Quantitative determination of noncovalent binding interactions using soft ionization mass spectrometry

For a number of years, soft ionization mass spectrometry has been used for studying noncovalently bound complexes. An intriguing question in this context is whether MS experiments can be used to measure the interaction strength. A number of recent studies have addressed this question. The results of these studies, as well as the methods employed are reviewed here. We distinguish between liquid-phase methods such as mass spectrometrically detected melting curves, titration experiments, or competition experiments, and gas-phase methods such as cone voltage-driven dissociation, collision-induced dissociation, blackbody infrared radiative dissociation, or thermal dissociation of gas-phase complex ions. With a few exceptions, no agreement exists between solution-phase and gas-phase binding energies. The main reason is that electrostatic and dipolar noncovalent interactions are strengthened in the absence of solvent shielding, while other noncovalent interactions, in particular hydrophobic interactions, become less important in the absence of solvent. The possibility to quantitatively measure solution-phase as well as gas-phase noncovalent interaction strengths by mass spectrometry opens fascinating perspectives for very high sensitivity screening assays as well as for improved fundamental understanding of the nature of noncovalent interactions. (C) 2002 Elsevier Science B.V All rights reserved.