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1.
Acta Crystallogr C Struct Chem ; 75(Pt 8): 1091-1101, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31380792

RESUMO

A new set of differently hydrated barium and strontium squarates, namely poly[[triaqua(µ-1,2-dioxocyclobut-3-ene-1,2-diolato)barium] monohydrate], {[Ba(C4O4)(H2O)3]·H2O}n (1), poly[[diaqua(µ-1,2-dioxocyclobut-3-ene-1,2-diolato)strontium] monohydrate], {[Sr(C4O4)(H2O)2]·H2O}n (2), and poly[[triaqua(µ-1,2-dioxocyclobut-3-ene-1,2-diolato)barium/strontium(0.85/0.15)] monohydrate], {[Ba0.85Sr0.15(C4O4)(H2O)3]·H2O}n (3), is reported. The study of their crystal structures indicates that all the complexes crystallize in the triclinic space group P-1. Complexes 1 and 3 have a rare combination of squarate units coordinated through monodentate O atoms to two different metal atoms and through two bidentate O atoms to three different metal atoms. Furthermore, they have three coordinated water molecules to give a coordination number of nine. The squarate ligands in complex 2 exhibit two different coordination modes: (i) monodentate O atoms coordinated to four different Sr atoms and (ii) two monodentate O atoms coordinated to two different metal atoms with the other two O atoms bidentate to four different Sr atoms. All the compounds decompose to give the respective carbonates when heated to 800 °C, as evidenced by thermogravimetry/differential thermal analysis (TG-DTA), which are clusters of nanoparticles. Complexes 1 and 3 show additional endothermic peaks at 811 and 820 °C, respectively, indicating the phase transition of BaCO3 from an orthorhombic (α-Pmcn) to a trigonal phase (ß-R3m). All three complexes have significant DNA-binding constants, ranging from 2.45 × 104 to 9.41 × 104 M-1 against EB-CT (ethidium bromide-calf thymus) DNA and protein binding constants ranging from 1.1 × 105 to 8.6 × 105 with bovine serum albumin. The in vitro cytotoxicity of the complexes is indicated by the IC50 values, which range from 128.8 to 261.3 µg ml-1. Complex 3 shows better BSA binding, antioxidant activity against the DPPH radical and cytotoxicity than complexes 1 and 2.


Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Ciclobutanos/farmacologia , Depuradores de Radicais Livres/farmacologia , Substâncias Intercalantes/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/metabolismo , Bário/química , Bovinos , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Complexos de Coordenação/metabolismo , Cristalografia por Raios X , Ciclobutanos/síntese química , Ciclobutanos/química , Ciclobutanos/metabolismo , DNA/metabolismo , Depuradores de Radicais Livres/síntese química , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/metabolismo , Humanos , Ligações de Hidrogênio , Substâncias Intercalantes/síntese química , Substâncias Intercalantes/química , Substâncias Intercalantes/metabolismo , Ligantes , Células MCF-7 , Estrutura Molecular , Ligação Proteica , Soroalbumina Bovina/metabolismo , Estrôncio/química , Água/química
2.
Inorg Chem ; 58(16): 10611-10615, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31380629

RESUMO

Luminescent lanthanides provide a promising alternative to organic chromophores for cellular bioimaging and bioassay applications; efficacy is closely governed by their respective quantum yields. Conventionally utilized quantum-yield measurements for lanthanides are laborious and not amenable to rapid relative comparison of compound performance. Here, we introduce a high-throughput optical imaging method to determine and directly compare relative quantum yield using Cherenkov-radiation-mediated excitation of luminescent lanthanide complexes.


