Rhodamine Derivative Research Articles

Direct Detection of Products from S-Adenosylmethionine-Dependent Enzymes Using a Competitive Fluorescence Polarization Assay.

S-Adenosylmethionine (AdoMet)-dependent methyltransferases (MTases) are an essential superfamily of enzymes that catalyze the transfer of a methyl group to several biomolecules. Alterations in the methylation of cellular components crucially impact vital biological processes, making MTases attractive drug targets for treating infectious diseases and diseases caused by overactive human-encoded MTases. Several methods have been developed for monitoring the activity of MTases, but most MTase assays have inherent limitations or are not amenable for high-throughput screening. We describe a universal, competitive fluorescence polarization (FP) assay that directly measures the production of S-adenosylhomocysteine (AdoHcy) from MTases. Our developed assay monitors the generation of AdoHcy by displacing a fluorescently labeled AdoHcy molecule complexed to a catalytically inert 5'-methylthioadenosine nucleosidase (MTAN-D198N) variant performed in a mix-and-read format. Producing the fluorescently labeled molecule involves a one-pot synthesis by combining AdoHcy with an amine-reactive rhodamine derivative, which possesses a Kd value of 11.3 ± 0.7 nM to MTAN-D198N. The developed competitive FP assay expresses a limit of detection for AdoHcy of 6 nM and exhibits a 34-fold preference to AdoHcy in comparison to AdoMet. We demonstrate the utility of the developed assay by performing a pilot screen with the NIH Clinical Collection as well as determining the kinetic parameters of l-histidine methylation for EgtD from Mycobacterium tuberculosis. Additionally, the developed assay is applicable to other AdoMet-dependent and ATP-dependent enzymes by detecting various adenosine-containing molecules including 5'-methylthioadenosine, AMP, and ADP.

A novel mitochondria-targeted fluorescent probe for imaging hydrazine in living cells, tissues and animals

The cytotoxicity of hydrazine (N2H4) is closely associated with mitochondria damages, and real-timely detecting mitochondrial N2H4 is of great importance for the in-depth study of the pathophysiological functions of N2H4 in living system. Although some of N2H4 fluorescent probes have been developed, the selective fluorescence imaging of mitochondrial N2H4 has rarely been reported. Herein, we present a novel mitochondria-targeted fluorescent probe (Rho-N2H4) for imaging N2H4 in living system. In the Rho-N2H4 system, a rhodamine derivative Rho with red emission was employed as the fluorophore, and acetyl group was utilized as response site for hydrazine. Upon treatment with N2H4, Rho-N2H4 displayed a drastically fluorescent signal at 645 nm. With the aid of Rho-N2H4, the fluorescence imaging of mitochondrial N2H4 in living cells was achieved. Assisted by high-definition 3D imaging, Rho-N2H4 can be applied for the imaging of N2H4 in living tissues with a penetration depth of about 50 μm with red emission manner. Furthermore, in vivo experiments demonstrated that Rho-N2H4 can be capable of imaging N2H4 in living animals. We expect that Rho-N2H4 could act as a promising tool for in-depthly unveiling the physiological and pathological roles of mitochondrial N2H4 in living system.

Novel double-networked polyurethane composites with multi-stimuli responsive functionalities

Functionalized microcrystal cellulose and a rhodamine derivative are developed as two dual-functional modifiers to construct heterogeneously assembled polyurethane double-networks with property improvement and multi-stimuli responsive functionalities.

Al(iii)-responsive "off-on" chemosensor based on rhodamine derivative and its application in cell imaging.

In this work, a new rhodamine chemosensor (P) with excellent photochromic properties upon vis irradiation was designed and synthesized. The fabricated chemosensor P could detect Al3+via the opening of the spirolactam ring of the rhodamine unit with high selectivity and sensitivity. The spirolactam ring opening was confirmed by NMR and infrared spectroscopy. Upon binding with Al3+, the generated 1 : 1 P-Al3+ complex, confirmed by Job's plot titrations and mass spectrometry analysis, could exhibit a remarkable fluorescence enhancement with a limit of detection (LOD) of 0.16 μM. Furthermore, the sensing of P to Al3+in vivo was also studied quantitatively and qualitatively in detail, and the results showed that the coordination between P with Al3+ was reversible in living cells.

