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1.
Chem Commun (Camb) ; 57(4): 476-479, 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33326521

RESUMO

Replacing coenzyme F430, an Ni(i) F430-like cofactor derived from vitamin B12 (F430-B12) is revealed by DFT calculations to be able to catalyze methane formation in methyl-coenzyme M reductase with a barrier of 13.3 kcal mol-1, demonstrating the correctness of the route starting from vitamin B12. The structure-activity relationships of F430 and F430-B12 (especially the roles of the F ring) are discovered and several sources of inspiration promoting the application of F430-B12 are also obtained, coming closer to using F430 chemistry in man-made catalysis.


Assuntos
Metaloporfirinas/química , Oxirredutases/química , Vitamina B 12/análogos & derivados , Proteínas Arqueais/química , Proteínas Arqueais/metabolismo , Domínio Catalítico , Cristalografia por Raios X , Teoria da Densidade Funcional , Metaloporfirinas/metabolismo , Metano/biossíntese , Methanobacteriaceae/enzimologia , Modelos Químicos , Estrutura Molecular , Níquel/química , Oxirredutases/metabolismo , Ligação Proteica , Relação Estrutura-Atividade , Termodinâmica , Vitamina B 12/metabolismo
2.
Int J Nanomedicine ; 15: 7687-7702, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33116495

RESUMO

Background: Recent studies have validated and confirmed the great potential of nanoscale metal-organic framework (NMOF) in the biomedical field, especially in improving the efficiency of cancer diagnosis and therapy. However, most previous studies only utilized either the metal cluster or the organic ligand of the NMOF for cancer treatments and merely reported limited theranostic functions, which may not be optimized. As a highly designable and easily functionalized material, prospective rational design offers a powerful way to extract the maximum benefit from NMOF for cancer theranostic applications. Materials and Methods: A NMOF based on hafnium (Hf) cluster and Mn(III)-porphyrin ligand was rational designed and synthesized as a high-performance multifunctional theranostic agent. The folic acid (FA) was modified on the NMOF surface to enhance the cancer targeting efficacy. The proposed "all-in-one" FA-Hf-Mn-NMOF (fHMNM) was characterized and identified using various analytical techniques. Then, in vitro and in vivo studies were performed to further explore the effects of fHMNM both as the magnetic resonance imaging (MRI)/computed tomography (CT)/photoacoustic imaging (PAI) contrast agent and as the photothermal therapy (PTT)/radiotherapy (RT) agent. Results: A tumour targeting multifunctional fHMNM was successfully synthesized with high performance for MRI/CT/PAI enhancements and image-guided PTT/RT synergistic therapy properties. Compared with the current clinical CT and MR contrast agents, the X-ray attenuation and T1 relaxation rate of this integrated nanosystem increased 1.7-fold and 3-5-fold, respectively. More importantly, the catalase-like Mn(III)-porphyrin ligand can decompose H2O2 into O2 in tumour microenvironments to improve the synergistic treatment efficiency of PTT and RT. Significant tumour growth inhibition was achieved in mouse cancer models without obvious damage to the other organs. Conclusion: This work highlights the potential of fHMNM as an easily designable material for biomedical applications, could be an effective tool for in vivo detection and subsequent treatment of tumour.


Assuntos
Háfnio/química , Hipertermia Induzida , Estruturas Metalorgânicas/química , Metaloporfirinas/química , Nanopartículas/química , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Fototerapia , Animais , Meios de Contraste/química , Fluorescência , Ácido Fólico/uso terapêutico , Células HeLa , Humanos , Imagem por Ressonância Magnética , Camundongos Endogâmicos BALB C , Nanopartículas/ultraestrutura , Neoplasias/radioterapia , Técnicas Fotoacústicas , Radioterapia Guiada por Imagem
3.
J Med Chem ; 63(13): 7268-7292, 2020 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-32462865