Assuntos
Complexos de Coordenação/química , Ensaios de Triagem em Larga Escala , Elementos da Série dos Lantanídeos/química , Teoria Quântica , Luminescência , Conformação Molecular
3.
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
4.
Chem Biol Interact ; 311: 108789, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31401089

RESUMO

The cytotoxicity of a dinuclear imine-copper (II) complex 2, and its analogous mononuclear complex 1, toward different melanoma cells, particularly human SKMEL-05 and SKMEL-147, was investigated. Complex 2, a tyrosinase mimic, showed much higher activity in comparison to complex 1, and its reactivity was verified to be remarkably activated by UVB-light, while the mononuclear compound showed a small or negligible effect. Further, a significant dependence on the melanin content in the tumor cells, both from intrinsic pigmentation or stimulated by irradiation, was observed in the case of complex 2. Similar tests with keratinocytes and melanocytes indicated a much lower sensitivity to both copper (II) complexes, even after exposition to UV light. Clonogenic assays attested that the fractions of melanoma cells survival were much lower under treatment with complex 2 compared to complex 1, both with or without previous irradiation of the cells. The process also involves generation of reactive oxygen species (ROS), as verified by EPR spectroscopy, and by using fluorescence indicators. Autophagic assays indicated a remarkable formation of cytoplasmic vacuoles in melanomas treated with complex 2, while this effect was not observed in similar treatment with complex 1. Monitoring of specific protein LC3 corroborated the simultaneous occurrence of autophagy. A balance interplay between different modes of cell death, apoptosis and autophagy, occurs when melanomas were treated with the dinuclear complex 2, in contrast to the mononuclear complex 1. These results pointed out to different mechanisms of action of such complexes, depending on its nuclearity.


Assuntos
Complexos de Coordenação/química , Cobre/química , Iminas/química , Monofenol Mono-Oxigenase/metabolismo , Animais , Autofagia/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Complexos de Coordenação/metabolismo , Complexos de Coordenação/farmacologia , Espectroscopia de Ressonância de Spin Eletrônica , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos da radiação , Humanos , Melaninas/metabolismo , Melanoma/metabolismo , Melanoma/patologia , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Tubulina (Proteína)/metabolismo , Raios Ultravioleta
5.
Inorg Chem ; 58(15): 10129-10138, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31310108

RESUMO

A series of 16 "3 + 2" mixed-ligand complexes of the general composition [ReO(L1)(L2)] (H2L1a-H2L1d = tridentate thiosemicarbazones having a phenyl group with 4-H, 4-F, 3,5-di-F, and 4-CF3 substituents; HL2a-HL2d = bidentate N,N-diethyl-N'-benzoylthioureas with 4-H, 4-F, 3,5-di-F, and 4-CF3 substituents at the benzoyl groups) have been synthesized and characterized by spectroscopic methods and X-ray diffraction. Irrespective of the individual fluorine substitution, the complexes are stable and possess the same general structure. Some systematic electronic effects of the fluorine-substitution patterns of the ligands have been found on the 13C NMR chemical shifts of the N-C═N carbon atoms of the {L1}2- and the C═O carbon atoms of the {L2}- ligands. Antiparasitic properties of the rhenium complexes have been tested against epimastigotes and trypomastigotes forms of two Trypanosoma cruzi strains and the amastigotes form of one of them. The results of this study indicate that the activity of the rhenium complexes can clearly be modulated by fluorine substitution of their ligands. Some of the fluorinated compounds show a high activity against epimastigotes and trypomastigotes forms of the parasites. Reactions between (NBu4)[TcOCl4] and two representatives of the fluorinated ligands (H2L1b, 4-F-substituted, and H2L1c, 4-CF3-substituted) form stable complexes of the composition [TcOCl(L1b)] and [TcOCl(L1c)]. Subsequent reactions of these products with HL2b (4-F-substituted) give the corresponding [TcO(L1)(L2)] mixed-ligand complexes. Also, the technetium compounds are stable as solids and in solutions and have structures corresponding to those of their rhenium analogues.


