A deoxygenation-switch-based red-emitting fluorogenic light-up probe for the detection of highly toxic free bilirubin in human blood serum.

Reaction-based chemical switches are attracting great interest due to their high selectivity, and their use has become a powerful technique for developing fluorogenic probes. Herein, a benzorhodol-derivative-attached N-oxide probe (DEBNox) has been designed as a new fluorogenic probe for the detection of the biologically toxic species bilirubin based on a deoxygenation switching mechanism. Upon reaction with added Fe3+, bilirubin produces Fe2+ ions in situ, which in turn promote a deoxygenation reaction with DEBNox to generate the corresponding high-red-fluorescence (λem: ∼623 nm) benzorhodol derivative (DEB). This type of Fe3+-mediated response helps the probe to act as a qualified turn on selective fluorescence sensor for bilirubin with a detection range as low as 33 nM. Moreover, the probe was successfully employed to detect free bilirubin in human blood serum specimens with acceptable accuracy and reliability. This DEBNox-based light-up strategy also facilitates the construction of reliable and highly sensitive assays based on a paper-based strategy, similar to pH-indicator paper, as is demonstrated here via bilirubin detection in real serum samples. These findings could be useful for developing powerful diagnostic tools for the detection of free bilirubin in the near further.

Encapsulation and Stabilization of a Donor-Acceptor Stenhouse Adduct Isomer in Water Inside the Blue Box: A Combined Experimental and Theoretical Approach.

We synthesized two types of donor-acceptor Stenhouse adducts (DASAs), a new type of photochromic molecules showing dual color in two different isomeric forms in solution phase, using Meldrum acid (DASA-Mel) and barbituric acid (DASA-Bar), along with a naphthalimide derivative to obtain interesting fluorescence properties. DASA-Mel was found to have fast photochromic conversion in comparison to DASA-Bar, evident from ultraviolet-visible (UV-vis) and fluorescence spectroscopic studies. The colored form of DASA-Mel was encapsulated inside the water-soluble Stoddart's blue box and became soluble in water much faster than DASA-Bar. Interestingly, the competitive encapsulation experiment showed that DASA-Mel was selectively encapsulated inside the blue box in water whereas DASA-Bar was mostly separated out from the solution after centrifugation, and this phenomenon was confirmed by 1H and DOSY NMR and mass spectroscopies. Moreover, we found through density functional theory (DFT) optimization that the open form of DASA-Mel was more stable during the encapsulation reaction in a water medium in comparison to DASA-Bar. The calculated binding energies of encapsulated DASA-Mel and DASA-Bar are -10.2 and -9.9 kcal/mol, respectively, clearly showing that the former is more stable by 0.3 kcal. Consequently, the organic macrocycle selectively separating one kind of DASA from a mixture by encapsulation in water is reported for the first time with experimental and theoretical support in the literature.

A new half-condensed Schiff base platform: structures and sensing of Zn2+ and H2PO4- ions in an aqueous medium.

A newly designed and synthesized half-condensed organic moiety 2-hydroxy-5-methyl-3-[(2-phenylamino-phenylimino)-methyl]-benzaldehyde (HL') and a Zn2L4 complex sequentially detect Zn2+ and H2PO4- ions as low as 1.13 nM and1.23 µM, respectively. HL' and a dinuclear Zn(ii) complex of in situ generated L- in a solution formulated as Zn2L4 under investigation were characterized by physicochemical and spectroscopic studies along with detailed structural analyses by single-crystal X-ray crystallography. The selectivity and sensitivity of HL' towards Zn2+ ions and of the Zn2L4 complex towards H2PO4- ions are based on CHEF and via displacement pathways, respectively. Dual sensing of Zn2+ ions and H2PO4-ions in an aqueous medium via "Green-Blue-Green" emission with the reversible transformation of in situ formed HL' to HL was established by detailed electronic absorption and emission spectroscopic studies. This non-cytotoxic probe (HL', i.e. produced HL in solution) and Zn2L4 complexes are able to monitor the subcellular distribution changes of Zn2+ and H2PO4- ions, respectively, by fluorescence microscopy using the human semen sample.

