nus , Estrutura Molecular , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Niacina/química , Platina/química , Rutênio/química , Relação Estrutura-Atividade
8.
Chem Commun (Camb) ; 56(20): 3047-3049, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32048688

RESUMO

A series of aminocarboxylic acid analogues of aspergillomarasmine A (AMA) and ethylenediamine-N,N'-disuccinic acid (EDDS) were chemoenzymatically synthesized via the addition of various mono- and diamine substrates to fumaric acid catalyzed by the enzyme EDDS lyase. Many of these novel AMA and EDDS analogues demonstrate potent inhibition of the bacterial metallo-ß-lactamase NDM-1. Isothermal titration calorimetry assays revealed a strong correlation between the inhibitory potency of the compounds and their ability to bind zinc. Compounds 1a (AMA), 1b (AMB), 5 (EDDS), followed by 1d and 8a, demonstrate the highest synergy with meropenem resensitizing an NDM-1 producing strain of E. coli to this important carbapenem of last resort.


Assuntos
Ácido Aspártico/análogos & derivados , Complexos de Coordenação/farmacologia , Proteínas de Escherichia coli/antagonistas & inibidores , Etilenodiaminas/farmacologia , Succinatos/farmacologia , Zinco/farmacologia , Inibidores de beta-Lactamases/farmacologia , Aminoácidos/química , Aminoácidos/farmacologia , Ácido Aspártico/química , Ácido Aspártico/farmacologia , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Relação Dose-Resposta a Droga , Proteínas de Escherichia coli/metabolismo , Etilenodiaminas/química , Estrutura Molecular , Relação Estrutura-Atividade , Succinatos/química , Zinco/química , Inibidores de beta-Lactamases/síntese química , Inibidores de beta-Lactamases/química , beta-Lactamases/metabolismo
9.
Dalton Trans ; 49(7): 2331-2336, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32022093

RESUMO

The goal of this study was to design a ligand system which can accommodate single lanthanide(iii)-ions and investigate the properties of the resulting complexes. The complexes of all the accesible lanthanides and yttrium with the new ligand LH6 = N,N'-dimethyl-N,N'-ethylene-bis(5-bromo-3-(1H-benzimidazol-2-yl)hydrazineylidene)-2-hydroxybenzylamine) were obtained in high yield at room temperature under aerobic reaction conditions. The corresponding compounds were characterised using X-ray diffraction, FT-IR, elemental analysis and the optical properties of all complexes were investigated using UV-vis and fluorescence spectroscopy. The air stable complexes efficiently transform biomass furfural to trans-4,5-cyclopentenones in high yield.


Assuntos
Complexos de Coordenação/síntese química , Ciclopentanos/metabolismo , Elementos da Série dos Lantanídeos/química , Biomassa , Biotransformação , Catálise , Complexos de Coordenação/química , Cristalografia por Raios X , Ciclopentanos/química , Ligantes , Modelos Moleculares , Estrutura Molecular , Estereoisomerismo
10.
Inorg Chem ; 59(5): 2978-2987, 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32037809

RESUMO

We have synthesized and structurally characterized three tetra-(p-tolyl)antimony(III)-containing heteropolytungstates, [{(p-tolyl)SbIII}4(A-α-XW9O34)2]n- [X = PV (1-P), AsV (1-As), or GeIV (1-Ge)], in aqueous solution using conventional, one-pot procedures. The polyanions 1-P, 1-As, and 1-Ge were fully characterized in the solid state and in solution and were shown to be soluble and stable in aqueous medium at pH 7. Biological studies demonstrated that all three polyanions possess significant antibacterial and antitumor activities. The minimum inhibitory concentrations of 1-P, 1-As, and 1-Ge were determined against four kinds of bacteria, including the two pathogenic bacteria strains, Vibrio parahaemolyticus and Vibrio vulnificus. The three novel polyanions also showed high cytotoxic potency in the human cell lines A549 (non-small cell lung cancer), CH1/PA-1 (ovarian teratocarcinoma), and SW480 (colon carcinoma).


