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

Near-infrared (NIR) fluorescent sensors have emerged as promising molecular tools for imaging biomolecules in living systems. However, NIR fluorescent sensors are very challenging to be developed. Herein, we describe the discovery of a new class of NIR fluorescent dyes represented by 1a/1c/1e, which are superior to the traditional 7-hydroxycoumarin and fluorescein with both absorption and emission in the NIR region while retaining an optically tunable hydroxyl group. Quantum chemical calculations with the B3LYP exchange functional employing 6-31G(d) basis sets provide insights into the optical property distinctions between 1a/1c/1e and their alkoxy derivatives. The unique optical properties of the new type of fluorescent dyes can be exploited as a useful strategy for development of NIR fluorescent sensors. Employing this strategy, two different types of NIR fluorescent sensors, NIR-H2O2 and NIR-thiol, for H2O2 and thiols, respectively, were constructed. These novel sensors respond to H2O2 or thiols with a...

A unique approach to development of near-infrared fluorescent sensors for in vivo imaging.

Nitroreductase (NTR) can be overexpressed in hypoxic tumors, thus the selective and efficient detection of NTR is of great importance. To date, although a few optical methods have been reported for the detection of NTR in solution, an effective optical probe for NTR monitoring in vivo is still lacking. Therefore, it is necessary to develop a near-infrared (NIR) fluorescent detection probe for NTR. In this study, five NIR cyanine dyes with fluorescence reporting structure decorated with different nitro aromatic groups, Cy7-1–5, have been designed and explored for possible rapid detection of NTR. Our experimental results presented that only a para-nitro benzoate group modified cyanine probe (Cy7-1) could serve as a rapid NIR fluorescence-enhanced probe for monitoring and bioimaging of NTR. The structure–function relationship has been revealed by theoretical study. The linker connecting the detecting and fluorescence reporting groups and the nitro group position is a key factor for the formation of hydrogen ...

Ultrasensitive near-infrared fluorescence-enhanced probe for in vivo nitroreductase imaging.

Coumarin compounds represent an important type of naturally occurring and synthetic oxygen-containing heterocycles with typical benzopyrone framework. This type of special benzopyrone structure enables its derivatives readily interact with a diversity of enzymes and receptors in organisms through weak bond interactions, thereby exhibit wide potentiality as medicinal drugs. So far, some coumarin-based drugs such as anticoagulant and antineurodegenerative agents have been extensively used in clinic. Coumarin-containing supramolecular medicinal agents as a new increasing expansion of supramolecular chemistry in pharmaceutical science have also been actively investigated in recent years. Coumarin-derived artificial ion receptors, fluorescent probes and biological stains are growing quickly and have a variety of potential applications in monitoring timely enzyme activity, complex biological events as well as accurate pharmacological and pharmacokinetic properties. This review provides a systematic summary and insight of the whole range of medicinal chemistry in the current developments of coumarin compounds as anticoagulant, antineurodegenerative, anticancer, antioxidative, antibacterial, antifungal, antiviral, antiparasitic, antiinflammatory and analgesic, antidiabetic, antidepressive and other bioactive agents as well as supramolecular medicinal drugs, diagnostic agents and pathologic probes, and biological stains. Some rational design strategies, structure-activity relationships and action mechanisms are discussed. The perspectives of the future development of coumarinbased medicinal chemistry are also presented.

Current Developments of Coumarin Compounds in Medicinal Chemistry

A highly selective and sensitive fluorescence probe, 7-[(5-nitrofuran-2-yl)methoxy]-3H-phenoxazin-3-one (1), is developed for imaging the hypoxic status of tumor cells via the indirect detection of nitroreductase. The detection mechanism is based on the fact that nitroreductase can selectively catalyze the reduction of the nitro group in 1 to a hydroxylamine or amino group in the presence of reduced nicotinamide adenine dinucleotide as an electron donor that is indispensable, followed by the 1,6-rearrangement–elimination and the release of resorufin. As a result, the reaction produces a distinct color and fluorescence change from almost colorless and nonfluorescent to pink and strong red fluorescence. The fluorescence increase of probe 1 at λ550/585 nm is directly proportional to the concentration of nitroreductase in the range of 15–300 ng/mL, with a detection limit of 0.27 ng/mL. The ready reduction of the nitro group in 1 under hypoxic conditions leads to the establishment of a sensitive and selective ...

Nitroreductase Detection and Hypoxic Tumor Cell Imaging by a Designed Sensitive and Selective Fluorescent Probe, 7-[(5-Nitrofuran-2-yl)methoxy]-3H-phenoxazin-3-one

Development of a sensitive long-wavelength fluorogenic probe for nitroreductase: A new fluorimetric indictor for analyte determination by dehydrogenase-coupled biosensors

The synthesis and optical characterization of novel iminocoumarin derivatives

Salicylate hydroxylase (SHL) catalyzes the production of catechol (plus CO2 and H2O) from salicylate, NADH, and O2. Coimmobilization of SHL with a NAD(P)+-dependent dehydrogenase in front of a Clark-type oxygen electrode has been investigated in the development of a general type of dehydrogenase-based biosensors that can detect various biological analytes; however, currently, no fluorophores are available for these applications. We synthesized the first new long-wavelength latent fluorogenic substrate SHLF (3) for SHL. In the presence of NADH and under aerobic conditions, SHL catalyzes the decarboxylative hydroxylation of SHLF followed by a quinone−methide-type rearrangement reaction concomitant with the ejection of a fluorescence coumarin 2, which is spontaneous and irreversible at physiological temperatures in aqueous media. The fluorescence signal generated by this process is specific and, in the near red spectral region with an emission maximum at 595 nm, is suppressed by salicylic acid. The fluoresce...

Design and synthesis of a long-wavelength latent fluorogenic substrate for salicylate hydroxylase: a useful fluorimetric indicator for analyte determination by dehydrogenase-coupled biosensors.

Kun Li Wang

Papers

Development of a sensitive long-wavelength fluorogenic probe for nitroreductase: A new fluorimetric indictor for analyte determination by dehydrogenase-coupled biosensors

The synthesis and optical characterization of novel iminocoumarin derivatives

Design and synthesis of a long-wavelength latent fluorogenic substrate for salicylate hydroxylase: a useful fluorimetric indicator for analyte determination by dehydrogenase-coupled biosensors.