Recent Advances in Dual-target-activated Fluorescent Probes for Biosensing and Bioimaging.

Fluorescent probes have been powerful tools for visualizing and quantifying multiple dynamic processes in living cells. However, the currently developed probes are often constructed by conjugation a fluorophore with a recognition moiety and given signal-output after triggering with one singly target interest. Compared with the single-target-activated fluorescent probes mentioned above, the dual-target-activated ones, triggering with one target under stimulus (such as photoirradiation, microenvironment) or another targets, have the advantages of advoiding nonspecific activation and "false positive" results in complicated environments. In recent years, many dual-target-activated fluorescent probes have been developed to detect various biologically relevant species. In view of the importance of a comprehensive understanding of dual-target- activated fluorescent probes, a thorough summary of this topic is urgently needed. However, no comprehensive and critical review on dual target activated fluorescent probes has been published recently. In this review, we focus on the dual-target-activated fluorescent probes and briefly outline their types and current state of development. In each type, the chemical structure, proposed responsive mechanism and application of probes are highlighted. At last, the challenges and prospective opportunities of every type were proposed.

Efficient fluorescence resonance energy transfer-based ratiometric fluorescent cellular imaging probe for Zn(2+) using a rhodamine spirolactam as a trigger.

This letter described the design and synthesis of a novel fluorescein-appended rhodamine spirolactam derivative and its preliminary application as a ratiometric fluorescent cellular imaging probe for Zn(2+). The ratiometric fluorescent signal change of the probe is based on an intramolecular fluorescence resonance energy transfer (FRET) mechanism modulated by a specific metal ion induced ring-opening process of the rhodamine spirolactam (acting as a trigger). In the new developed sensing system, the emission peaks of the two fluorophores are well-resolved, which can avoid the emission spectra overlap problem generally met by spectra-shift type probes and benefits for observation of fluorescence signal change at two different emission wavelengths with high resolution. It also benefits for a large range of emission ratios, thereby a high sensitivity for Zn(2+)detection. Under optimized experimental conditions, the probe exhibits a stable response for Zn(2+) over a concentration range from 2.0 x 10(-7) to 2.0 x 10(-5) M, with a detection limit of 4.0 x 10(-8) M. Most importantly, the novel probe has well solved the problem of serious interferences from other transition metal ions generally met by previously reported typical fluorescent probes for Zn(2+) with the di(2-picolyl)amine moiety as the receptor (in this case, the fluorescence response induced by Cd(2+)is even comparable to that of Zn(2+)) and shows a reversible and fast response toward Zn(2+). All these unique features make it particularly favorable for ratiometric cellular imaging investigations. It has been preliminarily used for ratiometric imaging of Zn(2+) in living cells with satisfying resolution.

Highly sensitive and selective colorimetric and off-on fluorescent chemosensor for Cu2+ in aqueous solution and living cells.

The design and synthesis of a novel rhodamine spirolactam derivative and its application in fluorescent detections of Cu(2+) in aqueous solution and living cells are reported. The signal change of the chemosensor is based on a specific metal ion induced reversible ring-opening mechanism of the rhodamine spirolactam. It exhibits a highly sensitive "turn-on" fluorescent response toward Cu(2+) in aqueous solution with an 80-fold fluorescence intensity enhancement under 10 equiv of Cu(2+) added. This indicates that the synthesized chemosensor effectively avoided the fluorescence quenching for the paramagnetic nature of Cu(2+) via its strong binding capability toward Cu(2+). With the experimental conditions optimized, the probe exhibits a dynamic response range for Cu(2+) from 8.0 x 10(-7) to 1.0 x 10(-5) M, with a detection limit of 3.0 x 10(-7) M. The response of the chemosensor for Cu(2+) is instantaneous and reversible. Most importantly, both the color and fluorescence changes of the chemosensor are remarkably specific for Cu(2+) in the presence of other heavy and transition metal ions (even those that exist in high concentration), which meet the selective requirements for biomedical and environmental monitoring application. The proposed chemosensor has been used for direct measurement of Cu(2+) content in river water samples and imaging of Cu(2+) in living cells with satisfying results, which further demonstrates its value of practical applications in environmental and biological systems.

A ratiometric chemosensor for fluorescent determination of Hg(2+) based on a new porphyrin-quinoline dyad.

Quinolin-8-ol p-[10',15',20'-triphenyl-5'-porphyrinyl]benzoate (1) was synthesized for the first time and developed as a ratiometric fluorescent chemosensor for recognition of Hg(2+) ions in aqueous ethanol with high selectivity. The 1-Hg(2+) complexation quenches the fluorescence of porphyrin at 646nm and induces a new fluorescent enhancement at 603nm. The fluorescent response of 1 towards Hg(2+) seems to be caused by the binding of Hg(2+) ion with the quinoline moiety, which was confirmed by the absorption spectra and (1)H NMR spectrum. The fluorescence response fits a Hill coefficient of 1 (1.0308), indicating the formation of a 1:1 stoichiometry for the 1-Hg(2+) complex. The analytical performance characteristics of the chemosensor were investigated. The sensor shows a linear response toward Hg(2+) in the concentration range of 3x10(-7) to 2x10(-5)M with a limit of detection of 2.2x10(-8)M. Chemosensor 1 shows excellent selectivity to Hg(2+) over transition metal cations except Cu(2+), which quenches the fluorescence of 1 to some extent when it exists at equal molar concentration. Moreover, the chemosensor are pH-independent in 5.0-9.0 and show excellent selectivity for Hg(2+) over transition metal cations.

