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1.
Anal Chem ; 96(11): 4570-4579, 2024 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-38441542

RESUMO

Ferroptosis, as a new form of regulated cell death, is implicated in various physiological and pathological processes. Developing a single probe for an independent analysis of multiple analytes related to ferroptosis can provide more accurate information and simplify the detection procedures, but it faces great challenges. In this work, we develop a fluorescent probe for the simultaneous detection of GSH through ratiometric fluorescence response and microviscosity via a fluorescence lifetime model. Based on the reversible Michael addition reaction between GSH and unsaturated C═C bond, the probe responds reversibly to GSH with a ratiometric fluorescence variation and a fast response time (t1/2 = 4.7 s). At the same time, the probe is sensitive to environmental viscosity by changing its fluorescence lifetimes. The probe was applied to monitor the drug-induced ferroptosis process through both the classical Xc-/GSH/GPX4- and DHODH-mediated defense mechanisms. We hope that the probe will provide a useful molecular tool for the real-time live-cell imaging of GSH dynamics, which is benefit to unveiling related physiological and pathological processes.


Assuntos
Ferroptose , Viscosidade , Corantes Fluorescentes/química , Microscopia de Fluorescência/métodos , Imagem Óptica , Glutationa/análise
2.
Angew Chem Int Ed Engl ; : e202413595, 2024 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-39448378

RESUMO

Although Type-I photodynamic therapy has attracted increasingly growing interest due to its reduced dependence on oxygen, the design of effective Type-I photosensitizers remains a challenge. In this work, we report a design strategy for Type-I photosensitizers by the involvement of hydrogen atom transfer (HAT). As a proof of concept, a HAT-involved Type-I PS, which simultaneously generates superoxide and carbon-centered radicals under light-irradiation, was synthesized. This photosensitizer is comprised of a fluorene-substituted BODIPY unit as an electron acceptor covalently linked with a triphenylamine moiety as an electron donor. Under light-irradiation, photo-induced intramolecular electron transfer occurs to generate the BODIPY anion radical and triphenylamine cation radical. The former transfers electrons to oxygen to generate O2-•, while the latter loses a proton to produce a benzyl carbon-centered radical which is well characterized. The resulting carbon-centered radicals efficiently oxidize NADH by HAT reaction. This photosensitizer demonstrates remarkable photocytotoxicity even under hypoxic conditions, along with outstanding in vivo antitumor efficacy in mouse models bearing HeLa tumors. This work offers a novel strategy for the design of Type-I photosensitizers by involvement of HAT.

3.
Angew Chem Int Ed Engl ; 63(12): e202318783, 2024 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-38258371

RESUMO

We herein present an approach of photo-induced disproportionation for preparation of Type-I photodynamic agents. As a proof of concept, BODIPY-based photosensitizers were rationally designed and prepared. The photo-induced intermolecular electron transfer between homotypic chromophores leads to the disproportionation reaction, resulting in the formation of charged intermediates, cationic and anionic radicals. The cationic radicals efficiently oxidize the cellularimportant coenzyme, tetrahydrobiopterin (BH4 ), and the anionic radicals transfer electrons to oxygen to produce superoxide radicals (O2 - ⋅). One of our Type-I photodynamic agents not only self-assembles in water but also effectively targets the endoplasmic reticulum. It displayed excellent photocytotoxicity even in highly hypoxic environments (2 % O2 ), with a half-maximal inhibitory concentration (IC50 ) of 0.96 µM, and demonstrated outstanding antitumor efficacy in murine models bearing HeLa tumors.


Assuntos
Biopterinas/análogos & derivados , Fotoquimioterapia , Superóxidos , Camundongos , Animais , Fármacos Fotossensibilizantes/farmacologia , Espécies Reativas de Oxigênio , Oxigênio
4.
Angew Chem Int Ed Engl ; 63(8): e202318856, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38169084

RESUMO

Chirality, with its intrinsic symmetry-breaking feature, is frequently utilized in the creation of acentric crystalline functional materials that exhibit intriguing optoelectronic properties. On the other hand, the development of chiral crystals from achiral molecules offers a solution that bypasses the need for enantiopure motifs, presenting a promising alternative and thereby expanding the possibilities of the self-assembly toolkit. Nevertheless, the rational design of achiral molecules that prefer spontaneous symmetry breaking during crystallization has so far been obscure. In this study, we present a series of six achiral molecules, demonstrating that when these conformationally flexible molecules adopt a cis-conformation and engage in multiple non-covalent interactions along a helical path, they collectively self-assemble into chiral superstructures consisting of single-handed supramolecular columns. When these homochiral supramolecular columns align in parallel, they form polar crystals that exhibit intense luminescence upon grinding or scraping. We therefore demonstrate our molecular design strategy could significantly increase the likelihood of symmetry breaking in achiral molecular synthons during self-assembly, offering a facile access to novel chiral crystalline materials with unique optoelectronic properties.

