RESUMO
Telomerase, oncogenes and tumor suppressors are closely associated with tumour occurrence, therefore these structures are being recognized as targets for the development of new anticancer drugs. The efficacy of several molecules in telomerase inhibition and regulation of genes expression, by adduct formation with G-quadruplexes (G4), has been studied by biophysical and biochemical methods with promising results. We report here the synthesis and structural characterization of a small positively charged diketopyrrolo[3,4-c]pyrrole derivative, identified as DPP(PyMe)2, that showed very promising results as G4 stabilizing ligand. The data obtained from UV-Vis and fluorescence experiments suggest that DPP(PyMe)2 presents high affinity to G4 structures. Docking studies and molecular dynamics simulations unraveled the binding modes of the ligand with four G4 structures. The obtained results also allowed us to conclude that the DPP(PyMe)2 ligand binds into the top G-tetrad or in a mixed binding mode depending on the GQ structure. A remarkable selectivity of DPP(PyMe)2 for c-MYC and KRAS 32R in the presence of ds26 was observed by circular dichroism (CD) and fluorescence resonance energy transfer (FRET) melting experiments. CD titrations revealed a stabilization higher than 30 °C in the case of c-MYC G4 structure and, for the same sequence, DPP(PyMe)2 showed the ability to block the activity of Taq polymerase in a dose-dependent manner. The subcellular localization obtained with confocal microscopy corroborates the results obtained by the other techniques and the obtained data suggest that DPP(PyMe)2 is an attractive ligand for the development of G4 labelling probes.
Assuntos
Quadruplex G , DNA/química , Ligantes , Pirróis/farmacologia , TelômeroRESUMO
In this study, we report the preparation of new mono-charged benzoporphyrin complexes by reaction of the appropriate neutral benzoporphyrin with (2,2'-bipyridine)dichloroplatinum(II) and of the analogs' derivatives synthesized through alkylation of the neutral scaffold with iodomethane. All derivatives were incorporated into polyvinylpyrrolidone (PVP) micelles. The ability of the resultant formulations to generate reactive oxygen species was evaluated, mainly the singlet oxygen formation. Then, the capability of the PVP formulations to act as photosensitizers against bladder cancer cells was assessed. Some of the studied formulations were the most active photosensitizers causing a decrease in HT-1376 cells' viability. This creates an avenue to further studies related to bladder cancer cells.
Assuntos
Antineoplásicos/farmacologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/farmacologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Antineoplásicos/síntese química , Antineoplásicos/química , Cátions/síntese química , Cátions/química , Cátions/farmacologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Porfirinas/síntese química , Porfirinas/química , Relação Estrutura-Atividade , Neoplasias da Bexiga Urinária/patologiaRESUMO
Photodynamic inactivation of bacterial and fungal pathogens is a promising alternative to the extensive use of conventional single-target antibiotics and antifungal agents. The combination of photosensitizers and adjuvants can improve the photodynamic inactivation efficiency. In this regard, it has been shown that the use of potassium iodide (KI) as adjuvant increases pathogen killing. Following our interest in this topic, we performed the co-encapsulation of a neutral porphyrin photosensitizer (designated as P1) and KI into micelles and tested the obtained nanoformulations against the human pathogenic fungus Candida albicans. The results of this study showed that the micelles containing P1 and KI displayed a better photodynamic performance towards C. albicans than P1 and KI in solution. It is noteworthy that higher concentrations of KI within the micelles resulted in increased killing of C. albicans. Subcellular localization studies by confocal fluorescence microscopy revealed that P1 was localized in the cell cytoplasm, but not in the nuclei or mitochondria. Overall, our results show that a nanoformulation containing a photosensitizer plus an adjuvant is a promising approach for increasing the efficiency of photodynamic treatment. Actually, the use of this strategy allows a considerable decrease in the amount of both photosensitizer and adjuvant required to achieve pathogen killing.
Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Micelas , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/farmacologia , Iodeto de Potássio/farmacologia , Antifúngicos/química , Cápsulas/química , Cápsulas/farmacologia , Testes de Sensibilidade Microbiana , Estrutura Molecular , Fármacos Fotossensibilizantes/química , Porfirinas/química , Iodeto de Potássio/químicaRESUMO
This review covers the functionalization reactions of meso-arylcorroles, both at the inner core, as well as the peripheral positions of the macrocycle. Experimental details for the synthesis of all known metallocorrole types and for the N-alkylation reactions are presented. Key peripheral functionalization reactions such as halogenation, formylation, carboxylation, nitration, sulfonation, and others are discussed in detail, particularly the nucleophilic aromatic substitution and the participation of corroles in cycloaddition reactions as 2π or 4π components (covering Diels-Alder and 1,3-dipolar cycloadditions). Other functionalizations of corroles include a large diversity of reactions, namely Wittig reactions, reactions with methylene active compounds, formation of amines, amides, and imines, and metal catalyzed reactions. At the final section, the reactions involving oxidation and ring expansion of the corrole macrocycle are described comprehensively.
RESUMO
The post-functionalization of 5,10,15-tris(1-methylpyridinium-4-yl)-20-(pentafluorophenyl)porphyrin tri-iodide, known as a highly efficient photosensitizer (PS) for antimicrobial photodynamic therapy (aPDT), in the presence of 3- or 4-mercaptobenzoic acid, afforded two new tricationic porphyrins with adequate carboxylic pending groups to be immobilized on chitosan or titanium oxide. The structural characterization of the newly obtained materials confirmed the success of the porphyrin immobilization on the solid supports. The photophysical properties and the antimicrobial photodynamic efficacy of the non-immobilized porphyrins and of the new conjugates were evaluated. The results showed that the position of the carboxyl group in the mercapto units or the absence of these substituents in the porphyrin core could modulate the action of the photosensitizer towards the bioluminescent Gram-negative Escherichia coli bacterium. The antimicrobial activity was also influenced by the interaction between the photosensitizer and the type of support (chitosan or titanium dioxide). The new cationic porphyrins and some of the materials were shown to be very stable in PBS and effective in the photoinactivation of E. coli bacterium. The physicochemical properties of TiO2 allowed the interaction of the PS with its surface, increasing the absorption profile of TiO2, which enables the use of visible light, inactivating the bacteria more efficiently than the corresponding PS immobilized on chitosan.
Assuntos
Antibacterianos/química , Quitosana/análogos & derivados , Fármacos Fotossensibilizantes/química , Porfirinas/química , Titânio/química , Antibacterianos/síntese química , Antibacterianos/farmacologia , Cátions/síntese química , Cátions/química , Cátions/farmacologia , Quitosana/síntese química , Quitosana/farmacologia , Escherichia coli/efeitos dos fármacos , Infecções por Escherichia coli/tratamento farmacológico , Humanos , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/síntese química , Porfirinas/farmacologia , Titânio/farmacologiaRESUMO
Porphyrins show great promise for future purification demands. This is largely due to their unique features as host binding molecules that can be modified at the synthetic level, and largely improved by their incorporation into inorganic based materials. In this study, we assessed the efficacy of a hybrid material obtained from the immobilization of 5,10,15,20-tetrakis(pentafluorophenyl)-porphyrin on silica surface to remove Pb(II), Cu(II), Cd(II), and Zn(II) ions from water. The new organic-inorganic hybrid adsorbent was fully characterized by adequate techniques and the results show that the hybrid exhibits good chemical and thermal stability. From batch assays, it was evaluated how the efficacy of the hybrid was affected by the pH, contact time, initial metal concentration, and temperature. The adsorption kinetic and isotherms showed to fit the recent developed fractal-like pseudo-second-order model and Langmuirâ»Freundlich model respectively. The highest adsorption capacities for Pb(II), Cu(II), Cd(II), and Zn(II) ions were 187.36, 125.17, 82.45, and 56.23 mg g-1, respectively, at pH 6.0 and 25 °C. This study also shows that metal cations from real river water samples can be efficient removed in the presence of the new adsorbent material.