A Nuclear-Localized Naphthalimide-Based Fluorescent Light-Up Probe for Selective Detection of Carbon Monoxide in Living Cells.

A nuclear-localized fluorescent light-up probe, NucFP-NO2, was designed and synthesized that can detect CO selectively in an aqueous buffer (pH 7.4, 37 °C) through the CO-mediated transformation of the nitro group into an amino-functionalized moiety. This probe triggered a more than 55-fold "turn-on" fluorescence response to CO without using any metal ions, e.g., Pd, Rh, Fe, etc. The enhanced response is highly selective over a variety of relevant reactive oxygen, nitrogen, and sulfur species and also various biologically important cationic, anionic, and neutral species. The detection limit of this probe for CO is as low as 0.18 µM with a linear range of 0-70 µM. Also, this fluorogenic probe is an efficient candidate for monitoring intracellular CO in living cells (RAW 264.7, A549 cells), and the fluorescence signals predominantly localize in the nuclear region.

Recent Advances in Fluorescence Light-Up Endogenous and Exogenous Carbon Monoxide Detection in Biology.

Considerable attention has been paid by the scientific community to detect toxic carbon monoxide (CO) in sub-cellular organelles like mitochondria, lysosomes, nuclei, etc. due to their generation and accumulation through numerous biological processes and their role as signal transducer, therapeutics, etc. Various methods are also available for detection of CO, but fluorescence light-up detection is considered the best due to its easy and accurate sensing capability. As of now, no review is available in the literature dedicated to fluorescent detection of only CO both in vitro and in vivo, but considering the huge amount of work reporting every year, it is necessary to have an account of all the recent significant works devoted to it. This review will give special attention to the most noteworthy development of fluorescent light-up probes for the detection of cellular and sub-cellular targetable CO starting from 2012 and emphasizing also the mechanism of action and the applications.

Bilirubin Quantification in Human Blood Serum by Deoxygenation Reaction Switch-Triggered Fluorescent Probe.

A coumarin-based fluorescent compound, bilirubin fluorescent probe N-oxide (BFPNox), was successfully designed and synthesized for highly selective and sensitive detection of free bilirubin with short response time. The fluorescence "turn-on" response of the probe is based on the in situ generated Fe2+-mediated deoxygenation reaction of N-oxide from the diethylarylamine group of the probe, where the group attached to the coumarin π-conjugated system is responsible for the fluorescence quenching state of the probe, BFPNox. Here, the reaction of the added Fe3+ ions with bilirubin produces Fe2+ ions in situ in aqueous buffer. Fluorescence enhancement of BFPNox was achieved by more than 12-fold when a double equivalent of bilirubin solution was added in reaction buffer at pH 7.2 (50 mM HEPES, 5% DMSO) at 25 °C under excitation at 400 nm. It detected free bilirubin as low as 76 nM in an aqueous system without any interference of metal ions, anions, and other important biomolecules with a linear concentration range of 0-10 µM (R2 = 0.991). The probe was also employed in the estimation of free bilirubin in human serum specimens to verify the efficacy of this probe. With these, it is revealed that this probe is a good candidate to be used as a powerful diagnostic tool for the assessment of free bilirubin with significant accuracy and reliability.

A Lysosome-Targetable Fluorescence Sensor for Ultrasensitive Detection of Hg2+ in Living Cells and Real Samples.

