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1.
Nat Commun ; 11(1): 3530, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32669576

RESUMO

Resistance change under mechanical stimuli arouses mass operational heat, damaging the performance, lifetime, and reliability of stretchable electronic devices, therefore rapid thermal heat dissipating is necessary. Here we report a stretchable strain sensor with outstanding thermal management. Besides a high stretchability and sensitivity testified by human motion monitoring, as well as long-term durability, an enhanced thermal conductivity from the casted thermoplastic polyurethane-boron nitride nanosheets layer helps rapid heat transmission to the environments, while the porous electrospun fibrous thermoplastic polyurethane membrane leads to thermal insulation. A 32% drop of the real time saturated temperature is achieved. For the first time we in-situ investigated the dynamic operational temperature fluctuation of stretchable electronics under repeating stretching-releasing processes. Finally, cytotoxicity test confirms that the nanofillers are tightly restricted in the nanocomposites, making it harmless to human health. All the results prove it an excellent candidate for the next-generation of wearable devices.


Assuntos
Técnicas Biossensoriais/instrumentação , Movimento , Dispositivos Eletrônicos Vestíveis , Técnicas Biossensoriais/métodos , Compostos de Boro/química , Elastômeros , Eletrônica , Células HEK293 , Temperatura Alta , Humanos , Nanocompostos , Nanoestruturas , Polímeros/química , Poliuretanos/química , Reprodutibilidade dos Testes
2.
J Vis Exp ; (160)2020 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-32568221

RESUMO

Single molecule localization microscopy (SMLM) techniques overcome the optical diffraction limit of conventional fluorescence microscopy and can resolve intracellular structures and the dynamics of biomolecules with ~20 nm precision. A prerequisite for SMLM are fluorophores that transition from a dark to a fluorescent state in order to avoid spatio-temporal overlap of their point spread functions in each of the thousands of data acquisition frames. BODIPYs are well-established dyes with numerous conjugates used in conventional microscopy. The transient formation of red-shifted BODIPY ground-state dimers (DII) results in bright single molecule emission enabling single molecule localization microscopy (SMLM). Here we present a simple but versatile protocol for SMLM with conventional BODIPY conjugates in living yeast and mammalian cells. This procedure can be used to acquire super-resolution images and to track single BODIPY-DII states to extract spatio-temporal information of BODIPY conjugates. We apply this procedure to resolve lipid droplets (LDs), fatty acids, and lysosomes in living yeast and mammalian cells at the nanoscopic length scale. Furthermore, we demonstrate the multi-color imaging capability with BODIPY dyes when used in conjunction with other fluorescent probes. Our representative results show the differential spatial distribution and mobility of BODIPY-fatty acids and neutral lipids in yeast under fed and fasted conditions. This optimized protocol for SMLM can be used with hundreds of commercially available BODIPY conjugates and is a useful resource to study biological processes at the nanoscale far beyond the applications of this work.


Assuntos
Compostos de Boro/química , Corantes Fluorescentes/química , Microscopia de Fluorescência/métodos , Imagem Individual de Molécula/métodos , Animais , Compostos de Boro/metabolismo , Sobrevivência Celular , Cor , Ácidos Graxos/metabolismo , Corantes Fluorescentes/metabolismo , Gotículas Lipídicas/metabolismo , Lisossomos/metabolismo , Leveduras/citologia
3.
J Chromatogr A ; 1621: 461063, 2020 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-32360060

RESUMO

A new turn-on fluorescent probe, based on a hydrazine group placed in the meso-position of the BODIPY molecule, was synthesized. It was then used for detecting long-chain fatty aldehydes, which can be harmful to human health, in edible vegetable oils. In acetonitrile, the probe produced strong "turn on" and 100-fold fluorescence enhancement with high sensitivity and rapid response to saturated fatty aldehydes. A highly sensitive detection method for long-chain fatty aldehydes was established using pre-column derivation fluorescence procedure by high-performance liquid chromatography. The chromatographic method established provided satisfactory precision (1.91%-5.93%), good linearity (R2 ≥ 0.999), an acceptable accuracy (83.7%-108%) and a low limit of detection (6.4-12.4 ng/mL). The experimental results indicated that the probe could qualitatively and quantitatively detect six fatty aldehydes in vegetable oils, thus providing the potential for use in routine analysis for identifying the type of vegetable oil and for controlling its quality and safety.