Assuntos
Antibacterianos/farmacologia , Antimônio/farmacologia , Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Tungstênio/farmacologia , Células A549 , Antibacterianos/síntese química , Antibacterianos/química , Antimônio/química , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Bacillus subtilis/efeitos dos fármacos , 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 , Escherichia coli/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Células Tumorais Cultivadas , Tungstênio/química , Vibrio parahaemolyticus/efeitos dos fármacos , Vibrio vulnificus/efeitos dos fármacos
11.
Inorg Chem ; 59(5): 3281-3289, 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32073260

RESUMO

Metal complexes provide a versatile platform to develop novel anticancer pharmacophores, and they form stable compounds with N-heterocyclic carbene (NHC) ligands, some of which have been shown to inhibit the cancer-related selenoenzyme thioredoxin reductase (TrxR). To expand a library of isostructural NHC complexes, we report here the preparation of RhIII- and IrIII(Cp*)(NHC)Cl2 (Cp* = η5-pentamethylcyclopentadienyl) compounds and comparison of their properties to the RuII- and OsII(cym) analogues (cym = η6-p-cymene). Like the RuII- and OsII(cym) complexes, the RhIII- and IrIII(Cp*) derivatives exhibit cytotoxic activity with half maximal inhibitory concentration (IC50) values in the low micromolar range against a set of four human cancer cell lines. In studies on the uptake and localization of the compounds in cancer cells by X-ray fluorescence microscopy, the Ru and Os derivatives were shown to accumulate in the cytoplasmic region of treated cells. In an attempt to tie the localization of the compounds to the inhibition of the tentative target TrxR, it was surprisingly found that only the Rh complexes showed significant inhibitory activity at IC50 values of ∼1 µM, independent of the substituents on the NHC ligand. This indicates that, although TrxR may be a potential target for anticancer metal complexes, it is unlikely the main target or the sole target for the Ru, Os, and Ir compounds described here, and other targets should be considered. In contrast, Rh(Cp*)(NHC)Cl2 complexes may be a scaffold for the development of TrxR inhibitors.


Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Inibidores Enzimáticos/farmacologia , Tiorredoxina Dissulfeto Redutase/antagonistas & inibidores , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Compostos Heterocíclicos/química , Compostos Heterocíclicos/farmacologia , Humanos , Ligantes , Metais Pesados/química , Metais Pesados/farmacologia , Metano/análogos & derivados , Metano/química , Metano/farmacologia , Conformação Molecular , Relação Estrutura-Atividade , Tiorredoxina Dissulfeto Redutase/metabolismo
12.
Dalton Trans ; 49(4): 1143-1156, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31894801

RESUMO

A series of 2-phenyl and 2-pyridyl tris-benzimidazole ligands was reacted with the [Ru(p-cymene)Cl2]2 dimer to yield the corresponding neutral cyclometallated and cationic organoruthenium(ii) complexes. All of the synthesized compounds were characterized using an array of spectroscopic and analytical techniques, including 1H, 13C nuclear magnetic resonance (NMR), infrared spectroscopy and mass spectrometry. The trinuclear compounds were screened for their cytotoxicy against the MCF-7 breast cancer cell line and the triple negative MDA-MB-231 breast cancer cell line at concentrations of 10 and 20 µM. Overall, the 2-pyridyl ligands 10 and 11, and their corresponding trinuclear complexes [16][PF6]3 and [17][PF6]3, show the most promising activity as these compounds significantly reduce the percentage cell survival of MCF-7 and MDA-MB-231 breast cancer cell lines at the aforementioned fixed concentrations. It was observed that 10 and [16][PF6]3 show potency greater than that of cisplatin against the MCF-7 breast cancer cell line, and [17][PF6]3 shows potency comparable to that of cisplatin against the MCF-7 cell line. Additionally, the synthesized compounds were observed to have relatively low cytotoxicty towards MCF-12A breast epithelial cells and relatively higher selectivity towards MCF-7 breast cancer cells compared to cisplatin.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Benzimidazóis/química , Quelantes/química , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Rutênio/química , Antineoplásicos/síntese química , Proliferação de Células/efeitos dos fármacos , Técnicas de Química Sintética , Complexos de Coordenação/síntese química , Humanos , Células MCF-7 , Modelos Moleculares , Conformação Molecular
13.
Dalton Trans ; 49(4): 1276-1291, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31909778

