Fundamental studies of electrospray mass spectrometry

Electrospray is a new soft ionization technique in which intact gas phase ions of large, nonvolatile molecules present in a solution are produced at atmospheric pressure. In this work, some of the parameters that control the electrospray response of analytes are examined. These are the surface tension of the solution, analyte surface activity, ion-solvation and ion-pairing interactions, acidity/basicity effects, and polarizabilities. The effect of surface tension is studied in samples where the surface tension is modified by addition of cationic, anionic, and nonionic surfactants. The results show an inverse correlation between the surface tension of the solution and the electrospray response of the analyte. Surface activity effects are assessed in solutions containing equimolar amounts of the cationic surfactants, n-alkyltrimethylammonium bromides, C_nH_2n+1N⁺(CH₃)₃Br^- (n = 6, 10, 12, 14, 16, 18). Equal intensities are observed for the various n-alkyltrimethylammonium salts present in the mixtures, when the concentration of each component is ≤ 2 μM. At higher concentrations, a linear correlation is observed between the electrospray response of a given species and its surface activity presumably because of competition for surface sites on the electrosprayed droplets. To study the effects of ion-solvent interactions on the electrospray response of analytes, a set of tetraalkylammonium bromides (quats) with known solvation enthalpies is utilized. An inverse correlation between the observed intensities and solvation enthalpies suggests that minimizing electrostatic interactions with the solvent improves desorption efficiencies. Ion pairing interactions are also observed in diquaternary ammonium salts with counterions that show different ion association tendencies and in two tetraalkylammonium salts. Ion pairing interactions, primarily noted at high analyte concentrations (≥ 5 μM), reduce the observed response of singly charged species and slightly enhance the overall response of doubly charged diquats. The electrospray behavior of a group of amines and amino acids is studied in the final part of this work. The goal is to determine whether thermodynamic measures of acidity/basicity, solvation energies, and polarizabilities could be used to predict their electrospray response. The results of these studies suggest that the calculated polarizabilities of analytes can provide a rough estimate of their electrospray response (in positive mode electrospray) when their pK_a is greater than approximately 9.0.