Assuntos
Aldeídos/análise , Compostos de Boro/química , Cromatografia Líquida de Alta Pressão/métodos , Ácidos Graxos/análise , Corantes Fluorescentes , Óleos Vegetais/química
4.
Anal Chim Acta ; 1113: 43-51, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32340668

RESUMO

This study fabricated a dual-emission probe consisting of monolayer MoS2 quantum dots (M - MoS2 QDs) and L-cystine-linked boron-dipyrromethene (L-Cys-BODIPY) molecules for ratiometric sensing of biothiols, thiol product-related enzyme reactions, and ratiometric imaging of glutathione (GSH)-related reactions in HeLa cells. The formation of L-Cys-BODIPY-adsorbed M - MoS2 QDs (named as BODIPY-M-MoS2 QDs) was demonstrated by comparing them with M - MoS2 QDs using transmission electron microscopy, atomic force microscopy, and X-ray photoelectron spectroscopy. The BODIPY-M-MoS2 QDs exhibited dual-emission bands, excellent biocompatibility, and good resistance to photobleaching. It was found that the adsorbed L-Cys-BODIPY molecules rarely quenched the fluorescence of M - MoS2 QDs, and meanwhile, they were self-quenched by π-π stacking between each BODIPY backbones. The presence of biothiols induced the reduction of weakly fluorescent L-Cys-BODIPY to strongly fluorescent of L-cysteine-conjugated BODIPY. Since having a much higher molar absorption coefficient than L-Cys-BODIPY, the liberated L-cysteine-conjugated BODIPY behaved as an effective inner filter to absorb the excitation light and subsequently quenched the fluorescence of M - MoS2 QDs. The appearance of L-cysteine-conjugated BODIPY could barely affected to the fluorescence lifetime of M - MoS2 QDs, confirming the inner filter effect of L-cysteine-conjugated BODIPY onto the fluorescence of M - MoS2 QDs. The present probe not only provided a linear ratiometric response to 1-10 mM GSH, 1-10 µM cysteine, and 1-10 µM of homocysteine but also remarkably showed the ratiometric detection of thiol products from the reactions of 1-900 units L-1 S-adenosylhomocysteine (SAH) hydrolase and SAH as well as 1-850 units L-1 GSH reductase and disulfide GSH. Additionally, the present probe was well-suited for ratiometric imaging of intracellular GSH levels in non-treated and drug-treated HeLa cells.


Assuntos
Cisteína/análise , Corantes Fluorescentes/química , Glutationa/análise , Homocisteína/análise , Pontos Quânticos/química , Compostos de Boro/química , Cistina/química , Dissulfetos/química , Células HeLa , Humanos , Limite de Detecção , Molibdênio/química , Espectrometria de Fluorescência/métodos
5.
Chemistry ; 26(39): 8608-8620, 2020 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-32319110

RESUMO

An unsymmetrical guanidine-cyclopropenimine proton sponge DAGUN and the related BF2 -chelate DAGBO are reported. Insight into the structural, electronic, bonding and photophysical properties of these two molecules are presented. Joint experimental and theoretical studies reveal the protonated form of DAGUN possesses an intramolecular N⋅⋅⋅H-N hydrogen bond which affords a high experimental pKBH+ of 26.6 (computed=26.3). Photophysical studies show that in solution DAGUN displays a green emission at 534 nm, with a large Stokes shift of 235 nm (14,718 cm-1 ). In contrast, the conjugate acid DAGUN-H+ is only weakly emissive due to attenuated intramolecular charge transfer. X-ray diffraction studies reveal that DAGBO contains a stable tetracoordinate boronium cation, reminiscent of the well-established BODIPY family of dyes. In solution, DAGBO exhibits a strong blue emission at 450 nm coupled with a large Stokes shift (Δλ=158 nm, Δν=11,957 cm-1 ) and quantum yield of 62 %, upon excitation at 293 nm. DAGBO sets the stage as the first entry into a new class of boron-difluoride diaminonaphthalenes (BOFDANs) that represent highly fluorescent and tunable next-generation dyes with future promise for biosensing and bioimaging applications.