RESUMO

An experimental approach is described for late-stage lead diversification of frontrunner drug candidates using nanomole-scale amounts of lead compounds for structure-activity relationship development. The process utilizes C-H bond activation methods to explore chemical space by transforming candidates into newly functionalized leads. A key to success is the utilization of microcryoprobe nuclear magnetic resonance (NMR) spectroscopy, which permits the use of low amounts of lead compounds (1-5 µmol). The approach delivers multiple analogues from a single lead at nanomole-scale amounts as DMSO-d6 stock solutions with a known structure and concentration for in vitro pharmacology and absorption, distribution, metabolism, and excretion testing. To demonstrate the feasibility of this approach, we have used the antihistamine agent loratadine (1). Twenty-six analogues of loratadine were isolated and fully characterized by NMR. Informative SAR analogues were identified, which display potent affinity for the human histamine H1 receptor and improved metabolic stability.


Assuntos
Loratadina/análogos & derivados , Loratadina/farmacocinética , Relação Estrutura-Atividade , Animais , Cromatografia Líquida de Alta Pressão , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Dimetil Sulfóxido/química , Cães , Descoberta de Drogas/métodos , Antagonistas dos Receptores Histamínicos H1 não Sedativos/química , Antagonistas dos Receptores Histamínicos H1 não Sedativos/farmacologia , Humanos , Ligação de Hidrogênio , Inativação Metabólica , Loratadina/química , Espectroscopia de Ressonância Magnética , Metaloporfirinas/química , Metaloporfirinas/metabolismo , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/metabolismo , Coelhos , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Espectrometria de Massas em Tandem , Distribuição Tecidual
4.
Adv Colloid Interface Sci ; 277: 102108, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32028075

RESUMO

Recently, as a new sub-family of porous coordination polymers (PCPs), porphyrinic-MOFs (Porph-MOFs) with biomimetic features have been developed using porphyrin macrocycles as ligands and/or pillared linkers. The control over the coordination of the porphyrin ligand and its derivatives however remains a challenge for engineering new tunable Porph-MOF frameworks by self-assembly methods. The key challenges exist in the following respects: (i) collapse of the large open pores of Porph-MOFs during synthesis, (ii) deactivation of unsaturated metal-sites (UMCs) by axial coordination, and (iii) the tendency of both coordinated moieties (at peripheral meso- and beta-carbon sites) and the N4-pyridine core to coordinate with metal cations. In this respect, this review covers the advances in the design of Porph-MOFs relative to their counterpart covalent organic frameworks (Porph-COFs). The potential utility of custom-designed porphyrin/metalloporphyrins ligands is highlighted. Synthesis strategies of Porph-MOFs are also illustrated with modular design of hybrid guest@host composites (either Porph@MOFs or guest@Porph-MOFs) with exceptional topologies and stability. This review summarizes the synergistic benefits of coordinated porphyrin ligands and functional guest molecules in Porph-MOF composites for enhanced catalytic performance in various redox applications. This review shed lights on the engineering of new tunable hetero-metals open active sites within (metallo)porphyrin-MOFs as out-of-the-box platforms for enhanced catalytic processes in chemical and biological media.


Assuntos
Estruturas Metalorgânicas/química , Metaloporfirinas/química , Catálise , Sistemas de Liberação de Medicamentos , Estruturas Metalorgânicas/síntese química , Metaloporfirinas/síntese química , Tamanho da Partícula , Porosidade
5.
Sensors (Basel) ; 20(4)2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32053932

RESUMO

Gout is a condition that affects over 8 million Americans. This condition is characterized by severe pain, and in more advanced cases, bone erosion and joint destruction. This study explores the fabrication and characterization of an optical, enzymatic urate biosensor for gout management, and the optimization of the biosensor response through the tuning of hydrogel matrix properties. Sensors were fabricated through the co-immobilization of oxygen-quenched phosphorescent probes with an oxidoreductase within a biocompatible copolymer hydrogel matrix. Characterization of the spectral properties and hydrogel swelling was conducted, as well as evaluation of the response sensitivity and long-term stability of the urate biosensor. The findings indicate that increased acrylamide concentration improved the biosensor response by yielding an increased sensitivity and reduced lower limit of detection. However, the repeatability and stability tests highlighted some possible areas of improvement, with a consistent response drift observed during repeatability testing and a reduction in response seen after long-term storage tests. Overall, this study demonstrates the potential of an on-demand, patient-friendly gout management tool, while paving the way for a future multi-analyte biosensor based on this sensing platform.


