Mercury ions can easily pass through biological membranes and cause serious damage to the central nervous and endocrine systems. [1] Therefore, imaging of Hg 2+ ions in living cells is crucial for the elucidation of their biological effects. Fluorescence spectroscopy has become a powerful tool for sensing and imaging trace amounts of samples because of its simplicity and sensitivity. [2] Thus, the development of fluorescent Hg 2+ probes, [3] particularly those that have practical application in living cells, [4] has attracted much attention. Most reported examples of fluorescent sensing of Hg 2+ ions in living cells function by the enhancement of fluorescence signals. However, as the change in fluorescence intensity is the only detection signal, factors such as instrumental efficiency, environmental conditions, and the probe concentration can interfere with the signal output. [5] Ratiometric sensors can eliminate most or all ambiguities by selfcalibration of two emission bands. [6] Ratiometric probes can be designed to function following two mechanisms: intramolecular charge transfer (ICT) and fluorescence resonance energy transfer (FRET). ICT probes have been frequently reported and some work well under physiological conditions. Two aspects which potentially influence the accuracy of ICT probes are: 1) Binding of the target ions promotes or inhibits ICT interactions, which results in remarkable shifts of the sensors absorption maxima; but if multiple excitation wavelengths are used to match the different excitation maxima, their difference in efficiency may be a potential origin of inaccuracy. 2) Relatively broad fluorescence spectra are often observed for ICT fluorophores; in a significant number of cases the broad fluorescence spectra before and after binding target ions have a high degree of overlap (or in an extreme case, a broad spectrum with high intensity completely covers one with lower intensity), which makes it difficult to accurately determine the ratio of the two fluorescence peaks. Theoretically, the above problems can be avoided by using a FRET-based sensor for which the single excitation wavelength of a donor fluorophore results in emission of the acceptor at a longer wavelength. [7] Herein we present a BODIPY-rhodamine (BODIPY = boron-dipyrromethene) FRET "off-on" system 3 as a ratiometric and intracellular Hg 2+ sensor. A leuco-rhodamine derivative was chosen as a sensitive and selective chemosensor for Hg 2+ ions. This was inspired by Tae and co-workers as well as other research groups, [8] , who used these leuco derivatives with unconjugated structures as fluorogenic and chromogenic sensors. A highly efficient ring-opening reaction induced by Hg 2+ generates the long-wavelength rhodamine fluorophore which can act as the energy acceptor. BODIPY [9] was chosen as the energy donor because its intense fluorescence is insensitive to environmental factors and its fluorescence spectrum matches well with the absorption spectrum of rhodamine. The choice of the connection between the donor and acceptor ...

It is still a significant challenge to develop a Zn(2+)-selective fluorescent sensor with the ability to exclude the interference of some heavy and transition metal (HTM) ions such as Fe(2+), Co(2+), Ni(2+), Cu(2+), Cd(2+), and Hg(2+). Herein, we report a novel amide-containing receptor for Zn(2+), combined with a naphthalimide fluorophore, termed ZTRS. The fluorescence, absorption detection, NMR, and IR studies indicated that ZTRS bound Zn(2+) in an imidic acid tautomeric form of the amide/di-2-picolylamine receptor in aqueous solution, while most other HTM ions were bound to the sensor in an amide tautomeric form. Due to this differential binding mode, ZTRS showed excellent selectivity for Zn(2+) over most competitive HTM ions with an enhanced fluorescence (22-fold) as well as a red-shift in emission from 483 to 514 nm. Interestingly, the ZTRS/Cd(2+) complex showed an enhanced (21-fold) blue-shift in emission from 483 to 446 nm. Therefore, ZTRS discriminated in vitro and in vivo Zn(2+) and Cd(2+) with green and blue fluorescence, respectively. Due to the stronger affinity, Zn(2+) could be ratiometrically detected in vitro and in vivo with a large emission wavelength shift from 446 to 514 nm via a Cd(2+) displacement approach. ZTRS was also successfully used to image intracellular Zn(2+) ions in the presence of iron ions. Finally, we applied ZTRS to detect zinc ions during the development of living zebrafish embryos.

A Cu(II)-sensing, ratiometric, and selective fluorescent sensor 1, N-butyl-4,5-di[(pyridin-2-ylmethyl)amino]-1,8-naphthalimide, was designed and synthesized on the basis of the mechanism of internal charge transfer (ICT). In aqueous ethanol solutions of 1, the presence of Cu(II) induces the formation of a 1:1 metal-ligand complex, which exhibits a strong, increasing fluorescent emission centered at 475 nm at the expense of the fluorescent emission of 1 centered at 525 nm. [structure: see text]

A selective and sensitive fluorescent chemosensor for Hg2+, which was composed of two aminonaphthalimide fluorophores and a receptor of 2,6-bis(aminomethyl)pyridine, was synthesized through the reaction of 2,6-bis(chloromethyl)pyridine and N-[2-(2-hydroxyethoxy)ethyl]-4-piperazino-1,8-naphthalimide. The chemosensor showed an about 17-fold increase in fluorescence quantum yield upon addition of 1 equiv of Hg2+ in neutral buffer aqueous solution, and the other common metal ions did not notably disturb the detection of Hg2+.

Replacement of the oxygen with a silicon atom on the rhodamine framework produces a strong red-emission fluorophore which has a high molar extinction coefficient and 90 nm red shift relative to rhodamine dye PY.

The novel luminescent gold(I) complex [N-(N',N'-dimethylaminoethyl)-1,8-naphthalimide-4-sulfide](triethylphosphine)gold(I) was prepared and investigated for its primary biological properties. Cell culture experiments revealed strong antiproliferative effects and induction of apoptosis via mitochondrial pathways. Biodistribution studies by fluorescence microscopy and atomic absorption spectroscopy showed the uptake into cell organelles, an accumulation in the nuclei of tumor cells, and a homogeneous distribution in zebrafish embryos. In vivo monitoring of vascularisation in developing zebrafish embryos revealed a significant anti-angiogenic potency of the complex. Mechanistic experiments indicated that the inhibition of thioredoxin reductase (based on the covalent binding of a gold triethylphosphine fragment) might be involved in the pharmacodynamic behavior of this novel gold species.

A highly selective and sensitive OFF-ON fluorescent sensor 1, employing the PET mechanism, was designed and synthesized. It could be used to detect Cd(2+) ion in aqueous solution and to image Cd(2+) ion in living cells. The fluorescence intensity significantly enhanced about 195-fold and the quantum yield increased almost 100-fold. Moreover the fluorescence intensity of 1 increased linearly with high sensitivity (0-1 microM) toward Cd(2+).

Based on the hypoxia prodrug moiety of p-nitrobenzyl, a selective ratiometric fluorescent sensor (RHP) for the detection of microenvironment hypoxia was designed and synthesized. RHP can be selectively activated by bioreductive enzymes (NTR) and results in an evident blue to green fluorescent emission wavelength change in both solution phases and in cell lines, which might be the first fluorescent ratiometric probe for hypoxia in solid tumors.