A fluorescent probe for zinc ions based on N-methyltetraphenylporphine with high selectivity.

N-methyl-alpha,beta,gamma,delta-tetraphenylporphine (NMTPPH) has been used to detect trace amount of zinc ions in ethanol-water solution by fluorescence spectroscopy. The fluorescent probe undergoes a fluorescent emission intensity enhancement upon binding to zinc ions in EtOH/H(2)O (1:1, v/v) solution. The fluorescence enhancement of NMTPPH is attributed to the 1:1 complex formation between NMTPPH and Zn(II) which has been utilized as the basis for the selective detection of Zn(II). The linear response range covers a concentration range of Zn(II) from 5.0x10(-7) to 1.0x10(-5)mol/L and the detection limit is 1.5x10(-7)mol/L. The fluorescent probe exhibits high selectivity over other common metal ions except for Cu(II).

A porphyrin derivative containing 2-(oxymethyl)pyridine units showing unexpected ratiometric fluorescent recognition of Zn2+ with high selectivity.

A porphyrin derivative (1), containing two 2-(oxymethyl)pyridine units has been designed and synthesized as chemosensor for recognition of metal ions. Unlike many common porphyrin derivatives that show response to different heavy metal ions, compound 1 exhibits unexpected ratiometric fluorescence response to Zn(2+) with high selectivity. The response of the novel chemosensor to zinc was based on the porphyrin metallation with cooperating effect of 2-(oxymethyl)pyridine units. The change of fluorescence of 1 was attributed to the formation of an inclusion complex between porphyrin ring and Zn(2+) by 1:1 complex ratio (K=1.04x10(5)), which has been utilized as the basis of the fabrication of the Zn(2+)-sensitive fluorescent chemosensor. The analytical performance characteristics of the proposed Zn(2+)-sensitive chemosensor were investigated. The sensor can be applied to the quantification of Zn(2+) with a linear range covering from 3.2x10(-7) to 1.8x10(-4) M and a detection limit of 5.5x10(-8) M. The experiment results show that the response behavior of 1 to Zn(2+) is pH-independent in medium condition (pH 4.0-8.0) and show excellent selectivity for Zn(2+) over transition metal cations.

A highly selective potentiometric sensor of molybdate based on a mu-oxo-bridged manganeseporphyrin dimer.

A novel high-selective potentiometric sensor for molybdate was prepared with a PVC membrane combining mu-oxo-bis[5,10,15,20-tetra(p-methylphenyl)porphinatomanganese(III)] [[Mn(p-Me)TPP](2)O] as an electroactive material and 2-nitrophenyl octyl ether (o-NPOE) as a plasticizer in the percentage ratio of 3:65:32, [Mn(p-Me)TPP](2)O:o-NPOE:PVC (w:w). The sensor exhibited a linear response with a Nernstian slope of 30.5 mV per decade within a concentration range of 2.1 x 10(-6) to 1.0 x 10(-1) M MoO4(2-), with a working pH range from 5.0 to 12.5, and a fast response time of less than 15 s. The electrode showed improved selectivity toward molybdate with respect to common coexisting anions compared to monometalloporphyrin counterparts. Several electroactive materials and solvent mediators were compared and the experimental conditions were optimized. The sensor is preliminary applied to the assay of MoO4(2-) in corrosion inhibitor samples with satisfactory results.

A wide pH range optical sensing system based on a sol-gel encapsulated amino-functionalized corrole.

The synthesis of a new compound, 10-(4-aminophenyl)-5,15-dimesitylcorrole, and its application for the preparation of optical chemical pH sensors is described. The dye materials were immobilized in a sol-gel glass matrix and characterised upon exposure to aqueous buffer solutions. The response of the sensor is based on the fluorescence intensity changing of corrole owing to multiple steps of protonation and deprotonation. Due to its containing several proton sensitive centers, the 10-(4-aminophenyl)-5,15-dimesitylcorrole based optode shows a wider response range toward pH than that of tetraphenylporphyrin (TPPH(2)) and 5,10,15-tris(pentafluorophenyl)corrole (H(3)(tpfc)). It shows a linear pH response in the range of 2.17-10.30. The effect of the composition of the sensor membrane has been studied and the experimental conditions were optimized. The optode showed good reproducibility and reversibility, and common co-existing inorganic ions did not show obvious interference to its pH measurement.

A fluorescent chemical sensor for Hg(II) based on a corrole derivative in a PVC matrix.

A fluorescent chemical sensor for Hg(II) using 5,10,15-tris(pentafluorophenyl)corrole (H(3)(tpfc)) as fluorophore is described in this paper. The response of the sensor is based on the fluorescence quenching of H(3)(tpfc) by coordination with Hg(II). H(3)(tpfc) based sensor shows a linear response towards Hg(II) in the concentration range from 1.2x10(-7) to 1.0x10(-4)M, with a working pH range from 5.0 to 8.0. The response time for Hg(II) concentration