Assuntos
Compostos de Boro/química , Corantes Fluorescentes/química , Guanidinas/química , Ionóforos/química , Guanidinas/síntese química , Ligação de Hidrogênio , Prótons
6.
Phys Chem Chem Phys ; 22(14): 7193-7200, 2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32195495

RESUMO

We report a joint negative ion photoelectron spectroscopy (NIPES) and computational study on the electronic structures and noncovalent interactions of a series of cyclodextrin-closo-dodecaborate dianion complexes, χ-CD·B12X122- (χ = α, ß, γ; X = H, F). The measured vertical/adiabatic detachment energies (VDEs/ADEs) are 1.15/0.93, 3.55/3.20, 3.90/3.60, and 3.85/3.60 eV for B12H122- and its α-, ß-, γ-CD complexes, respectively; while the corresponding values are 1.90/1.70, 4.00/3.60, 4.33/3.95, and 4.30/3.85 eV for the X = F case. These results show that the inclusion of B12X122- into the CD cavities greatly increases the electronic stability of the dianions. The effect of electronic stabilization for ß-CD is roughly the same as for γ-CD, both being considerably stronger than that for α-CD. Density functional theory (DFT) based geometry optimization reveals that B12X122- are inserted into CDs increasingly deeper from α-CD to γ-CD. The calculated VDEs and ADEs agree with the experiments well, particularly, reproducing the electron binding energy (EBE) trends. The molecular orbital analyses indicate that the most loosely bound photodetached electrons originate from the guest B12X122- moieties. In addition to a shift of all signals to a larger EBE, significant changes in the signal patterns are observed. At low EBE, this is due to the splitting of highly degenerate B12X122- orbitals, while at high EBE, photodetachment from CD oxygens contributes to the new bands. The guest B12X122- and host CD noncovalent, size-specific interaction based on the independent gradient model (IGM) and energy decomposition analysis (EDA) is dominated by electrostatic interactions. The analysis further unravels unambiguously the existence of dihydrogen bonding and how it affects the total energy that stabilizes the host-guest complexes of CDs·B12H122- compared to the general hydrogen bonding interaction in CDs·B12F122-. This work clearly exhibits strong influences on the electronic structures of dodecaborates upon clustering with CDs, with both size (α-, ß-, and γ-) and molecular (X = H or F) specificities, thus providing critical molecular-level information on the cyclodextrin-closo-dodecaborate interactions of interest to medical applications, e.g., boron neutron capture therapy.


Assuntos
Ânions/química , Compostos de Boro/química , Espectroscopia Fotoeletrônica , Química Computacional , Estrutura Molecular
7.
Chem Commun (Camb) ; 56(18): 2695-2698, 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32030397

RESUMO

A BODIPY-based fluorescent sensor PS with an NO4S2 podand ligand was studied for the selective detection of Pt2+ over 21 cations as well as selected platinum drugs in aqueous medium. The platinum sensor PS shows 28-fold, 22-fold and 14-fold fluorescence turn-on enhancements to Pt2+, cisplatin and nedaplatin, and was thereby employed to detect platinum drugs in A-549 human lung cancer cells.