A new lysosome-targetable fluorescence sensor, Lyso-HGP, was designed and synthesized based on 4-methyl-2,6-diformylphenol as a fluorophore. Lyso-HGP displays highly sensitive fluorescent detection of Hg2+ in HEPES buffer solution (10 mM, DMSO 1%) of pH 7.0 at 37 °C due to the formation of highly fluorescent formyl-functionalized derivative Lyso-HGP-CHO. The sensor triggered a "turn-on" fluorescence response to Hg2+ with a simultaneous increase of fluorescence intensity by 180-fold just after 10 min. The response is very selective over a variety of biologically relevant cations, anions, molecules, and competitive toxic heavy metal cations. The limit of detection (LOD) was calculated as low as 6.82 nM. So, it can be utilized to detect this toxic heavy metal in biology and environmental samples in an aqueous buffer medium. Also, the sensor is able to monitor the subcellular distribution of Hg2+ specifically localized in the lysosome's compartment in the MCF7 human breast cancer cell line by fluorescence microscopy.

Highly Sensitive Ratiometric Chemosensor and Biomarker for Cyanide Ions in the Aqueous Medium.

A newly designed cyanide-selective chemosensor based on chromone containing benzothiazole groups [3-(2,3-dihydro-benzothiazol-2-yl)-chromen-4-one (DBTC)] was synthesized and structurally characterized by physico-chemical, spectroscopic, and single-crystal X-ray diffraction analyses. The compound DBTC can detect cyanide anions based on nucleophilic addition as low as 5.76 nM in dimethyl sulfoxide-N-(2-hydroxyethyl)piperazine-N'-ethanesulfonic acid buffer (20 mM, pH 7.4) (v/v = 1:3). The binding mode between receptor DBTC and cyanide nucleophile has also been demonstrated by experimental studies using various spectroscopic tools and theoretical studies, and the experimental work has also been verified by characterizing one supporting compound of similar probable structure of the final product formed between DBTC and cyanide ion (DBTC-CN compound) by single-crystal X-ray analysis for detailed structural analyses. In theoretical study, density functional theory procedures have been used to calculate the molecular structure and the calculation of the Fukui function for evaluation of the electrophilic properties of each individual acceptor atom. Furthermore, the efficacy of the probe (DBTC) to detect the distribution of CN- ions in living cells has been checked by acquiring the fluorescence image using a confocal microscope. Notably, the paper strips with DBTC were prepared, and these could serve as efficient and suitable CN- test kits successfully.

A New Lysosome-Targetable Turn-On Fluorogenic Probe for Carbon Monoxide Imaging in Living Cells.

A lysosome-targetable fluorogenic probe, LysoFP-NO2, was designed and synthesized based on a naphthalimide fluorophore that can detect selectively carbon monoxide (CO) in HEPES buffer (pH 7.4, 37 °C) through the transformation of the nitro group into an amino-functionalized system in the presence of CO. LysoFP-NO2 triggered a "turn-on" fluorescence response to CO with a simultaneous increase of fluorescence intensity by more than 75 times. The response is selective over a variety of relevant reactive nitrogen, oxygen, and sulfur species. Also, the probe is an efficient candidate for monitoring changes in intracellular CO in living cells (MCF7), and the fluorescence signals specifically localize in the lysosome compartment.

A fluorescent probe for the selective detection of creatinine in aqueous buffer applicable to human blood serum.

A naphthalimide-based fluorescence light-up probe, FCP-Pd, has been designed and synthesized for selective detection and quantitation of creatinine in PBS buffer of pH 7.2 at 37 °C with a 'turn-on' response over a variety of interfering metal ions and/or anions and several biologically significant species. This probe is highly effective in estimating creatinine in human blood serum, which confirms the reliability and accuracy of this new system to be applied in clinical and toxicological analysis.

A new fluorogenic probe for the selective detection of carbon monoxide in aqueous medium based on Pd(0) mediated reaction.

A coumarin-based fluorogenic probe, PCO-1, senses carbon monoxide (CO) selectively in HEPES buffer at pH 8.0 through the intramolecular cyclization-elimination pathway based on Pd(0) mediated reaction. The probe exhibits a 'turn-on' response of CO over a variety of relevant reactive oxygen, nitrogen and sulfur species.