Assuntos
Metais Pesados/isolamento & purificação , Porfirinas/química , Purificação da Água , Água/química , Cádmio/química , Cádmio/isolamento & purificação , Cobre/química , Cobre/isolamento & purificação , Humanos , Concentração de Íons de Hidrogênio , Íons/química , Íons/isolamento & purificação , Cinética , Chumbo/química , Chumbo/isolamento & purificação , Metais Pesados/toxicidade , Dióxido de Silício , Poluentes Químicos da ÁguaRESUMO
The stabilization of G-Quadruplex DNA structures by ligands is a promising strategy for telomerase inhibition in cancer therapy since this enzyme is responsible for the unlimited proliferation of cancer cells. To assess the potential of a compound as a telomerase inhibitor, selectivity for quadruplex over duplex DNA is a fundamental attribute, as the drug must be able to recognize quadruplex DNA in the presence of a large amount of duplex DNA, in the cellular nucleus. By using different spectroscopic techniques, such as ultraviolet-visible, fluorescence and circular dichroism, this work evaluates the potential of a series of multicharged phthalocyanines, bearing four or eight positive charges, as G-Quadruplex stabilizing ligands. This work led us to conclude that the existence of a balance between the number and position of the positive charges in the phthalocyanine structure is a fundamental attribute for its selectivity for G-Quadruplex structures over duplex DNA structures. Two of the studied phthalocyanines, one with four peripheral positive charges (ZnPc1) and the other with less exposed eight positive charges (ZnPc4) showed high selectivity and affinity for G-Quadruplex over duplex DNA structures and were able to accumulate in the nucleus of UM-UC-3 bladder cancer cells.
Assuntos
DNA/química , Inibidores Enzimáticos/química , Corantes Fluorescentes/química , Quadruplex G/efeitos dos fármacos , Indóis/química , Linhagem Celular Tumoral , Complexos de Coordenação/química , Humanos , Isoindóis , Ligantes , Espectrometria de Fluorescência/métodos , Relação Estrutura-Atividade , Telomerase/antagonistas & inibidores , Zinco/químicaRESUMO
Porphyrins bearing formyl or vinyl groups have been explored as starting materials to prepare new compounds with adequate features for different applications. In this review it is discussed mainly synthetic strategies based on the reaction of meso-tetraarylporphyrins bearing those groups at ß-pyrrolic positions. The use of some of the obtained porphyrin derivatives for further transformations, namely via pericyclic reactions, is also highlighted.
Assuntos
Porfirinas/química , Porfirinas/síntese química , Animais , HumanosRESUMO
A new 3,5-disubstituted pyridine with two porphyrin moieties was prepared through an efficient synthetic approach involving 2-formyl-5,10,15,20-tetraphenylporphyrin (1), piperidine, and catalytic amounts of [La(OTf)3]. 3,5-Bis(5,10,15,20-tetraphenylporphyrin-2-ylmethyl)pyridine (2) was fully characterized and its sensing ability towards Zn(2+), Cu(2+), Hg(2+), Cd(2+), and Ag(+) was evaluated in solution by absorption and fluorescence spectroscopy and in gas phase by using matrix-assisted laser desorption/ionization (MALDI)-TOF mass spectrometry. Strong changes in the ground and excited state were detected in the case of the soft metal ions Zn(2+), Cd(2+), Hg(2+), and Cu(2+). A three-metal-per-ligand molar ratio was obtained in all cases and a significant ratiometric behavior was observed in the presence of Zn(2+) with the appearance of a new band at 608â nm, which can be assigned to a metal-to-ligand charge transfer. The system was able to quantify 79â ppb of Zn(2+) and the theoretical calculations are in accordance with the stoichiometry observed in solution. The gas-phase sensorial ability of compound 2 towards all metal ions was confirmed by using MALDI-TOF MS and in solid state by using polymeric films of polymethylmethacrylate (PMMA) doped with ligand 2. The results showed that compound 2 can be analytically used to develop new colorimetric molecular devices that are able to discriminate between Hg(2+) and Zn(2+) in solid phase. The crystal structure of Zn(II) complex of 3,5-bisporphyrinylpyridine was unequivocally elucidated by using single-crystal X-ray diffraction studies.
