Solution reactivity of brevetoxins as monitored by electrospray ionization mass spectrometry and implications for...

The reactivities of brevetoxin compounds in acid and base and under oxidizing conditions were studied using electrospray ionization mass spectrometry (ESI-MS) to monitor reaction products. Brevetoxins are determined to be unstable in acidic and basic solutions. Under acidic conditions, brevetoxins containing an aldehyde functional group in the terminal "tail" side chain are easily converted to acetal structures, while "head" side lactone ring opening proceeds more slowly. Measurement of reaction rate constants indicates the following order of reactivity under acidic conditions: Btx-1 > Btx-2 > Btx-9. Under basic conditions, hydroxide ion attack at the head portion leads to lactone ring opening. Base hydrolysis (0.01 N NaOH in 50:50 methanol/water) goes to completion in 120 min for Btx-2 and Btx-9, but Btx-1 did not react to completion. Both acid and base hydrolyses can lead to reversible lactone ring opening, but base hydrolysis proceeds faster than acid hydrolysis under comparable conditions. Acid treatment is not an effective method for detoxifying brevetoxins. Base treatment can open the lactone ring (type B brevetoxins proceed faster than type A brevetoxins), leading to a product that is reportedly nontoxic, but the reaction is reversible. Brevetoxins are shown to be readily oxidized by permanganate in an irreversible and relatively fast reaction, likely through addition to double bonds followed by bond cleavage, suggesting that it is a viable method for detoxification.