5.
Angew Chem Int Ed Engl ; 63(42): e202407135, 2024 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-39018249

RESUMO

Herein we report on circularly polarized luminescence (CPL) emission originating from supramolecular chirality of organic microcrystals with a |glum| value up to 0.11. The microcrystals were prepared from highly emissive difluoroboron ß-diketonate (BF2dbk) dyes R-1 or S-1 with chiral binaphthol (BINOL) skeletons. R-1 and S-1 exhibit undetectable CPL signals in solution but manifest intense CPL emission in their chiral microcrystals. The chiral superstructures induced by BINOL skeletons were confirmed by single-crystal XRD analysis. Spectral analysis and theoretical calculations indicate that intermolecular electronic coupling, mediated by the asymmetric stacking in the chiral superstructures, effectively alters excited-state electronic structures and facilitates electron transitions perpendicular to BF2bdk planes. The coupling increases cosθµ,m from 0.05 (monomer) to 0.86 (tetramer) and triggers intense optical activity of BF2bdk. The results demonstrate that optical activity of chromophores within assemblies can be regulated by both orientation and extent of intermolecular electronic couplings.

6.
J Am Chem Soc ; 2023 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-36779824

RESUMO

The highly oxygen-dependent nature of photodynamic therapy (PDT) limits its therapeutic efficacy against hypoxic solid tumors in clinics, which is an urgent problem to be solved. Herein, we develop an oxygen-independent supramolecular photodynamic agent that produces hydroxyl radical (•OH) by oxidizing water in the presence of intracellularly abundant pyruvic acid under oxygen-free conditions. A fluorene-substituted BODIPY was designed as the electron donor and coassembled with perylene diimide as the electron acceptor to form the quadruple hydrogen-bonded supramolecular photodynamic agent. Detailed mechanism studies reveal that intermolecular electron transfer and charge separation upon light irradiation result in an efficient generation of radical ion pairs. Under oxygen-free conditions, the cationic radicals directly oxidize water to generate highly cytotoxic •OH, and the anionic radicals transfer electrons to pyruvic acid, realizing the catalytic cycle. Thus, this photodynamic agent exhibited superb photocytotoxicity even under severe hypoxic environments and excellent in vivo antitumor efficacy on HeLa-bearing mouse models. This work provides a strategy for constructing oxygen-independent photodynamic agents, which opens up an avenue for effective PDT against hypoxic tumors.

7.
Angew Chem Int Ed Engl ; 62(2): e202214211, 2023 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-36374590

RESUMO

Without external chiral intervention, it is a challenge to form homochirality from achiral molecules with conformational flexibility. We here report on a rational strategy that uses multivalent noncovalent interactions to clamp the molecular conformations of achiral D-A molecules. These interactions overcome the otherwise dominant dipole-dipole interactions and thus disfavor their symmetric antiparallel stacking. It in turn facilitates parallel packing, leading to spontaneous symmetry breaking during crystallization and thus the formation of homochiral conglomerates. When this emergent homochirality is coupled with optical gain characteristics of the molecules, the homochiral crystals are explored as excellent circularly polarized micro-lasers with low lasing threshold (16.4 µJ cm-2 ) and high dissymmetry factor glum (0.9). This study therefore provides a facile design strategy for supramolecular chiral materials and active laser ones without the necessity of intrinsic chiral element.


Assuntos
Bandagens , Lasers , Cristalização , Conformação Molecular
8.
Anal Chem ; 93(8): 3922-3928, 2021 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-33586972

RESUMO

Clarifying the signaling pathway associated with nitric oxide (NO) and glutathione (GSH) in cardiovascular disease therapy is important for understanding its physiological and pathological processes but is challenging due to the lack of efficient analytical techniques. Herein, we report a BODIPY-based fluorescent probe for recognition of NO and GSH in sequence with high sensitivity and selectivity. The probe exhibits turn-on fluorescence triggered by NO, followed by red-shifted emission in the presence of GSH. The sequentially activated mechanism allows the visualization of NO-induced GSH upregulation in drug-treated endothelial cells and zebrafish for the first time, revealing a signal pathway during the therapy. We hope that it can be used as a convenient and efficient tool for the study of the interplay between NO and GSH and for the screening of effective drugs for cardiovascular disease therapy.


