Complexation of the Mycotoxin Cyclopiazonic Acid with Lanthanides Yields Luminescent Products

摘要

Cycopiazonic acid (CPA) is a neurotoxin that acts through inhibition of the sarco(endo)plasmic reticulum Ca 2+ -ATPase (SERCA). CPA blocks the calcium access channel of the enzyme. The inhibition may involve the binding of CPA with a divalent cation such as Mg 2+ . The potential for CPA to act as a chelator also has implications for methods to detect this toxin. Certain of the lanthanide metals undergo a dramatic increase in luminescence upon coordination with small molecules that can transfer excitation energy to the metal. This report is the first to describe the coordination of CPA with lanthanide metals, resulting in a substantial enhancement of their luminescence. The luminescence expressed was dependent upon the type of lanthanide, its concentration, and the environment (solvent, water content, pH). Based upon the phenomenon, a competitive assay was also developed wherein terbium (Tb 3+ ) and a series of metal cations competed for binding with CPA. With increasing cation concentration, the luminescence of the CPA/Tb 3+ complex was inhibited. The chlorides of ten metals were tested. Inhibition was best with Cu 2+ , followed by Co 2+ , Al 3+ , Fe 3+ , Mn 2+ , Au 3+ , Mg 2+ , and Ca 2+ . Two cations in oxidation state one (Na + , K + ) did not inhibit the interaction significantly. The interaction of CPA with lanthanides provides a novel recognition assay for this toxin. It also provides a novel way to probe the binding of CPA to metals, giving insights into CPA’s mechanism of action.