Assuntos
Complexos de Coordenação/farmacologia , Halogenação , Rênio/farmacologia , Tiossemicarbazonas/farmacologia , Tioureia/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Cristalografia por Raios X , Haplorrinos , Ligantes , Modelos Moleculares , Estrutura Molecular , Testes de Sensibilidade Parasitária , Rênio/química , Tiossemicarbazonas/química , Tioureia/química , Tripanossomicidas/síntese química , Tripanossomicidas/química
6.
Chem Commun (Camb) ; 55(57): 8329-8332, 2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31257378

RESUMO

Cell imaging heavily depends on fluorescent labels typically incompatible with Raman microscopy. The europium(iii) complex based on dipicolinic acid (DPA) presented here is an exception from this rule. Although its luminescence bands are very narrow, their intensity is comparable to the background Raman bands. This makes it complementary to less luminous compounds referred to as Raman tags. Through several examples we show that the complex provides a morphological context in otherwise unstained cells, thus acting as a spectral-counterstaining agent.


Assuntos
Complexos de Coordenação/química , Análise Espectral Raman , Candida albicans/metabolismo , Parede Celular/química , Células Epiteliais/química , Células Epiteliais/citologia , Európio/química , Células HeLa , Humanos , Microscopia de Fluorescência , Ácidos Picolínicos/química
7.
J Phys Chem A ; 123(29): 6241-6250, 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31268328

RESUMO

The association of Ca2+ to serine and the subsequent gas-phase unimolecular reactivity of the [Ca(Ser)]2+ (Ser = Serine) adduct was investigated throughout the use of tandem mass spectrometry techniques and B3LYP/6-311+G(3df,2p)//B3LYP/6-311+G(d,p) density functional theory calculations. In a first step, the structure and relative stability of all possible conformers of serine were obtained and analyzed, as well as the most stable [serine-Ca]2+ adducts. For the analysis of the different potential energy surfaces associated with the gas-phase unimolecular reactivity of these adducts, only those that differ by less than 100 kJ·mol-1 from the global minimum were taken into account. In agreement with previous studies, the serine-Ca2+ global minimum corresponds to a charge-solvated structure in which Ca is tricoordinated to neutral serine. The major peaks observed in the nanoelectrospray-MS/MS spectrum of [Ca(Ser)]2+ adduct correspond to both Coulomb explosions, yielding either CaOH+ + [C3,H6,N,O2]+ or [C2,H4,O,N]+ + [Ca(C,H3,O2)]+, and to the loss of neutrals, namely, CH2O and H2O. Our theoretical survey of the energy profile allow us to conclude that, although all the aforementioned fragmentation processes can have their origin at the global minimum, similar fragmentations involving low-lying conformers, both zwitterionic and nonzwitterionic, compete and should be considered to account for the observed reactivity. We have also found that in some specific cases post-transition state dynamics similar to the ones described before in the literature for formamide-Ca2+ reactions, may also play a role.


Assuntos
Cálcio/química , Complexos de Coordenação/química , Gases/química , Serina/química , Teoria da Densidade Funcional , Espectrometria de Massas , Modelos Químicos , Conformação Molecular , Termodinâmica
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.
Chem Commun (Camb) ; 55(58): 8494-8497, 2019 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-31268095

RESUMO

A rational strategy was reported to construct boranil complexes (DPFB derivatives) with unique aggregation-induced emission effects by installing phenyl rings in the anil ligand as the intramolecular rotors. In view of the good biocompatibility and suitable lipophilicity, DPFB derivatives can serve as excellent fluorescent probes for specific imaging of lipid droplets in living cells and yolk lipids in zebrafish.


Assuntos
Compostos de Anilina/química , Compostos de Boro/química , Complexos de Coordenação/química , Corantes Fluorescentes/química , Gotículas Lipídicas/metabolismo , Compostos de Anilina/síntese química , Animais , Compostos de Boro/síntese química , Complexos de Coordenação/síntese química , Fluorescência , Corantes Fluorescentes/síntese química , Células HeLa , Humanos , Ligantes , Microscopia Confocal/métodos , Estrutura Molecular , Peixe-Zebra
10.
Analyst ; 144(16): 4908-4916, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31312834

