Molecule Signals Presence Of Ion Trio

Sets of three or more chemical species are important in many biological processes and are implicated in some diseases. Renal failure, for example, is indicated by raised levels of potassium, urea, and creatinine.

The use of one test, rather than three separate tests, to detect the presence of three analytes could therefore potentially improve the efficiency of screening for various medical conditions. Chemists at Queen's University, Belfast, Ireland, have now shown that such a test is, in principle, possible, using a relatively simple prototype molecule that they dub "lab-on-a-molecule" (J. Am. Chem. Soc., published online March 28, dx.doi.org/10.1021/ja058295+).

The molecule, designed by chemistry professor A. Prasanna de Silva, postdoc David C. Magri, and coworkers, switches on a fluorescence signal when Na⁺, H⁺, and Zn²⁺ ions are present in aqueous solution above preset concentration thresholds. It is an example of a three-input molecular AND logic gate as it requires all three inputs for an enhanced fluorescence output.

"To the best of our knowledge, the paper describes the first molecular AND logic gate driven by three chemical inputs that serves as a molecular device capable of intelligent diagnostics," de Silva tells C&EN. "It shows that molecules are becoming 'clever' enough to perform a combination of serial and parallel tasks internally before releasing a simple decision. Such molecular devices can clearly support health practitioners by combining testing and diagnosis in disease screening programs."

The molecule is a photoinduced electron-transfer system in which a fluorophore and three different receptors are linked sequentially by spacer units. The three receptors—a benzo-15-crown-5 ether, a tertiary amine, and a phenyliminodiacetate—detect the electrolytes Na⁺, H⁺, and Zn²⁺, respectively. The fluorophore is an anthracene moiety. The three methylene spacer units minimize the distance between the receptors and the fluorophore and therefore facilitate efficient photoinduced electron transfer.

"This is a superb example of how to put simple components together to produce a molecule that is exquisitely selective in its function," comments David A. Leigh, professor of organic chemistry at the University of Edinburgh, in Scotland. "It is carefully designed so that the three receptors act orthogonally in terms of substrate binding, and collectively in terms of quenching fluorophore emission. The high concentration of one ion therefore does not swamp the other receptor sites. This is clearly the way to go in terms of single-molecule sensing devices."

De Silva points out that the modular nature of the system allows it to be changed to tackle other trios of species. "We made the system as a prototype of the 'lab-on-a-molecule' concept and chose this one as it was not too hard to make," he says. "We can choose modules with the appropriate binding strengths to match required biological concentrations. Renal failure is a realistic goal since species such as electrolytes and small molecules are amenable to our design."