Assuntos
Porfirinas/química , Espectrometria de Fluorescência , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Zinco/análise , Cristalografia por Raios X , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/química , Gases/química , Íons/química , Conformação Molecular , Piperidinas/química , Polimetil Metacrilato/química , Porfirinas/síntese químicaRESUMO
In view of increasing demands for efficient photosensitizers for photodynamic therapy (PDT), we herein report the synthesis and photophysical characterizations of new chlorinâ e6 trimethyl ester and protoporphyrinâ IX dimethyl ester dyads as free bases and Zn(II) complexes. The synthesis of these molecules linked at the ß-pyrrolic positions to pyrano[3,2-c]coumarin, pyrano[3,2-c]quinolinone, and pyrano[3,2-c]naphthoquinone moieties was performed by using the domino Knoevenagel hetero Diels-Alder reaction. The α-methylenechromanes, α-methylenequinoline, and ortho-quinone methides were generated in situ from a Knoevenagel reaction of 4-hydroxycoumarin, 4-hydroxy-6-methylcoumarin, 4-hydroxy-N-methylquinolinone, and 2-hydroxy-1,4-naphthoquinone, respectively, with paraformaldehyde in dioxane. All the dyads as free bases and as Zn(II) complexes were obtained in high yields. All new compounds were fully characterized by 1D and 2D NMR techniques, UV/Vis spectroscopy, and HRMS. Their photophysical properties were evaluated by measuring the fluorescence quantum yield, the singlet oxygen quantum yield by luminescence detection, and also the triplet lifetimes were correlated by flash photolysis and intersystem crossing (ISC) rates. The fluorescence lifetimes were measured by a time-correlated single photon count (TCSPC) method, fluorescence decay associated spectra (FDAS), and anisotropy measurements. Magnetic circular dichroism (MCD) and circular dichroism (CD) spectra were recorded for one Zn(II) complex in order to obtain information, respectively, on the electronic and conformational states, and interpretation of these spectra was enhanced by molecular orbital (MO) calculations. Electrochemical studies of the Zn(II) complexes were also carried out to gain insights into their behavior for such applications.
Assuntos
Complexos de Coordenação/síntese química , Fármacos Fotossensibilizantes/síntese química , Porfirinas/síntese química , Protoporfirinas/síntese química , Zinco/química , Clorofilídeos , Complexos de Coordenação/química , Reação de Cicloadição , Técnicas Eletroquímicas , Metilação , Fármacos Fotossensibilizantes/química , Porfirinas/química , Protoporfirinas/química , Análise EspectralRESUMO
New pyrazole-porphyrin conjugates were successfully prepared from a reaction of ß-porphyrin-chalcone derivatives with phenylhydrazine in acetic acid followed by an oxidative step. This fast and efficient synthetic approach provided the expected compounds in yields up to 82%. The sensing ability of the new porphyrin-pyrazole derivatives to detect the metal ions Ag(+), Na(+), K(+), Mg(2+), Ca(2+), Ni(2+), Cu(2+), Zn(2+), Cd(2+), Hg(2+), Pb(2+), and Cr(3+) was studied by spectrophotometric and spectrofluorimetric titrations. In the presence of Zn(2+), the conjugates exhibit changes in the emission spectra that are desired for a ratiometric-type fluoroionophoric detection probe. The studies were extended to gas phase, where the pyrazole-porphyrin conjugates show ability to sense metal ions with high selectivity toward Cu(2+) and Ag(+), and in poly(methyl methacrylate) doped films with promising results for Zn(2+) detection.
RESUMO
Antimicrobial photodynamic treatment (aPDT) offers an alternative option for combating microbial pathogens, and in this way, addressing the challenges of growing antimicrobial resistance. In this promising and effective approach, cationic porphyrins and related macrocycles have emerged as leading photosensitizers (PS) for aPDT. In general, their preparation occurs via N-alkylation of nitrogen-based moieties with alkyl halides, which limits the ability to fine-tune the features of porphyrin-based PS. Herein, is reported that the conjugation of porphyrin macrocycles with triphenylphosphonium units created a series of effective cationic porphyrin-based PS for aPDT. The presence of positive charges at both the porphyrin macrocycle and triphenylphosphonium moieties significantly enhances the photodynamic activity of porphyrin-based PS against both Gram-positive and Gram-negative bacterial strains. Moreover, bacterial photoinactivation is achieved with a notable reduction in irradiation time, exceeding 50%, compared to 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin (TMPyP), used as the reference and known as good PS. The improved capability of the porphyrin macrocycle to generate singlet oxygen combined with the enhanced membrane interaction promoted by the presence of triphenylphosphonium moieties represents a promising approach to developing porphyrin-based PS with enhanced photosensitizing activity.
