RESUMO
Organohalides are widespread pollutants that pose significant environmental hazards due to their high degree of halogenation and elevated redox potentials, making them resistant to natural attenuation. Traditional bioremediation approaches, primarily relying on bioaugmentation and biostimulation, often fall short of achieving complete detoxification. Furthermore, the emergence of complex halogenated pollutants, such as per- and polyfluoroalkyl substances (PFASs), further complicates remediation efforts. Therefore, there is a pressing need to reconsider novel approaches for more efficient remediation of these recalcitrant pollutants. This review proposes novel redox-potential-mediated hybrid bioprocesses, tailored to the physicochemical properties of pollutants and their environmental contexts, to achieve complete detoxification of organohalides. The possible scenarios for the proposed bioremediation approaches are further discussed. In anaerobic environments, such as sediment and groundwater, microbial reductive dehalogenation coupled with fermentation and methanogenesis can convert organohalides into carbon dioxide and methane. In environments with anaerobic-aerobic alternation, such as paddy soil and wetlands, a synergistic process involving reduction and oxidation can facilitate the complete mineralization of highly halogenated organic compounds. Future research should focus on in-depth exploration of microbial consortia, the application of ecological principles-guided strategies, and the development of bioinspired-designed techniques. This paper contributes to the academic discourse by proposing innovative remediation strategies tailored to the complexities of organohalide pollution.
Assuntos
Biodegradação Ambiental , Oxirredução , Poluentes Ambientais/metabolismo , Hidrocarbonetos Halogenados/metabolismo , Hidrocarbonetos Halogenados/química , Anaerobiose , Metano/metabolismo , Halogenação , Bactérias/metabolismo , Bactérias/genéticaRESUMO
New derivatives of tropane scaffold were prepared from the reaction of their thione or thioamide derivatives with α-halocarbonyl compounds. The structures of all new derivatives were assured and proved with their spectral data. The novel tropane derivatives were examined for their cytotoxicity on two colon tumor cell lines; Caco2 and HCT116 cells. The most active compounds 3, 4, 5, 9d and 14a displayed significant antitumor activities with IC50 range of 9.50 - 30.15 µM compared to doxorubicin. Moreover, they revealed reduced cytotoxic effect on WI-38 normal ones, signifying their great safety. With the aim of better understanding the inhibitory potential of such compounds on heat-shock protein 90 (Hsp90), there activities were assessed against such enzyme demonstrating high inhibitory activities with IC50 range of 56.58-78.85 nM. Western blotting was carried out to ensure the inhibitory activity on Hsp90, results showed that 3 markedly suppressed Hsp90 expression on Caco2 cell line. Additionally, a molecular docking analysis of the most potent derivatives at the Hsp90 binding site was carried out in order to approve the performed in vitro assays.
Assuntos
Antineoplásicos , Neoplasias do Colo , Ensaios de Seleção de Medicamentos Antitumorais , Proteínas de Choque Térmico HSP90 , Simulação de Acoplamento Molecular , Tropanos , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Neoplasias do Colo/metabolismo , Relação Dose-Resposta a Droga , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Proteínas de Choque Térmico HSP90/metabolismo , Estrutura Molecular , Relação Estrutura-Atividade , Tropanos/farmacologia , Tropanos/química , Tropanos/síntese química , Hidrocarbonetos Halogenados/química , Hidrocarbonetos Halogenados/farmacologiaRESUMO
The discovery of naturally occurring organohalogen compounds has increased astronomically in the 55 years since they were first discoveredâfrom fewer than 50 in 1968 to a combined 7,958 described examples in three comprehensive reviews. The present survey, which covers the period 2021-2023, brings the number of known natural organohalogens to approximately 8,400. The organization is according to species origin, and coverage includes marine and terrestrial plants, fungi, bacteria, marine sponges, corals, cyanobacteria, tunicates, and other marine organisms.
