Study of metal complexation of cardenolides with divalent metal ions by Electrospray Ionization Mass Spectrometry

SILESS, GASTÓN E.; CABRERA, GABRIELA M.; BUTLER, MATIAS

INTERNATIONAL JOURNAL OF MASS SPECTROMETRY

ELSEVIER SCIENCE BV

Año: 2017 vol. 419 p. 44 - 51

1387-3806

Cardenolides are natural products with positive inotropic and cytotoxic activity that are able to interact withmetals, although the possible role that these interactions may play in their biological activity is not known.Mixtures of the following cardenolides: digoxigenin (DgG), gitoxigenin (GxG), digitoxigenin (DxG), uzarigenin(UzG) and a butenolide, 2(5H)-furanone (Fur), with different metal cations, namely Ca2+, Mg2+, Cu2+, Co2+and Zn2+,were studied by Electrospray Ionization Mass Spectrometry in a Quadrupole-Time of Flight. Therelative stability of the most important adducts was studied by threshold collision induced dissociation, E1/2.Computational modeling of the observed complexes with calcium was performed using DFT B3LYP/6-31G+(d,p) level of theory.Complexes of stoichiometry [nM+Me]2+, with n = 4 to 6 ligands and Me a metal cation, were observed forall studied compounds. The adducts [4M+Me]2+ corresponded to the most intense peaks in most of the massspectra and showed the highest E1/2. GxG showed a higher tendency to form complexes with low coordinationnumbers. Calculations showed that the carbonyl oxygen of the butenolide moiety is the most important site ofcoordination and allowed the proposal of different binding modes to explain the differences observed in the GxGMS spectra.A direct relationship was observed between experimental and computational data, which allowed to predictthe MS behavior of these or similar compounds. The analysis can be extrapolated to other compounds with afuranone ring, and used as an analytical tool to characterize furanone compounds, or for the differentiation ofDgG and GxG