Angewandte Chemie International Edition
© WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
For full article and contact information, see Angew. Chem. Int. Ed. 2000, 39 (12), 2120 - 2122
Sensor for Molecular Turn-on
New method detects NO
selectively and sensitively
The discovery of the occurrence of nitric oxide in human metabolism was a big surprise in 1987. Since then, many biological processes have been discovered in which this gas acts as a messenger. NO plays an important role in the relaxation of muscles, in immune reactions, and in boosting our memory. The little molecule with a big impact became a media star in 1998, when Viagra came on the market: the blue wonder-pill releases NO into the body, where its vasodilatory effect counteracts erectile disfunction.
Sufficiently sensitive methods for the detection of NO are in high demand, but are hard to come by. This could soon change, because Stephen Lippard, Katherine J. Franz and Nisha Singh at the Massachusetts Institute of Technology have developed a promising new strategy for the detection of NO.
The basis of the new detection method is a special cobalt complex. The complex consists of a central cobalt atom that is surrounded by two "arms" of an organic ligand. The ligand attaches itself to the cobalt atom through four binding sites. When the complex comes in contact with nitric oxide, two NO molecules force two of the binding sites of the ligand off of the cobalt. The ligand is then only bound by one of its two "arms". The key to this method lies in the changes to the fluorescence characteristics of the ligand: as long as the ligand is bound to the cobalt atom through four sites, the fluorescence of the ligand is suppressed through interactions with the central atom. However, when one of its "arms" is released, the ligand can once again fluoresce. In this way, the fluorescence indicates the presence of NO. This indicator is also selective: it does not react to other molecules, such as oxygen.
"Many of the NO detectors used today are based on identification of its decomposition products, nitrite and nitrate. In contrast, our fluorescence indicator reacts directly with NO. It has the potential to track the formation of NO in real time," hopes Lippard. The scientists are now working on the development of more sensitive, water-soluble sensors with a stronger fluorescence. "With this future generation of sensors it should be possible to measure NO in cell cultures. In the distant future, applications to understand NO-triggered neurobiological events in living organisms, and possibly even medical applications, could emerge," Lippard says optimistically.