Assuntos
Cianobactérias , Estrutura Molecular , Animais , Cianobactérias/química , Poríferos/química , Produtos Biológicos/química , Bactérias , Fungos/química , Antozoários/química , Urocordados/química , Plantas/química , Hidrocarbonetos Halogenados/química , Organismos AquáticosRESUMO
Novel 2-arylmethoxy-4-(2,2'-dihalogen-substituted biphenyl-3-ylmethoxy) benzylamine derivatives were designed, synthesized, and evaluated in vitro and in vivo against cancers as PD-1/PD-L1 inhibitors. Through the computer-aided structural optimization and the homogeneous time-resolved fluorescence (HTRF) assay, compound A56 was found to most strongly block the PD-1/PD-L1 interaction with an IC50 value of 2.4 ± 0.8 nM and showed the most potent activity. 1H NMR titration results indicated that A56 can tightly bind to the PD-L1 protein with KD < 1 µM. The X-ray diffraction data for the cocrystal structure of the A56/PD-L1 complex (3.5 Å) deciphered a novel binding mode in detail, which can account for its most potent inhibitory activity. Cell-based assays further demonstrated the strong ability of A56 as an hPD-1/hPD-L1 blocker. Especially in an hPD-L1 MC38 humanized mouse model, A56 significantly inhibited tumor growth without obvious toxicity, with a TGI rate of 55.20% (50 mg/kg, i.g.). In conclusion, A56 is a promising clinical candidate worthy of further development.
Assuntos
Inibidores de Checkpoint Imunológico , Neoplasias , Animais , Camundongos , Antígeno B7-H1 , Benzilaminas/farmacologia , Receptor de Morte Celular Programada 1/metabolismo , Hidrocarbonetos Halogenados/química , Hidrocarbonetos Halogenados/farmacologiaRESUMO
The reactivities of halido[1,3-diethyl-4,5-diphenyl-1H-imidazol-2-ylidene]gold(I) (chlorido (5), bromido (6), iodido (7)), bis[1,3-diethyl-4,5-diphenyl-1H-imidazol-2-ylidene]gold(I) (8), and bis[1,3-diethyl-4,5-diphenyl-1H-imidazol-2-ylidene]dihalidogold(III) (chlorido (9), bromido (10), iodido (11)) complexes against ingredients of the cell culture medium were analyzed by HPLC. The degradation in the RPMI 1640 medium was studied, too. Complex 6 quantitatively reacted with chloride to 5, while 7 showed additionally ligand scrambling to 8. Interactions with non-thiol containing amino acids could not be detected. However, glutathione (GSH) reacted immediately with 5 and 6 yielding the (NHC)gold(I)-GSH complex 12. The most active complex 8 was stable under in vitro conditions and strongly participated on the biological effects of 7. The gold(III) species 9-11 were completely reduced by GSH to 8 and are prodrugs. All complexes were tested for inhibitory effects in Cisplatin-resistant cells, as well as against cancer stem cell-enriched cell lines and showed excellent activity. Such compounds are of utmost interest for the therapy of drug-resistant tumors.
Assuntos
Antineoplásicos , Neoplasias , Antineoplásicos/farmacologia , Antineoplásicos/química , Compostos de Bifenilo , Técnicas de Cultura de Células , Ouro/química , Hidrocarbonetos Halogenados/químicaRESUMO
Halogenated organic pollutants are often found in wastewater effluent although it has been usually treated by advanced oxidation processes. Atomic hydrogen (H*)-mediated electrocatalytic dehalogenation, with an outperformed performance for breaking the strong carbon-halogen bonds, is of increasing significance for the efficient removal of halogenated organic compounds from water and wastewater. This review consolidates the recent advances in the electrocatalytic hydro-dehalogenation of toxic halogenated organic pollutants from contaminated water. The effect of the molecular structure (e.g., the number and type of halogens, electron-donating or electron-withdrawing groups) on dehalogenation reactivity is firstly predicted, revealing the nucleophilic properties of the existing halogenated organic pollutants. The specific contribution of the direct electron transfer and atomic hydrogen (H*)-mediated indirect electron transfer to dehalogenation efficiency has been established, aiming to better understand the dehalogenation mechanisms. The analyses of entropy and enthalpy illustrate that low pH has a lower energy barrier than that of high pH, facilitating the transformation from proton to H*. Furthermore, the quantitative relationship between dehalogenation efficiency and energy consumption shows an exponential increase of energy consumption for dehalogenation efficiency increasing from 90% to 100%. Lastly, challenges and perspectives are discussed for efficient dehalogenation and practical applications.