Assuntos
Doenças Cardiovasculares , Corantes Fluorescentes , Animais , Doenças Cardiovasculares/tratamento farmacológico , Células Endoteliais , Glutationa , Células HeLa , Humanos , Óxido Nítrico , Transdução de Sinais , Peixe-Zebra
9.
Angew Chem Int Ed Engl ; 60(36): 19912-19920, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34227724

RESUMO

Developing Type-I photosensitizers is considered as an efficient approach to overcome the deficiency of traditional photodynamic therapy (PDT) for hypoxic tumors. However, it remains a challenge to design photosensitizers for generating reactive oxygen species by the Type-I process. Herein, we report a series of α,ß-linked BODIPY dimers and a trimer that exclusively generate superoxide radical (O2-. ) by the Type-I process upon light irradiation. The triplet formation originates from an effective excited-state relaxation from the initially populated singlet (S1 ) to triplet (T1 ) states via an intermediate triplet (T2 ) state. The low reduction potential and ultralong lifetime of the T1 state facilitate the efficient generation of O2-. by inter-molecular charge transfer to molecular oxygen. The energy gap of T1 -S0 is smaller than that between 3 O2 and 1 O2 thereby precluding the generation of singlet oxygen by the Type-II process. The trimer exhibits superior PDT performance under the hypoxic environment.


Assuntos
Compostos de Boro/metabolismo , Neoplasias/metabolismo , Fotoquimioterapia , Fármacos Fotossensibilizantes/metabolismo , Oxigênio Singlete/metabolismo , Superóxidos/metabolismo , Compostos de Boro/química , Compostos de Boro/uso terapêutico , Humanos , Luz , Estrutura Molecular , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico , Oxigênio Singlete/química , Superóxidos/química
10.
Anal Chem ; 92(15): 10800-10806, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32605361

RESUMO

Biothiols and SO2 derivatives, as essential reactive sulfur species (RSS), play vital roles in various physiological processes and have a close network of generation and metabolic pathways among them. To clarify their complex correlations, fluorescent probes to simultaneously detect GSH, Cys, and SO2 derivatives are highly desirable. Herein, we develop the first fluorescent probe (BO-HEM) to simultaneously discriminate GSH, Cys, and SO2 derivatives. The fluorescent probe is designed by integration of hemicyanine and BODIPY fluorophores through an ether bond. The ether bond of the probe is rapidly replaced by thiolates through nucleophilic aromatic substitution (SNAr) to generate hemicyanine with NIR fluorescence and sulfur-BODIPY. The amino groups of Cys but not GSH then further replace the thiolate to form amino-BODIPY. As for SO32-, nucleophilic addition to the double bond of BO-HEM generates adduct O-BODIPY with green fluorescence. To further improve the sensing performance, the nanoprobe with increased reactivity and biocompatibility is constructed by encapsulation of BO-HEM into the polymeric micelle. More importantly, by taking advantage of the hydrophilicity of the reaction products, the spectral discrimination was further enhanced to avoid signal interference. The nanoprobe is applied to discriminate biothiols and SO2 derivatives in living cells through three-color fluorescence imaging.


Assuntos
Cisteína/análise , Cisteína/química , Corantes Fluorescentes/química , Glutationa/análise , Glutationa/química , Dióxido de Enxofre/análise , Dióxido de Enxofre/química , Compostos de Boro/química , Células Hep G2 , Humanos , Compostos de Sulfidrila/química , Fatores de Tempo
11.
J Phys Chem A ; 124(48): 10082-10089, 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33226240

RESUMO

We report several novel thermometers resulting from the temperature-induced aggregation of difluoroboron ß-diketonate chromophores. These thermometers exhibit a much wider temperature-dependent fluorescence emission from 445 to 592 nm along with the color change from blue to red in a dilute chloroform solution. Spectroscopy measurements and theoretical calculations confirm that the thermochromic luminescence originates from the reversible change in the noncovalent intermolecular interactions and the abrupt volume shrinkage of the solvent at its melting point. The present work provides a new strategy for rationally designing high-performance thermometers having a wide emission property.

12.
Angew Chem Int Ed Engl ; 59(25): 10032-10036, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32043718

RESUMO

An organic crystal of 4,4'-bis(N-carbazolyl)-1,1'-biphenyl (pCBP) exhibits time-dependent afterglow color from blue to orange over 1 s. Both experimental and computational data confirm that the color evolution results from well-separated, long-persistent thermally activated delayed fluorescence (TADF) and room-temperature phosphorescence (RTP) with different but comparable decay rates. TADF is enabled by a small S1 -T1 energy gap of 0.7 kcal mol-1 . The good separation of TADF and RTP is due to a 11.8 kcal mol-1 difference in the S0 energies of the S1 and T1 structures, indicating that apart from the excited-state properties, tuning the ground state is also important for luminescence properties. This afterglow color evolution of pCBP allows its applications in anticounterfeiting and data encryption with high security levels.

