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1.
Angew Chem Int Ed Engl ; : e202411635, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38963679

RESUMO

Over the years, polynuclear cyclic or torus complexes have attracted increasing interest due to their unique metal topologies and properties. However, the isolation of polynuclear cyclic organometallic complexes is extremely challenging due to their inherent reactivity, which stems from the labile and reactive metal-carbon bonds. In this study, the pyrazine ligand undergoes a radical-radical cross-coupling reaction leading to the formation of a decanuclear [(Cp*)20Dy10(L1)10]·12(C7H8) (1; where L1 = anion of 2-prop-2-enyl-2H-pyrazine) complex, where all DyIII metal centers are bridged by the anionic L1 ligand. Amongst the family of polynuclear Ln organometallic complexes bearing CpR2Lnx units, 1 features the highest nuclearity obtained to date. In-depth computational studies were conducted to elucidate the proposed reaction mechanism and formation of L1, while probing of the magnetic properties of 1, revealed slow magnetic relaxation upon application of a static dc field.

2.
Toxicol Res ; 39(3): 455-475, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37398567

RESUMO

Lung cancer is the most often reported cancer with a terrible prognosis worldwide. Flavonoid metal complexes have exhibited potential chemotherapeutic effects with substantially low adverse effects. This study investigated the chemotherapeutic effect of the ruthenium biochanin-A complex on lung carcinoma in both in vitro and in vivo model systems. The synthesized organometallic complex was characterized via UV‒visible spectroscopy, FTIR, mass spectrometry, and scanning electron microscopy. Moreover, the DNA binding activity of the complex was determined. The in vitro chemotherapeutic assessment was performed on the A549 cell line through MTT assay, flow cytometry, and western blot analysis. An in vivo toxicity study was performed to determine the chemotherapeutic dose of the complex, and subsequently, chemotherapeutic activity was assessed in benzo-α-pyrene-induced lung cancer mouse model by evaluating the histopathology, immunohistochemistry, and TUNEL assays. The IC50 value of the complex in A549 cells was found to be 20 µM. The complex demonstrated significant apoptosis induction, enhanced caspase-3 expression and cell cycle arrest with downregulated PI3K, PPARγ, TGF-ß, and TNF-α expression in A549 cells. The in vivo study suggested that ruthenium biochanin-A therapy restored the morphological architecture of lung tissue in a benzo-α-pyrene-induced lung cancer model and inhibited the expression of Bcl2. Additionally, increased apoptotic events were identified with upregulation of caspase-3 and p53 expression. In conclusion, the ruthenium biochanin-A complex successfully amelioratedlung cancer incidence in both in vitro and in vivo models through the alteration of the TGF-ß/PPARγ/PI3K/TNF-α axis with the induction of the p53/caspase-3-mediated apoptotic pathway.

3.
ACS Appl Mater Interfaces ; 15(24): 28851-28878, 2023 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-37293760

RESUMO

The use of molecularly modified electrodes in catalysis heralds a new paradigm in designing chemical transformations by allowing control of catalytic activity. Herein, we provide an overview of reported methods to develop electrodes functionalized with organometallic complexes and a summary of commonly used techniques for characterizing the electrode surface after immobilization. In addition, we highlight the implications of surface functionalization in catalysis to emphasize the key aspects that should be considered during the development and optimization of functionalized electrodes. Particularly, surface-molecule electronic coupling and electrostatic interactions within a hybrid system are discussed to present effective handles in tuning catalytic activity. We envision that this emerging type of hybrid catalytic system has the potential to combine the advantages of homogeneous catalysis and heterogeneous supports and could be applied to an expanded range of transformations beyond energy conversion.