RESUMO

A new, facile Cu(ii) template method has been employed for the unsymmetrical dicondensation of 1,2-ethylenediamine with salicylaldehyde and o-vanillin. The mononuclear complex, [CuL] (1), thus obtained, has been used as an O3 donor metalloligand for the synthesis of four new Cu(ii)-Mn(ii) complexes, [(CuL)MnCl2] (2), [(CuL)Mn(NO3)2(CH3OH)]n (3), {[(CuL)Mn(benz)(H2O)]2·(CuL)2(ClO4)2} (4) and [(CuL)Mn(benz)Cl]2 (5) (where benz = benzoate). Single-crystal structural analyses reveal that 2 is a dinuclear complex while complex 3 is polymeric with a repeating dinuclear [(CuL)Mn(NO3)2(CH3OH)] unit, linked via the nitrate ion. Both 4 and 5 are discrete tetranuclear complexes, where the dinuclear units [(CuL)Mn(benz)(H2O)] and [(CuL)Mn(benz)Cl] are connected by double benzoate and double chloride bridges, respectively. In complex 4, two monomeric [CuL] units are cocrystallized with the tetranuclear complex. An important difference in the structure of 4 from the other three complexes is that one solvent water molecule is coordinated to each Mn(ii) ion, which makes complex 4 catalytically very active towards mimicking catecholase and phenoxazinone synthase-like oxidation reactions. The turnover numbers (kcat) for the aerial oxidation of 3,5-di-tert-butylcatechol and o-aminophenol are 399 h-1 and 230 h-1, respectively. The evidence of the intermediate species in the mass spectra indicates possible heterometallic cooperation where the Mn(ii) center helps in substrate binding and Cu(ii) participates in the oxidation reactions with molecular oxygen. Cyclic voltammetry measurements suggest the reduction of Cu(ii) to Cu(i) during the catalytic process. Temperature-dependent dc molar magnetic susceptibility measurements reveal that complexes 2-5 are antiferromagnetically coupled with the exchange coupling constants (J) of J = -13.5 cm-1 and J = -13.5 cm-1 for 2 and 3, respectively, J1 = -12.6 cm-1 and J2 = -1.20 cm-1 for complex 4 and J1 = -13.24 cm-1 and J2 = 0.36 cm-1 for complex 5 as is expected from the Cu-O-Mn bridging angles.


Assuntos
Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Cobre/química , Fenômenos Magnéticos , Manganês/química , Oxirredutases/metabolismo , Materiais Biomiméticos/síntese química , Materiais Biomiméticos/química , Catálise , Técnicas de Química Sintética , Eletroquímica , Ligantes , Modelos Moleculares , Conformação Molecular
14.
Inorg Chem ; 59(3): 2070-2082, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-31940188

RESUMO

The thermodynamic stability of a metal-ligand complex, as measured by the formation constant (log ß), is one of the most important parameters that determines metal ion selectivity and potential applications in, for example, radiopharmaceutical science. The stable coordination chemistry of radioactive 89Zr4+ in an aqueous environment is of paramount importance when developing positron-emitting radiotracers based on proteins (usually antibodies) for use with positron emission tomography. Desferrioxamine B (DFO) remains the chelate of choice for clinical applications of 89Zr-labeled proteins, but the coordination of DFO to Zr4+ ions is suboptimal. Many alternative ligands have been reported, but the challenges in measuring very high log ß values with metal ions such as Zr4+ that tend to hydrolyze mean that accurate thermodynamic data are scarce. In this work, density functional theory (DFT) calculations were used to predict the reaction energetics for metal ion complexation. Computed values of pseudoformation constants (log ß') are correlated with experimental data and showed an excellent linear relationship (R2 = 0.97). The model was then used to estimate the absolute and relative formation constants of 23 different Zr4+ complexes using a total of 17 different ligands, including many of the alternative bifunctional chelates that have been reported recently for use in 89Zr4+ radiochemistry. In addition, detailed computational studies were performed on the geometric isomerism and hydration state of Zr-desferrioxamine. Collectively, the results offer new insights into Zr4+ coordination chemistry that will help guide the synthesis of future ligands. The computational model developed here is straightforward and reproducible and can be readily applied in the design of other metal coordination compounds.


Assuntos
Quelantes/química , Complexos de Coordenação/química , Desferroxamina/química , Termodinâmica , Zircônio/química , Quelantes/síntese química , Complexos de Coordenação/síntese química , Teoria da Densidade Funcional , Ligantes , Modelos Moleculares , Tomografia por Emissão de Pósitrons , Traçadores Radioativos
15.
Inorg Chem ; 59(3): 2051-2061, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-31967459

