Practical Investigation of Molecular and Biomolecular Noncovalent Recognition Processes in Solution by ESI‐MS

Abstract

278j 8 Practical Investigation of Noncovalent Recognition by ESI-MS reduced in the gas phase. In contrast, complexes held together strictly by solvophobic forces will not survive the phase transfer process as solvent is removed. Figure 8.1 illustrates this concept. In general, it is reasonable to expect that enthalpically-driven recognition processes are most amenable to analysis by ESI-MS, whereas those that are entropically-driven must be stabilized by some enthalpic component in order to survive the electrospray process. This leads to a system dependency in the application of ESI-MS for studying noncovalent interactions, which is perhaps the most significant limitation. That said, work continues to elucidate the possibility of ESI-MS for studying hydrophobic interactions [43,44].One must also realize that ESI is a competitive ionization process. This phenomenon is best described by the work of Enke [45], and later was extended to host-guest interactions by Brodbelt and coworkers [46,47] on an equilibrium partitioning model (EPM). This model elegantly describes those factors which give rise to a limited linear dynamic range as a fixed number of charged sites on the surface of a droplet are taken up by surface-active species. This model also allows one to better understand matrix and ionization saturation effects, which can give rise to noncorrelation between gas-phase ion abundances and solution-phase concentrations as multiple analytes in the droplet compete for ionization. Species initially in the electrically neutral core of the droplet partition to the surface of the droplet according to their respective solvation energies and surface activities. The equilibrium partition model for hostguest complexation and competitive ionization is depicted in Figure 8.2. As a final general point, the preponderance of nonspecific interactions and adduct ion formation, often observed when relatively high concentrations of analytes and solution modifiers are employed, must be carefully considered, monitored, and controlled in order to avoid false positives and false negatives during both qualitative screening and quantitative binding experiments.A basic understanding of the caveats involved in performing physical binding measurements with ESI-MS is a necessity. Good experimental design is also Figure 8.

Controlled band dispersion for quantitative binding determination and analysis with electrospray ionization‐mass spectrometry

“… The dynamic electrospray process, and the influence of phase‐transfer on noncovalent complexes. Adapted from Schug (in press). …”