Assuntos
Compostos de Boro/química , Cisplatino/análise , Corantes Fluorescentes/química , Neoplasias Pulmonares/diagnóstico por imagem , Platina/análise , Células A549 , Cisplatino/uso terapêutico , Humanos , Ligantes , Neoplasias Pulmonares/tratamento farmacológico , Estrutura Molecular , Imagem Óptica , Espectrometria de Fluorescência
8.
Chemistry ; 26(26): 5780-5783, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32092185

RESUMO

Activity of acid sphingomyelinase has been implicated in a number of diseases like acute lung injury, sepsis or metastasis of melanoma cells. Here, we present a sphingomyelinase FRET probe based on FAM/BODIPY dyes for real-time monitoring of acid sphingomyelinase. The probe gives rise to a tremendous increase in fluorescence of the fluorescein FRET donor upon cleavage and we show that this is, to a significant part, due to cleavage-associated phase transition, suggesting a more systematic consideration of such effects for future probe development. The probe allows for the first time to monitor relative sphingomyelinase activities of intact living cells by flow cytometry.


Assuntos
Compostos de Boro/química , Transferência Ressonante de Energia de Fluorescência/métodos , Esfingomielina Fosfodiesterase/química , Citometria de Fluxo , Fluorescência , Humanos , Esfingomielina Fosfodiesterase/metabolismo
9.
Sci Adv ; 6(4): eaaz1722, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-32010792

RESUMO

In the current clinical boron neutron capture therapy (BNCT), p-boronophenylalanine (BPA) has been the most powerful drug owing to its ability to accumulate selectively within cancers through cancer-related amino acid transporters including LAT1. However, the therapeutic success of BPA has been sometimes compromised by its unfavorable efflux from cytosol due to their antiport mechanism. Here, we report that poly(vinyl alcohol) (PVA) can form complexes with BPA through reversible boronate esters in aqueous solution, and the complex termed PVA-BPA can be internalized into cancer cells through LAT1-mediated endocytosis, thereby enhancing cellular uptake and slowing the untoward efflux. In in vivo study, compared with clinically used fructose-BPA complexes, PVA-BPA exhibited efficient tumor accumulation and prolonged tumor retention with quick clearance from bloodstream and normal organs. Ultimately, PVA-BPA showed critically enhanced antitumor activity in BNCT. The facile technique proposed in this study offers an approach for drug delivery focusing on drug metabolism.


Assuntos
Compostos de Boro/farmacologia , Terapia por Captura de Nêutron de Boro , Metabolismo Energético/efeitos dos fármacos , Fenilalanina/análogos & derivados , Álcool de Polivinil/farmacologia , Radiossensibilizantes/farmacologia , Animais , Compostos de Boro/química , Compostos de Boro/farmacocinética , Linhagem Celular Tumoral , Modelos Animais de Doenças , Sinergismo Farmacológico , Humanos , Espectrometria de Massas , Camundongos , Neoplasias/terapia , Fenilalanina/química , Fenilalanina/farmacocinética , Fenilalanina/farmacologia , Álcool de Polivinil/química , Álcool de Polivinil/farmacocinética , Radiossensibilizantes/química , Radiossensibilizantes/farmacocinética , Transdução de Sinais/efeitos dos fármacos , Distribuição Tecidual , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Chem Asian J ; 15(7): 1022-1024, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32034862

RESUMO

We have demonstrated B2 pin2 as superior deoxidizing agent for the reductive deoxygenation of quinol derivatives under basic conditions. A wide range of highly functionalized phenols were obtained in good yields including a complex drug molecule, which revealed the high functional group tolerance of this protocol.


Assuntos
Hidrocarbonetos Aromáticos/química , Hidroquinonas/química , Oxigênio/química , Derivados de Benzeno/química , Compostos de Boro/química , Oxirredução , Fenóis
11.
J Chromatogr A ; 1619: 460913, 2020 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-32007220

