Differential Cationization of Fatty Acids with Monovalent Cations Studied by ESI-MS/MS and Computational Approach

The intercellular and intracellular transport of charged species (Na⁺ /K⁺ ) entail interaction of the ions with neutral organic molecules and formation of adduct ions. The rate of transport of the ions across the cell membrane(s) may depend on the stability of the adduct ions, which in turn rely on structural aspects of the organic molecules that interact with the ions.

Positive ion ESI mass spectra were recorded for the solutions containing fatty acids (FAs) and monovalent cations (X=Li⁺ , Na⁺ , K⁺ , Rb⁺ and Cs⁺ ). Product ion spectra of the [FA+X]⁺ ions were recorded at different collision energies. Theoretical studies were exploited under both gas phase and solvent phase to investigate the structural effects of the fatty acids during cationization. Stability of [FA+X]⁺ adduct ions were further estimated by means of AIM topological analyses and interaction energy (IE) values.

Positive ion ESI-MS analyses of the solution of FAs and X⁺ ions showed preferential binding of the K⁺ ions to FAs. The K⁺ ion binding increased with the increase in number of double bonds of FAs, while decreased with increase in the number of carbons of FAs. Dissociation curves of [FA+X]⁺ ions indicated the relative stability order of the [FA+X]⁺ ions and it was in line with the observed trends in ESI-MS. The solvent phase computational studies divulged the mode of binding and the binding efficiencies of different FAs with monovalent cations.

Among the studied monovalent cations, the cationization of FAs follow the order K⁺ >>Na⁺ >Li⁺ >Rb⁺ >Cs⁺ . The docosahexaenoic acid showed high efficiency in binding with K⁺ ion. The K⁺ ion binding efficiency of FAs depends on the number of double bonds in unsaturated FAs and the carbon chain length in saturated FAs. The cationization trends of FAs obtained from the ESI-MS, ESI-MS/MS analyses were in good agreement with solvent phase computational studies.