A rhodamine-based fluorescent chemosensor for Al3+: is it possible to control the metal ion selectivity of a rhodamine-6G based chemosensor?

A rhodamine derivative 3′,6′-bis(ethylamino)-2-(2-(2-hydroxy-5-methylbenzylideneamino)ethyl)-2′,7′-dimethylspiro[isoindoline-1,9′-xanthen]-3-one has been found to be highly selective and sensitive chemosensor for Al3+ ion.

A tumor-mitochondria dual targeted aza-BODIPY-based nanotheranostic agent for multimodal imaging-guided phototherapy.

Mitochondria targeted phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), has excelled as an effective approach among other non-specific techniques for its high selectivity, non-invasiveness and low systemic toxicity. Derivatives of porphyrins, indocyanine dyes and rhodamine are widely utilized for cancer PDT or PTT. However, limitations, such as hypoxia and heat resistance of PDT and PTT, have restricted their efficacy in tumor treatment, making it urgent to develop highly efficient theranostic agents with synergistic effects. Aza-boron-dipyrromethene (aza-BODIPY) has shown promising prospects for synergistic phototherapy due to its outstanding reactive oxygen species (ROS) generation and photothermal effect. Herein, we designed and synthesized a near-infrared (NIR) aza-BODIPY derivative MeOABBr (ΦΔ = 84%). By encapsulating it with polyethylene glycol-folic acid (PEG-FA) and polyethylene glycol-triphenylphosphonium (PEG-TPP), tumor and mitochondria dual targeting nanoparticles (FMAB NPs) have been obtained. Triggered by NIR irradiation, FMAB NPs could generate ROS and hyperthermia (η = 40%) to cause mitochondrial dysfunction, resulting in cell apoptosis. Simultaneously, FMAB NPs, with unique optical properties, can be monitored precisely by photoacoustic, fluorescence and photothermal imaging in vivo. In particular, as proved by both in vitro and in vivo experiments, tumor-mitochondria dual targeted FMAB NPs exhibit high phototherapeutic efficacy without toxicity to normal tissues.

A reversible frequency upconversion probe for real-time intracellular lysosome-pH detection and subcellular imaging.

Lysosomal pH is known to be acidic, which plays a vital role in various processes in living organisms. Frequency upconversion luminescence exhibits the unique ability to convert low energy photons into high energy photons, which can be used in live samples due to its deep penetration, low tissue damage, etc. The development of sensitive frequency upconversion probes with a low pKa, high sensitivity, and specific selectivity for lysosomal pH detection is of great importance. Herein, we report a novel frequency upconversion luminescence probe, NRH-Lyso, by conjugating the rhodamine derivative NRH and the lysosome targeting functional group 4-(2-aminoethyl)morpholine. NRH-Lyso shows a sensitive response to acidic pH and excellent selectivity in the presence of metal ions, anions, and small molecules. Due to the structural transformation of lactam ring opening and closing of NRH-Lyso, the probe shows an almost 80-fold enhancement in emission intensity when the pH changes from 7.0 to 4.0 under 808 nm laser excitation. The living cell imaging data reveals that NRH-Lyso can selectively detect lysosomal pH changes with excellent photostability and low cytotoxicity. All these features make NRH-Lyso a good candidate to investigate the lysosomal pH-associated physiological and pathological processes.

On-line microchip electrophoresis-mediated preconcentration of cationic compounds utilizing cationic polyacrylamide gels fabricated by in situ photopolymerization.

A simple and efficient method was developed for the fabrication of a cationic sample preconcentrator on a channel of a commercial poly(methyl methacrylate) (PMMA) microchip. This approach is based on a simple photochemical copolymerization for the fabrication of a permselective preconcentrator. The intersection of the PMMA microchip was filled with a gel solution comprising acrylamide, N,N-methylene-bis-acrylamide, (3-acrylamidopropyl) trimethylammonium, and riboflavin that functioned as a photocatalytic initiator. In situ polymerization near the cross of the sample outlet channel was performed by pinpoint irradiation with a 488 nm SHG laser beam, which is also used as the light source for fluorimetric detection. The electrokinetic property and electric repulsion between sample components and cationic groups on the polyacrylamide gel layer enables trapping and preconcentration of cations at the boundary of the anodic side of the gel layer. Reproducibility is about 20% RSD due to the variation of the position of the hand-made electrode in sample reservoir, but the preconcentration factors exceeded over 104-fold. The utility of the cationic preconcentrator gel was demonstrated by analyzing rhodamine derivatives, oligosaccharides labeled with rhodamine 110 and cytochrome C labeled with fluorescein isothiocyanate.