RESUMO

Traditional boron affinity materials usually capture cis-diol-containing molecules under alkaline condition, but some cis-diol-containing molecules, such as polyphenols, are unstable and easy to be oxidized and degraded under alkaline condition. Teamed boronate affinity (TBA) can specifically capture cis-diol-containing molecules under neutral condition. However, the report about combination of TBA and magnetic nanoparticle for the extraction was rare. Here, we fabricated two kinds of teamed boronate affinity magnetic nanoparticles (TBAMP), including Fe3O4@TBAP and Fe3O4@SiO2@TBAP. Adsorption capacities of cis-diol-containing molecules on the latter were similar to these on the former, but the latter possessed more superior regeneration performance than the former. Therefore, the TBAMP with more superior regeneration performance was used as magnetic solid-phase extraction (MSPE) adsorbent for capturing polyphenols under neutral condition. The TBAMP MSPE was optimized in detail, and combined with high-performance liquid chromatography-mass spectrometry (HPLC-MS) for the simultaneous determination of 13 kinds of polyphenols from Flos Lonicerae Beverage. The proposed method showed low limit of detection between 0.01 and 0.20 ng mL-1. In blank Flos Lonicerae Beverage, 11 kinds of polyphenols ranged from 0.54 ng mL-1 to 52.99 ng mL-1 were detected. In the standard addition method, recoveries of cis-diol-containing polyphenols were between 85.7% and 102.1% with intra-day and inter-day relative standard deviation ranging from 3.2% to 5.1% and 5.3% to 7.3%, respectively.


Assuntos
Bebidas/análise , Compostos de Boro/química , Cromatografia Líquida de Alta Pressão , Nanopartículas de Magnetita/química , Espectrometria de Massas , Extratos Vegetais/química , Polifenóis/análise , Extração em Fase Sólida/métodos , Adsorção , Concentração de Íons de Hidrogênio , Limite de Detecção , Polifenóis/isolamento & purificação
12.
J Mol Model ; 26(3): 54, 2020 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-32036483

RESUMO

Using molecular dynamics simulations, the adsorption and diffusion of doxorubicin drug molecules in boron nitride nanotubes are investigated. The interaction between doxorubicin and the nanotube is governed by van der Waals attraction. We find strong adsorption of doxorubicin to the wall for narrow nanotubes (radius of 9 Å). For larger radii (12 and 15 Å), the adsorption energy decreases, while the diffusion coefficient of doxorubicin increases. It does, however, not reach the values of pure water, as adsorption events still hinder the doxorubicin mobility. It is concluded that nanotubes wider than around 4 nm diameter can serve as efficient drug containers for targeted drug delivery of doxorubicin in cancer chemotherapy.


Assuntos
Compostos de Boro/química , Doxorrubicina , Sistemas de Liberação de Medicamentos , Modelos Químicos , Simulação de Dinâmica Molecular , Nanotubos/química , Doxorrubicina/química , Doxorrubicina/farmacocinética
13.
Chem Commun (Camb) ; 56(13): 1956-1959, 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-31956868

RESUMO

Herein, we report a pH stimulus-disaggregated BODIPY sensitizer (PTS) with low background-toxicity for achieving activated photodynamic/photothermal tumor therapy. Both the photodynamic and photothermal properties of PTS can be activated under acidic conditions, and PTS exhibits excellent antitumor properties, which is revealed by both in vitro and in vivo tests.


Assuntos
Compostos de Boro/química , Fármacos Fotossensibilizantes/química , Animais , Compostos de Boro/farmacologia , Compostos de Boro/uso terapêutico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Luz , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias/tratamento farmacológico , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fototerapia , Transplante Heterólogo
14.
Comput Biol Chem ; 84: 107190, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31918171