4.
Toxicol Res ; 39(2): 213-229, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37008693

RESUMO

Throughout the last decades flavonoids have been considered as a powerful bioactive molecule. Complexation of these flavonoids with metal ions demonstrated the genesis of unique organometallic complexes which provide improved pharmacological and therapeutic activities. In this research, the fisetin ruthenium-p-cymene complex was synthesized and characterized via different analytical methods like UV-visible spectroscopy, Fourier-transform infrared spectroscopy, mass spectroscopy, and scanning electron microscope. The toxicological profile of the complex was evaluated by acute and sub-acute toxicity. Additionally, the mutagenic and genotoxic activity of the complex was assessed by Ames test, chromosomal aberration test, and micronucleus based assay in Swiss albino mice. The acute oral toxicity study exhibited the LD50 of the complex at 500 mg/kg and subsequently, the sub-acute doses were selected. In sub-acute toxicity study, the hematology and serum biochemistry of the 400 mg/kg group showed upregulated white blood cells, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine, glucose and cholesterol. However, there was no treatment related alteration of hematological and serum biochemical parameters in the 50, 100, and 200 mg/kg group. In the histopathological analysis, the 50, 100, and 200 mg/kg groups were not associated with any toxicological alterations, whereas the 400 mg/kg group showed prominent toxicological incidences. Nevertheless, the treatment with fisetin ruthenium-p-cymene complex did not exhibit any mutagenic and genotoxic effect in Swiss albino mice. Thus, the safe dose of this novel organometallic complex was determined as 50, 100, and 200 mg/kg without any toxicological and genotoxic potential.

5.
Sensors (Basel) ; 23(8)2023 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-37112406

RESUMO

While standard surface plasmon resonance (bio) sensing, relaying on propagating surface plasmon polariton sensitivity on homogeneous metal/dielectric boundaries, represents nowadays a routine sensing technique, other alternatives, such as inverse designs with nanostructured plasmonic periodic hole arrays, have been far less studied, especially in the context of gas sensing applications. Here, we present a specific application of such a plasmonic nanostructured array for ammonia gas sensing, based on a combination of fiber optics, extraordinary optical transmission (EOT) effect, and chemo-optical transducer selectively sensitive to ammonia gas. The nanostructured array of holes is drilled in a thin plasmonic gold layer by means of focused ion beam technique. The structure is covered by chemo-optical transducer layer showing selective spectral sensitivity towards gaseous ammonia. Metallic complex of 5-(4'-dialkylamino-phenylimino)-quinoline-8-one dye soaked in polydimethylsiloxane (PDMS) matrix is used in place of the transducer. Spectral transmission of the resulting structure and its changes under exposition to ammonia gas of various concentrations is then interrogated by fiber optics tools. The observed VIS-NIR EOT spectra are juxtaposed to the predictions performed by the rigorous Fourier modal method (FMM), providing useful theoretical feedback to the experimental data, and ammonia gas sensing mechanism of the whole EOT system and its parameters are discussed.

6.
Regul Toxicol Pharmacol ; 137: 105303, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36427689

RESUMO

The flavonoid-based organometallic complexes have been identified as novel bioactive compounds with enhanced pharmacological and therapeutic activity. In this study, the ruthenium-p-cymene diosmetin complex was synthesized, characterized, and investigated for toxicological profiling through different toxicological and genotoxicological studies which include acute and sub-acute toxicity, chromosomal aberration, and bone marrow micronucleus study. The acute oral toxicity study demonstrated the LD50 dose of the complex at 500 mg/kg body weight which further instigated the sub-acute doses i.e. 50, 100, and 200 mg/kg. The histopathological analysis demonstrated that the 400 mg/kg dose was associated with severe toxicological incidences of the vital organs (liver, kidney, pancreas, testis, and stomach) except the ovary with increased levels of ALP, AST, ALT, and WBC count. However, 50, 100, and 200 mg/kg doses did not show any toxicological alteration and maintained the normal levels of hematological and serum biochemical parameters. The genotoxicological assessment of the complex depicted no such genetic damage or mutagenicity in any complex treated groups. In conclusion, the 50, 100, and 200 mg/kg doses were determined as therapeutic dose of the novel ruthenium-p-cymene diosmetin complex without any genotoxic and mutagenic potential which can be further implemented in the investigation of various pharmacological and therapeutic interventions.


Assuntos
Rutênio , Masculino , Feminino , Ratos , Animais , Testes de Toxicidade Aguda , Flavonoides/toxicidade , Mutagênicos
7.
Materials (Basel) ; 15(15)2022 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-35897589

RESUMO

The article presents research on the potential use of organometallic compounds with the addition of antimony (III) oxide Sb2O3 as a coating additive that will make coatings susceptible to electroless metallization after prior surface irradiation with 193 nm wavelength laser radiation and a different number of laser pulses. The surface modification and activation effects were assessed by optical-imagining as well as by scanning electron microscopy (SEM) with energy dispersive analysis (EDX). It was found that the presence of Sb2O3 in the coating made it possible to reduce the content of the copper complex, causing an intensive surface ablation, resulting in the formation of a conical structure with a higher content of metallic copper nuclei.

