Mass Spectrometry Directed Structural Elucidation of Isomeric [2 + 2] Photocycloadducts

Abstract

[2 + 2] Photocycloaddition reactions are powerful tools for synthetic chemistry. However, analysis of the head-to-head or head-to-tail conformation of the resulting cycloadducts is often challenging by conventional spectroscopic methods. Herein, we report the analysis of coumarin and styrylpyrene cycloadducts by cyclic ion-mobility tandem mass spectrometry (cIM-MS/MS) to characterize the regioisomeric products of this important class of photoresponsive groups. Photodissociation (PD) and collision-induced dissociation (CID) of the cycloadduct ions in the gas phase gave similar products to photodissociation in solution with regiospecific fragmentation of the core cyclobutane ring. The styrylpyrene cycloadduct ion was observed to be more stable than the coumarin analog under CID conditions, reflecting the impact of different substituents on the stability of the cyclobutane ring. Exploiting the difference in cyclobutane fragmentation for head-to-head and head-to-tail styrylpyrene cycloadduct isomers, ion mobility enabled CID-MS/MS was applied successfully to differentiate and identify these isomers. The developed method proved to be robust even to complex molecular structures and enabled the identification and separation of photocycloadducts resulting from styrylpyrene terminated peptides, providing access to a rapid analysis of challenging cycloadduct isomers.