Assuntos
Técnicas Biossensoriais/métodos , Metaloporfirinas/química , Urato Oxidase/metabolismo , Ácido Úrico/análise , Técnicas Biossensoriais/instrumentação , Enzimas Imobilizadas , Humanos , Hidrogéis/química , Luz , Limite de Detecção , Oxigênio/química , Oxigênio/metabolismo , Urato Oxidase/química , Ácido Úrico/metabolismo
6.
Chem Commun (Camb) ; 56(20): 3089-3092, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32052805

RESUMO

Reaction of FeIII(O2˙-)(TPP) with 2,3-dimethylindole at -40 °C gives the ring-opened, dioxygenated N-(2-acetyl-phenyl)-acetamide product. The reaction was monitored in situ by low-temperature UV-vis and 1H NMR spectroscopies. This work demonstrates that a discrete iron(iii)(superoxo) porphyrin is competent to carry out indole oxidation, as proposed for the tryptophan and indoleamine 2,3-dioxygenases.


Assuntos
Compostos Férricos/química , Indolamina-Pirrol 2,3,-Dioxigenase/química , Indóis/química , Metaloporfirinas/química , Superóxidos/química , Triptofano Oxigenase/química , Compostos Férricos/metabolismo , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Indóis/metabolismo , Metaloporfirinas/metabolismo , Estrutura Molecular , Oxirredução , Superóxidos/metabolismo , Triptofano Oxigenase/metabolismo
7.
Biosens Bioelectron ; 150: 111963, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31929091

RESUMO

In this work, pyrrolidyl C60 derivative was recruited as an unadulterated and congruent nano-hub to converge three zinc porphyrins on its monopole. Such peculiar assembly was convinced via micro-imaging and spectrophotometry. Making the best of fullerenyl proficiency in catalytic singlet O2 generation and excited-state preservation, a multiplied electrochemiluminescence (ECL) emission bursted out from the porphyrin trinity in a synergistic manner. Without any prebio-conjugation, this orderly ECL-active individual turned to anchor in the toroid of a peripherally modified gamma-cyclodextrin in a good shape match. From the facile direct mounting of the latter derives a universal bio-probing technique based upon such host-guest inclusion. Its binding pattern and the concomitant effects on interfacial properties were revealed by systematic process characterizations. Taking advantages of this uniform ensemble in both size and stoichiometry, an in situ terminal labelling strategy during the recognition-induced allosteric event came into being, which managed a neat signal enhancement for the detection of model miRNA marker. Even in real samples, the developed sensing approach could achieve high precision, comparable sensitivity and satisfactory selectivity. The adaptation of macrocyclic chemistry for refined biotransducers and efficient ECL amplifiers would offer a generic and potent alternative to the analyte-specified ECL indicator-receptor build in bioassays.


Assuntos
Técnicas Biossensoriais/métodos , Fulerenos/química , Metaloporfirinas/química , MicroRNAs/análise , Técnicas Eletroquímicas/métodos , Humanos , Medições Luminescentes/métodos , MicroRNAs/sangue , Modelos Moleculares , gama-Ciclodextrinas/química
8.
Chemistry ; 26(37): 8262-8266, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31968144

RESUMO

Free base, zinc and palladium π-extended porphyrins containing fused naphthalenediamide units were employed as photosensitizers in antimicrobial photodynamic therapy (aPDT). Their efficacy, assessed by photophysical and in vitro photobiological studies on Gram-positive bacteria, was found to depend on metal coordination, showing a dramatic enhancement of photosensitizing activity for the palladium complex.