Assuntos
Antibacterianos , Teste de Materiais , Compostos Organofosforados , Fármacos Fotossensibilizantes , Porfirinas , Porfirinas/química , Porfirinas/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Compostos Organofosforados/química , Compostos Organofosforados/farmacologia , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Testes de Sensibilidade Microbiana , Estrutura Molecular , Tamanho da Partícula , Fotoquimioterapia , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacosRESUMO
Research has demonstrated the presence of viruses in wastewater (WW), which can remain viable for a long period, posing potential health risks. Conventional WW treatment methods involving UV light, chlorine and ozone efficiently reduce microbial concentrations, however, they produce hazardous byproducts and microbial resistance that are detrimental to human health and the ecosystem. Hence, there is a need for novel disinfection techniques. Antimicrobial Photodynamic Inactivation (PDI) emerges as a promising strategy, utilizing photosensitizers (PS), light, and dioxygen to inactivate viruses. This study aims to assess the efficacy of PDI by testing methylene blue (MB) and the cationic porphyrin TMPyP as PSs, along a low energy consuming white light source (LED) at an irradiance of 50 mW/cm2, for the inactivation of bacteriophage Phi6. Phi6 serves as an enveloped RNA-viruses surrogate model in WW. PDI experiments were conducted in a buffer solution (PBS) and real WW matrices (filtered and non-filtered). Considering the environmental release of the treated effluents, this research also evaluated the ecotoxicity of the resulting solution (post-PDI treatment effluent) on the model organism Daphnia magna, following the Organisation for Economic Cooperation and Development (OECD) immobilization technical 202 guideline. Daphnids were exposed to WW containing the tested PS at different concentrations and dilutions (accounting for the dilution factor during WW release into receiving waters) over 48 h. The results indicate that PDI with MB efficiently inactivated the model virus in the different aqueous matrices, achieving reductions superior to 8 log10 PFU/mL, after treatments of 5 min in PBS and of ca. 90 min in WW. Daphnids survival increased when subjected to the PDI-treated WW with MB, considering the dilution factor. Overall, the effectiveness of PDI in eliminating viruses in WW, the fading of the toxic effects on daphnids after MB' irradiation and the rapid dilution effect upon WW release in the environment highlight the possibility of using MB in WW PDI-disinfection.
Assuntos
Daphnia , Desinfecção , Azul de Metileno , Fármacos Fotossensibilizantes , Águas Residuárias , Águas Residuárias/química , Desinfecção/métodos , Daphnia/efeitos dos fármacos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Animais , Azul de Metileno/farmacologia , Azul de Metileno/química , Porfirinas/química , Porfirinas/farmacologia , Bacteriófagos/efeitos dos fármacos , Eliminação de Resíduos Líquidos/métodos , Purificação da Água/métodos , EcotoxicologiaRESUMO
DNA chains with sequential guanine (G) repeats can lead to the formation of G-quadruplexes (G4), which are found in functional DNA and RNA regions like telomeres and oncogene promoters. The development of molecules with adequate structural features to selectively stabilize G4 structures can counteract cell immortality, highly described for cancer cells, and also downregulate transcription events underlying cell apoptosis and/or senescence processes. We describe here, the efficiency of four highly charged porphyrins-phosphonium conjugates to act as G4 stabilizing agents. The spectrophotometric results allowed to select the conjugates P2-PPh3 and P3-PPh3 as the most promising ones to stabilize selectively G4 structures. Molecular dynamics simulation experiments were performed and support the preferential binding of P2-PPh3 namely to MYC and of P3-PPh3 to KRAS. The ability of both ligands to block the activity of Taq polymerase was confirmed and also their higher cytotoxicity against the two melanoma cell lines A375 and SK-MEL-28 than to immortalized skin keratinocytes. Both ligands present efficient cellular uptake, nuclear co-localization and high ability to generate 1O2 namely when interacting with G4 structure. The obtained data points the synthesized porphyrins as promising ligands to be used in a dual approach that can combine G4 stabilization and Photodynamic therapy (PDT).