RESUMO

Dioxygen O-O bond activation is a process for oxygenases and oxidases to perform biological functions and synthetic biomimetic catalysts to carry out oxygenation reactions using molecular O2 as an oxidant. Inspired by the experimental development of a CoIII-peroxo complex (i.e., [CoIII(TBDAP)(O2)]+, TBDAP = N,N-ditert-butyl-2,11-diaza[3.3](2,6)-pyridinophane) that exhibits dioxygenase-like reactivity to activate nitriles, a density functional theory (DFT) mechanistic study has been carried out to understand how the peroxo ligand is broken to activate nitriles. The study unveils that the O-O bond cleavage takes place via conversion to a CoII-superoxo complex aided by nitrile coordination, followed by formation of a five-membered intermediate via superoxo O2 radical nucleophilic attack at the nitrile carbon. Finally, a [1,3]-sigmatropic rearrangement-like process breaks the dioxygen bond. The otherwise difficult [1,3]-sigmatropic rearrangement is enabled by the mediation of CoIII(TBDAP) which alters a concerted rearrangement to a sequential process of O-O bond cleavage and N-O bond formation. Expectedly, the unveiling of the O-O bond cleavage mechanism could offer a clue for the development of biomimetic metal oxygenation catalysts.


Assuntos
Quelantes/química , Cobalto/química , Complexos de Coordenação/química , Teoria da Densidade Funcional , Dioxigenases/química , Peróxidos/química , Quelantes/síntese química , Quelantes/metabolismo , Cobalto/metabolismo , Complexos de Coordenação/síntese química , Complexos de Coordenação/metabolismo , Dioxigenases/metabolismo , Modelos Moleculares , Estrutura Molecular , Oxigênio/química , Oxigênio/metabolismo , Peróxidos/metabolismo
16.
Chem Commun (Camb) ; 56(14): 2087-2090, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-31967623

RESUMO

A dual-emissive tris-heteroleptic ruthenium complex is designed, synthesized and applied for the ratiometric photoluminescent detection of amyloid-ß (Aß) aggregation in both steady and transient states. The Aß aggregation is supported by transmission electron microscopy and confocal laser scanning microscopy analysis. In addition, molecular docking calculations have been performed to gain insights into the interaction mode between the ruthenium complex and Aß fibrils.


Assuntos
Peptídeos beta-Amiloides/análise , Complexos de Coordenação/química , Rutênio/química , Complexos de Coordenação/síntese química , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Agregados Proteicos
17.
Molecules ; 25(2)2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31936104

RESUMO

Metallation of biomacromolecular species forms the basis for the anticancer activity of many metallodrugs. A major limitation of these compounds is that their reactivity is indiscriminate and can, in principle, occur in healthy tissue as well as cancerous tissue, potentially leading to side effects in vivo. Here we present pH-dependent intramolecular coordination of an arene-tethered sulfonamide functionality in organometallic ruthenium(II) ethylenediamine complexes as a route to controlling the coordination environment about the central metal atom. Through variation of the sulfonamide R group and the length of the tether linking it to the arene ligand the acidity of the sulfonamide NH group, and hence the pH-region over which regulation of metal coordination occurs, can be modulated. Intramolecular sulfonamide ligation controlled the reactivity of complex 4 within the physiologically relevant pH-region, rendering it more reactive towards 5'-GMP in mildly acidic pH-conditions typical of tumour tissue compared to the mildly alkaline pH-conditions typical of healthy tissue. However, the activation of 4 by ring-opening of the chelate was found to be a slow process relative to the timescale of typical cell culture assays and members of this series of complexes were found not to be cytotoxic towards the HT-29 cell line. These complexes provide the basis for the development of analogues of increased potency where intramolecular sulfonamide ligation regulates reactivity and therefore cytotoxicity in a pH-dependent, and potentially, tissue-dependent manner.


Assuntos
Antineoplásicos/química , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Diaminas/química , Compostos Organometálicos/farmacologia , Rutênio/química , Sulfonamidas/química , Antineoplásicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Quelantes/química , Complexos de Coordenação/síntese química , Complexos de Coordenação/toxicidade , Cristalografia por Raios X , Diaminas/farmacologia , Etilenodiaminas/química , Etilenodiaminas/farmacologia , Guanosina Monofosfato/metabolismo , Células HT29 , Humanos , Concentração de Íons de Hidrogênio , Cinética , Ligantes , Modelos Moleculares , Compostos Organometálicos/química , Rutênio/farmacologia , Sulfonamidas/farmacologia
18.
Chem Commun (Camb) ; 56(16): 2439-2442, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-31996873

RESUMO

A Zr-cluster based metallogel is synthesized via an unusual one-pot solvothermal method. The resulting metallogel is robust, adaptive, self-healing, highly thermostable and conductive. Moreover, the metallogel exhibits reversible stimuli-responsive properties. The gel could respond to at least four kinds of stimuli such as light, aliphatic amines, electricity and metals with color and fluorescence tunability. Importantly, the metallogel with electrochromic properties could be used as soft electrochromic devices for smart windows and electro display boards, and metalchromism provides a practical way for coating corrosion monitoring of metal materials.


