Chemical Footnote

C &EN IS a chemistry newsmagazine. That means our pages contain the names and structures of lots of chemical compounds. It also means that we are vulnerable to chemical nomenclature and structure snafus and, in some cases, erroneous information. When that happens, we hear about it from our readers.

One recent example brought to our attention involves a well-known and important compound: vitamin C. Also known as ascorbic acid, or ascorbate in its active anionic form, vitamin C is a strong reducing agent. It serves as an antioxidant to scavenge free radicals that damage fatty acids and nucleic acids, and it functions as an enzyme cofactor for the synthesis of several important bioactive compounds.

A Science & Technology Concentrate that ran in C&EN's March 31 issue (page 26) described a research study published in the journal Cell (2008, 132, 1039) that showed how humans utilize vitamin C. Most animals and plants synthesize their own vitamin C from glucose in a multienzyme process. But because of an evolutionary glitch, the human gene that codes for the final enzyme in the pathway is defective.

That fact alone is fascinating. Were it not for the marginal amount of vitamin C in the fruits and veggies we eat, our species might have succumbed long ago by way of scurvy, a disease that is fatal if not treated by modification of the diet.

Our saving grace is that humans have developed an efficient vitamin C recycling system, which was the topic of the Cell paper. The researchers showed that a glucose transport protein on the surface of human red blood cells is altered by another protein called stomatin. As a result, dehydroascorbic acid (DHA), the oxidized form of ascorbic acid, is preferentially imported into red blood cells instead of glucose. DHA is then reduced to ascorbate inside the blood cells. This process recycles the ascorbate; otherwise, people would have to consume a lot more vitamin C.

So here is where the structural problem emerges. We thought it would be useful to include a structure of DHA with the concentrate, but the Cell paper didn't have one. When that situation arises, we sometimes ask the researchers for a structure, but more often we turn to "The Merck Index" and Chemical Abstracts Service's SciFinder program to obtain a structure, which a C&EN staff artist then draws.

The "tricarbonyl" DHA structure that appeared in C&EN has three carbonyl groups around the perimeter of a furan ring and is similar to the version in "Merck" and identical to the version in SciFinder. Robert C. Kerber, a chemistry professor at the State University of New York, Stony Brook, wrote in to say that the structure we used is "folkloric." By that, Kerber meant that the tricarbonyl structure is unlikely to exist in aqueous solution—that is, in the human body—for very long or possibly at all. "But unfortunately this structure has existed in textbooks for many decades," he says.

Kerber's scholarly interests focus on chemical education—in particular, studying how terminology generally accepted by experienced practitioners impedes understanding by novices, which includes reforming archaic or outdated information. And it just so happens that when the concentrate was published, he was finishing up an article on how the tricarbonyl structure of DHA has persisted in the literature, despite chemical evidence against it.

On the basis of his investigation, a "hydrated hemiacetal" structure is probably the best representation of DHA under physiological conditions, Kerber says. This bicyclic structure with its four hydroxyl groups should be a more suitable substrate for the glucose-transporting protein described in the Cell paper than the traditional tricarbonyl structure, he notes. Kerber's paper appears in the September issue of the Journal of Chemical Education (2008, 85, 1237).

THE TRICARBONYL STRUCTURE must have seemed logical to earlier researchers, Kerber points out. It can be formed by removing H₂ from ascorbic acid. But the structural representation was not based on any actual research findings, he believes. The tricarbonyl version came to be accepted by chemists who were uncritical or preferred simplicity, Kerber says. "Continued use of the oversimplified tricarbonyl structure is hard to excuse," he adds, "given that the actual structures of the various forms of DHA have now been known for at least 25 years."

If chemical structures are the basic language of chemistry, an inaccurate or oversimplified symbolic structure is a hindrance to communication and possibly to scientific progress, Kerber argues in his paper. "It remains useful to remind students that incorporation of material into a textbook does not assure its unimpeachability and that they should approach their reading with reasonable skepticism," he writes. The DHA example, Kerber asserts, provides an interesting case study in which to raise questions about the ability of the scientific community to correct oversimplifications and incorporate new knowledge into its dogma.

Taking time out to clear up ambiguities regarding chemical nomenclature and structures by providing a footnote, such as this one on DHA, adds value to C&EN's reporting on cutting-edge research. If there is any moral to this story, it is that the inherent richness of chemistry always presents opportunities for new learning and brushing up on our critical thinking skills, as well as for renewing our dedication to our craft.