RESUMO

A new benzothiazole azo dye [(E)-1-((6-methoxybenzo[d]thiazole-2-yl)diazenyl)naphthalene-2,6-diol] (also known as "BAN"), has been synthesised and used as a chemosensor for the rapid and selective detection of mercury(ii) ions in water. The pink coloured chemosensor turns blue when reacted with mercury(ii) ions due to the formation of a 2 : 1 coordination complex. The complex formation causes a bathochromic shift of the chemosensor's UV absorption peak from 540 to 585 nm and turns on a highly selective fluorescence emission at 425 nm. The change in the optical property of BAN upon complexation with mercury(ii) was confirmed by ab initio calculations. The new chemosensor was used to quantify mercury(ii) ions in water by fluorescence spectroscopy down to 5 × 10-8 M (10 ppb). The limit of detection (LOD) of Hg2+ was 9.45 nM (1.8 ppb) which satisfies the maximum allowable Hg2+ concentration in drinking water that is set by the WHO. The BAN-Hg(ii) complex was used for the determination of cysteine (Cys) in aqueous solution by UV-Vis spectroscopy down to 1 × 10-7 M. The thiol-containing amino acid preferentially coordinates the mercury ions of the BAN-Hg(ii) complex. This causes dissociation of the blue-coloured complex and the liberation of the pink-coloured BAN dye. The colour change of the BAN-Hg(ii) complex from blue to pink was selective to the Cys biothiol while other non-thiol containing amino acids did not cause a colour change. For the in-field application, filter paper strips were loaded with the BAN-Hg(ii) complex and used as a disposable sensor for the detection of cysteine (Cys) by the naked eye. Therefore, the BAN chemosensor offers a sensitive, and rapid tool for the detection of mercury(ii) in water. In addition, the BAN-Hg(ii) complex can be used as a simple and selective chemosensor of the screening of purified biothiols, such cysetine, homocysteine and glutathione in biology research and pharmaceutical/food industries.


Assuntos
Benzotiazóis/síntese química , Corantes Fluorescentes/síntese química , Mercúrio/análise , Compostos de Sulfidrila/análise , Poluentes Químicos da Água/análise , Cátions Bivalentes , Cor , Simulação por Computador , Complexos de Coordenação/química , Cisteína/análise , Teoria da Densidade Funcional , Glutationa/análise , Concentração de Íons de Hidrogênio , Ligantes , Limite de Detecção , Espectrometria de Fluorescência
11.
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
12.
Chem Commun (Camb) ; 55(49): 7085-7088, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31150032

RESUMO

A luminescent biosensor has been developed for matrix metalloproteinase 9 (MMP-9) assays based on the selective interaction between an Ir(iii) solvent complex and a histidine-rich peptide, which avoids the complicated double labeling of substrate polypeptides commonly-used in FRET MMP detections and provides a promising strategy for MMP detection in clinical applications.


Assuntos
Técnicas Biossensoriais , Complexos de Coordenação/química , Histidina/química , Irídio/química , Metaloproteinase 9 da Matriz/análise , Peptídeos/química , Complexos de Coordenação/metabolismo , Transferência Ressonante de Energia de Fluorescência , Histidina/metabolismo , Humanos , Metaloproteinase 9 da Matriz/metabolismo , Peptídeos/metabolismo , Solventes/química
13.
Chem Pharm Bull (Tokyo) ; 67(6): 594-598, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31155565

RESUMO

In this study, the total synthesis of 3-epi-juruenolide C is achieved in 10 steps (longest linear sequence) starting from ethyl (2E,4S,5S)-4,5-dihydroxy-2-hexenoate. The synthetic highlights of our approach include one-pot regioselective bromination, intramolecular carbonylation using bis(triphenylphosphine)dicarbonylnickel, and face-selective hydrogenation using a homogeneous Wilkinson's catalyst.