Assuntos
Antibacterianos/farmacologia , Bactérias Gram-Positivas/química , Metaloporfirinas/química , Porfirinas/química , Zinco/química , Antibacterianos/química , Humanos , Metaloporfirinas/farmacologia , Fotoquimioterapia , Fármacos Fotossensibilizantes , Porfirinas/farmacologia
9.
Int J Mol Sci ; 21(2)2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31968535

RESUMO

Photodynamic therapy is a non-invasive method where light activates a photosensitizer bound to cancer cells, generating reactive oxygen species and resulting in cell death. This study assessed the oncolytic potential of photodynamic therapy, comparing European Medicines Agency and United States Food and Drug Administration-approved 5-aminolevulinic acid (5-ALA) to a metalloporphyrin, Pd(T4), against a highly invasive uveal melanoma cell line (C918) in two- and three-dimensional models in vitro. Epithelial monolayer studies displayed strong oncolytic effects (>70%) when utilizing Pd(T4) at a fraction of the concentration, and reduced pre-illumination time compared to 5-ALA post-405 nm irradiance. When analyzed at sub-optimal concentrations, application of Pd(T4) and 5-ALA with 405 nm displayed cumulative effects. Lethality from Pd(T4)-photodynamic therapy was maintained within a three-dimensional model, including the more resilient vasculogenic mimicry-forming cells, though at lower rates. At high concentrations, modality of cell death exhibited necrosis partially dependent on reactive oxygen species. However, sub-optimal concentrations of photosensitizer exhibited an apoptotic protein expression profile characterized by increased Bax/Bcl-2 ratio and endoplasmic stress-related proteins, along with downregulation of apoptotic inhibitors CIAP-1 and -2. Together, our results indicate Pd(T4) as a strong photosensitizer alone and in combination with 5-ALA against C918 cells.


Assuntos
Ácido Aminolevulínico/farmacologia , Antineoplásicos/farmacologia , Melanoma/tratamento farmacológico , Metaloporfirinas/farmacologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Neoplasias Uveais/tratamento farmacológico , Ácido Aminolevulínico/química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Luz , Metaloporfirinas/química , Necrose/tratamento farmacológico , Fármacos Fotossensibilizantes/química , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteína X Associada a bcl-2/metabolismo
10.
Chemosphere ; 243: 125334, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31995864

RESUMO

Developing novel heterogeneous photo-Fenton catalysts with high efficiency and stability, driven by visible-light rather ultraviolet light at neutral pH has been a major challenge for degradation of organic pollutants. In this work, we successfully synthesized a metalloporphyrin-based porous organic polymer (FePPOP-1) by the Sonogashira cross-coupling reaction. UV-vis absorption spectra showed FePPOP-1 exhibits a significant coverage of the natural solar irradiance spectrum. As a result, the prepared FePPOP-1 has a significantly enhanced photocatalytic activity for the visible-light-driven degradation of methylene blue. By using only 4 mg of FePPOP-1 as a catalyst, it was found that 50 mL of organic wastewater containing 70 ppm MB could be totally degraded in 80 min even at neutral pH. The effects of the initial MB, H2O2 concentrations, pH value and common ions on MB degradation were studied in detail. Both the catalytic mechanism of FePPOP-1 and the degradation route of MB were also proposed.


Assuntos
Metaloporfirinas/química , Polímeros/química , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/química , Catálise , Peróxido de Hidrogênio/química , Concentração de Íons de Hidrogênio , Ferro , Luz , Azul de Metileno/química , Compostos Orgânicos/química , Processos Fotoquímicos , Porosidade , Espectrofotometria Ultravioleta
11.
Chemistry ; 26(20): 4552-4566, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-31981387

RESUMO

A robust dithiocarbamate tether allows novel gadolinium units based on DOTAGA (q=1) to be attached to the surface of gold nanoparticles (2.6-4.1 nm diameter) along with functional units offering biocompatibility, targeting and photodynamic therapy. A dramatic increase in relaxivity (r1 ) per Gd unit from 5.01 mm-1 s-1 in unbound form to 31.68 mm-1 s-1 (10 MHz, 37 °C) is observed when immobilised on the surface due to restricted rotation and enhanced rigidity of the Gd complex on the nanoparticle surface. The single-step synthetic route provides a straightforward and versatile way of preparing multifunctional gold nanoparticles, including examples with conjugated zinc-tetraphenylporphyrin photosensitizers. The lack of toxicity of these materials (MTT assays) is transformed on irradiation of HeLa cells for 30 minutes (PDT), leading to 75 % cell death. In addition to passive targeting, the inclusion of units capable of actively targeting overexpressed folate receptors illustrates the potential of these assemblies as targeted theranostic agents.