A water-soluble Fe3+ selective fluorescent turn-on chemosensor: Preparation, theoretical study and its optical vitro imaging

A rhodamine derivative bearing a thiazole receptor (probe 1) was developed and characterized. Probe 1 rendered a prominently chromogenic and turn-on fluorescent signal toward Fe3+ ion in aqueous media based on coordination reaction. Probe 1 also showed high sensitivity toward Fe3+ ion with the detection limit as low as 92nM. By means of the Job's plot, 2:1 binding mode of 1-Fe3+ complex was determined and a possible sensing mechanism was further proposed based on the changes in the Fourier Transform Infrared (FT-IR) and mass spectra. The turn-on fluorescence and sensing mechanism for 1-Fe3+ complex were well demonstrated by theoretical calculations. Importantly, probe 1 has been tested highly suitable for mapping Fe3+ ion in human colon cancer cells SW480, providing a wonderful candidate for tracking Fe3+ in biological processes.

Electrochemical switching fluorescence emission in rhodamine derivatives

Three rhodamine derivatives exhibiting electrofluorochromic properties were investigated by cyclic voltammetry and UV–Vis/fluorescence spectroelectrochemistry. Rhodamine 101 (Rh101, compound 1) was used as a reference model. In compound 2, the carboxylate anion of Rh101 was replaced by an alkyne moiety to allow further functionalization. The compound 3 was prepared from 2 by conversion of the alkyne to a triazole group bearing an alkyl chain with an alcohol function. These three rhodamine derivatives exhibited similar electrochemical behaviors. Their mono-electronic reductions produced the corresponding radical species which were stable on the time-scale of cyclic voltammetry. Additional reduction of electrogenerated radicals produced unstable anions which underwent subsequent chemical reaction, most likely protonation. Based on cyclic voltammetry investigations, absorption and fluorescence spectroelectrochemistry were then performed on compounds 1, 2, 3 and their parent reduced radicals 1a, 2a, 3a. UV–Vis spectroelectrochemistry, combined with TD-DFT calculation, confirmed the formation of radicals upon mono-electronic reduction of starting rhodamines. Fluorescence spectroelectrochemistry showed that, contrary to their parent molecules, electrogenerated radicals were non-fluorescent. Electrochemical fluorescence extinction was successfully achieved with all studied compounds. Moreover, compound 1 underwent on/off switching between fluorescent and non-fluorescent states repeatedly. Also, recovery of fluorescence in compound 3 was observed, which open interesting opportunities for the development of versatile rhodamine-based probes.

A chemosensor to recognize N-acyl homoserine lactone in bacterial biofilm

A simple, sensitive, and rapid assay has been developed for detection of N-acyl homoserine lactone (HSL) autoinducers involved in bacterial quorum sensing (QS) by a new coumarin appended rhodamine derivative (RNC) ensembled with Cu2+. RNC-Cu2+ conjugate shows “turn on” fluorescence while binding with HSLs. The interaction of ensemble with HSL is found to be 1:1 stoichiometry on the basis of absorption and fluorescence titrations with the detection limit of 2.4 μM at neutral pH. NMR, IR titrations and DFT calculations were performed in order to demonstrate the sensing mechanism and the electronic properties of the receptor-donor complex. The present chemosensor improves upon any previous biosensor-based approaches to selectively quantitate HSL, both in cell-free and in whole-cell assay system.