Assuntos
Poluentes Ambientais , Hidrocarbonetos Halogenados , Poluentes Químicos da Água , Águas Residuárias , Halogênios/química , Água , Hidrogênio , Poluentes Químicos da Água/análise , Hidrocarbonetos Halogenados/químicaRESUMO
Biocatalytic alkylation reactions can be performed with high chemo-, regio- and stereoselectivity using S-adenosyl-l-methionine (SAM)-dependent methyltransferases (MTs) and SAM analogs. Currently, however, this methodology is limited in application due to the rather laborious protocols to access SAM analogs. It has recently been shown that halide methyltransferases (HMTs) enable synthesis and recycling of SAM analogs with readily available haloalkanes as starting material. Here we expand this work by using substrate profiling of the anion MT enzyme family to explore promiscuous SAM analog synthesis. Our study shows that anion MTs are in general very promiscuous with respect to the alkyl chain as well as the halide leaving group. Substrate profiling further suggests that promiscuous anion MTs cluster in sequence space. Next to iodoalkanes, cheaper, less toxic, and more available bromoalkanes have been converted and several haloalkanes bearing short alkyl groups, alkyl rings, and functional groups such as alkene, alkyne and aromatic moieties are accepted as substrates. Further, we applied the SAM analogs as electrophiles in enzyme-catalyzed regioselective pyrazole allylation with 3-bromopropene as starting material.
Assuntos
Hidrocarbonetos Halogenados/metabolismo , Metiltransferases/metabolismo , S-Adenosilmetionina/metabolismo , Ânions/metabolismo , Biocatálise , Hidrocarbonetos Halogenados/química , Modelos Moleculares , Estrutura Molecular , S-Adenosilmetionina/química , Especificidade por SubstratoRESUMO
Antimicrobial resistance is one of the current public health challenges to be solved. The World Health Organization (WHO) has urgently called for the development of strategies to expand the increasingly limited antimicrobial arsenal. The development of anti-virulence therapies is a viable option to counteract bacterial infections with the possibility of reducing the generation of resistance. Here we report on the chemical structures of pyrrolidones DEXT 1-4 (previously identified as furan derivatives) and their anti-virulence activity on Pseudomonas aeruginosa strains. DEXT 1-4 were shown to inhibit biofilm formation, swarming motility, and secretion of ExoU and ExoT effector proteins. Also, the anti-pathogenic property of DEXT-3 alone or in combination with furanone C-30 (quorum sensing inhibitor) or MBX-1641 (type III secretion system inhibitor) was analyzed in a model of necrosis induced by P. aeruginosa PA14. All treatments reduced necrosis; however, only the combination of C-30 50 µM with DEXT-3 100 µM showed significant inhibition of bacterial growth in the inoculation area and systemic dispersion. In conclusion, pyrrolidones DEXT 1-4 are chemical structures capable of reducing the pathogenicity of P. aeruginosa and with the potential for the development of anti-virulence combination therapies.
Assuntos
Antibacterianos , Furanos , Hidrocarbonetos Halogenados , Infecções por Pseudomonas , Pseudomonas aeruginosa , Pirrolidinonas , Sistemas de Secreção Tipo III/antagonistas & inibidores , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Furanos/química , Furanos/farmacologia , Humanos , Hidrocarbonetos Halogenados/química , Hidrocarbonetos Halogenados/farmacologia , Camundongos , Necrose , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/metabolismo , Pseudomonas aeruginosa/crescimento & desenvolvimento , Pseudomonas aeruginosa/patogenicidade , Pirrolidinonas/química , Pirrolidinonas/farmacologia , Percepção de Quorum/efeitos dos fármacos , Sistemas de Secreção Tipo III/metabolismo , Fatores de Virulência/metabolismoRESUMO
The halogen elimination of 1,2-diiodoethane (C2H4I2) and 1,2-diiodotetrafluoroethane (C2F4I2) serves as a model reaction for investigating the influence of fluorination on reaction dynamics and solute-solvent interactions in solution-phase reactions. While the kinetics and reaction pathways of the halogen elimination reaction of C2H4I2 were reported to vary substantially depending on the solvent, the solvent effects on the photodissociation of C2F4I2 remain to be explored, as its reaction dynamics have only been studied in methanol. Here, to investigate the solvent dependence, we conducted a time-resolved X-ray liquidography (TRXL) experiment on C2F4I2 in cyclohexane. The data revealed that (â °) the solvent dependence of the photoreaction of C2F4I2 is not as strong as that observed for C2H4I2, and (â ±) the nongeminate recombination leading to the formation of I2 is slower in cyclohexane than in methanol. We also show that the molecular structures of the relevant species determined from the structural analysis of TRXL data provide an excellent benchmark for DFT calculations, especially for investigating the relevance of exchange-correlation functionals used for the structural optimization of haloalkanes. This study demonstrates that TRXL is a powerful technique to study solvent dependence in the solution phase.