RESUMO

The electron conformational genetic algorithm (EC-GA) method had been employed by distinguishing between enantiomers for the first time as a 4D-QSAR approach to reveal the pharmacophore (Pha) and to predict the bioactivity of the dipeptidyl boron compounds. The Electron Conformational Matrices of Congruity (ECMCs) were prepared for all conformers of compounds in the data set based on the quantum chemical calculations at HF/3-21 G level in an aqueous medium. The comparison of the ECMCs within the certain tolerances by the EMRE program revealed the pharmacophore for some dipeptidyl boron derivatives. For the selection of the most influential parameters on the activity and the calculation of theoretical activities, the genetic algorithm with the non-linear least square method was used. The final model was validated by the cross-validation method with the division of the data set into training and test items. The 12-parameter model gave excellent statistical results (R2training = 0.850, R2test = 0.809, q2 = 0.755, q2ext1 = 0.776, q2ext2 = 0.759, q2ext3 = 0.735, CCCtr = 0.922, CCCtest = 0.846, CCCall = 0.905). Because of the inexistence of 4D-QSAR studies on the dipeptidyl boron derivatives and the stereoisomerism effect on the biological activity was examined for the first time for these compounds, this study plays an important role in the development of new boron-containing compounds.


Assuntos
Compostos de Boro/química , Dipeptídeos/química , Inibidores de Proteassoma/química , Algoritmos , Conformação Molecular , Relação Quantitativa Estrutura-Atividade , Estereoisomerismo
15.
J Phys Chem Lett ; 11(3): 877-884, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-31931562

RESUMO

BODIPY chromophores can serve as organic-based triplet photosensitizers for a wide range of applications. To perform this function, the formation of the triplet state is critical, and a better understanding of how to modulate the formation of the triplet state could lead to further advances in BODIPY-based sensitizers for solar energy conversion and photodynamic therapy. In this work we investigate the ability of halogen bonding, a noncovalent solvent interaction, to facilitate intersystem crossing in a diiodo-BODIPY. Ultrafast transient absorption spectroscopy is applied to diiodo-BODIPY in the presence of pyridine-based halogen bonding solvent molecules to determine the rate constants for intersystem crossing. We find that halogen bonding facilitates the formation of the triplet state by increasing the intersystem crossing rate constant of diiodo-BODIPY. The results are interpreted in terms of the Marcus expression for intersystem crossing. Quantum chemical calculations show that halogen bonding acts to alter both the spin-orbit coupling terms and the relative energetics of the singlet and triplet states.


Assuntos
Compostos de Boro/química , Halogênios/química , Cinética , Piridinas/química , Teoria Quântica , Solventes/química
16.
Org Biomol Chem ; 18(4): 707-714, 2020 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-31907494

RESUMO

Fluorescence bioimaging is very significant in studying biological processes. Fluorescent nanoparticles (NPs) manufactured from aggregation-induced emission (AIE) materials, as promising candidates, have attracted more attention. However, it is still a challenge to explore suitable AIE NPs for bioimaging. Herein, we synthesized pyrazoline-BODIPY (PZL-BDP) with a donor and acceptor (D-A) structure by a condensation reaction, cultured its single crystal, and studied its twisted intramolecular charge transfer (TICT) and AIE effects. PZL-BDP could self-assemble to form red fluorescent nanoparticles (PZL-BDP NPs) which showed a good fluorescence quantum yield of 15.8% in water. PZL-BDP NPs with excellent stability and biocompatibility exhibited a large Stokes shift (Δλ = 111 nm) which resulted in the reduction of external interference and enhancement of the fluorescence contrast. Furthermore, these nanoparticles could be readily internalized by HeLa cells and they stain the cells in just five seconds, indicating an ultrafast bioimaging protocol. Moreover, long-term tracking fluorescence signals in vivo for about 12 days were obtained. The bright red fluorescence, ultrafast cell staining ability, and long-term in vivo tracking competence outline the great potential of rational design nanomaterials with AIE characteristics for monitoring biological processes.