Assuntos
Complexos de Coordenação/química , Temperatura , Zircônio/química , Aminas/química , Complexos de Coordenação/síntese química , Géis/síntese química , Géis/química , Estrutura Molecular , Tamanho da Partícula , Propriedades de Superfície
19.
Biochemistry ; 59(5): 717-726, 2020 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-31967788

RESUMO

Up to 20% of solid tumors are characterized by DNA mismatch repair (MMR) deficiency and microsatellite instability that confer resistance to standard of care chemotherapy. MMR-deficient cancers have an increased mutation rate, and DNA mismatches accumulate as part of these cancers. We previously described a class of compounds, rhodium metalloinsertors, that bind DNA mismatches with high specificity and selectivity and have potential as targeted therapy. [Rh(chrysi)(phen)(PPO)]2+ (RhPPO) is the most potent, selective compound in this class and acts by targeting DNA mismatches, resulting in preferential cytotoxicity to MMR-deficient cancers. To explore further the cellular mechanism of action of RhPPO, we conjugated the metal complex to a fluorescent probe, cyanine 3 (Cy3). RhPPO-Cy3 binds DNA mismatches and retains the selectivity and potent cytotoxic activity of RhPPO for MMR-deficient cell lines. RhPPO-Cy3 forms discrete foci in the cell nucleus that overlap with sites of DNA damage, suggesting that the lesions occur at or near DNA mismatch sites. RhPPO-Cy3 foci persist over time, despite initial processing of the lesion and recruitment of repair proteins, consistent with the idea that the complex binding to a mismatch prevents repair. RhPPO-Cy3 binding does not lead to activation of p53 and the apoptotic pathway. Together, these findings support the idea that RhPPO-Cy3 binding leads to irreversible DNA damage at DNA mismatches that enables selective cytotoxicity to MMR-deficient cells.


Assuntos
Antineoplásicos/farmacologia , Carbocianinas/farmacologia , Complexos de Coordenação/farmacologia , Dano ao DNA , Corantes Fluorescentes/farmacologia , Ródio/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Carbocianinas/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Reparo de Erro de Pareamento de DNA/efeitos dos fármacos , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/química , Células HCT116 , Humanos , Estrutura Molecular , Imagem Óptica , Ródio/química
20.
Inorg Chem ; 59(4): 2367-2378, 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-31984731

RESUMO

Reaction of [ReOCl3(PPh3)2] or [ReO2I(PPh3)2] with 2,2'-diphenylglycine (dpgH2) in refluxing ethanol afforded the air-stable complex [ReO(dpgH)(dpg)(PPh3)] (1). Treatment of [ReO(OEt)I2(PPh3)2] with 1,2,3-triaza-7-phosphaadamantane (PTA) afforded the complex [ReO(OEt)I2(PTA)2] (2). Reaction of [ReOI2(PTA)3] with dpgH2 led to the isolation of the complex [Re(NCPh2)I2(PTA)3]·0.5EtOH (3·0.5EtOH). A similar reaction but using [ReOX2(PTA)3] (X = Cl, Br) resulted in the analogous halide complexes [Re(NCPh2)Cl2(PTA)3]·2EtOH (4·2EtOH) and [Re(NCPh2)(PTA)3Br2]·1.6EtOH (5·1.6EtOH). Using benzilic acid (2,2'-diphenylglycolic acid, benzH) with 2 afforded the complex [ReO(benz)2(PTA)][PTAH]·EtOH (6·EtOH). The potential for the formation of complexes using radioisotopes with relatively short half-lives suitable for nuclear medicine applications by developing conditions for [Re(NCPh2)(dpg)I(PTA)3] (7)[ReO4]- in a 4 h time scale was investigated. A procedure for the technetium analog of complex [Re(NCPh2)I2(PTA)3] (3) from 99mTc[TcO4]- was then investigated. The molecular structures of 1-7 are reported; complexes 3-7 have been studied using in vitro cell assays (HeLa, HCT116, HT-29, and HEK 293) and were found to have IC50 values in the range of 29-1858 µM.


Assuntos
Complexos de Coordenação/química , Complexos de Coordenação/toxicidade , Linhagem Celular Tumoral , Complexos de Coordenação/síntese química , Células HEK293 , Humanos , Estrutura Molecular , Compostos de Organotecnécio/síntese química , Compostos de Organotecnécio/química , Fosfinas/síntese química , Fosfinas/química , Fosfinas/toxicidade , Rênio/química , Solubilidade , Água/química
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