8.
Biochem Pharmacol ; 202: 115124, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35688179

RESUMO

Among the new Pt complexes with anticancer properties, phenanthroline derivatives have aroused great interest due to their different mode of action compared to cisplatin. We previously examined cytotoxic effects of a new Pt(II)-complex containing 1,10-phenantroline (phen), [Pt(η1-C2H4OMe)(DMSO)(phen)]Cl, in a panel of eight human cancer cell lines, and showed that it exerted the greatest cytotoxic effect in the neuroblastoma SH-SY5Y cell line. In this study, the antiproliferative and antimetastatic potential of [Pt(η1-C2H4OMe)(DMSO)(phen)]+ (in short Pt-EtOMeSOphen) was investigated in neuroblastoma SH-SY5Y, SK-N-SH and SK-N-BE(2) cells. Pt-EtOMeSOphen provoked the early signs of apoptosis induction (cleavage of PARP and activation of caspases-9 and -7); it also increased the level of proapoptotic Bax protein whereas it decreased the level of the antiapoptotic Bcl-2 protein. The effects of Pt-EtOMeSOphen on migration and invasion processes were also evaluated. A decrease of cell migration/invasion by Pt-EtOMeSOphen was observed through 2D and 3D in vitro assays. Pt-EtOMeSOphen was found to exert its actions by decreasing MMP-9 and MMP-2 expressions and activities. Pt-EtOMeSOphen provoked the phosphorylation of both ERK1/2 and p38 MAPKs. All the effects of Pt-EtOMeSOphen on SH-SY5Y cell vitality, migration and metalloproteases activities described here were due to the activation of p38 MAPK since pharmacological p38 MAPK inhibition or small interfering RNAs to p38 MAPK mRNA blocked such effects. Results suggest that Pt-EtOMeSOphen inhibits neuroblastoma cancer cells survival, motility, and invasion. This could lead to the reduction of neuroblastoma metastatic potential.


Assuntos
Antineoplásicos/farmacologia , Neuroblastoma , Compostos de Platina/farmacologia , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Dimetil Sulfóxido/farmacologia , Humanos , Neuroblastoma/tratamento farmacológico , Neuroblastoma/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
9.
J Oleo Sci ; 71(2): 167-175, 2022 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-35034943

RESUMO

Metallosurfactants are emerging as a relatively new class of surfactants whose ligand moieties bind to various transition metals. Because transition metal centers are incorporated into the surfactant frameworks, they can form various self-assembled structures with metallic interfaces such as micelles, vesicles, and lyotropic liquid crystals. To reduce the lability of transition metal complexes under aqueous conditions, various amphiphilic ligands have been developed as surfactant frameworks. This review discusses some aspects of the design and chemical structures of amphiphilic ligands, as well as focus on various functions and types of chemical bonds present in metallosurfactants.


Assuntos
Ligantes , Compostos Organometálicos/química , Tensoativos/química , Desenho de Fármacos , Cristais Líquidos/química , Micelas , Água/química
10.
Pharmaceutics ; 13(5)2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33946459

RESUMO

Starting from the [PtCl(η1-C2H4OMe)(phen)] (phen = 1,10-phenanthroline, 1) platinum(II) precursor, we synthesized and characterized by multinuclear NMR new [Pt(η1-C2H4OMe)(L)(phen)]+ (L = NH3, 2; DMSO, 3) complexes. These organometallic species, potentially able to interact with cell membrane organic cation transporters (OCT), violating some of the classical rules for antitumor activity of cisplatin analogues, were evaluated for their cytotoxicity. Interestingly, despite both complexes 2 and 3 resulting in greater cell uptake than cisplatin in selected tumor cell lines, only 3 showed comparable or higher antitumor activity. General low cytotoxicity of complex 2 in the tested cell lines (SH-SY5Y, SK-OV-3, Hep-G2, Caco-2, HeLa, MCF-7, MG-63, ZL-65) appeared to depend on its stability towards solvolysis in neutral water, as assessed by NMR monitoring. Differently, the [Pt(η1-C2H4OMe)(DMSO)(phen)]+ (3) complex was easily hydrolyzed in neutral water, resulting in a comparable or higher cytotoxicity in cancer cells with respect to cisplatin. Further, both IC50 values and the uptake profiles of the active complex appeared quite different in the used cell lines, suggesting the occurrence of diversified biological effects. Nevertheless, further studies on the metabolism of complex 3 should be performed before planning its possible use in tissue- and tumor-specific drug design.