Assuntos
Compostos de Boro/química , Corantes Fluorescentes/química , Nanopartículas/química , Pirazóis/química , Animais , Compostos de Boro/síntese química , Compostos de Boro/toxicidade , Linhagem Celular Tumoral , Cor , Feminino , Fluorescência , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/toxicidade , Humanos , Camundongos , Nanopartículas/toxicidade , Neoplasias/diagnóstico por imagem , Imagem Óptica/métodos , Pirazóis/síntese química , Pirazóis/toxicidade
17.
Nanotechnology ; 31(21): 215101, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31978926

RESUMO

The molecular stress caused by a drug administered to treat a disorder on healthy cells appears as a side effect. In this study, we aim to understand the potential of hexagonal boron nitrides (hBNs) as a therapeutic agent to relieve the cellular stress exerted by drugs. First, the cytotoxicity of hBNs and their possible degradation product, boric acid (BA), on the embryonic mouse hippocampal cell line mHippo E-14 was assessed in a wide concentration range (4.4-440 µg ml-1) of boron including hBNs and BA for 24 and 72 h exposure. Then, cell cycle, reactive oxygen species generation, cell death mechanism and apoptotic body formation in nuclei with hBN and BA exposure were evaluated at increased concentrations and incubation times. Finally, the cells, exposed to doxorubicin (DOX), an anti-cancer chemotherapy drug, to exert oxidative stress, were treated with hBNs and BA. The results indicate that hBNs decrease the oxidative stress at the concentrations that are nontoxic to cells. The study suggests that hBNs can open new venues for their investigation to reduce or eliminate the adverse effects of toxic drugs used in the treatment of several fatal diseases including neurological disorders and cancer with their slow degradation feature.


Assuntos
Compostos de Boro/farmacologia , Doxorrubicina/efeitos adversos , Hipocampo/embriologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Compostos de Boro/síntese química , Compostos de Boro/química , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Hipocampo/citologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Camundongos , Nanoestruturas , Tamanho da Partícula , Espécies Reativas de Oxigênio/metabolismo
18.
Org Biomol Chem ; 18(5): 912-919, 2020 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-31919486

RESUMO

Cytosine 2'-deoxyribonucleoside dCTBdp and its triphosphate (dCTBdpTP) bearing tetramethylated thiophene-bodipy fluorophore attached at position 5 were designed and synthesized. The green fluorescent nucleoside dCTBdp showed a perfect dependence of fluorescence lifetime on the viscosity. The modified triphosphate dCTBdpTP was substrate to several DNA polymerases and was used for in vitro enzymatic synthesis of labeled oligonucleotides (ONs) or DNA by primer extension. The labeled single-stranded ONs showed a significant decrease in mean fluorescence lifetime when hybridized to the complementary strand of DNA or RNA and were also sensitive to mismatches. The labeled dsDNA sensed protein binding (p53), which resulted in the increase of its fluorescence lifetime. The triphosphate dCTBdpTP was transported to live cells where its interactions could be detected by FLIM but it did not show incorporation to genomic DNA in cellulo.


Assuntos
Compostos de Boro/química , Proteínas de Ligação a DNA/metabolismo , DNA/metabolismo , Hibridização de Ácido Nucleico , Nucleotídeos/química , Sondas de Oligonucleotídeos/metabolismo , Tiofenos/química , Sequência de Bases , Cátions , Linhagem Celular Tumoral , DNA Polimerase Dirigida por DNA/metabolismo , Humanos , Lipídeos/química , Nucleotídeos/síntese química , Ligação Proteica , Solventes/química , Espectrometria de Fluorescência , Temperatura , Viscosidade
19.
Chemistry ; 26(24): 5388-5399, 2020 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31999023

RESUMO

A series of fluorescent boron-dipyrromethene (BODIPY, 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) dyes have been designed to participate, as aglycons, in synthetic oligosaccharide protocols. As such, they served a dual purpose: first, by being incorporated at the beginning of the process (at the reducing-end of the growing saccharide moiety), they can function as fluorescent glycosyl tags, facilitating the detection and purification of the desired glycosidic intermediates, and secondly, the presence of these chromophores on the ensuing compounds grants access to fluorescently labeled saccharides. In this context, a sought-after feature of the fluorescent dyes has been their chemical robustness. Accordingly, some BODIPY derivatives described in this work can withstand the reaction conditions commonly employed in the chemical synthesis of saccharides; namely, glycosylation and protecting-group manipulations. Regarding their photophysical properties, the BODIPY-labeled saccharides obtained in this work display remarkable fluorescence efficiency in water, reaching quantum yield values up to 82 %, as well as notable lasing efficiencies and photostabilities.