RESUMO
Alzheimer's disease is characterized by a progressive deterioration of cognitive function and memory loss, and it is closely associated with the dysregulation of cholinergic neurotransmission. Since acetylcholinesterase (AChE) is a critical enzyme in the nervous system, responsible for breaking down the neurotransmitter acetylcholine, its inhibition holds a significant interest in the treatment of various neurological disorders. Therefore, it is crucial to develop efficient AChE inhibitors capable of increasing acetylcholine levels, ultimately leading to improved cholinergic neurotransmission. The results reported here represent a step forward in the development of novel thiazoloindazole-based compounds that have the potential to serve as effective AChE inhibitors. Molecular docking studies revealed that certain of the evaluated nitroindazole-based compounds outperformed donepezil, a well-known AChE inhibitor used in Alzheimer's disease treatment. Sustained by these findings, two series of compounds were synthesized. One series included a triazole moiety (Tl45a-c), while the other incorporated a carbazole moiety (Tl58a-c). These compounds were isolated in yields ranging from 66 to 87% through nucleophilic substitution and Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC) reactions. Among the synthesized compounds, the thiazoloindazole-based 6b core derivatives emerged as selective AChE inhibitors, exhibiting remarkable IC50 values of less than 1.0 µM. Notably, derivative Tl45b displays superior performance as an AChE inhibitor, boasting the lowest IC50 (0.071 ± 0.014 µM). Structure-activity relationship (SAR) analysis indicated that derivatives containing the bis(trifluoromethyl)phenyl-triazolyl group demonstrated the most promising activity against AChE, when compared to more rigid substituents such as carbazolyl moiety. The combination of molecular docking and experimental synthesis provides a suitable and promising strategy for the development of new efficient thiazoloindazole-based AChE inhibitors.
Assuntos
Acetilcolinesterase , Inibidores da Colinesterase , Indazóis , Simulação de Acoplamento Molecular , Tiazóis , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/química , Inibidores da Colinesterase/síntese química , Simulação de Acoplamento Molecular/métodos , Indazóis/farmacologia , Indazóis/química , Acetilcolinesterase/metabolismo , Acetilcolinesterase/efeitos dos fármacos , Humanos , Tiazóis/farmacologia , Tiazóis/química , Desenho de Fármacos , Relação Estrutura-AtividadeRESUMO
Corrole macrocycles are very appealing dyes for incorporation into light harvesting devices. This work shows the sensorial ability of 5,10,15-tris(pentafluorophenyl)corrole 1 and its monoanionic species toward Na(+), Ca(2+), Cu(2+), Cd(2+), Pb(2+), Hg(2+), Ag(+), and Al(3+) metal ions in toluene and acetonitrile. The photophysical studies toward metal ions were carried out by absorption and emission spectroscopy. From all metal ions studied, corrole 1 shows to be colorimetric for Hg(2+) allowing a naked-eye detection of Hg(2+) through a change of color from purple to blue in acetonitrile and from green to yellow in toluene. In addition a new ß-imine corrole 4 was successful synthesized and further functionalized with 3-isocyanatopropyl-trimethoxysilane resulting in an alkoxysilane derivative 5. The grafting of alkoxysilane derivative 5 with optically transparent silica nanoparticles (SiNPs) was achieved succesfully. The new-coated silica nanoparticles with corrole 5 were studied in the presence of Cu(2+), Hg(2+), and Ag(+) as metal ion probes. Interestingly, upon addition of Ag(+), groups of satellite AgNPs were formed around the SiNPs and were checked by transmission electron microscopy (TEM). At same time, a change of color from green to yellow was observed.
Assuntos
Técnicas de Química Analítica/instrumentação , Nanopartículas/química , Porfirinas/química , Dióxido de Silício/química , Prata/análise , Prata/química , Cobre/análise , Cobre/química , Mercúrio/análise , Mercúrio/química , EspectrofotometriaRESUMO
Safety assessment of carbon nanomaterials is of paramount importance since they are on the frontline for applications in sensing, bioimaging and drug delivery. The biocompatibility and safety of functionalized nanodiamonds (NDs) are here addressed through the study of the pro-inflammatory response of RAW-264.7 macrophages exposed to new nanodiamonds@corrole hybrids. The corrole unit selected is as a prototype for a hydrophobic organic molecule that can function as a NIR fluorophore reporter, an optical sensor, a photodynamic therapy agent or a photocatalyst. The new functional nanohybrids containing detonated nanodiamonds (NDs) were obtained through esterification using carboxylated NDs and glycol corroles. The success of the covalent functionalization via carbodiimide activation was confirmed through X-ray photoelectron spectroscopy (XPS), Raman and Fourier transform infrared (FTIR) spectroscopy. The UV-vis absorption and emission spectra of the hybrids are additive with respect to the corrole features. The cellular uptake, localization, cell viability and effects on immune cell activation of the new hybrids and of the precursors were carefully investigated using RAW-264.7 macrophages. Overall results showed that the ND@corrole hybrids had no pro-inflammatory effects on the RAW-264.7 macrophage cell line, making them an ideal candidate for a wide range of biomedical applications.