Effect of substituents on FRET in rhodamine based chemosensors selective for Hg2+ ions.

The effect of substituents on FRET in two newly designed rhodamine-based Hg(2+) ion selective chemosensors (L¹ and L²) has been explored by a systematic experimental and theoretical study. Comparison of these sensors in the analytical study and imaging of Hg(2+) ions in living cells has also been included.

A fluorescent probe for detection of histone deacetylase activity based on aggregation-induced emission.

A tetraphenylethylene-derivative fluorescent probe for the one-step detection of histone deacetylases (HDAC) was developed. The deacetylation of the probe triggers electrostatic interaction between the molecules and automatically leads to fluorescence enhancement based on aggregation-induced emission (AIE).

A ratiometric fluorescent chemosensor for iron: discrimination of Fe2+ and Fe3+ and living cell application.

A newly designed probe, 6-thiophen-2-yl-5,6-dihydrobenzo[4,5]imidazo-[1,2-c] quinazoline (HL(1)) behaves as a highly selective ratiometric fluorescent sensor for Fe(2+) at pH 4.0-5.0 and Fe(3+) at pH 6.5-8.0 in acetonitrile-HEPES buffer (1/4) (v/v) medium. A decrease in fluorescence at 412 nm and increase in fluorescence at 472 nm with an isoemissive point at 436 nm with the addition of Fe(2+) salt solution is due to the formation of mononuclear Fe(2+) complex [Fe(II)(HL)(ClO(4))(2)(CH(3)CN)(2)] (1) in acetonitrile-HEPES buffer (100 mM, 1/4, v/v) at pH 4.5 and a decrease in fluorescence at 412 nm and increase in fluorescence at 482 nm with an isoemissive point at 445 nm during titration by Fe(3+) salt due to the formation of binary Fe(3+) complex, [Fe(III)(L)(2)(ClO(4))(H(2)O)] (2) with co-solvent at biological pH 7.4 have been established. Binding constants (K(a)) in the solution state were calculated to be 3.88 × 10(5) M(-1) for Fe(2+) and 0.21 × 10(3) M(-1/2) for Fe(3+) and ratiometric detection limits for Fe(2+) and Fe(3+) were found to be 2.0 µM and 3.5 µM, respectively. The probe is a "naked eye" chemosensor for two states of iron. Theoretical calculations were studied to establish the configurations of probe-iron complexes. The sensor is efficient for detecting Fe(3+)in vitro by developing a good image of the biological organelles.

A new half-condensed Schiff base compound: highly selective and sensitive pH-responsive fluorescent sensor.

A new probe, 3-[(3-benzyloxypyridin-2-ylimino)methyl]-2-hydroxy-5-methylbenzaldehyde (1-H) behaves as a highly selective fluorescent pH sensor in a Britton-Robinson buffer at 25 °C. The pH titrations show a 250-fold increase in fluorescence intensity within the pH range of 4.2 to 8.3 with a pK(a) value of 6.63 which is valuable for studying many of the biological organelles.

A highly selective fluorescent chemosensor for zinc ion and imaging application in living cells.

A new 2,6-bis(5,6-dihydrobenzo[4,5]imidazo[1,2-c]quinazolin-6-yl)-4-methylphenol (1) serves as a highly selective and sensitive fluorescent probe for Zn(2+) in a HEPES buffer (50 mM, DMSO:water = 1:9 (v/v), pH = 7.2) at 25 °C. The increase in fluorescence in the presence of Zn(2+) is accounted for by the formation of dinuclear Zn(2+) complex [Zn(2)(C(35)H(25)N(6)O)(OH)(NO(3))(2)(H(2)O)] (2), characterized by X-ray crystallography. The fluorescence quantum yield of the chemosensor 1 is only 0.019, and it increases more than 12-fold (0.237) in the presence of 2 equiv of the zinc ion. Interestingly, the introduction of other metal ions causes the fluorescence intensity to be either unchanged or weakened. By incubation of cultured living cells (A375 and HT-29) with the chemosensor 1, intracellular Zn(2+) concentrations could be monitored through selective fluorescence chemosensing.

