Science: A cellular litmus test

litmus test. A color-changing organic ring with a lan- thanide metal at its center could act as a cellular litmus test, according to research- ers at ...
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News ment allows the use of a simple flowinjection system, and the samples (e.g. serum or beverages) need no preparation. The Diaz-Garcia group found the probe they were seeking in the form of a palladium complex (palladium-tetrakis(lmethyl-4-pyridyl)porphine) that shows intense RTP in the presence of dsDNA in aqueous solution. Time-resolved discrimination of the weak signals, which might come from RNA, single-stranded DNA (ssDNA), or other nucleotides or surfactants, is easily done. The approach requires the exclusion of oxygen from the system, which is accomplished with sodium sulfite. The nature of the DNApalladium-porphine complex is not yet known, a question that should be answered by X-ray analysis after crystals are obtained. So far, only preliminary experiments have been performed with the DNApalladium complex, but they show that this strategy is promising. An opttcal sensing device that incorporates the complex is the

next step for Diaz-Garcia's group. "This optical sensor will be thefirstfor nucleic acids based on RTP," she says. Besides a sensor for dsDNA another application could be the detection of ssDNA If ssDNA in the sample intercalates wiih ssDNA immobilized on an optical fiber, ,he palladium complex will emit a phosphorescence signall A look into the future? Diaz-Garcia is full of ideas: "A more demanding scientific dream consists in die possibility of using RTP probes for flow cytometry. Howeverr the few microseconds during which a single sample, such as a cell, traverses the light beam in a flow cytometer imposes some constraints on the luminescing probe; long emission lifetimes are less useful. But RTP systems are simple with regard to sample preparation and the reagents needed. Therefore, it will be necessary to alter the flow cytometer by introducing a pulsed excitation source and a synchronized detector, for example." Veronika R. Meyer

A cellular litmus test A color-changing organic ring with a lanthanide metal at its center could act as a cellular litmus test, according to researchers at the University of Durham (U.K.). David Parker usually designs clinical imaging and targeting agents but realized that his chemical know-how could help in designing a pH-responsive probe molecule. Parker and his team have built a tetraMacrocycles function as cellular pH probes. azacyclododecane derivative that complexes a single europium (III) ion; the red nescence, says Parker, is at least 500-fold luminescence from the metal ion is stronger than that seen at neutral pH, switched on only under acidic conditions when the antennae are switched off. This and switched off at basic pH. Additionally, strength, Parker says, creates a "genuine reacting this complex with methyl iodide pH switch." The pH at which the effect alters its structure slightly and makes it occurs can be controlled by simple respond to hydroxide ions in the same changes in the molecular structure of the way, such as a molecular equivalent of a antenna. In the presence of hydroxide litmus strip. The work is described in the ions above pH 10, the red luminescence Oct. 15 issue of Chemical Communicationsfrom europium is switched off. (1997, p. 1777). A deliberate, but slight, delay in emisAccording to Parker, chemically robust sion from the complex, says Parker, allows single-component luminescent sensors are them to remove background cellular fluoneeded, not only for analyzing ionic compo- rescence. The team is now figuring out how nents of industrial and environmental samto incorporate the europium complex into a ples but also for studying ionic changes in fiber-optic sensor for use in medical cellular living cells. For example, changes in local imaging. Sensor scientist James Ingle of pH often accompany tumor growth or indi- Oregon State University adds, "This certainly cate a failed oxygen supply to an organ. has many potential uses for micro-scale pH measurements," although he points out that When they excited the complex with "the range of pH over which the 'switch' radiation at 375 nm at pH