Assuntos
Gadolínio/química , Ouro/química , Nanopartículas Metálicas/química , Metaloporfirinas/química , Fármacos Fotossensibilizantes/uso terapêutico , Células HeLa , Humanos , Imagem por Ressonância Magnética/métodos , Nanopartículas Metálicas/uso terapêutico , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Nanomedicina Teranóstica
12.
Macromol Rapid Commun ; 41(1): e1900478, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31709712

RESUMO

The photocatalyst Zn(II) meso-tetra(4-sulfonatophenyl)porphyrin (ZnTPPS) is found to substantially accelerate visible-light-initiated (red, yellow, green light) single unit monomer insertion (SUMI) of N,N-dimethylacrylamide into the reversible addition-fragmentation chain transfer (RAFT) agent, 4-((((2-carboxyethyl)thio)carbonothioyl)thio)-4-cyanopentanoic acid (RAFT1 ), in aqueous solution. Thus, under irradiation with red (633 nm) or yellow (593 nm) light with 50 mpm (moles per million mole of monomer) ZnTPPS at 30 °C, the rate enhancement provided by photoinduced energy or electron transfer (PET) is ≈sevenfold over the rate of direct photoRAFT-SUMI (without catalyst), which corresponds to achieving full and selective reaction in hours versus days. Importantly, the selectivity, as judged by the absence of oligomers, is retained. Under green light at similar power, higher rates of SUMI are also observed. However, the degree of enhancement provided by PET-RAFT-SUMI over direct photoRAFT-SUMI as a function of catalyst concentration is less and some oligomers are formed.


Assuntos
Luz , Água/química , Catálise , Transporte de Elétrons , Transferência de Energia , Metaloporfirinas/química , Polimerização , Polímeros/síntese química , Polímeros/química
13.
ACS Nano ; 13(12): 14024-14032, 2019 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-31820930

RESUMO

Lifetime imaging methods using phosphorescence quenching by oxygen for molecular oxygen concentration measurement have been developed and used for noninvasive oxygen monitoring. This study reports photoacoustic (PA) oxygen imaging powered by polyacrylamide (PAAm) hydrogel nanoparticles (NP) which offer advantages including improved biocompatibility, reduced toxicity, and active tumor targeting. A known oxygen indicator, oxyphor G2, was conjugated with the matrix of the NPs, giving G2-PAA NPs, followed by PEGylation for biocompatibility and F3 surface modification for tumor targeting. Using two lasers providing pump and probe pulses, respectively, PA imaging was performed so as to quantitatively map the oxygen concentration in biological tissues in vivo, including cancer tumors and normal thigh muscles. Furthermore, via the imaging at the pump wavelength and two additional wavelengths, the accumulation of the G2-PAA NPs in the tumors were also determined. The successful imaging experiment accomplished on animal models renders a method for in vivo noninvasive imaging and assessment of hypoxic tumor microenvironments, which is critical for assessing cancer progression, metastasis, and treatment.