A new functionalized mesoporous matrix supported Pd(II)-Schiff base complex: an efficient catalyst for the Suzuki-Miyaura coupling reaction.

A new Pd(II) bounded 2D-hexagonally ordered functionalized MCM-41 type material (IV) has been synthesized. Functionalization was carried out by the anchoring of 3-aminopropyltriethoxysilane in the MCM-41 type mesoporous material, followed by grafting with 2,6-diacetylpyridine (DAP) to give a N3-type Schiff base chelating attachment for the Pd(II) species. Fourier transform infrared (FTIR), powder X-ray diffraction (PXRD) and high resolution transmission electron microscopy (HRTEM) studies have been used to characterize the material. Material IV behaves as a highly active catalyst towards Suzuki-Miyaura cross-coupling reaction for the synthesis of biaryl organics. In addition, IV acts as a true heterogeneous catalyst in coupling reaction. It was found that this catalyst is highly efficient and recyclable towards Suzuki-Miyaura reaction with high turn over frequencies. X-Ray photoelectron spectroscopic (XPS) analysis was employed to understand the oxidation state of the palladium atom in the catalyst (IV) and its loading in the material.

A new water-soluble copper(II) complex as a selective fluorescent sensor for azide ion.

{[Cu(2)(H(2)L)(OH)(H(2)O)].(ClO(4))(2)(H(2)O)} (1) serves as a selective azide ion fluorescent sensor in aqueous medium. 1 binds with N(3)(-) to give [Cu(6)(HL)(2)(mu(1,1)-N(3))(6)] (2) which imposes rigidity and decreases the non-radiative decay of the excited state to give rise to fluorescent enhancement. 1 is highly selective over other various anions in aqueous medium.

Nanowires of metal-organic complex by photocrystallization: a system to achieve addressable electrically bistable devices and memory elements.

A new method has been achieved to form a Cu:benzoquinone derivative (DDQ) charge-transfer complex by the photoexcitation of [Cu(DDQ)2(CH 3COO)2] ( 1) that has been synthesized by the reaction of DDQ and hydrated cupric acetate in acetonitrile. Photoexcitation of coordinated complex 1 leads to the formation of charge-transfer complex Cu2+(DDQ(.-)2 ( 2). The charge transfer complex 2, when spun on solid substrates, forms nanowires. Sandwich structures of 2 exhibit electrical bistability associated with memory phenomenon. Read-only and random-access memory phenomena are evidenced in nanowires of 2 providing a route to attend the issues pertaining to the addressibility of organic memory devices.

A two-dimensional coordination compound as a zinc ion selective luminescent probe for biological applications.

A 2D coordination compound {[Cu2(HL)(N3)]ClO4}infinity (1; H3L = 2,6-bis(hydroxyethyliminoethyl)-4-methyl phenol) was synthesized and characterized by single-crystal X-ray diffraction to be a polymer in the crystalline state. Each [Cu2(HL)(N3)]+ species is connected to its adjacent unit by a bridging alkoxide oxygen atom of the ligand to form a helical propagation along the crystallographic a axis. The adjacent helical frameworks are connected by a ligand alcoholic oxygen atom along the crystallographic b axis to produce pleated 2D sheets. In solution, 1 dissociates into [Cu2(HL)2(H3L)]2H2O (2); the monomer displays high selectivity for Zn2+ and can be used in HEPES buffer (pH 7.4) as a zinc ion selective luminescent probe for biological application. The system shows a nearly 19-fold Zn2+-selective chelation-enhanced fluorescence response in the working buffer. Application of 2 to cultured living cells (B16F10 mouse melanoma and A375 human melanoma) and rat hippocampal slices was also studied by fluorescence microscopy.