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

This review discusses recent emerging techniques that have been used to couple flow-injection analysis (FIA) and electrospray ionization-mass spectrometry (ESI-MS) for the quantitation of noncovalent binding interactions. Focus is placed predominantly on two such methods. Diffusion-based measurements, developed by Konermann and co-workers, uses controlled-band dispersion prior to ESI-MS to determine diffusion constants and binding constants based on the temporal variation of ligand signal measured in the mass spectrum (an indirect technique). Dynamic titration, developed by Schug and co-workers, is a direct method, where a temporal compositional gradient of a guest molecule is induced in the presence of host in solution to monitor the concentration dependence of complex formation as a function of observed complex ion abundance after ESI-MS. Further discussion places these techniques in the context of a variety of other direct and indirect ESI-MS-based binding determination methods, and highlights advantages, disadvantages, and practical considerations for their proper use to investigate a broad range of macromolecular and small-molecule interaction systems.