Assuntos
Cicloexanos/química , Hidrocarbonetos Halogenados/química , Soluções/química , Termodinâmica , Halogênios/química , Cinética , Metanol/química , Estrutura Molecular , Radiografia , Solventes/química , Difração de Raios XRESUMO
The recent success of nickel catalysts in stereoconvergent cross-coupling and cross-electrophile coupling reactions partly stems from the ability of monovalent nickel species to activate C(sp3) electrophiles and generate radical intermediates. This electroanalytical study of the commonly applied (bpy)Ni catalyst elucidates the mechanism of this critical step. Data rule out outer-sphere electron transfer and two-electron oxidative addition pathways. The linear free energy relationship between rates and the bond-dissociation free energies, the electronic and steric effects of the nickel complexes and the electrophiles, and DFT calculations support a variant of the halogen-atom abstraction pathway, the inner-sphere electron transfer concerted with halogen-atom dissociation. This mechanism accounts for the observed reactivity of different electrophiles in cross-coupling reactions and provides a mechanistic rationale for the chemoselectivity obtained in cross-electrophile coupling over homocoupling.
Assuntos
Complexos de Coordenação/química , Radicais Livres/química , Hidrocarbonetos Halogenados/química , Níquel/química , 2,2'-Dipiridil/análogos & derivados , Catálise , Teoria da Densidade Funcional , Técnicas Eletroquímicas , Modelos Químicos , TermodinâmicaRESUMO
Small organic photothermal agents (SOPTAs) that absorb in the second near-infrared (NIR-II, 1000-1700â nm) window are highly desirable in photothermal therapy for their good biocompatibility and deeper tissue penetration. However, the design of NIR-II absorbing SOPTAs remains a great challenge. Herein, we report that molecular engineering of BF2 complex via strengthening the donor-acceptor conjugation and increasing the intramolecular motions is an efficient strategy to achieve NIR-II absorbing SOPTAs with high photothermal performance. Based on this strategy, a BF2 complex, BAF4, was designed and synthesized. BAF4 exhibits an intense absorption maximum at 1000â nm and negligible fluorescence. Notably, the nanoparticles of BAF4 achieve a high photothermal conversion efficiency value of 80 % under 1064â nm laser irradiation (0.75â W cm-2 ). In vitro and in vivo studies reveal the great potential of BAF4 nanoparticles in photoacoustic imaging-guided photothermal therapy in the NIR-II window.
Assuntos
Antineoplásicos/farmacologia , Corantes Fluorescentes/farmacologia , Hidrocarbonetos Halogenados/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Terapia Fototérmica , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Corantes Fluorescentes/química , Humanos , Hidrocarbonetos Halogenados/química , Raios Infravermelhos , Camundongos , Estrutura Molecular , Fármacos Fotossensibilizantes/químicaRESUMO
The development of non-natural reaction mechanisms is an attractive strategy for expanding the synthetic capabilities of substrate promiscuous enzymes. Here, we report an "ene"-reductase catalyzed asymmetric hydroalkylation of olefins using α-bromoketones as radical precursors. Radical initiation occurs via ground-state electron transfer from the flavin cofactor located within the enzyme active site, an underrepresented mechanism in flavin biocatalysis. Four rounds of site saturation mutagenesis were used to access a variant of the "ene"-reductase nicotinamide-dependent cyclohexanone reductase (NCR) from Zymomonas mobiles capable of catalyzing a cyclization to furnish ß-chiral cyclopentanones with high levels of enantioselectivity. Additionally, wild-type NCR can catalyze intermolecular couplings with precise stereochemical control over the radical termination step. This report highlights the utility for ground-state electron transfers to enable non-natural biocatalytic C-C bond forming reactions.
Assuntos
Ciclopentanos/síntese química , Elétrons , Cetonas/síntese química , Oxirredutases/química , Alcenos/química , Alquilação , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Biocatálise , Ciclização , Dinitrocresóis/química , Evolução Molecular Direcionada , Hidrocarbonetos Halogenados/química , Mutação , Oxirredutases/genética , Engenharia de Proteínas , Estereoisomerismo , Zymomonas/enzimologiaRESUMO
Heme, a biomolecule with complex structure and unique properties and strong adsorption of oxygen, is utilized as an adsorbing material for haloalkene gas molecules. It has been systematically investigated employing density functional theory. Among the haloalkene gases chosen in the present study, the interaction energy is maximum for CDFM (-10.66 kcal/mol) and lowest for TFM (-5.02 kcal/mol). The calculated bond stabilization energy for heme-haloalkene complexes correlates with findings of interaction energy. The noncovalent interaction between heme and haloalkenes is confirmed from the topological analysis. The energy gap values decrease on adsorption of haloalkenes along with a decrease in reactivity of the complexes.