13.
J Am Chem Soc ; 141(12): 5045-5050, 2019 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-30827093

RESUMO

Pure organic room temperature phosphorescence (RTP) has unique advantages and various potential applications. However, it is challengeable to achieve organic RTP under visible and near-infrared (NIR)-light excitation, especially in aqueous solution. Herein we assemble difluoroboron ß-diketonate compounds to form organic nanoparticles (NPs) in water. The resulting NPs are able to show efficient RTP, effective uptake, and bright imaging of HeLa cells under both visible- and NIR-light excitation. More strikingly, spectroscopic study, single-crystal X-ray diffraction, and DFT calculation reveal that the efficient RTP in organic NPs is originated from dimers in their excited states. The multiple interactions and intermolecular charge transfer in the dimer structures are of significance in promoting the production of dimer triplet excited states and suppressing the nonradiative decays to boost the RTP under visible- and NIR-light irradiation in water.

14.
Anal Chem ; 91(7): 4301-4306, 2019 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-30829471

RESUMO

Nitric oxide (NO) and glutathione (GSH) have interplaying roles in oxidant-antioxidant balance. In this work, we developed the first example of a single fluorescent probe that displayed a turn-on fluorescence response toward NO and GSH from dual emission channels. The probe was synthesized by introducing 4-amino-3-(methylamino)-phenol to a BODIPY scaffold. Specifically, the NO-mediated transformation of diamine into a triazole triggered the fluorescence in the green channel, and the GSH-induced SNAr substitution reaction led to the red-shifted emission in the red channel. The probe was successfully applied to detect the exogenous and endogenous NO and GSH in macrophage cells. More importantly, the probe revealed that NO induced by interferon-γ (IFN-γ), lipopolysaccharide (LPS), and l-arginine (l-Arg) could also elicit the augmentation of intracellular GSH. We anticipate the probe would hold great potential for investigating the redox balance in biological processes.


Assuntos
Compostos de Boro/química , Corantes Fluorescentes/química , Glutationa/análise , Óxido Nítrico/análise , Fenilenodiaminas/química , Animais , Arginina/farmacologia , Compostos de Boro/toxicidade , Teoria da Densidade Funcional , Corantes Fluorescentes/toxicidade , Glutationa/metabolismo , Interferon gama/farmacologia , Limite de Detecção , Lipopolissacarídeos/farmacologia , Camundongos , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Modelos Químicos , Óxido Nítrico/metabolismo , Fenilenodiaminas/toxicidade , Células RAW 264.7
15.
Angew Chem Int Ed Engl ; 58(46): 16480-16484, 2019 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-31584750

RESUMO

Electrochemical sensors are essential for point-of-care testing (POCT) and wearable sensing devices. Establishing an efficient electron transfer route between redox enzymes and electrodes is key for converting enzyme-catalyzed reactions into electrochemical signals, and for the development of robust, sensitive, and selective biosensors. We demonstrate that the site-specific incorporation of a novel synthetic amino acid (2-amino-3-(4-mercaptophenyl)propanoic acid) into redox enzymes, followed by an S-click reaction to wire the enzyme to the electrode, facilitates electron transfer. The fabricated biosensor demonstrated real-time and selective monitoring of tryptophan (Trp) in blood and sweat samples, with a linear range of 0.02-0.8 mm. Further developments along this route may result in dramatic expansion of portable electrochemical sensors for diverse health-determination molecules.


Assuntos
Oxirredutases/metabolismo , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas , Eletrodos , Transporte de Elétrons , Células HeLa , Humanos , Oxirredutases/química , Sistemas Automatizados de Assistência Junto ao Leito , Suor/metabolismo , Triptofano/análise , Triptofano/sangue , Triptofano Oxigenase/química , Triptofano Oxigenase/metabolismo , Dispositivos Eletrônicos Vestíveis
16.
Chemistry ; 24(51): 13549-13555, 2018 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-29952087

RESUMO

The first example of the synthesis of mono-N,O-B-chelated dipyrromethene (BODIPY) derivatives through an unexpected intramolecular nucleophilic displacement of the fluorine by alkenols in the presence of boron trifluoride as Lewis acid is reported. The chlorine in the indacene core allowed for further structural modifications through nucleophilic substitutions or palladium-catalysed coupling reactions to afford new fluorophores with tuneable photophysical properties. Their expanded conjugation structure resulted in distinct red-shifted absorption and emission spectra in organic solutions. Furthermore, the twisted steric hindrance of the benzene substitution patterns suppressed aggregation-induced quenching, leading to an enhanced NIR emission in the aggregate/solid state, which was rarely observed for BODIPY dyes. Nanoparticles of the fluorophores formed by the assembly with the polymeric surfactant F127 were successfully used for bioimaging of living cells and for tumour-targeted imaging in a tumour-bearing mouse model.

