Protonation of Curcumin Triggers Sequential Double Cyclization in the Gas-Phase: An Electrospray Mass Spectrometry and DFT Study.

ESI-protonated natural curcumin (1) undergoes gas-phase cyclization and dissociates via competitive expulsions of 2-methoxy phenol and C4H4O2 (diketene or an isomer). Evidence from mechanistic mass spectrometry and from Density Functional Theory (DFT) reveals that a two-step sequential cyclization occurs for the protonated molecule prior to the unusual loss of the elements of 2-methoxy phenol. Furthermore, the presence of the methoxy group at postion-3 is essential for the second cyclization. The transformation of curcumin upon protonation in the gas phase may be predictive of its solution chemistry and explain how curcumin plays a protective role in biology.