Assuntos
Resinas Acrílicas/química , Metaloporfirinas/química , Nanosferas/química , Neoplasias/diagnóstico por imagem , Oxigênio/análise , Técnicas Fotoacústicas , Animais , Calibragem , Feminino , Imageamento Tridimensional , Metaloporfirinas/síntese química , Camundongos Nus , Neoplasias/patologia
14.
Dalton Trans ; 48(45): 16861-16868, 2019 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-31710076

RESUMO

The efficiency of photosensitizers in tumor photodynamic therapy (PDT) often compromises their poor water solubility, low extinction coefficients, photobleaching, and dissatisfactory reactive oxygen species (ROS) generation efficiency. Herein, a nanoscale 2D metal-organic framework, Sm-H2TCPP nanosheets, was first synthesized by Sm3+-driven coordination with a porphyrin derivative (tetrakis(4-carboxyphenyl)porphyrin (H2TCPP)) for highly effective PDT of breast cancer. The prepared Sm-H2TCPP possessed nanoplate morphology with ultrathin thickness at the sub-10 nm level and an ultrasmall plane size at the sub-100 nm level. Compared with free H2TCPP, the prominent ROS generation capacity of the well-defined Sm-H2TCPP nanosheets is mainly attributed to their improved physicochemical properties and the enhanced intersystem crossing caused by heavy Sm nodes. The significantly improved PDT efficacy of the Sm-H2TCPP nanosheets was further investigated in vitro and in vivo based on the MCF-7 breast cancer model. It is envisaged that the Sm-H2TCPP nanosheets will offer a new avenue for the development of a new class of potential PDT agents.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Estruturas Metalorgânicas/farmacologia , Metaloporfirinas/farmacologia , Nanopartículas/química , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Células MCF-7 , Estruturas Metalorgânicas/síntese química , Estruturas Metalorgânicas/química , Metaloporfirinas/síntese química , Metaloporfirinas/química , Tamanho da Partícula , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Espécies Reativas de Oxigênio/metabolismo , Propriedades de Superfície
15.
J Photochem Photobiol B ; 201: 111640, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31734545

RESUMO

Fluorescence image guided surgical resection (FIGR) of high grade gliomas (HGGs) takes advantage of the accumulation of the tracer protoporphyrin IX (PpIX) in glioma cells following administration of 5-aminolevulinic acid (5-ALA). Occasionally, PpIX fluorescence intensity may be insufficient, thus compromising the efficacy and precision of the surgical intervention. The cause for the signal variation is unclear and strategies to improve the intensity of PpIX fluorescence are considered necessary. We have previously shown that differential expression of the epidermal growth factor receptor in glioblastoma cells affects PpIX fluorescence. Herein, we investigated other factors impairing PpIX accumulation and pharmacological treatments able to enhance PpIX fluorescence in glioblastoma cells displaying lower signal. In the present study we demonstrate that presence of serum in cell culture medium and differences in cellular confluence can negatively influence PpIX accumulation in U87 cell lines. We hypothesized that PpIX fluorescence intensity results from the interplay between the metabolic clearance of PpIX mediated by ferrochelatase and heme oxygenase-1 and the cellular efflux of PpIX through the ATP-binding cassette subfamily G member 2 (ABCG2). Based on the availability of compounds targeting these proteins and inhibiting them, in this study we used modulators such as genistein, an isoflavone able to inhibit ABCG2; deferoxamine, which chelate iron ions impairing FECH activity and tin protoporphyrin IX (SnPP), the specific HO-1 inhibitor. Finally, we showed the efficacy of a precisely tuned pharmacological treatment in increasing PpIX accumulation and consequently fluorescence in glioblastoma cells. This strategy may translate in more sensitive tracing of tumor cells in-vivo and improved FIGR of HGGs and possibly low grade gliomas (LGGs).


Assuntos
Corantes Fluorescentes/química , Microscopia Confocal , Protoporfirinas/química , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Ácido Aminolevulínico/química , Ácido Aminolevulínico/metabolismo , Ácido Aminolevulínico/farmacologia , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Receptores ErbB/metabolismo , Corantes Fluorescentes/metabolismo , Genisteína/metabolismo , Genisteína/farmacologia , Glioblastoma/patologia , Heme Oxigenase-1/antagonistas & inibidores , Heme Oxigenase-1/metabolismo , Humanos , Metaloporfirinas/química , Metaloporfirinas/metabolismo , Metaloporfirinas/farmacologia , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/metabolismo , Protoporfirinas/metabolismo , Protoporfirinas/farmacologia
16.
Analyst ; 145(1): 70-75, 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31720591