11.
Materials (Basel) ; 14(4)2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33669595

RESUMO

This paper presents a comparative assessment of Cu(acac)2 and {[Cu(µ-O,O'-NO3) (L-arg)(2,2'-bpy)]·NO3}n as potential precursors for the electroless metallization of laser activated polymer materials. Coatings consisting of polyurethane resin, one of the two mentioned precursor compounds, and antimony oxide (Sb2O3), as a compound strongly absorbing infrared radiation, were applied on the polycarbonate substrate. The coatings were activated with infrared Nd: YAG laser radiation (λ = 1064 nm) and electroless metallized. It was found that after laser irradiation, a micro-rough surface structure of the coatings was formed, on which copper was present in various oxidation states, as well as in its metallic form. For selected parameters of laser irradiation, it was possible to deposit a copper layer on the coating containing Cu(acac)2 and Sb2O3, which is characterized by high adhesion strength. It was also found that the {[Cu(µ-O,O'-NO3) (L-arg)(2,2'-bpy)]·NO3}n complex was not an effective precursor for the electroless metallization of Nd:YAG laser activated coatings. An attempt was made to determine the influence of the precursor chemical structure on the obtained metallization effects.

12.
ChemCatChem ; 12(18): 4512-4516, 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-33777249

RESUMO

Through a rapid screening of Cp*Ir complexes based on a turn-on type fluorescence readout, a [Cp*Ir(dipyrido[3,2-a : 2',3'-c]phenazine)Cl]+ complex was found to catalyze the blue-light promoted dehydrogenation of N-heterocycles under physiological conditions. In the dehydrogenation of tetrahydroisoquinolines, the catalyst preferentially yielded the monodehydrogenated product, accompanying H2O2 generation. We surmise that this mechanism may be reminiscent of flavin-dependent oxidases.

13.
Front Microbiol ; 11: 608924, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33384677

RESUMO

Chikungunya fever is a disease caused by the Chikungunya virus (CHIKV) that is transmitted by the bite of the female of Aedes sp. mosquito. The symptoms include fever, muscle aches, skin rash, and severe joint pains. The disease may develop into a chronic condition and joint pain for months or years. Currently, there is no effective antiviral treatment against CHIKV infection. Treatments based on natural compounds have been widely studied, as many drugs were produced by using natural molecules and their derivatives. Alpha-phellandrene (α-Phe) is a naturally occurring organic compound that is a ligand for ruthenium, forming the organometallic complex [Ru2Cl4(p-cymene)2] (RcP). Organometallic complexes have shown promising as candidate molecules to a new generation of compounds that presented relevant biological properties, however, there is a lack of knowledge concerning the anti-CHIKV activity of these complexes. The present work evaluated the effects of the RcP and its precursors, the hydrate ruthenium(III) chloride salt (RuCl3⋅xH2O) (Ru) and α-Phe, on CHIKV infection in vitro. To this, BHK-21 cells were infected with CHIKV-nanoluciferase (CHIKV-nanoluc), a viral construct harboring the nanoluciferase reporter gene, at the presence or absence of the compounds for 16 h. Cytotoxicity and impact on infectivity were analyzed. The results demonstrated that RcP exhibited a strong therapeutic potential judged by the selective index > 40. Antiviral effects of RcP on different stages of the CHIKV replicative cycle were investigated; the results showed that it affected early stages of virus infection reducing virus replication by 77% at non-cytotoxic concentrations. Further assays demonstrated the virucidal activity of the compound that completely blocked virus infectivity. In silico molecular docking calculations suggested different binding interactions between aromatic rings of RcP and the loop of amino acids of the E2 envelope CHIKV glycoprotein mainly through hydrophobic interactions. Additionally, infrared spectroscopy spectral analysis indicated interactions of RcP with CHIKV glycoproteins. These data suggest that RcP may act on CHIKV particles, disrupting virus entry to the host cells. Therefore, RcP may represent a strong candidate for the development of anti-CHIKV drugs.