Mitochondrial specific photodynamic therapy by rare-earth nanoparticles mediated near-infrared graphene quantum dots

Photodynamic therapy (PDT) has been proposed in cancer treatment for decades, but its clinical translation is significantly impeded by the low yield of ROS, poor tissue penetration depth of most current photosensitizers, and short lifetime of ROS. These limitations directly affect the therapeutic effect of PDT in cancer therapy. Here we proposed a new strategy by collaboratively integrating rare-earth doped upconversion nanoparticles (UCNP) with graphene quantum dot (GQD) for highly efficacious PDT, based on the merits of UCNP, which can emit UV–vis light under near-infrared light (NIR) excitation, and GQD, which can produce 1O2 efficiently. For GQD-decorated UCNP nanoparticles (UCNP-GQD), the emission light from UCNP can further excite GQD with prominent 1O2 generation for NIR-triggered PDT. Furthermore, a hydrophilic rhodamine derivative, TRITC, is covalently tethered to afford the resultant UCNP-GQD/TRITC, possessing distinct mitochondrial targeting property. Thus mitochondrial specific PDT with in-situ1O2 burst in mitochondria induces sharp decrease of mitochondrial membrane potential, which initiates the tumor cell apoptosis irreversibly. Importantly, in vivo experiments demonstrate the tumor inhibition of mitochondrial targeting UCNP-GQD/TRITC with improved therapeutic efficiency compared with non-targeting UCNP-GQD. The proposed strategy highlights the advantages of precision organelles-specific PDT in cancer therapy.

A near-infrared lysosomal pH probe based on rhodamine derivative

A near-infrared fluorescent probe (NRL) for lysosomal pH was presented by integrating 4-(2-aminoethyl)morpholine moiety, a lysosome-targetable group, into the rhodamine derivative. The addition of H+ led to significant fluorescence intensity increase at 739nm, thus enabling it to monitor pH changes at weakly acidic pH. NRL showed negligible response to common species and short response time. Furthermore, the probe was successfully applied in living cells, and the results indicated that the probe could target lysosomes and detect lysosomal pH. We believe that NRL had great potential as a practical tool for lysosomal pH biology.

Synthesis, characterization and nitrite ion sensing performance of reclaimable composite samples through a core-shell structure

The following paper reported and discussed a nitrite ion optical sensing platform based on a core-shell structure, using superamagnetic nanoparticles as the core, a silica molecular sieve MCM-41 as the shell and two rhodamine derivatives as probe, respectively. This superamagnetic core made this sensing platform reclaimable after finishing nitrite ion sensing procedure. This sensing platform was carefully characterized by means of electron microscopy images, porous structure analysis, magnetic response, IR spectra and thermal stability analysis. Detailed analysis suggested that the emission of these composite samples was quenchable by nitrite ion, showing emission turn off effect. A static sensing mechanism based on an additive reaction between chemosensors and nitrite ion was proposed. These composite samples followed Demas quenching equation against different nitrite ion concentrations. Limit of detection value was obtained as low as 0.4μM. It was found that, after being quenched by nitrite ion, these composite samples could be reclaimed and recovered by sulphamic acid, confirming their recyclability.

A Far-Red-Emitting Fluorescence Probe for Sensitive and Selective Detection of Peroxynitrite in Live Cells and Tissues.

In this study, the far-red-emitting fluorescence probe 1, containing a rhodamine derivative and a hydrazide reactive group, was developed for peroxynitrite detection and imaging. This probe, which is cell permeable and shows high sensitivity and selectivity in fluorometric detection of peroxynitrite over other ROS/RNS, was successfully utilized to detect exogenous and endogenous peroxynitrite in HeLa and RAW 264.7 cells, respectively. More importantly, 1 can also be used to detect endogenous peroxynitrite generated in Pseudomonas aeruginosa (PAO1)-infected mouse bone marrow-derived neutrophils. We anticipate that the new probe will serve as a powerful molecular imaging tool in investigations of the role(s) played by peroxynitrite in a variety of physiological and pathological contexts.

Fluorescent Determination of Mercury(II) Using Rhodamine B Immobilized on Polystyrene Microspheres

ABSTRACTA novel microsphere-based fluorescent sensor 1 for determination of Hg(II) in food samples has been successfully synthesized and its fluorescent sensing properties were investigated in detail. Polystyrene microsphere was innovatively surface modified by a rhodamine derivative; therefore sensor 1 was a fluorescent sensor with high polymer material properties of polystyrene and the optical properties of a fluorescent probe. Sensor 1 displayed high selectivity, good anti-interference performance, and instantaneous response to Hg(II). The fluorescence intensity of sensor 1 showed a linear response to Hg(II) in the concentration range of 0 µM to 8 µM with a detection limit of 0.439 µM. The most valuable advantage was that sensor 1 was recyclable and environmentally-friendly. This proposed sensor 1 was applied to monitor the content of Hg(II) in real food samples, such as tap water, rice, and anglerfish. The recovery range of tap water was from 92.60 to 105.80%, the recovery range of rice was from 90.45 to 106.10%, and the recovery range of anglerfish was from 91.30 to 105.84%. The relative error was below 10% in spiked recovery studies, suggesting that fluorescent sensor 1 provides a simple, efficient, and promising method for determination of Hg(II) in complex matrices.

