If you have an ACS member number, please enter it here so we can link this account to your membership. (optional)

ACS values your privacy. By submitting your information, you are gaining access to C&EN and subscribing to our weekly newsletter. We use the information you provide to make your reading experience better, and we will never sell your data to third party members.


Analytical Chemistry

Photoacoustic molecular probe detects hypoxia

Low oxygen levels trigger a switch from N-oxide to aniline, with an observable spectral signature

by Celia Henry Arnaud
December 4, 2017 | A version of this story appeared in Volume 95, Issue 48

Structures of the two probe molecules HyP-1 and red-HyP-1, highlighting the switch from an N-oxide to an aniline.
Credit: Nat. Commun.
At low oxygen levels, the N-oxide of HyP-1 is reduced to the aniline of red-HyP-1, which enables hypoxia detection.

Hypoxia—damage to tissue caused by low oxygen levels—can be difficult to detect. Jefferson Chan and coworkers at the University of Illinois, Urbana-Champaign, have developed a small molecule probe they call HyP-1 that improves hypoxia detection by using photoacoustic imaging (Nat. Commun. 2017, DOI: 10.1038/s41467-017-01951-0). In photoacoustic imaging, near-infrared light induces temperature and pressure changes in tissue that result in the production of ultrasound waves. Because sound scatters less in tissue than light does, the sound waves can be used to produce images from deep in tissue. HyP-1 contains an N-oxide trigger that undergoes reduction to the corresponding aniline (red-HyP-1) in the absence of oxygen. This reduction depends on competitive binding of oxygen to the heme iron in various enzymes. Because red-HyP-1 absorbs light at longer wavelengths than HyP-1 does, any photoacoustic signal produced by excitation at those longer wavelengths corresponds exclusively to red-Hyp-1, which indicates hypoxia. The researchers used HyP-1 to detect hypoxia in cultured cells, in tumors in mice, and in hind limb ischemia in mice. Although HyP-1 was designed for photoacoustic imaging, the fact that both it and red-HyP-1 fluoresce in the near-infrared means that the probe pair can also be used for comparative fluorescence imaging.


This article has been sent to the following recipient:

Chemistry matters. Join us to get the news you need.