Hydrogen/deuterium exchange mass spectrometry in the world of small molecules
Résumé
The combined use of hydrogen/deuterium exchange (HDX) and massspectrometry (MS), referred to as HDX‐MS, is a powerful tool for exploringmolecular edifices and has been used for over 60 years. Initially for structuraland mechanistic investigation of low‐molecular weight organic compounds,then to study protein structure and dynamics, then, the craze to study smallmolecules by HDX‐MS accelerated and has not stopped yet. The purpose ofthis review is to present its different facets with particular emphasis onrecent developments and applications. Reversible H/D exchanges of mobi-lizable protons as well as stable exchanges of non‐labile hydrogen are con-sidered whether they are taking place in solution or in the gas phase, orenzymatically in a biological media. Some fundamental principles arerestated, especially for gas‐phase processes, and an overview of recentapplications, ranging from identification to quantification through the studyof metabolic pathways, is given.