Solution Chemistry of Dihydroxyacetone and Synthesis of Monomeric Dihydroxyacetone

Abstract

Dihydroxyacetone (DHA) is a major byproduct of e-cigarette combustion and is the active ingredient in sunless tanning products. Mounting evidence points to its damaging effects on cellular functions. While developing a simple synthetic route to monomeric [ 13 C 3 ]DHA for flux metabolic studies that compared DHA and glyceraldehyde (GA) metabolism, we uncovered that solid DHA ages upon storage and differences in the relative abundance of each of its isomer occur when reconstituted in an aqueous solution. While all three of the dimeric forms of DHA ultimately resolve to the ketone and hydrated forms of monomeric DHA once in water at room temperature, these species require hours rather than minutes to reach an equilibrium favoring the monomeric species. Consequently, when used in bolus or flux experiments, the relative abundance of each isomer and its effects at the time of application is dependent on the initial DHA isomeric composition and concentration, and time of equilibration in solution before use. Here, we make recommendations for the more consistent handling of DHA as we report conditions that ensure that DHA is present in its monomeric form while in solutions, conditions used in an isotopic tracing study that specifically compared monomeric DHA and GA metabolism in cells.

Dihydroxyacetone: A User Guide for a Challenging Bio-Based Synthon

“…These electron-withdrawing groups increase the reactivity of the carbonyl, compared to non-hydroxylated analogs, such as acetone, for example [ 102 ]. Therefore, although DHA is a ketone with a chemical structure close to that of acetone, when dissolved in water it reaches a ketone/hydrate equilibrium of 4:1, whereas hydrated acetone is present in water only in trace amounts ( Figure 10 ) [ 9 , 88 , 97 ].…”

“…For example, it has been reported to be present at the very early stages of life on Earth, as one of the earliest sugars produced by reaction of formaldehyde containing traces of glycolaldehyde heated in calcium hydroxide solution [ 6 , 7 ]. It has also been reported as a major component of e-cigarette smokes and was proven to react with DNA in vitro [ 8 , 9 ]. This close relationship with biochemical processes in living organisms makes DHA a well-known, yet seldom studied chemical.…”