17.
Chemphyschem ; 19(17): 2131-2133, 2018 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-29797758

RESUMO

It is urgent to develop a universal strategy for producing small organic molecules exhibiting efficient room temperature phosphorescence (RTP). An important contribution made by Ma and Tian et al. provides a general and applicable strategy to obtain amorphous organic molecules with efficient RTP emission by simply modifying phosphors onto ß-cyclodextrin (ß-CD). The nonradiative decay processes and oxygen quenching have been significantly suppressed by the strong intermolecular hydrogen bonding between ß-CD derivatives. Furthermore, the cavity of ß-CDs endows them with the ability to incorporate the adamantane moiety of the fluorescent guest molecules to construct a supramolecular system which exhibits excellent RTP-fluorescence dual emission properties and multicolor emission by altering the host to guest ratio and the excitation wavelength.

18.
Org Biomol Chem ; 15(5): 1072-1075, 2017 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-28059419

RESUMO

We report a fluorescent probe for the selective detection of mitochondrial glutathione (GSH). The probe, containing triphenylphosphine as a mitochondrial targeting group, exhibited ratiometric and selective detection of GSH over Cys/Hcy. The probe was used for imaging mitochondrial GSH in living HeLa cells.


Assuntos
Corantes Fluorescentes/química , Glutationa/análise , Mitocôndrias/química , Corantes Fluorescentes/análise , Corantes Fluorescentes/síntese química , Células HeLa , Humanos , Estrutura Molecular
19.
Proc Natl Acad Sci U S A ; 111(24): 8717-22, 2014 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-24889610

RESUMO

Control over structural transformations in supramolecular entities by external stimuli is critical for the development of adaptable and functional soft materials. Herein, we have designed and synthesized a dipyridyl donor containing a central Z-configured stiff-stilbene unit that self-assembles in the presence of two 180° di-Pt(II) acceptors to produce size-controllable discrete organoplatinum(II) metallacycles with high efficiency by means of the directional-bonding approach. These discrete metallacycles undergo transformation into extended metallosupramolecular polymers upon the conformational switching of the dipyridyl ligand from Z-configured (0°) to E-configured (180°) when photoirradiated. This transformation is accompanied by interesting morphological changes at nanoscopic length scales. The discrete metallacycles aggregate to spherical nanoparticles that evolve into long nanofibers upon polymer formation. These fibers can be reversibly converted to cyclic oligomers by changing the wavelength of irradiation, which reintroduces Z-configured building blocks owing to the reversible nature of stiff-stilbene photoisomerization. The design strategy defined here represents a novel self-assembly pathway to deliver advanced supramolecular assemblies by means of photocontrol.


Assuntos
Metais/química , Polímeros/química , Estilbenos/química , Biomimética , Ligantes , Luz , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Teste de Materiais , Microscopia Eletrônica de Transmissão , Processos Fotoquímicos , Fótons , Solventes/química , Temperatura
20.
Chemistry ; 22(50): 18132-18139, 2016 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-27791294

RESUMO

A platinum(II) bipyridyl complex bearing bis-ureidopyrimidinone (Pt-bisUPy) has been designed and its self-assembling behavior has been thoroughly investigated by 1 H NMR, DOSY NMR, Ubbelohde viscometry analysis, UV/Vis, and emission spectroscopies. Pt-bisUPy underwent concentration-dependent ring-chain polymerization in apolar solvents. Hydrogen-bonding interactions play an important role during the formation of the supramolecular polymers. Hydrogen-bonded supramolecular polymers were transformed to nanoparticles in water through the miniemulsion method. These nanoparticles showed strong π-π excimeric emission. Metal-metal-to-ligand charge transfer (MMLCT) from Pt-Pt interactions was not significant in the emission spectrum. The phosphorescence of the nanoparticle persisted even under aerobic conditions. The triplet state of these phosphorescent nanomaterials were long-lived and possessed moderate emission quantum yields. Furthermore, the low toxicity of these materials promises a place for them in in vitro and in vivo bioimaging.

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