Recyclable nitrite ion sensing nanocomposites based on a magnetic-emissive core–shell structure: Characterization and performance

In this paper, two nitrite ion sensing nanocomposites based on a magnetic-emissive core–shell structure were designed and synthesized, using Fe3O4 particles as core, a silica molecular sieve (MCM-41) as supporting matrix and two rhodamine derivatives as chemosensors, respectively. These two composite sensing samples were characterized carefully by means of electron microscopy, mesoporous analysis, magnetic response, IR spectra and thermal stability analysis. Emission of these two composite sensing samples was found quenchable by nitrite ion, with limit of detection as low as 1.2μM. Detailed analysis suggested that these chemosensors followed a static sensing mechanism towards nitrite ion through an additive reaction. These chemosensors could be recycled and recovered by sulphamic acid after nitrite ion sensing.

A fluorescent probe for copper and hypochlorite based on rhodamine hydrazide framework

A rhodamine derivative (1) was synthesized as a fluorescence turn-on probe for copper (Cu2+) and hypochlorite (ClO−). The probe gave a fluorescence turn-on change at 587nm with a color change from colorless to pink in the presence of Cu2+ or ClO− ions in aqueous solution. It was found that the Cu2+ ion bound to 1 in a 1:1 stoichiometry and induced a spirolactam ring opening of the rhodamine moiety leading to a fluorescence turn-on, confirmed by Job’s plot, ESI-Mass, and 1H NMR analyses. In the presence of ClO− ion, probe 1 underwent a hypochlorite-mediated oxidation and hydrolysis to produce a ring-opened rhodamine B with a fluorescence enhancement. However, these changes were not monitored in case of other metal ions, anions, and reactive redox species. In addition, probe 1 can readily react with the ClO− to provide a distinct fluorescence enhancement along with a pink color even in the presence of various competitive species.

(E)-3′,6′-bis(Diethylamine)-2-[(2-methoxynaphthalen-1-yl)methyleneamino]spiro[isoindoline-1,9′-xanthen]-3-one

The title compound, (E)-3′,6′-bis(diethylamine)-2-[(2-methoxynaphthalen-1-yl)methyleneamino]spiro[isoindoline-1,9′-xanthen]-3-one, was synthesized in 92% isolated yield using microwave-assisted organic synthesis. This new rhodamine derivative was fully characterized by 1H-NMR, 13C-NMR, FTIR and high resolution MS.

Colorimetric and fluorimetric detection of Hg2 + and Cr3 + by boronic acid conjugated rhodamine derivatives: Mechanistic aspects and their bio-imaging application in bacterial cells

Colorimetric and fluorimetric detection of toxic metal ions such as Hg2+ and Cr3+ has gained tremendous popularity over the conventional methods due to their operational simplicity, high selectivity, and speediness. Although numerous colorimetric and fluorescent receptors for Hg2+ or Cr3+ were reported in the literature, boronic acid-based receptors for these metal ions are rather scarce in the literature. Hence, in the present study dual function boronic acid conjugated rhodamine derivatives were developed, and their toxic metal ion detection abilities were studied by absorption, emission and visual detection methods. Absorption and emission spectral studies revealed that these derivatives displayed selectivity towards Hg2+, Cr3+ and Fe3+ among the other metal ions studied by forming new absorption band. Both the derivatives exhibited colorimetric response towards Hg2+ and Cr3+ by the change in color of the solution to pink and reddish pink with Fe3+. The detailed mechanism involved in the detection of Hg2+ was deduced by 1H NMR and ESI-MS studies. Further, these derivatives were used for fluorescence imaging of Hg2+ and Cr3+ in S. aureus bacterial cells. Thus the present manuscript demonstrated the use of boronic acid conjugated rhodamine derivatives as a dual function (colorimetric and fluorescent) probes and as imaging agents for Hg2+ and Cr3+, which are known for their toxic influence on bacterial cells.