Assuntos
Heme/química , Hidrocarbonetos Halogenados/química , Modelos Moleculares , Adsorção , Teoria da Densidade Funcional , TermodinâmicaRESUMO
Devising artificial photoenzymes for abiological bond-forming reactions is of high synthetic value but also a tremendous challenge. Disclosed herein is the first photobiocatalytic cross-coupling of aryl halides enabled by a designer artificial dehalogenase, which features a genetically encoded benzophenone chromophore and site-specifically modified synthetic NiII(bpy) cofactor with tunable proximity to streamline the dual catalysis. Transient absorption studies suggest the likelihood of energy transfer activation in the elementary organometallic event. This design strategy is viable to significantly expand the catalytic repertoire of artificial photoenzymes for useful organic transformations.
Assuntos
Engenharia Genética , Hidrocarbonetos Halogenados/metabolismo , Hidrolases/metabolismo , Fármacos Fotossensibilizantes/metabolismo , Biocatálise , Hidrocarbonetos Halogenados/química , Hidrolases/química , Modelos Moleculares , Estrutura Molecular , Fármacos Fotossensibilizantes/químicaRESUMO
Marine fungi produce many halogenated metabolites with a variety of structures, from acyclic entities with a simple linear chain to multifaceted polycyclic molecules. Over the past few decades, their pharmaceutical and medical application have been explored and still the door is kept open due to the need of new drugs from relatively underexplored sources. Biological properties of halogenated compounds such as anticancer, antiviral, antibacterial, anti-inflammatory, antifungal, antifouling, and insecticidal activity have been investigated. This review describes the chemical structures and biological activities of 217 halogenated compounds derived mainly from Penicillium and Aspergillus marine fungal strains reported from 1994 to 2019.
Assuntos
Organismos Aquáticos , Aspergillus , Hidrocarbonetos Halogenados , Penicillium , Organismos Aquáticos/química , Organismos Aquáticos/metabolismo , Aspergillus/química , Aspergillus/metabolismo , Hidrocarbonetos Halogenados/química , Hidrocarbonetos Halogenados/metabolismo , Penicillium/química , Penicillium/metabolismoRESUMO
Halogenation brings about dramatic variations to the performance of self-assembled organic species, such as luminescence and crystallinity, but it has seldom been utilized for chirality control. Here we show the halogenation effect of self-assembling organic building units on supramolecular chirality and chiroptical responses. N-terminal aromatic amino acids with different substituted halogen atoms at p-phenylalanine residues self-assembled into one-dimensional fibrous structures. Halogenation induced the emergence of macroscopic chirality regardless of halogen properties like electronegativity, generating exclusive homochiral helical structures. Solid-state X-ray structures and time-dependent density functional theory were utilized for calculated electronic circular dichroism spectra, which evidenced the diverse driving forces to enable chiral molecular arrangements, including H-bonds and halogen bonds. Red-shifted luminescence was observed in brominated building units, giving rise to active circularly polarized luminescence. This work elucidates the multiple roles of halogen in chiral self-assembly systems, which provides insight into the rational control over supramolecular chirality and their chiroptical applications.
Assuntos
Aminoácidos Aromáticos/química , Hidrocarbonetos Halogenados/química , Halogenação , Hidrocarbonetos Halogenados/síntese química , Substâncias Macromoleculares/síntese química , Substâncias Macromoleculares/química , Simulação de Dinâmica Molecular , Estrutura Molecular , Nanoestruturas/química , Tamanho da PartículaRESUMO
Novel halogenated aromatic dichlorodiazadienes were prepared via copper-mediated oxidative coupling between the corresponding hydrazones and CCl4. These rare azo-dyes were characterized using 1H and 13C NMR techniques and X-ray diffraction analysis for five halogenated dichlorodiazadienes. Multiple non-covalent halogen···halogen interactions were detected in the solid state and studied by DFT calculations and topological analysis of the electron density distribution within the framework of Bader's theory (QTAIM method). Theoretical studies demonstrated that non-covalent halogen···halogen interactions play crucial role in self-assembly of highly polarizable dichlorodiazadienes. Thus, halogen bonding can dictate a packing preference in the solid state for this class of dichloro-substituted heterodienes, which could be a convenient tool for a fine tuning of the properties of this novel class of dyes.
