Sensing a turn on

Having the sense to say NO.

The list of biological processes that rely on nitric oxide (NO) continues to grow - it is involved in muscle relaxation, the immune response, memory and, of course, sexual arousal and plenty more besides.

Now, Stephen Lippard, Katherine Franz and Nisha Singh at the Massachusetts Institute of Technology, have developed a promising new strategy for the detection of NO that could lead to a far more sensitive detector for the little molecules with the big job.

Lippard's team have designed a fluorescent cobalt complex that can trap NO. The oxygen-stable complex consists of a central cobalt atom with two fluorophore-substituted arms of the aminotroponiminate ligand DATI-4, providing four binding sites to the metal ion. While the ligand is engaged in holding on to the cobalt, the complex cannot fluoresce due to quenching by the cobalt metal. However, if nitric oxide is present, two of the binding sites are dissociated so the complex can grab on to the NO units. This leaves the ligand hanging on by only one of its two arms, which is then free from the quenching environment of the metal and can fluoresce.

The complex is sensitive down to 50 to 100 micromolar of NO, as well as being selective; it is unaffected by oxygen for instance. "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", explains Lippard.

The team is now developing a more sensitive, water-soluble version with a stronger fluorescence signal. Ultimately, Lippard hopes to be able to use the sensor to measure NO in cell cultures and eventually to exploit such a device in understanding NO-triggered neurobiological events in living organisms.

Reference:
Angew Chem Engl Edn, 2000, 39(12), 2120.