Assuntos
Dioxóis/síntese química , Lactonas/síntese química , Catálise , Complexos de Coordenação/química , Dioxóis/química , Halogenação , Hidrogenação , Lactonas/química , Níquel/química , Compostos Organofosforados/química , Estereoisomerismo
14.
Top Curr Chem (Cham) ; 377(3): 18, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31161309

RESUMO

Manganese(III) porphyrin complexes with various metal-containing/non-metal bridges reported during the past two decades, including their structural characteristics and magnetic properties, are summarized. As the porphyrin ligands usually adopt a planar chelate form, it is possible that the porphyrin-based complexes, being a coordination-acceptor building block, have two coordination labile sites in trans positions. In particular, the coordination labile sites in an octahedral field face the direction of the Jahn-Teller elongated axis occupying the dz2 orbital. As a result of this characteristic orbital arrangement, the activity and magnetic-electronic properties of the manganese complexes can be tuned by modulating the porphyrin ligand, which is equatorially located around the manganese ion and coupled with the dx2-y2 orbital. The high-spin Mn(III) porphyrin complexes (S = 2) display strong magnetic uniaxial anisotropy with the Jahn-Teller axis as the magnetic easy axis. So far, various manganese(III) porphyrin magnetism systems, including multinuclear clusters, one-dimensional chains, and two- or three-dimensional networks, have been designed and structurally and magnetically characterized. This review shows that the manganese(III) porphyrin complexes have potential as versatile sources for the design of unique magnetic materials as well as other molecular functional materials with various structures.


Assuntos
Imãs/química , Metaloporfirinas/química , Complexos de Coordenação/química , Cristalografia por Raios X , Cianetos/química , Dimerização , Magnetismo/métodos , Modelos Moleculares
15.
Inorg Chem ; 58(13): 8685-8693, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31247868

RESUMO

In this study, we present the synthesis and characterization of the octadentate bispidine ligand, H2bispox2 and its complexes with medicinally useful radiometal nuclides (111In3+ and 177Lu3+), including their X-ray diffraction single crystal structures with the stable isotopes. 111InCl3 radiolabels the ligand quantitatively at ambient conditions ([L] = 10-5 M, room temperature, pH 7 and 15 min) and the in vitro human serum stability assays demonstrated high stability of the [111In(bispox2)]+ complex over 5 days. Moreover, the ß - emitter 177Lu radiolabels the ligand at 37 °C in 30 min (pH 8). These initial investigations reveal the potential of the octadentate bispidine ligand H2bispox2 as a useful chelator for 111In and 177Lu-based radiopharmaceuticals.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes/química , Complexos de Coordenação/química , Oxiquinolina/análogos & derivados , Compostos Radiofarmacêuticos/química , Animais , Compostos Bicíclicos Heterocíclicos com Pontes/sangue , Compostos Bicíclicos Heterocíclicos com Pontes/síntese química , Quelantes/síntese química , Quelantes/química , Complexos de Coordenação/sangue , Complexos de Coordenação/síntese química , Estabilidade de Medicamentos , Humanos , Radioisótopos de Índio , Ligantes , Lutécio , Camundongos , Estrutura Molecular , Oxiquinolina/sangue , Oxiquinolina/síntese química , Oxiquinolina/química , Radioisótopos , Compostos Radiofarmacêuticos/sangue , Compostos Radiofarmacêuticos/síntese química
16.
Inorg Chem ; 58(13): 8800-8819, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31247881

RESUMO

Very few inorganic antineoplastic drugs have entered the clinic in the last decades, mainly because of toxicity issues. Because copper is an essential trace element of ubiquitous occurrence, decreased side effects could be expected in comparison with the widely used platinum anticancer compounds. In the present work, two novel hydrazonic binucleating ligands and their µ-hydroxo dicopper(II) complexes were prepared and fully characterized. They differ by the nature of the aromatic group present in their aroylhydrazone moieties: while H3L1 and its complex, 1, possess a thiophene ring, H3L2 and 2 contain the more polar furan heterocycle. X-ray diffraction indicates that both coordination compounds are very similar in structural terms and generate dimeric arrangements in the solid state. Positive-ion electrospray ionization mass spectrometry analyses confirmed that the main species present in a 10% dimethyl sulfoxide (DMSO)/water solution should be [Cu2(HL)(OH)]+ and the DMSO-substituted derivative [Cu2(L)(DMSO)]+. Scattering techniques [dynamic light scattering (DLS) and small-angle X-ray scattering] suggest that the complexes and their free ligands interact with bovine serum albumin (BSA) in a reversible manner. The binding constants to BSA were determined for the complexes through fluorescence spectroscopy. Moreover, to gain insight into the mechanism of action of the compounds, calf thymus DNA binding studies by UV-visible and DLS measurements using plasmid pBR322 DNA were also performed. For the complexes, DLS data seem to point to the occurrence of DNA cleavage to Form III (linear). Both ligands and their dicopper(II) complexes display potent antiproliferative activity in a panel of four cancer cell lines, occasionally even in the submicromolar range, with the complexes being more potent than the free ligands. Our data on cellular models correlate quite well with the DNA interaction experiments. The results presented herein show that aroylhydrazone-derived binucleating ligands, as well as their dinuclear µ-hydroxodicopper(II) complexes, may represent a promising structural starting point for the development of a new generation of highly active potential antitumor agents.


Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Hidrazonas/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/toxicidade , Bovinos , Linhagem Celular Tumoral , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Complexos de Coordenação/toxicidade , Cobre/química , DNA/química , Clivagem do DNA/efeitos dos fármacos , Cães , Humanos , Hidrazonas/síntese química , Hidrazonas/química , Hidrazonas/toxicidade , Isomerismo , Ligantes , Células Madin Darby de Rim Canino , Camundongos , Plasmídeos/química , Multimerização Proteica/efeitos dos fármacos , Soroalbumina Bovina/metabolismo
17.
J Photochem Photobiol B ; 197: 111516, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31170508

RESUMO

In the search for new therapeutic agents we have synthesized 13 new organotin(IV) carboxylate derivatives of (E)-4-((4-methoxy-2-nitrophenyl)amino)-4-oxobut-2-enoic acid. The synthesized complexes were characterized by several spectroscopic techniques. A chelating or bridging bidentate nature of the carboxylate ligand was suggested from the solid state FT-IR results. Solution state multinuclear NMR (1H, 13C and 119Sn) results reveal that the geometry around the Sn atom in triorganotin(IV) complexes is trigonal bipyramidal and in diorganotin(IV) complexes is octahedral. The ligand, (E)-4-((4-methoxy-2-nitrophenyl)amino)-4-oxobut-2-enoic acid, complex 1 and complex 2 were also analyzed by single crystal X-ray technique and the results fully supports the spectroscopic data. For 1 and 2 the geometry optimized by the single crystal X-ray analyses is distorted trigonal bipyramidal. The interaction of the studied compounds with SS-DNA was investigated by UV-Vis. Spectroscopy and Molecular docking showing an intercalative mode of binding. The evaluation of the screened compounds for cancer treatment displays even higher than that of the vincristine used as a standard drug. Similarly the performance of the tested compounds as an antileishmanial agent considers them very close in activity to the standard drug, amphotericin B. The antibacterial results show that the most of the compounds have a moderate sensitivity against the studied bacterial pathogens.


Assuntos
Complexos de Coordenação/química , Compostos Orgânicos de Estanho/química , Sítios de Ligação , Ácidos Carboxílicos/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/farmacologia , Cristalografia por Raios X , DNA/química , DNA/metabolismo , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Leishmania tropica/efeitos dos fármacos , Ligantes , Espectroscopia de Ressonância Magnética , Conformação Molecular , Simulação de Acoplamento Molecular , Conformação de Ácido Nucleico , Espectroscopia de Infravermelho com Transformada de Fourier
18.
Water Sci Technol ; 79(9): 1667-1674, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31241472

RESUMO

A series of EDTA-metal complexes was prepared for the Fenton oxidation catalysts and Fe(II)L exhibits high catalytic performance for degradation of hydroxypropyl guar gum in a wide pH range 7.0-13.0. The viscosity of hydroxypropyl guar gum can be reduced with the 10.0% H2O2 and 5.0% Fe(II)L. The viscosity average molecular weight of hydroxypropyl guar gum was decreased from almost 2 million to 3,199. Most important of all, the chemical oxygen demand (COD) value can be decreased to 104 mg/L from 8,080 mg/L with enough H2O2, and Fe(II)L also shows great catalytic ability in the degradation of various polymers by H2O2. The proposed mechanism of the activation of H2O2 by the complex was studied.


