Hyo Sung Jung

Coumarin-Derived Cu2+-Selective Fluorescence Sensor: Synthesis, Mechanisms, and Applications in Living Cells

A novel coumarin-based fluorogenic probe bearing the 2-picolyl unit (1) was developed as a fluorescent chemosensor with high selectivity and suitable affinity in biological systems toward Cu(2+) over other cations tested. The fluorescence on-off mechanism was studied by femtosecond time-resolved fluorescence (TRF) upconversion technique and ab initio calculations. The receptor can be applied to the monitoring of Cu(2+) ion in aqueous solution with a pH span 4-10. To confirm the suitability of 1 for biological applications, we also employed it for the fluorescence detection of the changes of intracellular Cu(2+) in cultured cells. The results indicate that 1 should be useful for the fluorescence microscopic imaging and the study on the biological functions of Cu(2+).

Recent progress in luminescent and colorimetric chemosensors for detection of thiols

In the past few decades, the development of optical probes for thiols has attracted great attention because of the biological importance of the thiol-containing molecules such as cysteine (Cys), homocysteine (Hcy), and glutathione (GSH). This tutorial review focuses on various thiol detection methods based on luminescent or colorimetric spectrophotometry published during the period 2010-2012. The discussion covers a diversity of sensing mechanisms such as Michael addition, cyclization with aldehydes, conjugate addition-cyclization, cleavage of sulfonamide and sulfonate esters, thiol-halogen nucleophilic substitution, disulfide exchange, native chemical ligation (NCL), metal complex-displace coordination, and nanomaterial-related and DNA-based chemosensors.

Coumarin-based thiol chemosensor: synthesis, turn-on mechanism, and its biological application.

A new chemodosimetric probe (1) is reported that selectively detects thiols over other relevant biological species by the turning on of its fluorescence through a Michael type reaction. The fluorogenic process upon its reaction was revealed to be mediated by intramolecular charge transfer, as confirmed by time-dependent density functional theory calculations. The application of probe 1 to cells is also examined by confocal microscopy, and its cysteine preference was observed by an ex vivo LC-MS analysis of the cellular metabolite.

Cu2+ Ion-Induced Self-Assembly of Pyrenylquinoline with a Pyrenyl Excimer Formation

Synthesis of a novel pyrene derivative sensor (1) and its intermolecular binding pattern to Cu(2+) in CH(3)CN were investigated. Upon Cu(2+) binding, the sensor exhibited a strong static excimer emission at 460 nm, along with a weak monomer emission at 388 nm. The excimer emission intensity induced by the Cu(2+) ion declined as the spacer length between the pyrene and quinolinylamide unit increased. The Cu(2+) ion-induced self-assembled pyrenyl excimer formation is rationalized by fluorescence experiments and theoretical DFT calculations.

Molecular modulated cysteine-selective fluorescent probe.

We have synthesized a series of coumarins (1-3) that can emit fluorescence in a turn-on manner through a Michael-type reaction with thiol-containing compounds. The only difference among the coumarins is the position of a carboxyl group on its benzene ring moiety near the double-bond conjugated coumarin. Their selectivity for Cys, GSH, and Hcy as well as the associated fluorogenic mechanism were illustrated by fluorescence spectroscopy, DFT calculations, and kinetic studies. All isomers prefer Cys over GSH in the reaction from 48.6 (probe 3) to 111-fold (probe 1) as demonstrated in a second order kinetics. The high selectivity of probe 1 to Cys might be achieved since the ortho carboxyl group on its benzene ring prefers a less negatively charged nucleophile. During intracellular Cys detection using 1, a possible interference by a large amount of GSH in the HepG2 cells was evaluated. The cells were treated with l-buthionine sulfoximine (BSO), an inhibitor of γ-glutamylcysteine synthetase, providing an experimental condition where the cells could not synthesize GSH from Cys or other species. Then, the fluorescence intensity of 1 in HepG2 cells under BSO-H(2)O(2) treatment was strongly enhanced by N-acetylcysteine (NAC), a precursor of Cys, implicating that the fluorescence signal from the cells is mainly associated with changes in intracellular [Cys] rather than that in intracellular [GSH].

Rationally Designed Fluorescence Turn-On Sensors: A New Design Strategy Based on Orbital Control

Herein, we explore a new strategy in the chemo-sensor field for fluorescence amplification upon binding with metal ions based on controlled participation of the nitrogen lone pair orbital. The basic architecture of the sensor entails a fluorophore, the sp(2) hybridized nitrogen lone pair (-C═N-), and a chelator site referred to as the control part. Though nonplanar and nonfluorescent, compound IC1 achieved pseudo planarity from binding with Zn(2+) as indicated by the increased fluorescence signal. Its other analogue (IC2) is also planar, and unlike IC1-Zn(2+) was fluorescent with a lack of binding affinity to metal ions. The time-dependent density functional theory (TDDFT) calculations revealed that the fluorescence amplification was due to the blocking of the nitrogen lone pair orbital; unlikely geometrical rearrangements were insignificant. This could indicate a breakthrough concept in the future design of fluorescent turn-on sensors.

Enhanced NIR radiation-triggered hyperthermia by mitochondrial targeting.

Mitochondria are organelles that are readily susceptible to temperature elevation. We selectively delivered a coumarin-based fluorescent iron oxide nanoparticle, Mito-CIO, to the mitochondria. Upon 740 nm laser irradiation, the intracellular temperature of HeLa cells was elevated by 2.1 °C within 5 min when using Mito-CIO, and the treatment resulted in better hyperthermia and a more elevated cytotoxicity than HeLa cells treated with coumarin iron oxide (CIO), which was missing the mitochondrial targeting unit. We further confirmed these results in a tumor xenograft mouse model. To our knowledge, this is the first report of a near-infrared laser irradiation-induced hyperthermic particle targeted to mitochondria, enhancing the cytotoxicity in cancer cells. Our present work therefore may open a new direction in the development of photothermal therapeutics.

Fluorescent and colorimetric sensors for the detection of humidity or water content

In this tutorial review, we describe the current state of the art in water sensors and provide an overview of the major advances made in this field post 2000. The field is currently still in its early development stages and subject to continuous improvements, and the current work provides a structured approach describing different sensing mechanisms and potential future applications associated with each of these. With these developments and their potential implications for the diverse scientific fields requiring tight control over the water content, we strongly believe the discipline is potentially at the threshold of translation into more widespread application and we hope the current review might allow for an expedited process thereof.

Chromofluorescent Indicator for Intracellular Zn2+/Hg2+ Dynamic Exchange

The fluorescence of NABQ increases remarkably in the presence of Zn(2+) and is quenched by Hg(2+). As shown by confocal imaging, NABQ-Zn(2+) can penetrate cells, where the bound Zn(2+) is exchanged for Hg(2+). This results in the concomitant export of Hg(2+) from the cells, showing that NABQ can act as a Zn(2+) carrier and as a Hg(2+) extracting agent in living cells.

Chemical sensing of neurotransmitters

In the past few decades, the development of chemosensors for neurotransmitters has emerged as a research area of significant importance, which attracted a tremendous amount of attention due to its high sensitivity and rapid response. This current review focuses on various neurotransmitter detection based on fluorescent or colorimetric spectrophotometry published for the last 12 years, covering biogenic amines (dopamine, epinephrine, norepinephrine, serotonin, histamine and acetylcholine), amino acids (glutamate, aspartate, GABA, glycine and tyrosine), and adenosine.