Assuntos
Butadienos , Corantes , Hidrocarbonetos Halogenados , Modelos Químicos , Butadienos/síntese química , Butadienos/química , Corantes/síntese química , Corantes/química , Hidrocarbonetos Halogenados/síntese química , Hidrocarbonetos Halogenados/químicaRESUMO
A novel series of halogenated triarylpyrazoles 12a-l was designed and synthesized. All target compounds showed good in vitro COX-2 inhibitory activity (IC50 = 0.043-0.17 µM) over COX-1 (IC50 = 7.8 - 15.4 µM) relative to celecoxib (COX-1/IC50 = 9.87, COX-2/IC50 = 0.055), with acceptable selectivity index values (SI = 50.6-253.1). Also, they displayed moderate to potent in vivo anti-inflammatory activity (% edema inhibition = 16.9-87.9) comparable to celecoxib (% edema inhibition = 46.6-72.1) as standard drug. Three fluorinated pyrazoles 12a, 12g and 12j, exhibited superior anti-inflammatory activity at all time intervals (% edema inhibition = 42.1-87.9) with better gastric profile (UI = 1.25-2.5) than the traditional NSAID; indomethacin (UI = 14) and were close to the selective COX-2 inhibitor; celecoxib (UI = 1.75). In-silico docking and ADME studies of 12a, 12g and 12j supported the obtained biological data and pointed out their potential use for the development of bio-available, safe and potent anti-inflammatory drugs.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Inibidores de Ciclo-Oxigenase 2/farmacologia , Ciclo-Oxigenase 2/metabolismo , Edema/tratamento farmacológico , Hidrocarbonetos Halogenados/farmacologia , Pirazóis/farmacologia , Animais , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Carragenina , Inibidores de Ciclo-Oxigenase 2/síntese química , Inibidores de Ciclo-Oxigenase 2/química , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Edema/patologia , Humanos , Hidrocarbonetos Halogenados/síntese química , Hidrocarbonetos Halogenados/química , Simulação de Acoplamento Molecular , Estrutura Molecular , Pirazóis/síntese química , Pirazóis/química , Ratos , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/patologia , Relação Estrutura-AtividadeRESUMO
The solvatochromic fluorophore Nile Red, 9-diethylamino-5H-benzo[a]phenoxazine-5-one, is one of the most commonly used stains to enhance contrast of lipid-rich areas of microscopic biosamples. Quite surprisingly, relatively little is known about the spectrally-resolved two-photon absorption (2PA) properties of this dye despite its promising features for two-photon microscopy of biological matter. For this reason, the two-photon solvatochromism of Nile Red still remains an uncharted territory as well. Also, no study has yet reported on how electron-withdrawing substituents attached to the Nile Red backbone affect its solvatochromic properties and two-photon brightness. In this paper, we demonstrate how solvent polarity influences the one- and two-photon absorption spectra of Nile Red as well as its fluorescence parameters, and we present new analogues that contain -CF3, -F and -Br substituents on its eastern side. Two-photon excited fluorescence experiments in a broad spectral range (780-1240 nm) and electronic structure calculations show that both the nature and location of the substituent have particular influence on the strength of 2PA, peaking in all cases at approx. 860 and 1050 nm. 2PA cross sections are higher at 1050 nm than at 860 nm, which suggests that Nile Red and its analogues are best suited for two-photon imaging employing excitation in the NIR-II optical transparency window of biological tissues.
Assuntos
Corantes Fluorescentes/química , Hidrocarbonetos Halogenados/química , Oxazinas/química , Fótons , Teoria da Densidade Funcional , Estrutura Molecular , Espectrometria de FluorescênciaRESUMO
In the present study, 2-bromo-4-chlorophenyl-2-bromobutanoate (3) was synthesized via the reaction of 2-bromo-4-chlorophenol with 2-bromobutanoyl bromide in the presence of pyridine. A variety of 2-bromo-4-chlorophenyl-2-bromobutanoate derivatives (5a-f) were synthesized with moderate to good yields via a Pd-catalyzed Suzuki cross-coupling reaction. To find out the reactivity and electronic properties of the compounds, Frontier molecular orbital analysis, non-linear optical properties, and molecular electrostatic potential studies were performed.