Youngmi Kim

Aggregation-induced emission enhancement of a meso-trifluoromethyl BODIPY via J-aggregation

A CF3-BODIPY forms strongly luminescent aggregates, which contrasts with the quenched condensed-phase photophysics that are typical for BODIPY dyes. Examination of the luminescent properties of these aggregates – narrow red-shifted absorption and emission bands, minimal Stokes shift and increased fluorescence rate constants – and of the solid-state packing of the dye establish the CF3-BODIPY as the first structurally characterized genuine BODIPY J-aggregate.

A BODIPY-Based Probe for the Selective Detection of Hypochlorous Acid in Living Cells

Reactive oxygen species (ROS) are essential for a wide range of biological and pathological events. [1] During infection and inflammation, the phagocytic leukocytes, including neutrophils, monocytes, and macrophages generate reactive oxygen species (ROS) to kill invading bacteria and pathogens. [2] Among ROS, hypochlorous acid (HOCl/OCl )i s a highly reactive oxygen species produced from hydrogen peroxide (H2O2) and chloride ions (Cl ) by the enzyme myeloperoxidase (MPO), which is secreted by activated neutrophils. [3] Although hypochlorous acid plays important roles in the human immune-defense system, overproduction of ROS in living organism has detrimental effects on biological molecules, including nucleic acids, lipids, and proteins, resulting in the inhibition of various protein functions, and contributes to the progression of numerous human diseases, such as atherosclerosis, cancer, cardiovascular diseases, and rheumatoid arthritis. [4] Despite its importance in human health and disease, not as much is known about the mechanism of action and specific roles of HOCl in living systems in comparison with other ROS, owing to slower progress in the development of suitable probes. Several fluorescence probes for the detection and visualization of HOCl in living cells have recently been developed on the basis of the strong oxidizing properties of HOCl. [5–7] HOCl-induced oxidation reactions were employed in the design of fluorescent probes in which the fluorescence properties were regulated by the conversion of the spirocyclic form of rhodamine fluorophores into their ringopened form, [5] or through photoinduced-electron-transfer processes. [6] To facilitate practical applications of such probes, next-generation designs should emphasize higher analyte selectivity, limit susceptibility to autooxidation, and avoid demanding multistep syntheses. Herein, we report the facile synthesis and properties of a new boron-dipyrromethene (BODIPY) dye bearing a methylthioether group, and its biological application as a highly sensitive and selective

Excimers Beyond Pyrene: A Far‐Red Optical Proximity Reporter and its Application to the Label‐Free Detection of DNA

A family of organic chromophores that, like pyrene, forms emissive excimers is reported. Their chemical and photophysical properties are superior to pyrene for the design of chemo- and biosensors. Unlike hydrophobic pyrene, which requires excitation by cell-damaging UV irradiation, these polar dyes absorb strongly in the visible range, and their excimers emit brightly in the red to far-red region of the electromagnetic spectrum. The intensity of the emission signal is greatly increased upon formation of a preassociated dimer that is triggered upon aggregation or crystallization. In demonstration of the potential of this new family of excimer-forming dyes, a probe that is capable of detecting label-free DNA in water down to 10 pM and also doubles as a visualization agent for DNA in gel electrophoresis is reported.

A Gold Nanoparticle‐Based Fluorescence Turn‐On Probe for Highly Sensitive Detection of Polyamines

Herein, we report an ex-tension of this strategy to the design of a highly sensitiveand convenient fluorescence turn-on sensing of polyaminesbased on modulation of the efficiency of energy transfer be-tween fluorescent dyes and AuNPs.Figure 1 shows our approach for sensing polyamines. Wefirst adsorbed positively charged BODIPY dyes (2-PR

An Iminocoumarin-Based Fluorescent Probe for the Selective Detection of Dual-Specific Protein Tyrosine Phosphatases