Assuntos
Compostos de Boro/química , Boro/química , Corantes Fluorescentes/química , Porfobilinogênio/análogos & derivados , Fluorescência , Glicosilação , Luz , Porfobilinogênio/química
20.
Radiat Res ; 193(3): 249-262, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31910121

RESUMO

More effective boron-containing compounds are needed for use in boron neutron capture therapy (BNCT). Here, borate esters were synthesized by heating and dehydrating nucleotides adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), the nucleoside (inosine) or glycerol in the presence of boric acid (H3BO3). Borate ester products were compared to clinical boron agent boronophenylalanine (BPA) and several other borate esters for neutron-sensitization effects using the A549 cell line. Cells were incubated with boron agent solutions (2.3 mM) for 5 h, then washed, resuspended in fresh media, and irradiated with a neutron dose of 0.33 Sv followed by cell survival assessment using the CCK-8 method. Calculated radiosensitization values (control group cell survival rate/boron agent-treated experimental group cell survival rate) were 3.9 ± 0.2 (ATP borate ester), 2.4 ± 0.1 (BPA), 2.1 ± 0.1 (ADP borate ester), 1.9 ± 0.2 (AMP borate ester), 1.7 ± 0.3 (glycerin borate ester), 1.4 ± 0.1 (inosine borate ester), 1.3 ± 0.3 (triethanolamine borate ester) and 1.3 ± 0.5 (H3BO3). Borate esters derived from nucleotides ATP, ADP or AMP exhibited significantly higher sensitization values than did those derived from glycerol, inosine or triethanolamine. Notably, due to its relatively higher water solubility and degree of tumor cell enrichment, ATP borate ester exhibited the highest sensitization rate overall, significantly exceeding rates obtained for BPA and borate esters of ADP and AMP. Flow cytometric determinations of boron agent-treated cell survival at 24 h postirradiation revealed long-term apoptosis rates of 4.8-6.6 ± 0.2% (nucleotide borate ester groups) and 5.6 ± 0.3% (BPA group) compared to 3.9 ± 0.1% (irradiation control group without boron agent) and 2.6 ± 0.2% (blank control group). Significant differences between experimental and control groups demonstrated that nucleotide borate esters and BPA induced long-term radiosensitization effects. In particular, postirradiation percentages of ATP borate ester-treated cells progressing to DNA replication prophase (G1 phase) increased significantly, while percentages of cells progressing to S phase significantly decreased, demonstrating cellular DNA replication inhibition. Meanwhile, boron content values of tumor tissue, measured using inductively coupled plasma mass spectrometry (ICP-MS) and expressed as tumor-to-normal tissue boron ratios (T/N), were not significantly different between nucleotide borate ester- and BPA-fed groups of tumor-bearing mice. However, tumor tissue boron concentrations of nucleotide borate ester-fed mice (0.81-0.88 ± 0.04 µg/g) significantly exceeded those of BPA-fed mice (0.52 ± 0.05 µg/g) and thus provided greater tumor tissue boron enrichment for achieving a stronger neutron radiation-sensitizing effect. In conclusion, nucleotide borate esters, especially ATP borate ester, exhibited superior neutron radiosensitization effects than did other representative borate ester compounds and significantly greater long-term radiation effects as well. Thus, nucleotide borate esters have several advantages over other borate esters for BNCT and therefore warrant further study.


Assuntos
Compostos de Boro/uso terapêutico , Terapia por Captura de Nêutron de Boro , Nucleotídeos/uso terapêutico , Células A549 , Animais , Compostos de Boro/química , Compostos de Boro/farmacocinética , Ésteres/química , Xenoenxertos , Humanos , Camundongos , Camundongos Nus , Nucleotídeos/química , Radiossensibilizantes/química , Radiossensibilizantes/uso terapêutico , Distribuição Tecidual
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