Design strategies for water-soluble small molecular chromogenic and fluorogenic probes.

Hydrogen sulfide (H2S), a gaseous species produced by both bacteria and higher eukaryotic organisms, including mammalian vertebrates, has attracted attention in recent years for its contributions to human health and disease. H2S has been proposed as a cytoprotectant and gasotransmitter in many tissue types, including mediating vascular tone in blood vessels as well as neuromodulation in the brain. The molecular mechanisms dictating how H2S affects cellular signaling and other physiological events remain insufficiently understood. Furthermore, the involvement of H2S in metal-binding interactions and formation of related RSS such as sulfane sulfur may contribute to other distinct signaling pathways. Owing to its widespread biological roles and unique chemical properties, H2S is an appealing target for chemical biology approaches to elucidate its production, trafficking, and downstream function. In this context, reaction-based fluorescent probes offer a versatile set of screening tools to visualize H2S pools in living systems. Three main strategies used in molecular probe development for H2S detection include azide and nitro group reduction, nucleophilic attack, and CuS precipitation. Each of these approaches exploits the strong nucleophilicity and reducing potency of H2S to achieve selectivity over other biothiols. In addition, a variety of methods have been developed for the detection of other reactive sulfur species (RSS), including sulfite and bisulfite, as well as sulfane sulfur species and related modifications such as S-nitrosothiols. Access to this growing chemical toolbox of new molecular probes for H2S and related RSS sets the stage for applying these developing technologies to probe reactive sulfur biology in living systems.

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Chemical probes for molecular imaging and detection of hydrogen sulfide and reactive sulfur species in biological systems

Coordination chemistry plays an essential role in the design of photoluminescent probes for metal ions. Metal coordination to organic dyes induces distinct optical responses which signal the presence of metal species of interest. Luminescent lanthanide (Ln(3+)) and transition metal complexes of d(6), d(8) and d(10) configurations often exhibit unique luminescence properties different from organic dyes, such as high quantum yield, large Stokes shift, long emission wavelength and emission lifetimes, low sensitivity to microenvironments, and can be explored as lumophores to construct probes for metal ions, anions and neutral species. In this review, the design principles and coordination chemistry of metal probes based on mechanisms of PeT, PCT, ESIPT, FRET, and excimer formation will be discussed in detail. Particular attention will be given to rationales for the design of turn-on and ratiometric probes. Moreover, phosphorescent probe design based on Ln(3+) and d(6), d(8) and d(10)-metal complexes are also presented via discussing certain factors affecting the phosphorescence of these metal complexes. A survey of the latest progress in photoluminescent probes for identification of essential metal cations in the human body or toxic metal cations in the environment will be presented focusing on their design rationales and sensing behaviors. Metal complex-based photoluminescent probes for biorelated anions such as PPi, and neutral biomolecules ATP, NO, and H(2)S will be discussed also in the context of their metal coordination-related sensing behaviors and design approaches.

Metal coordination in photoluminescent sensing

Xin Zhou,†,‡ Songyi Lee,† Zhaochao Xu,* and Juyoung Yoon*,† †Department of Chemistry and Nanoscience, Ewha Womans University, Seoul 120-750, Republic of Korea ‡Research Center for Chemical Biology, Department of Chemistry, Yanbian University, Yanjii 133002, People’s Republic of China Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Shahekou, Dalian, Liaoning, People’s Republic of China

Recent Progress on the Development of Chemosensors for Gases.

A Ratiometric Fluorescent Probe for Rapid Detection of Hydrogen Sulfide in Mitochondria

A novel selective fluorescent chemosensor based on an 8-hydroxyquinoline-appended fluorescein derivative (L1) was synthesized and characterized. Once combined with Cu2+, it displayed high specificity for sulfide anion. Among the various anions, only sulfide anion induced the revival of fluoresecence of L1, which was quenched by Cu2+, resulting in “off–on”-type sensing of sulfide anion. What’s more, the sensor was retrievable to indicate sulfide anions with Cu2+, and S2–, in turn, increased. With the addition of Cu2+, compound L1 could give rise to a visible pink-to-yellow color change and green fluorescence quenching. The resulting yellow solution could change to pink and regenerate to green fluorescence immediately upon the addition of sulfide anion; however, no changes were observed in the presence of other anions, including CN–, P2O74–, and other forms of sulfate, making compound L1 an extremely selective and efficient sulfide chemosensor. The signal transduction occurs via reversible formation–separat...

A retrievable and highly selective fluorescent probe for monitoring sulfide and imaging in living cells.

We report the development of a fluorescein-based chemosensor (L1) for monitoring ions or micromolecules (H(2)S). Copper ions are known to be toxic at high concentrations and hydrogen sulfide induces various problems. Herein we develop a simple method for detecting Cu(II) and H(2)S with high selectivity and sensitivity. The chemosensor L1 displays on-off-on type fluorescence change with alternately added Cu(II) and H(2)S to the media along with reversible forming-separating of the complex. The potential biomedical relevance of the chemical mechanisms involved in the detection of L1 is described.

Recognition of copper and hydrogen sulfide in vitro using a fluorescein derivative indicator

In bone tissue engineering, it is imperative to design multifunctional biomaterials that can induce and assemble bonelike apatite that is close to natural bone. In this study, graphene oxide (GO) was functionalized by carrageenan. The resulting GO-carrageenan (GO-Car) composite was further used as a substrate for biomimetic and cell-mediated mineralization of hydroxyapatite (HA). It was confirmed that carrageenan on the GO surface facilitated the nucleation of HA. The observation of the effect of the GO-Car on the adhesion, morphology, and proliferation of MC3T3-E1 cells was investigated. In vitro studies clearly show the effectiveness of GO-Car in promoting HA mineralization and cell differentiation. The results of this study suggested that the GO-Car hybrid will be a promising material for bone regeneration and implantation.

Biomimetic and Cell-Mediated Mineralization of Hydroxyapatite by Carrageenan Functionalized Graphene Oxide

A sensitive colorimetric and ratiometric fluorescent probe for mercury species in aqueous solution and living cells.

A Fe3+ chemosensor L1 was successfully synthesized with a quinoline moiety bound to rhodamine 6G hydrazide. The sensor L1 shows high selectivity and sensitivity to Fe3+ in aqueous solution in the presence of other trace metal ions in organisms, abundant cellular cations and prevalent toxic metal ions in the environment. In addition, biological imaging and micro computed tomography (MCT) technology studies have demonstrated that L1 could act as a turn-on fluorescent chemosensor for Fe3+ in living cells.

Ju Cheng

Papers

A retrievable and highly selective fluorescent probe for monitoring sulfide and imaging in living cells.

Recognition of copper and hydrogen sulfide in vitro using a fluorescein derivative indicator

Biomimetic and Cell-Mediated Mineralization of Hydroxyapatite by Carrageenan Functionalized Graphene Oxide

A sensitive colorimetric and ratiometric fluorescent probe for mercury species in aqueous solution and living cells.

Selective off-on fluorescent chemosensor for detection of Fe3+ ions in aqueous media.