Structural Biochemistry/Carbohydrates/Carbohydrate Structure Elucidation through Periodic Acid Cleavage

One important method of elucidating the structure of carbohydrates is using periodic acid degradation. Periodic acid (HIO4) is a reagent that cleaves the carbon-carbon bonds in a sugar through oxidation. Periodic acid attacks the vicinal diols in carbohydrates and oxidizes these groups to form carbonyl compounds. The mechanism of this reaction involves a cyclic periodate ester that reacts with two neighboring alcohol functional groups which are oxidized to carbonyl functional groups.

How is a sugar degraded through periodic acid degradation?
When a sugar is reacted with excess periodic acid, each carbon-carbon bond is broken, forming a characteristic composition of one-carbon compounds that can provide some information about the structure of that carbohydrate. A quick rule of thumb for this reaction is that for any given carbon atom in the carbohydrate, for each carbon-carbon bond that is broken, that carbon atom will be oxidized once. Therefore, each broken bond will be replaced with an OH group. If there is a any carbon with two OH groups, it will lose water and become a carbonyl group. The final product will be either a ketone or an aldehyde.

For example, an aldehyde has one carbon-carbon bond and will react to form formic acid. Secondary alcohols will break 2 carbon-carbon bonds and will be oxidized twice, also forming formic acid. Primary alcohols will break one carbon-carbon bond and will be oxidized once to formaldehyde. Ketones will break two carbon-carbon bonds and form carbon dioxide (CO2).

Evidence that can be elucidated from periodic acid cleavage
This method can provide several clues to elucidate the structure of an unknown carbohydrate. By analyzing the ratios of the products mentioned above, some information about the types of functional groups present can be obtained. Specifically, because ketones oxidize to carbon dioxide when they are reacted with periodic acid, this method can provide clues as to whether the carbohydrate in question is an aldose or a ketose. Also, the size of the carbohydrate can be revealed by the amount of periodic acid that is consumed. One equivalent of periodic acid corresponds to one carbon-carbon bond cleavage. For example, a six-carbon carbohydrate would consume 5 equivalents of periodic acid.

Examples of periodic acid cleavage
One example of periodic acid cleavage involves the degradation of one equivalent of D-glucose into five equivalents of formic acid and one equivalent of formaldehyde.

Another example of periodic acid cleavage involves the degradation of one equivalent of D-fructose to three equivalents of formic acid, two equivalents of formaldehyde, and one equivalent of carbon dioxide.