Assuntos
Nanodiamantes , Porfirinas , Nanodiamantes/química , Sistemas de Liberação de Medicamentos , Porfirinas/farmacologia , MacrófagosRESUMO
Starch is a biodegradable and biocompatible carbohydrate that, when combined with bioactive molecules, can be processed as biomimetic platforms with enhanced performance, allowing its use as active wound dressing materials. Porphyrinoid photosensitizers can tune the physicochemical/functional profile of biomacromolecules, allowing their use in anti-infective strategies. In this work, the feasibility of using the cationic 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin tetraiodide (TMPyP) to enhance the physicochemical, mechanical, antimicrobial performance, and wound healing ability of casted starch-based films was studied. TMPyP conferred a reddish coloration to the films, maintaining their pristine transparency. It increased by 87 % the films hydrophobicity and, depending on the TMPyP used, conferred mobility to the starch polymeric chains. Starch/TMPyP-based films effectively photoinactivated Escherichia coli (>99.99 %) and favored the wound healing process, even in the absence of light. Therefore, the incorporation of TMPyP into starch-based formulations revealed to be a promising strategy to tune the films compaction degree while giving rise to water tolerant and photosensitive biomaterials that can act as multitarget antimicrobial medical dressings and glycocarriers of active compounds relevant for effective skin wound healing.
Assuntos
Anti-Infecciosos , Fármacos Fotossensibilizantes , Fármacos Fotossensibilizantes/farmacologia , Amido/química , Anti-Infecciosos/química , Bandagens , Escherichia coli , CicatrizaçãoRESUMO
The title compound, C(13)H(8)Cl(2)N(2)O(2), was obtained by the oxidation of diclofenac {systematic name: 2-[2-(2,6-dichloro-phenyl-amino)-phen-yl]acetic acid}, an anti-inflammatory drug, with hydrogen peroxide catalysed by chlorido[5,10,15,20-tetra-kis-(2,6-dichloro-phen-yl)porphyrinato]manganese(III), using ammonium acetate as co-catalyst. The asymmetric unit contains two crystallographically independent mol-ecules of the title compound (Z' = 2). The close packing of individual mol-ecules is mediated by a series of strong and rather directional N-Hâ¯Cl and N-Hâ¯O hydrogen bonds, plus weak π-π [distance between the individual double bonds of symmetry-related imino-quinone rings = 3.7604â (13)â Å] and Clâ¯O inter-actions [3.0287â (18)â Å].
RESUMO
Pathogenic viruses are frequently present in marine and estuarine waters, due to poor wastewater (WW) treatments, which consequently affect water quality and human health. Chlorination, one of the most common methods used to ensure microbiological safety in tertiarily treated effluents, may lead to the formation of toxic chemical disinfection by-products on reaction with organic matter present in the effluents. Antimicrobial photodynamic therapy (aPDT) can be a promising disinfecting approach for the inactivation of pathogens, without the formation of known toxic by-products. Additionally, some studies have reported the potentiator effect on aPDT of some compounds, such as potassium iodide (KI) and hydrogen peroxide (H2O2). In the present study, the aPDT efficiency of a PS formulation constituted of five cationic porphyrins (Form) in the inactivation of E. coli T4-like bacteriophage, a model of mammalian viruses, in different aqueous matrices with different organic matter content, was evaluated. Photoinactivation studies were performed at different concentrations of Form and in the presence of the adjuvants KI and H2O2. The results showed that the efficiency of bacteriophage photoinactivation is correlated with the Form concentration, the amount of the organic matter in WW, and the adjuvant type. Form can be an effective alternative to controlling viruses in WW, particularly if combined with H2O2, allowing to significantly reduce PS concentration and treatment time. When combined with KI, the Form is less effective in inactivating T4-like bacteriophage in WW.