14.
Micron ; 107: 85-93, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29471173

RESUMO

The structure-property correlation in the Cu-TCNQ organometallic complex is very important for explaining its unusual electrical, optical and magnetic properties. Consequently several morphological studies and their correlation with the properties of these materials can be found in the literature, although no systematic study of various morphologies with growth conditions and their correlation has been reported to the best of our knowledge. Therefore in this manuscript the interconversion of various morphologies is reported using electron and probe microscopies. A conventional Cu TEM grid acted as the copper source to form a Cu-TCNQ complex and the complex, which formed at the surface of the TEM grid. The complex thus prepared was characterized by FTIR and Raman spectroscopic techniques. The shifting of ̵-CN from 2221 cm-1 (TCNQ) to 2201 cm-1 indicates formation of a complex and the identical nature of IR spectra in two phases indicates that they are polymorphs. The morphologies of Cu-TCNQ were followed through FE-SEM and TEM studies. Various morphologies such as needle, square tube, platelet etc. were observed as a function of time. A distinct transition from needle to platelet morphology was observed as the complex grew. The conductance of various morphologies in phase-I as well as phase-II were also measured and compared by Spreading Resistance Imaging (SRI) at different bias voltage i.e. 1 V, 3 V and 5 V.

15.
Anal Chim Acta ; 990: 135-140, 2017 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-29029736

RESUMO

Quantitative determination of nitrite ion (NO2-) is of great importance in environmental and clinical investigations. A rapid visual and spectrophotometric assay for NO2- detection was developed based on a newly designed ruthenium complex, [Ru(npy)([9]aneS3)(CO)](ClO4) (denoted as RuNPY; npy = 2-(1-naphthyl)pyridine, [9]aneS3 = 1,4,7-trithiacyclononane). This complex traps NO+ produced in acidified NO2- solution, and yields observable color change within 1 min at room temperature. The assay features excellent dynamic range (1-840 µmol L-1) and high selectivity, and its limit of detection (0.39 µmol L-1) is also well below the guideline values for drinking water recommended by WHO and U.S. EPA. Practical use of this assay in tap water and human urine was successfully demonstrated. Overall, the rapidity and selectivity of this assay overcome the problems suffered by the commonly used modified Griess assays for nitrite determination.


Assuntos
Água Potável/análise , Nitritos/análise , Nitritos/urina , Rutênio/química , Urina/química , Humanos , Espectrofotometria
16.
ACS Nano ; 11(11): 11402-11408, 2017 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-29064665

RESUMO

Easy-axis magnetic anisotropy separates two magnetic states with opposite magnetic moments, and single magnetic atoms and molecules with large easy-axis magnetic anisotropy are highly desired for future applications in high-density data storage and quantum computation. By tuning the metalation reaction between tetra-pyridyl-porphyrin molecules and Fe atoms, we have stabilized the so-called initial complex, an intermediate state of the reaction, on Au(111) substrate, and investigated the magnetic property of this complex at a single-molecule level by low-temperature scanning tunneling microscopy and spectroscopy. As revealed by inelastic electron tunneling spectroscopy in magnetic field, this Fe-porphyrin complex has magnetic anisotropy energy of more than 15 meV with its easy-axis perpendicular to the molecular plane. Two magnetic states with opposite spin directions are discriminated by the dependence of spin-flip excitation energy on magnetic field and are found to have long spin lifetimes. Our density functional theory calculations reveal that the Fe atom in this complex, decoupled from Au substrate by a weak ligand field with elongated Fe-N bonds, has a high-spin state S = 2 and a large orbital angular momentum L = 2, which give rise to easy-axis anisotropy perpendicular to the molecular plane and large magnetic anisotropy energy by spin-orbit coupling. Since the Fe atom is protected by the molecular ligand, the complex can be processed at room or even higher temperatures. The reported system may have potential applications in nonvolatile data storage, and our work demonstrates on-surface metalation reactions can be utilized to synthesize organometallic complexes with large magnetic anisotropy.

17.
ACS Nano ; 11(3): 2675-2681, 2017 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-28234448

RESUMO

Iron atoms adsorbed on a Cu(111) surface and buried under polyphenyl dicarbonitrile molecules exhibit strongly spatial anisotropic Kondo features with directionally dependent Kondo temperatures and line shapes, as evidenced by scanning tunneling spectroscopy. First-principles calculations find nearly full polarization for the half-filled Fe 3dxz and 3dyz orbitals, which therefore can give rise to Kondo screening with the experimentally observed directional dependence and distinct Kondo temperatures. X-ray absorption spectroscopy and X-ray magnetic circular dichroism measurements confirm that the spin in both channels is effectively Kondo-screened. At ideal Fe coverage, these two-orbital Kondo impurities are arranged in a self-assembled honeycomb superlattice.