Protein tyrosine phosphatases (PTPs), together with protein tyrosine kinases (PTKs), are crucial modulators in regulating cellular signaling transduction pathways. Dysfunction in PTP activity is associated with several human diseases, such as cancer, diabetes, and autoimmune disorders. Therefore, sensitive assessment of PTP activity is highly valuable in biological and biomedical research. While several assays relying on radioactive, electroactive, and fluorescent labeling techniques have been developed, fluorescencebased assays are attractive tools to achieve label-free phosphatase activity measurements due to their high sensitivity, rapid detection, and applicability to high-throughput screening (HTS) for PTP inhibitors and activators. A fluorescence-based assay frequently employs fluorogenic enzyme substrates incorporating a chromophore, the fluorescence properties of which change as a result of enzymatic cleavage. The key advantages of such an assay lie in its simplicity and the fact that the signal produced is directly related to the enzyme-catalyzed reaction. The most popular fluorogenic probes for monitoring PTP activity have been commercially available coumarin or fluorescein derivatives, in which an increase in fluorescence intensity occurs upon the enzyme-catalyzed hydrolysis of a phosphate group. These probes are apt at detecting generic phosphatase activity, but lack the specificity required for profiling a specific PTP or group of PTPs among more than 100 PTPs with a highly conserved catalytic domain in the human body. Small-molecule-based fluorogenic probes to selectively detect a specific PTP remain underdeveloped. Very recently, we reported a highly specific fluorescent probe for PTP detection based on an excited-state intramolecular-proton-transfer (ESIPT) mechanism in aqueous solutions. This probe exhibited high selectivity for a single dual-specific PTP, MKP-6. The high selectivity for dual-specific PTPs was ascribed to the wider and shallower active sites of dual-specific PTPs in contrast to classical PTPs, which have deep and narrow active sites. As a continuation of our interest in the development of selective PTP probes, we envisioned a fluorescent probe with a dosimetric response to dual-specific PTPs. Herein, we report the design, synthesis, and application of a fluorescent probe for the detection of PTP activity with high sensitivity and selectivity and low background signal. An iminocoumarin scaffold was selected in the design of a fluorescence probe for monitoring PTP activity. This fluorophore is an analogue of coumarin dyes, and is characterized by its excellent photophysical properties, such as high photostability and high fluorescence quantum yields. 8] Iminocoumarins can be excited at longer wavelengths than coumarin analogues, hence increasing their suitability for biological applications. The chemical structure of probe 1 is based on the donor– acceptor dye, 9-(dicyanovinyl)julolidine (DCVJ), which is identified as a fluorescent molecular rotor. A julolidinebased molecular rotor usually exhibits low fluorescence quantum yield in solution, which is attributed to rapid nonradiative deactivation of the singlet excited state through torsional relaxation around the single bond interconnecting the julolidine and dicyanovinyl subunits. Increases in rigidity and viscosity tend to restrict the internal molecular rotation, hence leading to a decrease in the nonradiative decay rate and consequently to an increase in the fluorescence quantum yield. Scheme 1 depicts our proposed sensing scheme in which phosphatase-catalyzed hydrolysis triggers P O bond cleavage of weakly fluorescent probe 1 and subsequent intramolecular nucleophilic attack of the phenol[a] T.-I. Kim, Prof. Y. Kim Department of Chemistry, Dankook University 126 Jukjeon-dong, Yongin-si, Gyeonggi-do 448-701 (Korea) Fax: (+82) 31-8005-3148 E-mail : youngmi@dankook.ac.kr [b] M. S. Jeong, Dr. S. J. Chung BioNanotechnology Research Center KRIBB and Nanobio Division, UST 52 Eoeun-dong, Yuseong, Daejeon 305-333 (Korea) [] These authors contributed equally to this work. Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201000154.

Tailoring the Solid‐State Fluorescence Emission of BODIPY Dyes by meso Substitution

4,4-Difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) derivatives bearing varied substituents at the meso position (i.e., CF3 , CH3 , COOR, CHO, CN, Cl, iPr) were synthesized to elucidate the structure-property relationships that give rise to emissive J-aggregates. Several new BODIPY derivatives can be added to the previously reported 1,3,5,7-tetramethyl-8-trifluoromethyl derivative to the list of those forming J-aggregates, in addition to other dyes that are emissive in the solid state without forming J-aggregates.

An improved fluorogenic substrate for the detection of alkaline phosphatase activity.

We designed a new alkaline phosphatase (ALP)-sensitive fluorogenic probe in which a self-immolative spacer group, p-hydroxybenzyl alcohol, is linked to a profluorogenic compound to improve substrate specificity. Enzymatic hydrolysis converts the fluorogenic substrate 1 to a highly fluorescent reporter 3, thus allowing for the fast and quantitative analysis of ALP activity with greatly increased affinity for the enzyme.

A New Strategy for Fluorogenic Esterase Probes Displaying Low Levels of Non-specific Hydrolysis.

A new design for fluorescence probes of esterase activity that features a carboxylate-side pro-fluorophore is demonstrated with boron dipyrromethene (BODIPY)-based probes 1 a and 1 b. Because the design relies on the enzyme-catalyzed hydrolysis of an ester group that is not electronically activated, these probes exhibit a stability to background hydrolysis that is far superior to classical alcohol-side profluorophore-based probes, large signal-to-noise ratios, reduced sensitivity to pH variations, and high enzymatic reactivity. The utility of probe 1 a was established with a real-time fluorescence imaging experiment of endogenous esterase activity that does not require washing of the extracellular medium.

Fluorogenic assay of alkaline phosphatase activity based on the modulation of excited-state intramolecular proton transfer.

A new fluorogenic substrate 1, which enables the fast and quantitative analysis of alkaline phosphatase activity, has been developed. Selective enzymatic hydrolysis of 1 instantly generated fluorescent compound 2 in aqueous media, which undergo an excited-state intramolecular proton transfer process, resulting in a remarkable fluorescence turn-on signal with an unusually large Stokes shift.

Gold nanoparticle-based fluorescent “turn-on” sensing system for the selective detection of mercury ions in aqueous solution

In this study, a simple and straightforward fluorometric assay using dye-adsorbed gold nanoparticles (AuNPs) was used in the highly selective and sensitive detection of mercury ions in aqueous buffer solution. Through the strong affinity of Hg atoms for Au, Hg atoms in situ generated by the reduction of Hg(II) ions in the presence of citrate ions on the surface of AuNPs displaced cationic BODIPY dye (1-PPh3+) from the fluorescence-quenched AuNP/1-PPh3+ adsorbate, leading to a significant increase in fluorescence intensity. The AuNP/1-PPh3+ adsorbate-based sensing system provided a rapid response upon the addition of Hg(II) ions, with highly fluorescent turn-on signals and excellent selectivity.