Assuntos
Ácido Edético/química , Catálise , Complexos de Coordenação/química , Peróxido de Hidrogênio , Concentração de Íons de Hidrogênio , Polissacarídeos/química
19.
Anal Chim Acta ; 1072: 54-60, 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31146865

RESUMO

In this work, we reported a novel electrochemical sensor for enantiorecognition of electrochemically inactive aspartic acid (Asp) enantiomers. By combining sol-gel processing with molecular imprinting technology, an enantioselective interface of molecularly imprinted sol-gel (MIS) films with imprinted cavities was prepared on the surface of a glassy carbon electrode (GCE). In order to obtain the electrochemical responses of electrochemically inactive Asp, the ternary derivative of L-aspartic, (l-aspartic acid)Cu2+(N-carbobenzoxy-l-aspartic acid), was used as the template for fabrication of MIS. The stripping currents of target molecules could be detected by square-wave stripping voltammetry due to the reduction of cupric ion on the modified electrode. The resulted sensor showed good adsorbability to L-Asp derivative, and the recognition efficiency was obtained as 2.1. Meanwhile, the L-Asp was quantitatively determined by the MIS sensor. As a result, the proposed electrochemical sensor could be regarded as a potential platform for enantiorecognition of electrochemically inactive chiral compounds.


Assuntos
Ácido Aspártico/análise , Complexos de Coordenação/química , Cobre/química , Técnicas Eletroquímicas , Impressão Molecular , Géis/química , Conformação Molecular , Tamanho da Partícula , Estereoisomerismo , Propriedades de Superfície
20.
Eur J Med Chem ; 177: 291-301, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31158745

RESUMO

Based on our previous research on the fluorinated phenylquinoxaline scaffold, in this study, different positions of N,N-dimethyl amino group, and alkyl linkers with various lengths were introduced into this scaffold to regulate their lipophilicity and binding affinity to Tau. Four novel 99mTc/Re complexes with diethyl iminodiacetate chelator were synthesized and evaluated as Tau imaging tracers in the brain of Alzheimer's disease. Their specific binding to neurofibrillary tangles was verified by in vitro fluorescence staining and further confirmed by the results of immunofluorescence staining on the same brain sections from AD patient and Tg-tau mice. From in vitro binding assay using recombinant Tau aggregates, complex 4.2 with 6-N(CH3)2 and longer carbon chain (n = 4) displayed the highest affinity (Kd = 59.95 nM). [99mTc]4.2 was achieved by the ligand exchange reaction between dicarboxylic precursor and [99mTc(CO)3(H2O)3]+ intermediate with radiochemical yield over 45%. Ex vivo biodistribution studies on normal ICR mice revealed that [99mTc]4.2 exhibited moderate initial brain uptake (0.61% ID/g) and more structure optimizations are still required to improve the blood-brain barrier permeability.


Assuntos
Doença de Alzheimer/diagnóstico , Complexos de Coordenação/química , Corantes Fluorescentes/química , Compostos de Organotecnécio/química , Quinoxalinas/química , Proteínas tau/metabolismo , Idoso de 80 Anos ou mais , Peptídeos beta-Amiloides/metabolismo , Animais , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Quelantes/síntese química , Quelantes/química , Quelantes/metabolismo , Complexos de Coordenação/síntese química , Complexos de Coordenação/metabolismo , Feminino , Fluorescência , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/metabolismo , Humanos , Iminoácidos/síntese química , Iminoácidos/química , Iminoácidos/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Estrutura Molecular , Emaranhados Neurofibrilares/metabolismo , Emaranhados Neurofibrilares/patologia , Compostos de Organotecnécio/síntese química , Compostos de Organotecnécio/metabolismo , Fragmentos de Peptídeos/metabolismo , Quinoxalinas/síntese química , Quinoxalinas/metabolismo , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/metabolismo , Rênio/química , Distribuição Tecidual
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