18.
ChemSusChem ; 9(12): 1483-9, 2016 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-27219476

RESUMO

Inspired by the preparation of the hierarchically-porous carbon (HPC) derived from metal organic frameworks (MOFs) for energy storage, in this work, a simple iron-based metal- organic complex (MOC), which was simpler and cheaper compared with the MOF, was selected to achieve versatile energy storage. The intertwined 1 D nanospindles and enriched-oxygen doping of the HPC was obtained after one-step carbonization of the MOC. When employed in lithium-ion batteries, the HPC exhibited reversible capacity of 778 mA h g(-1) after 60 cycles at 50 mA g(-1) . Moreover, the HPC maintained a capacity of 188 mA h g(-1) after 400 cycles at 100 mA g(-1) as the anode material in a sodium-ion battery. In addition, the HPC served as the cathode matrix for evaluation of a lithium-sulfur battery. The general preparation process of the HPC is commercial, which is responsible for the large-scale production for its practical application.


Assuntos
Carbono/química , Fontes de Energia Elétrica , Ferro/química , Compostos Organometálicos/química , Lítio/química , Porosidade , Enxofre/química , Temperatura
19.
J Phys Chem Lett ; 4(9): 1502-6, 2013 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-26282305

RESUMO

The cis- and trans-bis(glycinato)copper(II) complexes in aqueous solution have been investigated by means of a combined theoretical and experimental approach. The conducted quantum mechanical charge field molecular dynamics (QMCF-MD) studies, being the first quantum mechanical simulations of organometallic complexes by this method, yielded accurate structural details of the investigated isomers as well as novel dynamic data, which has successfully been confirmed and extended by subsequent mid-infrared measurements. The spectroscopic results, critically assessed by adjacent multivariate data analysis, indicate an isomeric stability at ambient conditions, vanishing at elevated temperatures.

20.
RBCF, Rev. bras. ciênc. farm. (Impr.) ; 44(1): 85-95, jan.-mar. 2008. graf, tab
Artigo em Português | LILACS | ID: lil-484371

RESUMO

Análogos da timidina têm sido marcados com diferentes radioisótopos devido ao seu potencial em monitorar a proliferação incontrolável de células. Considerando que o radioisótopo tecnécio-99m ainda mantém uma posição privilegiada devido às suas propriedades químicas e nucleares, este trabalho constituiu-se no desenvolvimento da marcação da timidina com o 99mTc, mediante o emprego de compostos organometálicos. Os objetivos principais foram a síntese do precursor carbonil-tecnécio-99m, marcação da timidina com este precursor, estudo da estabilidade, e avaliações radioquímicas e biológicas com animais sadios e portadores de tumor. A síntese do precursor organometálico e a marcação da timidina com este precursor foi realizada com > 97 por cento e > 94 por cento de pureza radioquímica, respectivamente, obtendo-se também uma boa estabilidade em até 6 h em temperatura ambiente. A transquelação frente aos aminoácidos cisteína e histidina apresentou perdas entre 8 e 11 por cento para concentrações de até 300 mM. Os ensaios de biodistribuição em camundongos sadios indicaram que o complexo radiomarcado apresentou um rápido depuramento sangüíneo e baixa captação nos demais órgãos, com predominância de excreção da droga pelo sistema urinário e hepatobiliar. A captação tumoral foi de 0,28 e 0,18 por centoDI/g para tumor de pulmão e mama, respectivamente. Os resultados obtidos sugerem maiores investigações em outros análogos da timidina.


Thymidine analogs have been labeled with different radioisotopes due to their potential in monitoring the uncontrollable cell proliferation. Considering that the radioisotope technetium-99m still keeps a privileged position as a marker due to its chemical and nuclear properties, this work was designed to develop a new technique of labeling of thymidine analog with 99mTc, by means of the organometallic compounds. The aims of this research were: synthesis of the organometallic precursor technetium-99m-carbonyl, thymidine labeling with this precursor, study of stability, and radiochemical e biological evaluation with healthy and tumor-bearing animals. The organometallic precursor and the labeling of thymidine with this precursor were resulted with a radiochemical pureness of > 97 percent and > 94 percent, respectively, with good radiochemical stability up to 6 h in room temperature. The cysteine and histidine challenge indicated losses between 8 and 11 percent for concentrations until 300 mM. The biodistribution assay in healthy mice revealed rapid blood clearance and low uptake by general organs with renal and hepatobiliary excretion. The tumor concentration was of 0.28 and 0.18 percentID/g for lung and breast cancer, respectively. The results imply more studies in other thymidine analogs.


Assuntos
Animais , Camundongos , Neoplasias Pulmonares/diagnóstico , Radioisótopos , Tecnécio , Timidina , Compostos Radiofarmacêuticos
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