RESUMO

It is of interest to in vivo monitor the co-dynamics of different substances. However, the tracking of multiple species is still challenging. In this work, we demonstrate an in vivo electrochemical method by using multi-potential step amperometry to in vivo detect ascorbic acid (AA) and oxygen (O2) simultaneously. In order to achieve good selectivity and high sensitivity for both AA and O2, we design a cobalt corrole [Co(tpfc)(py)2] (tpfc = 5,10,15-tris(penta-fluorophenyl) corrole, py = pyridine, denoted as Co-TPFC) and carbon nanotube nanocomposite to modify a carbon fiber microelectrode (Co-TPFC/MWNT/CFE). This Co-TPFC/MWNT/CFE exhibits excellent electrocatalytic properties towards the reduction of O2 preceding a 4e process and facilitates the oxidation of AA at low potential in the physiological environment. Based on this, we realize simultaneous detection of AA and O2 using two-potential steps (one cathodic (-0.2 V) and the other anodic (+0.05 V)) with 1 second step time. Both in vitro and in vivo experiments proved the feasibility of this method. This demonstrated strategy is useful for us to understand various physiological and pathological processes associated with O2 and AA co-dynamics, and also provides an idea for detecting multiple substances simultaneously.


Assuntos
Ácido Ascórbico/análise , Encéfalo/metabolismo , Técnicas Eletroquímicas/métodos , Metaloporfirinas/química , Nanotubos de Carbono/química , Oxigênio/análise , Animais , Ácido Ascórbico/química , Isquemia Encefálica/metabolismo , Carbono/química , Cobalto/química , Técnicas Eletroquímicas/instrumentação , Masculino , Microeletrodos , Nanocompostos/química , Oxirredução , Oxigênio/química , Ratos Sprague-Dawley
17.
ACS Sens ; 4(10): 2819-2824, 2019 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-31573183

RESUMO

N-Nitrosamines are environmental genotoxicants that are widely encountered in air, water, and food. Contamination of indoor and outdoor air with N-nitrosamines has been reported on many occasions. Conventional detection of airborne N-nitrosamines requires sophisticated instrumentation, field sampling, and laboratory analysis. Herein, we report ultrasensitive carbon nanotube based chemiresistive sensors utilizing a cobalt(III) tetraphenylporphyrin selector element for the detection of N-nitrosamines. Concentrations as low as 1 ppb N-nitrosodimethylamine, N-nitrosodiethylamine, and N-nitrosodibutylamine were detected. We also demonstrate the integration of these sensors with a field deployable sensing node wherein the sensor response can be read online remotely.


Assuntos
Poluentes Atmosféricos/análise , Carcinógenos/análise , Nanotubos de Carbono/química , Nitrosaminas/análise , Poluentes Atmosféricos/química , Carcinógenos/química , Cobalto/química , Metaloporfirinas/química , Nitrosaminas/química
18.
J Biol Inorg Chem ; 24(7): 1127-1134, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31560098

RESUMO

Methane hydroxylation by metal-oxo oxidants is one of the Holy Grails in biomimetic and biotechnological chemistry. The only enzymes known to perform this reaction in Nature are iron-containing soluble methane monooxygenase and copper-containing particulate methane monooxygenase. Furthermore, few biomimetic iron-containing oxidants have been designed that can hydroxylate methane efficiently. Recent studies reported that µ-nitrido-bridged diiron(IV)-oxo porphyrin and phthalocyanine complexes hydroxylate methane to methanol efficiently. To find out whether the reaction rates are enhanced by replacing iron by ruthenium, we performed a detailed computational study. Our work shows that the µ-nitrido-bridged diruthenium(IV)-oxo reacts with methane via hydrogen atom abstraction barriers that are considerably lower in energy (by about 5 kcal mol‒1) as compared to the analogous diiron(IV)-oxo complex. An analysis of the electronic structure implicates similar spin and charge distributions for the diiron(IV)-oxo and diruthenium(IV)-oxo complexes, but the strength of the O‒H bond formed during the reaction is much stronger for the latter. As such a larger hydrogen atom abstraction driving force for the Ru complex than for the Fe complex is found, which should result in higher reactivity in the oxidation of methane.


