The unexpected formation of [M - H]⁺ species during MALDI and dopant-free APPI MS analysis of novel antineoplastic curcumin analogues

Unusual ionization behavior was observed with novel antineoplastic curcumin analogues during the positive ion mode of matrix-assisted laser desorption ionization (MALDI) and dopant-free atmospheric pressure photoionization (APPI). The tested compounds produced an unusual significant peak designated as [M - H]⁺ ion along with the expected [M + H]⁺ species. In contrast, electrospray ionization, atmospheric pressure chemical ionization and the dopant-mediated APPI (dopant-APPI) showed only the expected [M + H]⁺ peak. The [M - H]⁺ ion was detected with all evaluated curcumin analogues including phosphoramidates, secondary amines, amides and mixed amines/amides. Our experiments revealed that photon energy triggers the ionization of the curcumin analogues even in the absence of any ionization enhancer such as matrix, solvent or dopant. The possible mechanisms for the formation of both [M - H]⁺ and [M + H]⁺ ions are discussed in this paper. In particular, three proposed mechanisms for the formation of [M - H]⁺ were evaluated. The first mechanism involves the loss of H₂ from the protonated [M + H]⁺ species. The other two mechanisms include hydrogen transfer from the analyte radical cation or hydride abstraction from the neutral analyte molecule.