A solution of phenol red is used as a pH indicator: its color exhibits a gradual transition from yellow to red over the pH range 6.6 to 8.0. Above pH 8.1, phenol red turns a bright pink (fuchsia) color.
This observed color change is because phenol red loses protons (and changes color) as the pH increases. In crystalline form, and in solution under very acidic conditions (low pH), the compound exists as a zwitterion as in the structure shown above, with the sulfate group negatively charged, and the ketone group carrying an additional proton. This form is sometimes symbolically written as H2+PS− and is orange-red. If the pH is increased (pKa = 1.2), the proton from the ketone group is lost, resulting in the yellow negatively charged ion HPS−. At still higher pH (pKa = 7.7), the phenol's hydroxide group loses its proton, resulting in the red ion PS2−.
In several sources, the structure of phenol red is shown with the sulfur atom being part of a cyclic group, similar to the structure of phenolphthalein. However, this cyclic structure could not be confirmed by X-ray crystallography.
Several indicators share a similar structure to phenol red, including bromothymol blue, thymol blue, bromocresol purple, thymolphthalein, and phenolphthalein. (A table of other common chemical indicators is available in the article on pH indicators.)
The test is based on the fact that phenol red is excreted almost entirely in the urine. By measuring the amount of phenol red excreted colorimetrically, kidney function can be determined. Phenol red solution is administered intravenously, all of the urine produced is collected and the phenol red present determined.
In the event of problems, waste products produced by dying cells or overgrowth of contaminants will cause a change in pH, leading to a change in indicator color. For example, a culture of relatively slowly-dividing mammalian cells can be quickly overgrown by bacterial contamination. This usually results in an acidification of the medium, turning it yellow. Many biologists find this a convenient way to rapidly check on the health of tissue cultures. In addition, the waste products produced by the mammalian cells themselves will slowly decrease the pH, gradually turning the solution orange and then yellow. This color change is an indication that even in the absence of contamination, the medium needs to be replaced (generally, this should be done before the medium has turned completely orange).
An important breakthrough in biotechnology was reported in the scientific literature on May 5th, 2005. Using phenol red as a differentiation factor, scientists at the University of Tennessee produced human oocytes (eggs) from cells scraped from the surface of adult ovaries. These cells on the outer ovarian surface are known as ovarian surface epithelial cells. Such cells had been taken from five women aged 39 to 52 and were cultured in the presence of phenol red, inducing oogenesis.
Previously, human eggs had only been produced in vitro from totipotent, blastomeric embryonic stem cells. One of the significant aspects of this experiment is that it demonstrated viable human egg cells can easily be produced from an adult cell that already has some degree of specialization. Furthermore, it lessens the implications associated with the fact that women are born with all of the egg cells they will ever have throughout their lives. While this breakthrough was not without controversy, it provides hope for infertile women wishing to undergo in vitro fertilization, and hints at the possibility of new options for post-menopausal women as well. It also suggests that the future of stem cell research may not have to rely as heavily on human embryos as a source of unspecialized, totipotent cells for research.
Phenol red, sometimes labelled with a different name, such as "Guardex Solution #2", is used as a pH indicator in home swimming pool test kits.