Assuntos
Ferro/química , Metaloporfirinas/química , Rutênio/química , Modelos Moleculares , Conformação Molecular
19.
Free Radic Biol Med ; 143: 522-533, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31520768

RESUMO

The mechanisms of binary catalyst therapy (BCT) and photodynamic therapy (PDT) are based on the formation of reactive oxygen species (ROS). This ROS formation results from specific chemical reactions. In BCT, light exposure does not necessarily initiate ROS formation and BCT application is not limited to regions of tissues that are accessible to illumination like photodynamic therapy (PDT). The principle of BCT is electron transition, resulting in the interaction of a transition metal complex (catalyst) and substrate molecule. MnIII- tetraphenylporphyrin chloride (MnClTPP) in combination with an ascorbic acid (AA) has been proposed as an appropriate candidate for cancer treatment regarding the active agents in BCT. The goal of this study was to determine whether MnClTPP in combination with AA would be a promising agent for BCT. The problem of used MnClTPP's, low solubility in water, was solved by MnClTPP loading into PLGA matrix. H2O2 produced during AA decomposition oxidized MnClTPP to high-reactive oxo-MnV species. MnClTPP in presence AA leads to the production of excessive ROS levels in vitro. ROS are mainly substrates of catalase and superoxide dismutase (H2O2 and O2●-). SOD1 and catalase were identified as the key players of the MnClTPP ROS-induced cell defense system. The cytotoxicity of MnClTPP-loaded nanoparticles (NPs) was greatly increased in the presence of specific catalase inhibitor (3-amino-1,2,4-triazole (3AT)) and superoxide dismutase 1 (SOD1) inhibitor (diethyldithiocarbamate (DDC)). Cell death resulted from the combined activation of caspase-dependent (caspase 3/9 system) and independent pathways, namely the AIF translocation to nuclei. Preliminary acute toxicity and in vivo anticancer studies have been revealed the safe and potent anticancer effect of PLGA-entrapped MnClTPP in combination with AA. The findings indicate that MnClTPP-loaded PLGA NPs are promising agents for BCT.


Assuntos
Metaloporfirinas/química , Nanopartículas/administração & dosagem , Neoplasias/tratamento farmacológico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Espécies Reativas de Oxigênio/metabolismo , Animais , Apoptose , Movimento Celular , Proliferação de Células , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/química , Neoplasias/metabolismo , Neoplasias/patologia , Oxirredução , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
20.
J Phys Chem B ; 123(35): 7492-7503, 2019 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-31397573

RESUMO

We evaluate here, using synchrotron X-ray reflectivity, hemoglobin adsorption characteristics on silicon substrates with varying chemical functionalities. Hemoglobin at isoelectronic point and at negative charge is immobilized on functionalized hydrophilic (hydroxyl, carboxylic, amine) and hydrophobic (alkylated) silicon surfaces for the study. As a control, the bare cofactor hemin (containing only the metal and porphyrin with no amino acid residues) is also studied under similar conditions. Ordered layers (grown using the Langmuir-Blodgett technique) are observed to be less affected by the surface chemistry compared to the multilayers formed by physical absorption. Surface chemistry and charge of the proteins are critical in controlling the protein adsorption characteristics on silicon, such as thickness (correlated to molecule size) and roughness. In this study, this is very well realized by varying both the hydrophobicity and hydrophilicity of the substrate. The fundamental studies discussed here provide us with a set of important guidelines as to how electrode surface functionalization can control molecular conformation/orientation, especially protein adsorption on the substrate. This in turn is expected to have a significant impact on the protein electrochemical function and response of biomolecular devices.


Assuntos
Hemoglobinas/química , Metaloporfirinas/química , Silício/química , Síncrotrons , Modelos Moleculares , Estrutura Molecular , Tamanho da Partícula , Propriedades de Superfície , Raios X
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